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  • 301.
    Nordmark, Johanna
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Aspects of Induced Hypothermia following Cardiopulmonary Resuscitation: Cerebral and Cardiovascular Effects2009Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Hypothermia treatment with cooling to a body temperature of 32-34°C has been shown to be an effective way of improving neurological outcome and survival in unconscious patients successfully resuscitated after cardiac arrest (CA). The method is used clinically but there are still many questions on the biological mechanisms and on how the treatment is best performed. This thesis focuses on cerebral and haemodynamic effects of hypothermia and rewarming.

    A porcine model of CA was used. To shorten time to reach target temperature, induction of hypothermia, by means of infusion of 4°C cold fluid, was started already during ongoing cardiopulmonary resuscitation. The temperature was satisfactorily reduced without obvious haemodynamic disturbances.

    Cerebral effects of hypothermia and rewarming were studied. Microdialysis monitoring showed signs of cerebral energy failure (increased lactate/pyruvate-ratio) and excitotoxicity (increased glutamate) immediately after CA. There was a risk of secondary energy failure that was reduced by hypothermia. Intracranial pressure (ICP) increased gradually after CA irrespectively of if hypothermia was used or not. There were no indications of increasing cerebral disturbances during rewarming.

    Haemodynamic effects of hypothermia treatment and rewarming were examined in a study of patients successfully resuscitated after CA. Hypothermia was induced by means of cold intravenous infusion. No negative effects on the cardiovascular system were revealed. There were indications of decreased intravascular volume in spite of a positive fluid balance.

    Cerebral microdialysis and ICP recording were performed in four patients. All patients had signs of energy failure and excitotoxicity following CA. ICP was only exceptionally above 20 mmHg. In contrast to the experimental study indications of increasing ischemia were seen during rewarming. Glycerol had a biphasic pattern, perhaps due to an overspill of metabolites from the general circulation. As most patients become extensively anti-coagulated following CA, intracranial monitoring is not suitable to be used in routine care.

    Delarbeten
    1. Induction of mild hypothermia with infusion of cold (4°C)fluid during ongoing CPR
    Öppna denna publikation i ny flik eller fönster >>Induction of mild hypothermia with infusion of cold (4°C)fluid during ongoing CPR
    2005 (Engelska)Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 66, nr 3, s. 357-365Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    INTRODUCTION: Therapeutic hypothermia after resuscitation has been shown to improve the outcome regarding neurological state and to reduce mortality. The earlier hypothermia therapy is induced probably the better. We studied the induction of hypothermia with a large volume of intravenous ice-cold fluid after cardiac arrest during ongoing cardiopulmonary resuscitation (CPR). METHODS: Twenty anaesthetised piglets were subjected to 8 min of ventricular fibrillation, followed by CPR. They were randomized into two groups. The hypothermic group was given an infusion of 4 degrees C acetated Ringer's solution 30 ml/kg at an infusion rate of 1.33 ml/kg/min, starting after 1 min of CPR. The control group received the same infusion at room temperature. All pigs received a bolus dose of vasopressin after 3 min of CPR. After 9 min, defibrillatory shocks were applied to achieve restoration of spontaneous circulation (ROSC). Core temperature and haemodynamic variables were measured at baseline and repeatedly until 180 min after ROSC. Cortical cerebral blood flow was measured, using Laser-Doppler flowmetry. RESULTS: All pigs had ROSC, except one animal in the hypothermic group. Only one animal in the hypothermic group died during the observation period. The calculated mean temperature reduction was 1.6+/-0.35 degrees C (S.D.) in the hypothermic group and 1.1+/-0.37 degrees C in the control group (p=0.009). There was no difference in cortical cerebral blood flow and haemodynamic variables. CONCLUSION: Inducing hypothermia with a cold infusion seems to be an effective method that can be started even during ongoing CPR. This method might warrant consideration for induction of early therapeutic hypothermia in cardiac arrest victims.

    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Anestesiologi
    Identifikatorer
    urn:nbn:se:uu:diva-98091 (URN)16081199 (PubMedID)
    Tillgänglig från: 2009-02-12 Skapad: 2009-02-12 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    2. Cerebral energy failure following experimental cardiac arrest: Hypothermia treatment reduces secondary lactate/pyruvate-ratio increase
    Öppna denna publikation i ny flik eller fönster >>Cerebral energy failure following experimental cardiac arrest: Hypothermia treatment reduces secondary lactate/pyruvate-ratio increase
    2009 (Engelska)Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 80, nr 5, s. 573-579Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    AIM: This was an experimental study performed to investigate cerebral metabolism during hypothermia treatment and rewarming after resuscitation from cardiac arrest (CA). MATERIALS AND METHODS: Sixteen pigs underwent CA followed by cardiopulmonary resuscitation (CPR). After randomisation into one hypothermic (n=8) and one normothermic group (n=8) the animals received infusion of 4 or 38 degrees C saline, respectively. Following restoration of spontaneous circulation (ROSC) both groups were observed for 360min. The hypothermic group was cooled for 180 min and then rewarmed. Temperature was not modulated in the normothermic group. Cerebral microdialysis was conducted and lactate/pyruvate (L/P)-ratio and glutamate were analysed. Intracranial pressure probe was inserted. Oxygen saturation in venous jugular bulb blood (SjO2) was analysed. RESULTS: All animals initially had increased L/P-ratio (>30). A total of nine animals developed secondary increase. In the hypothermic group this was observed in 2/7 animals and in the normothermic group in 7/8 (p=0.04). Glutamate increased initially in all animals with secondary increases in two animals in each group. No differences in L/P-ratio or glutamate were detected during the rewarming phase compared to the hypothermic phase. The hypothermic group had higher SjO(2) (p=0.04). In both groups intracranial pressure increased after ROSC. CONCLUSION: After resuscitation from CA there was a risk of cerebral secondary energy failure (reflected as an increased L/P-ratio) but hypothermia treatment seemed to counteract this effect. Cerebral oxygen extraction, measured by SjO(2,) was increased in the hypothermic group probably due to reduced metabolism. Rewarming did not reveal any obvious harmful events.

    Nyckelord
    Cardiac arrest, Cardiopulmonary resuscitation, Hypothermia, Rewarming, Brain ischaemia, Microdialysis, Lactate, Glutamate
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-98092 (URN)10.1016/j.resuscitation.2009.02.003 (DOI)000266670300014 ()19328618 (PubMedID)
    Tillgänglig från: 2009-02-12 Skapad: 2009-02-12 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    3. Intracerebral monitoring in comatose patients treated withhypothermia after cardiac arrest
    Öppna denna publikation i ny flik eller fönster >>Intracerebral monitoring in comatose patients treated withhypothermia after cardiac arrest
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    2009 (Engelska)Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 53, nr 3, s. 289-298Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: Induced mild hypothermia (32-34 degrees C) has proven to reduce ischemic brain injury and improve outcome after a cardiac arrest (CA). The aim of this investigation was to study the occurrence of increased intracranial pressure (ICP) and neurochemical metabolic changes indicating cerebral ischemia, after CA and cardiopulmonary resuscitation (CPR), when induced hypothermia was applied. METHODS: ICP, brain chemistry and brain temperature were monitored during induced hypothermia and re-warming in four adult unconscious patients with restoration of spontaneous circulation after CA and CPR. RESULTS: ICP was occasionally above 20 mmHg. Neurochemical changes indicating cerebral ischemia (increased lactate/pyruvate ratio) and excitoxicity (increased glutamate) were found after CA, and signs of ischemia were also observed during the re-warming phase. A biphasic increase in glycerol was seen, which may have been a result of both membrane degradation and overspill from the general circulation. CONCLUSIONS: Intracerebral microdialysis and ICP monitoring may be used in selected patients not requiring anticoagulants and PCI to obtain information regarding the common disturbances of intracranial dynamics after CA. The results of this study underline the importance of inducing hypothermia quickly after CA and emphasize the need for developing tools for guidance of the re-warming.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-98093 (URN)10.1111/j.1399-6576.2008.01885.x (DOI)000263351600003 ()19243314 (PubMedID)
    Tillgänglig från: 2009-02-12 Skapad: 2009-02-12 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    4. Decreased intravascular volume following cardiac arrest: Patient observations with echocardiography during hypothermia and rewarming
    Öppna denna publikation i ny flik eller fönster >>Decreased intravascular volume following cardiac arrest: Patient observations with echocardiography during hypothermia and rewarming
    Visa övriga...
    (Engelska)Manuskript (Övrigt vetenskapligt)
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-98094 (URN)
    Tillgänglig från: 2009-02-12 Skapad: 2009-02-12 Senast uppdaterad: 2015-06-08Bibliografiskt granskad
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  • 302.
    Nordmark, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Induction of mild hypothermia with infusion of cold (4°C)fluid during ongoing CPR2005Ingår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 66, nr 3, s. 357-365Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Therapeutic hypothermia after resuscitation has been shown to improve the outcome regarding neurological state and to reduce mortality. The earlier hypothermia therapy is induced probably the better. We studied the induction of hypothermia with a large volume of intravenous ice-cold fluid after cardiac arrest during ongoing cardiopulmonary resuscitation (CPR). METHODS: Twenty anaesthetised piglets were subjected to 8 min of ventricular fibrillation, followed by CPR. They were randomized into two groups. The hypothermic group was given an infusion of 4 degrees C acetated Ringer's solution 30 ml/kg at an infusion rate of 1.33 ml/kg/min, starting after 1 min of CPR. The control group received the same infusion at room temperature. All pigs received a bolus dose of vasopressin after 3 min of CPR. After 9 min, defibrillatory shocks were applied to achieve restoration of spontaneous circulation (ROSC). Core temperature and haemodynamic variables were measured at baseline and repeatedly until 180 min after ROSC. Cortical cerebral blood flow was measured, using Laser-Doppler flowmetry. RESULTS: All pigs had ROSC, except one animal in the hypothermic group. Only one animal in the hypothermic group died during the observation period. The calculated mean temperature reduction was 1.6+/-0.35 degrees C (S.D.) in the hypothermic group and 1.1+/-0.37 degrees C in the control group (p=0.009). There was no difference in cortical cerebral blood flow and haemodynamic variables. CONCLUSION: Inducing hypothermia with a cold infusion seems to be an effective method that can be started even during ongoing CPR. This method might warrant consideration for induction of early therapeutic hypothermia in cardiac arrest victims.

  • 303.
    Nyberg, Christoffer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Metabolic and Endocrine Response in the Acute Stage of Subarachnoid Hemorrhage2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The rupture of an aneurysm in subarachnoid hemorrhage (SAH) is a dramatic event causing a severe impact on the brain and a transient or permanent ischemic condition. Several types of responses to meet the challenges of SAH have been found in the acute phase, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system, elevated levels of brain natriuretic peptide (BNP), and disturbances in cerebral and systemic metabolism.

    Cerebral metabolism and the endocrine stress response in the ultra-early phase was investigated in a novel porcine model of SAH in which autologous blood was injected to the anterior skull base. Early activation of the HPA axis was found with rapid elevation of adrenocorticotrophic hormone, cortisol and aldosterone. The peak values of these hormones were early and may be impossible to catch in patients. There were indications of a sympathetic nervous response with excretion of catecholamines in urine as well as plasma chromogranin-A elevation. Cerebral microdialysis suggested immediate substrate failure followed by hypermetabolism of glucose. The animal model seems suited for further studies of aneurysmal SAH.

    NT-proBNP was investigated in 156 patients with SAH, there was a dynamic course with increasing levels during the first 4 days of the disease. Factors predicting high NT-proBNP load included female sex, high age, high Troponin-I at admission, angiographic finding of an aneurysm and worse clinical condition at admission. High levels of NT-proBNP were correlated to factors indicating a more severe disease, suggesting the initial injury in aneurysmal SAH is an important factor in predicting high NT-proBNP during the acute stage of the disease.

    Measurements with indirect calorimetry were performed daily during the first week after SAH on 32 patients with SAH. There was a dynamic course with increasing energy expenditure (EE) the first week after SAH. Comparisons with three predictive equations indicated that measured EE generally is higher than predicted, but considerable variation exists within and between patients, indicating that prediction of EE in SAH is difficult.

    Altogether, the studies demonstrate a complicated response in acute SAH that needs to be further studied to increase possibility of good outcome in SAH patients.

    Delarbeten
    1. Metabolic Pattern of the Acute Phase of Subarachnoid Hemorrhage in a Novel Porcine Model: Studies with Cerebral Microdialysis with High Temporal Resolution
    Öppna denna publikation i ny flik eller fönster >>Metabolic Pattern of the Acute Phase of Subarachnoid Hemorrhage in a Novel Porcine Model: Studies with Cerebral Microdialysis with High Temporal Resolution
    2014 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 6, s. e99904-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Aneurysmal subarachnoid hemorrhage (SAH) may produce cerebral ischemia and systemic responses including stress. To study immediate cerebral and systemic changes in response to aneurysm rupture, animal models are needed. Objective: To study early cerebral energy changes in an animal model. Methods: Experimental SAH was induced in 11 pigs by autologous blood injection to the anterior skull base, with simultaneous control of intracranial and cerebral perfusion pressures. Intracerebral microdialysis was used to monitor concentrations of glucose, pyruvate and lactate. Results: In nine of the pigs, a pattern of transient ischemia was produced, with a dramatic reduction of cerebral perfusion pressure soon after blood injection, associated with a quick glucose and pyruvate decrease. This was followed by a lactate increase and a delayed pyruvate increase, producing a marked but short elevation of the lactate/pyruvate ratio. Glucose, pyruvate, lactate and lactate/pyruvate ratio thereafter returned toward baseline. The two remaining pigs had a more severe metabolic reaction with glucose and pyruvate rapidly decreasing to undetectable levels while lactate increased and remained elevated, suggesting persisting ischemia. Conclusion: The animal model simulates the conditions of SAH not only by deposition of blood in the basal cisterns, but also creating the transient global ischemic impact of aneurysmal SAH. The metabolic cerebral changes suggest immediate transient substrate failure followed by hypermetabolism of glucose upon reperfusion. The model has features that resemble spontaneous bleeding, and is suitable for future research of the early cerebral and systemic responses to SAH that are difficult to study in humans.

    Nationell ämneskategori
    Kirurgi
    Identifikatorer
    urn:nbn:se:uu:diva-229957 (URN)10.1371/journal.pone.0099904 (DOI)000338508200053 ()24940881 (PubMedID)
    Tillgänglig från: 2014-08-18 Skapad: 2014-08-18 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    2. The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage
    Öppna denna publikation i ny flik eller fönster >>The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage
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    2016 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 3, artikel-id e0151457Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Introduction In patients with severe illness, such as aneurysmal subarachnoid hemorrhage (SAH), a physiologic stress response is triggered. This includes activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The aim of this study was to investigate the very early responses of these systems. Methods A porcine animal model of aneurysmal SAH was used. In this model, blood is injected slowly to the basal cisterns above the anterior skull base until the cerebral perfusion pressure is 0 mm Hg. Sampling was done from blood and urine at -10, +15, +75 and +135 minutes from time of induction of SAH. Analyses of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, catecholamines and chromogranin-A were performed. Results Plasma ACTH, serum cortisol and plasma aldosterone increased in the samples following induction of SAH, and started to decline after 75 minutes. Urine cortisol also increased after SAH. Urine catecholamines and their metabolites were found to increase after SAH. Many samples were however below detection level, not allowing for statistical analysis. Plasma chromogranin-A peaked at 15 minutes after SAH, and thereafter decreased. Conclusions The endocrine stress response after aneurysmal SAH was found to start within 15 minutes in the HPA axis with early peak values of ACTH, cortisol and aldosterone. The fact that the concentrations of the HPA axis hormones decreased 135 minutes after SAH may suggest that a similar pattern exists in SAH patients, thus making it difficult to catch these early peak values. There were also indications of early activation of the sympathetic nervous system, but the small number of valid samples made interpretation difficult.

    Nationell ämneskategori
    Endokrinologi och diabetes Neurologi
    Identifikatorer
    urn:nbn:se:uu:diva-296872 (URN)10.1371/journal.pone.0151457 (DOI)000372701200055 ()
    Tillgänglig från: 2016-06-20 Skapad: 2016-06-20 Senast uppdaterad: 2017-11-28Bibliografiskt granskad
    3. Predictors of increased cumulative serum levels of the N-terminal prohormone of brain natriuretic peptide 4 days after acute spontaneous subarachnoid hemorrhage
    Öppna denna publikation i ny flik eller fönster >>Predictors of increased cumulative serum levels of the N-terminal prohormone of brain natriuretic peptide 4 days after acute spontaneous subarachnoid hemorrhage
    2014 (Engelska)Ingår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 120, nr 3, s. 599-604Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Object. The rupture of an intracranial aneurysm is followed by increased intracranial pressure and decreased cerebral blood flow. A major systemic stress reaction follows, presumably to restore cerebral blood flow. However, this reaction can also cause adverse effects, including myocardial abnormalities, which are common and can be serious, and increased levels of natriuretic peptides, especially brain natriuretic peptide (BNP). The association of BNP with fluid and salt balance, vasospasm, brain ischemia, and cardiac injury has been studied but almost exclusively regarding events after admission. Brain natriuretic peptide has also been measured at various time points and analyzed in different ways statistically. The authors approached BNP measurement in a new way; they used the calculated area under the curve (AUC) for the first 4 days to quantitatively measure the BNP load during the first critical part of the disease state. Their rationale was a suspicion that early BNP load is a marker of the severity of the ictus and will influence the subsequent course of the disease by disturbing the fluid and salt balance. Methods. The study included 156 patients with acute spontaneous subarachnoid hemorrhage (SAH). Mean patient age was 59.8 +/- 11.2 years, and 105 (67%) of the patients were female. An aneurysm was found in 138 patients. A total of 82 aneurysms were treated by endovascular coiling, 50 were treated by surgery, and 6 were untreated. At the time of admission, serum samples were collected for troponin-I analysis and for the N-terminal prohormone of BNP (NT-proBNP); daily thereafter, samples were collected for the NT-proBNP analysis. The cumulative BNP load was calculated as the AUC for NT-proBNP during the first 4 days. The following variables were studied in terms of their influence on the AUC for NT-proBNP: sex, age, World Federation of Neurosurgical Societies grade of SAH, Fisher grade, angiographic result, treatment of aneurysm,'clinical neurological deterioration, verified infections, vasospasm treatment, and 6-month outcome. Results. The AUC for NT-proBNP was larger when variables indicated a more severe SAH. These variables were higher Fisher and World Federation of Neurosurgical Societies grades, high levels of troponin-I at admission, an aneurysm, neurological deficits, and infections. The AUC for NT-proBNP was also larger among women, older patients, and patients with poor outcomes. Linear regression showed that the best predicting model for large AUC for NT-proBNP was the combination of the following: female sex, high levels of troponin-I, an aneurysm, neurological deficits, and advanced age. Conclusions. The cumulative BNP load during the first days after SAH can be predicted by variables describing the severity of the disease already known at the time of admission. This information can be used to identify patients at risk for an adverse course of the disease.

    Nyckelord
    subarachnoid hemorrhage, NT-proBNP, vascular disorders, brain natriuretic peptide, troponin-I
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-222748 (URN)10.3171/2013.8.JNS13625 (DOI)000332048800003 ()
    Tillgänglig från: 2014-04-14 Skapad: 2014-04-14 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    4. Daily Energy Expenditure in the Acute Phase of Aneurysmal Subarachnoid Hemorrhage
    Öppna denna publikation i ny flik eller fönster >>Daily Energy Expenditure in the Acute Phase of Aneurysmal Subarachnoid Hemorrhage
    (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Nationell ämneskategori
    Neurologi Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-328119 (URN)
    Tillgänglig från: 2017-08-17 Skapad: 2017-08-17 Senast uppdaterad: 2017-08-17
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  • 304.
    Nyberg, Christoffer
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Karlsson, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Daily Energy Expenditure in the Acute Phase of Aneurysmal Subarachnoid HemorrhageIngår i: Artikel i tidskrift (Refereegranskat)
  • 305.
    Nyberg, Joakim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Li, Husong
    Univ Texas Med Branch Hlth, Dept Anesthesiol, Galveston, TX USA.
    Wessmark, Pehr
    Royal Inst Technol, Stockholm, Sweden.
    Winther, Viktor
    Royal Inst Technol, Stockholm, Sweden.
    Prough, Donald S.
    Univ Texas Med Branch Hlth, Dept Anesthesiol, Galveston, TX USA.
    Kinsky, Michael P.
    Univ Texas Med Branch Hlth, Dept Anesthesiol, Galveston, TX USA.
    Svensen, Christer H.
    Univ Texas Med Branch Hlth, Dept Anesthesiol, Galveston, TX USA;Soder Sjukhuset, Karolinska Inst, Dept Clin Sci & Educ, Unit Anesthesiol & Intens Care, Stockholm, Sweden.
    Population Kinetics of 0.9% Saline Distribution in Hemorrhaged Awake and Isoflurane-anesthetized Volunteers2019Ingår i: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 131, nr 3, s. 501-511Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Population-based, pharmacokinetic modeling can be used to describe variability in fluid distribution and dilution between individuals and across populations. The authors hypothesized that dilution produced by crystalloid infusion after hemorrhage would be larger in anesthetized than in awake subjects and that population kinetic modeling would identify differences in covariates. Methods: Twelve healthy volunteers, seven females and five males, mean age 28 +/- 4.3 yr, underwent a randomized crossover study. Each subject participated in two separate sessions, separated by four weeks, in which they were assigned to an awake or an anesthetized arm. After a baseline period, hemorrhage (7 ml/kg during 20 min) was induced, immediately followed by a 25 ml/kg infusion during 20 min of 0.9% saline. Hemoglobin concentrations, sampled every 5 min for 60 min then every 10 min for an additional 120 min, were used for population kinetic modeling. Covariates, including body weight, sex, and study arm (awake or anesthetized), were tested in the model building. The change in dilution was studied by analyzing area under the curve and maximum plasma dilution. Results: Anesthetized subjects had larger plasma dilution than awake subjects. The analysis showed that females increased area under the curve and maximum plasma dilution by 17% (with 95% CI, 1.08 to 1.38 and 1.07 to 1.39) compared with men, and study arm (anesthetized increased area under the curve by 99% [0.88 to 2.45] and maximum plasma dilution by 35% [0.71 to 1.63]) impacted the plasma dilution whereas a 10-kg increase of body weight resulted in a small change (less than1% [0.93 to 1.20]) in area under the curve and maximum plasma dilution. Mean arterial pressure was lower in subjects while anesthetized (P < 0.001). Conclusions: In awake and anesthetized subjects subjected to controlled hemorrhage, plasma dilution increased with anesthesia, female sex, and lower body weight. Neither study arm nor body weight impact on area under the curve or maximum plasma dilution were statistically significant and therefore no effect can be established.

  • 306.
    Nyholm, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Quality systems to avoid secondary brain injury in neurointensive care2015Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Outcome after traumatic brain injury (TBI) depends on the extent of primary cell death and on the development of secondary brain injury. The general aim of this thesis was to find strategies and quality systems to minimize the extent of secondary insults in neurointensive care (NIC).

    An established standardized management protocol system, multimodality monitoring and computerized data collection, and analysis systems were used.

    The Uppsala TBI register was established for regular monitoring of NIC quality indexes. For 2008-2010 the proportion of patients improving during NIC was 60-80%, whereas 10% deteriorated. The percentage of ‘talk and die’ cases was < 1%. The occurrences of secondary insults were less than 5% of good monitoring time (GMT) for intracranial pressure (ICP) > 25 mmHg, cerebral perfusion pressure (CPP) < 50 mmHg and systolic blood pressure < 100 mmHg. Favorable outcome was achieved by 64% of adults.

    Nurse checklists of secondary insult occurrence were introduced. Evaluation of the use of nursing checklists showed that the nurses documented their assessments in 84-85% of the shifts and duration of monitoring time at insult level was significantly longer when secondary insults were reported regarding ICP, CPP and temperature. The use of nurse checklist was found to be feasible and accurate.

     A clinical tool to avoid secondary insults related to nursing interventions was developed. Secondary brain insults occurred in about 10% of nursing interventions. There were substantial variations between patients. The risk ratios of developing an ICP insult were 4.7 when baseline ICP ≥ 15 mmHg, 2.9 when ICP amplitude ≥ 6 mmHg and 1.7 when pressure autoregulation ≥ 0.3.

    Hyperthermia, which is a known frequent secondary insult, was studied. Hyperthermia was most common on Day 7 after admission and 90% of the TBI patients had hyperthermia during the first 10 days at the NIC unit. The effects of hyperthermia on intracranial dynamics (ICP, brain energy metabolism and BtipO2) were small but individual differences were observed. Hyperthermia increased ICP slightly more when temperature increased in the groups with low compliance and impaired pressure autoregulation. Ischemic pattern was never observed in the microdialysis samples. The treatment of hyperthermia may be individualized and guided by multimodality monitoring. 

    Delarbeten
    1. Introduction of the Uppsala Traumatic Brain Injury register for regular surveillance of patient characteristics and neurointensive care management including secondary insult quantification and clinical outcome
    Öppna denna publikation i ny flik eller fönster >>Introduction of the Uppsala Traumatic Brain Injury register for regular surveillance of patient characteristics and neurointensive care management including secondary insult quantification and clinical outcome
    2013 (Engelska)Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, nr 3, s. 169-180Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background. To improve neurointensive care (NIC) and outcome for traumatic brain injury (TBI) patients it is crucial to define and monitor indexes of the quality of patient care. With this purpose we established the web-based Uppsala TBI register in 2008. In this study we will describe and analyze the data collected during the first three years of this project. Methods. Data from the medical charts were organized in three columns containing: 1) Admission data; 2) Data from the NIC period including neurosurgery, type of monitoring, treatment, complications, neurological condition at discharge, and the amount of secondary insults; 3) Outcome six months after injury. Indexes of the quality of care implemented include: 1) Index of improvement; 2) Index of change; 3) The percentages of 'Talk and die' and `Talk and deteriorate' patients. Results. Altogether 314 patients were included 2008-2010: 66 women and 248 men aged 0-86 years. Automatic reports showed that the proportion of patients improving during NIC varied between 80% and 60%. The percentage of deteriorated patients was less than 10%. The percentage of Talk and die/Talk and deteriorate cases was <1%. The mean Glasgow Coma Score (Motor) improved from 5.04 to 5.68 during the NIC unit stay. The occurrences of secondary insults were less than 5% of good monitoring time for intracranial pressure (ICP) >25 mmHg, cerebral perfusion pressure (CPP) <50 mmHg, and systolic blood pressure <100 mmHg. Favorable outcome was achieved by 64% of adults. Conclusion. The Uppsala TBI register enables the routine monitoring of NIC quality indexes.

    Nyckelord
    Database, neurointensive care, outcome, quality register, secondary insults, traumatic brain injury
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-204853 (URN)10.3109/03009734.2013.806616 (DOI)000321587100004 ()
    Tillgänglig från: 2013-08-12 Skapad: 2013-08-12 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    2. The use of nurse checklists in a bedside computer-based information system to focus on avoiding secondary insults in neurointensive care
    Öppna denna publikation i ny flik eller fönster >>The use of nurse checklists in a bedside computer-based information system to focus on avoiding secondary insults in neurointensive care
    Visa övriga...
    2012 (Engelska)Ingår i: ISRN Neurology, ISSN 2090-5505, E-ISSN 2090-5513, Vol. 2012, s. 903954-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The feasibility and accuracy of using checklists after every working shift in a bedside computer-based information system for documentation of secondary insults in the neurointensive care unit were evaluated. The ultimate goal was to get maximal attention to avoid secondary insults. Feasibility was investigated by assessing if the checklists were filled in as prescribed. Accuracy was evaluated by comparing the checklists with recorded minute-by-minute monitoring data for intracranial pressure-ICP, cerebral perfusion pressure CPP, systolic blood pressure SBP, and temperature. The total number of checklist assessments was 2,184. In 85% of the shifts, the checklists were filled in. There was significantly longer duration of monitoring time at insult level when Yes was filled in regarding ICP (mean 134 versus 30 min), CPP (mean 125 versus 26 min) and temperature (mean 315 versus 120 min). When a secondary insult was defined as >5% of monitoring time spent at insult level, the sensitivity/specificity for the checklist assessments was 31%/100% for ICP, 38%/99% for CPP, and 66%/88% for temperature. Checklists were feasible and appeared relatively accurate. Checklists may elevate the alertness for avoiding secondary insults and help in the evaluation of the patients. This concept may be the next step towards tomorrow critical care.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-190818 (URN)10.5402/2012/903954 (DOI)22844615 (PubMedID)
    Tillgänglig från: 2013-01-08 Skapad: 2013-01-08 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    3. Secondary insults related to nursing interventions in neurointensive care: a descriptive pilot study
    Öppna denna publikation i ny flik eller fönster >>Secondary insults related to nursing interventions in neurointensive care: a descriptive pilot study
    2014 (Engelska)Ingår i: Journal of Neuroscience Nursing, ISSN 0888-0395, E-ISSN 1945-2810, Vol. 46, nr 5, s. 285-291Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The patients at a neurointensive care unit are frequently cared for in many ways, day and night. The aim of this study was to investigate the amount of secondary insults related to oral care, repositioning, endotracheal suctioning, hygienic measures, and simultaneous interventions at a neurointensive care unit with standardized care and maximum attention on avoiding secondary insults. The definition of a secondary insult was intracranial pressure > 20 mm Hg, cerebral perfusion pressure < 60 mm Hg and systolic blood pressure < 100 mm Hg for 5 minutes or more in a 10-minute period starting from when the nursing intervention began. The insult minutes did not have to be consecutive. The study included 18 patients, seven women and 11 men, aged 36-76 years with different neurosurgical diagnoses. The total number of nursing interventions analyzed was 1,717. The most common kind of secondary insults after a nursing measure was high intracranial pressure (n = 93) followed by low cerebral perfusion pressure (n = 43) and low systolic blood pressure (n = 14). Repositioning (n = 39) and simultaneous interventions (n = 32) were the nursing interventions causing most secondary insults. There were substantial variations between the patients; only one patient had no secondary insult. There were, overall, a limited number of secondary insults related to nursing interventions when a standardized management protocol system was applied to reduce the occurrence of secondary insults. Patients with an increased risk of secondary insults should be recognized, and their care and treatment should be carefully planned and performed to avoid secondary insults.

    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Neurokirurgi
    Identifikatorer
    urn:nbn:se:uu:diva-233431 (URN)10.1097/JNN.0000000000000077 (DOI)000341965200009 ()25188684 (PubMedID)
    Tillgänglig från: 2014-10-03 Skapad: 2014-10-03 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    4. A decision-making tool to prevent secondary ICP-insults related to nursing interventions: – Evaluation of the predictive value for baseline ICP, compliance and autoregulation
    Öppna denna publikation i ny flik eller fönster >>A decision-making tool to prevent secondary ICP-insults related to nursing interventions: – Evaluation of the predictive value for baseline ICP, compliance and autoregulation
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-252875 (URN)
    Tillgänglig från: 2015-05-13 Skapad: 2015-05-13 Senast uppdaterad: 2015-07-07
    5. The effects of hyperthermia on intracranial pressure, cerebral oxymetry, and cerebral metabolism in traumatic brain injury patients during neurointensive care
    Öppna denna publikation i ny flik eller fönster >>The effects of hyperthermia on intracranial pressure, cerebral oxymetry, and cerebral metabolism in traumatic brain injury patients during neurointensive care
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-252877 (URN)
    Tillgänglig från: 2015-05-13 Skapad: 2015-05-13 Senast uppdaterad: 2015-07-07
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  • 307.
    Nyholm, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Howells, Tim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    A decision-making tool to prevent secondary ICP-insults related to nursing interventions: – Evaluation of the predictive value for baseline ICP, compliance and autoregulationManuskript (preprint) (Övrigt vetenskapligt)
  • 308.
    Nyholm, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Howells, Tim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    The effects of hyperthermia on intracranial pressure, cerebral oxymetry, and cerebral metabolism in traumatic brain injury patients during neurointensive careManuskript (preprint) (Övrigt vetenskapligt)
  • 309.
    Nyholm, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Steffansson, Erika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Fröjd, Camilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Sjuksköterskeutbildningar.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Secondary insults related to nursing interventions in neurointensive care: a descriptive pilot study2014Ingår i: Journal of Neuroscience Nursing, ISSN 0888-0395, E-ISSN 1945-2810, Vol. 46, nr 5, s. 285-291Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The patients at a neurointensive care unit are frequently cared for in many ways, day and night. The aim of this study was to investigate the amount of secondary insults related to oral care, repositioning, endotracheal suctioning, hygienic measures, and simultaneous interventions at a neurointensive care unit with standardized care and maximum attention on avoiding secondary insults. The definition of a secondary insult was intracranial pressure > 20 mm Hg, cerebral perfusion pressure < 60 mm Hg and systolic blood pressure < 100 mm Hg for 5 minutes or more in a 10-minute period starting from when the nursing intervention began. The insult minutes did not have to be consecutive. The study included 18 patients, seven women and 11 men, aged 36-76 years with different neurosurgical diagnoses. The total number of nursing interventions analyzed was 1,717. The most common kind of secondary insults after a nursing measure was high intracranial pressure (n = 93) followed by low cerebral perfusion pressure (n = 43) and low systolic blood pressure (n = 14). Repositioning (n = 39) and simultaneous interventions (n = 32) were the nursing interventions causing most secondary insults. There were substantial variations between the patients; only one patient had no secondary insult. There were, overall, a limited number of secondary insults related to nursing interventions when a standardized management protocol system was applied to reduce the occurrence of secondary insults. Patients with an increased risk of secondary insults should be recognized, and their care and treatment should be carefully planned and performed to avoid secondary insults.

  • 310.
    Näslund, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Gavle Cent Hosp, Dept Anaesthes, S-801 87 Gavle, Sweden.
    Lindberg, Lars-Goran
    Linkoping Univ, Dept BioMed Engn, Linkoping, Sweden.
    Lund, Irene
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Naslund-Koch, Lui
    Bornholm Hosp, Dept Med, Ronne, Denmark.
    Larsson, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Measuring arterial oxygen saturation from an intraosseous photoplethysmographic signal derived from the sternum2020Ingår i: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 34, nr 1, s. 55-62Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Photoplethysmography performed on the peripheral extremities or the earlobes cannot always provide sufficiently rapid and accurate calculation of arterial oxygen saturation. The purpose of this study was to evaluate a novel photoplethysmography prototype to be fixed over the sternum. Our hypotheses were that arterial oxygen saturation can be determined from an intraosseous photoplethysmography signal from the sternum and that such monitoring detects hypoxemia faster than pulse oximetry at standard sites. Sixteen healthy male volunteers were subjected to incremental hypoxemia using different gas mixtures with decreasing oxygen content. The sternal probe was calibrated using arterial haemoglobin CO-oximetry (SaO2%). Sternal probe readings (SRHO2%) were then compared to SaO2% at various degrees of hypoxia. The time to detect hypoxemia was compared to measurements from standard finger and ear pulse oximeters. A significant association from individual regression between SRHO2% and SaO2% was found (r(2) 0.97), Spearman R ranged between 0.71 and 0.92 for the different inhaled gas mixtures. Limits of agreement according to Bland-Altman plots had a increased interval with decreasing arterial oxygen saturation. The sternal probe detected hypoxemia 28.7 s faster than a finger probe (95% CI 20.0-37.4 s, p < 0.001) and 6.6 s faster than an ear probe (95% CI 5.3-8.7 s, p < 0.001). In an experimental setting, arterial oxygen saturation could be determined using the photoplethysmography signal obtained from sternal blood flow after calibration with CO-oximetry. This method detected hypoxemia significantly faster than pulse oximetry performed on the finger or the ear.

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  • 311.
    Opitz, Lucas
    et al.
    Antoine Lacassagne Ctr, Dept Anesthesia, Nice, France.
    Tsang, Derek S.
    Princess Margaret Canc Ctr, Radiat Med Program, Toronto, ON, Canada.
    Vittinghoff, Maria
    Med Univ Graz, Dept Anaesthesiol & Intens Care Med, Graz, Austria.
    Frykholm, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Report from the First International Meeting on Iterative Pediatric Anesthesia2020Ingår i: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 30, nr 2, s. 84-85Artikel i tidskrift (Övrigt vetenskapligt)
  • 312.
    Otterbeck, Alexander
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hanslin, Katja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lantz, E. Lidberg
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Stålberg, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Inhalation of specific anti-Pseudomonas aeruginosa IgY antibodies transiently decreases P. aeruginosa colonization of the airway in mechanically ventilated piglets2019Ingår i: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 7, artikel-id 21Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: P. aeruginosa is a pathogen frequently resistant to antibiotics and a common cause of ventilator-associated pneumonia (VAP). Non-antibiotic strategies to prevent or treat VAP are therefore of major interest. Specific polyclonal avian IgY antibodies have previously been shown to be effective against pneumonia caused by P. aeruginosa in rodents and against P. aeruginosa airway colonization in patients. Objectives: To study the effect of specific polyclonal anti-P. aeruginosa IgY antibodies (Pa-IgY) on colonization of the airways in a porcine model. Method: The pigs were anesthetized, mechanically ventilated, and subject to invasive hemodynamic monitoring and allocated to either receive 10(9) CFU nebulized P. aeruginosa (control, n=6) or 10(9) CFU nebulized P. aeruginosa + 200 mg Pa-IgY antibodies (intervention, n=6). Physiological measurement, blood samples, and tracheal cultures were then secured regularly for 27 h, after which the pigs were sacrificed and lung biopsies were cultured. Results: After nebulization, tracheal growth of P. aeruginosa increased in both groups during the experiment, but with lower growth in the Pa-IgY-treated group during the experiment (p = 0.02). Tracheal growth was 4.6 x 10(3) (9.1 x 10(2)-3.1 x 10(4)) vs. 4.8 x 10(4) (7.5 x 10(3)-1.4 x 10(5)) CFU/mL in the intervention group vs. the control group at 1h and 5.0 x 10(0) (0.0 x 10(0)-3.8 x 10(2)) vs. 3.3 x 10(4) (8.0 x 10(3)-1.4 x 10(5)) CFU/mL at 12 h in the same groups. During this time, growth in the intervention vs. control group was one to two orders of ten lower. After 12 h, the treatment effect disappeared and bacterial growth increased in both groups. The intervention group had lower body temperature and cardiac index and higher static compliance compared to the control group. Conclusion: In this porcine model, Pa-IgY antibodies lessen bacterial colonization of the airways.

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  • 313.
    Otterbeck, Alexander
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hanslin, Katja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lidberg Lantz, Elin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Stålberg, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Correction to: Inhalation of specific anti-Pseudomonas aeruginosa IgY antibodies transiently decreases P. aeruginosa colonization of the airway in mechanically ventilated piglets.2019Ingår i: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 7, artikel-id 24Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Following publication of the original article, the authors flagged that an incorrect piece of data is given in the Materials and Methods section of the article.

  • 314.
    Oyenusi, Elizabeth E.
    et al.
    Lagos Univ Teaching Hosp, Dept Pediat, POB 4337, Lagos, Nigeria..
    Oduwole, Abiola O.
    Lagos Univ Teaching Hosp, Dept Pediat, POB 4337, Lagos, Nigeria..
    Aronson, A. Stefan
    Hallands Sjukhus, Halmstad, Sweden..
    Jonsson, Björn G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Albertsson-Wikland, Kerstin
    Gothenburg Univ, Queen Silvias Childrens Hosp, Sahlgrenska Acad, GP GRC,Dept Pediat,Inst Clin Sci, Gothenburg, Sweden..
    Njokanma, Olisamedua F.
    Lagos Univ Teaching Hosp, Dept Pediat, POB 4337, Lagos, Nigeria..
    Hyperglycemia in Acutely Ill Non-diabetic Children in the Emergency Rooms of 2 Tertiary Hospitals in Lagos, Nigeria2016Ingår i: Pediatric emergency care, ISSN 0749-5161, E-ISSN 1535-1815, Vol. 32, nr 9, s. 608-613Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives The study aimed to determine the prevalence of hyperglycemia in sick children admitted into the emergency rooms and to investigate its relationship with adverse outcomes. Methods A prospective study involving 2 tertiary hospitals in Lagos. Study subjects included all children aged beyond 1 month. An Accu-Chek Active glucometer was used for the bedside blood glucose determination. Hyperglycemia was defined as blood glucose greater than 7.8 mmol/L. Results A total of 1045 patients were recruited with hyperglycemia being recorded in 135 patients (prevalence rate of 12.9%). Mean age of the hyperglycemic patients was 29.0 31.23 months. Prevalence rates of hyperglycemia among the leading diagnoses were 17.4% in acute respiratory tract infections, 11% in malaria, 15.3% in septicemia, 14.9% in gastroenteritis, and 18.2% in burns. Other conditions include sickle cell anemia, meningitis, and malnutrition. Mortality rate was significantly higher overall in hyperglycemic compared with the normoglycemic patients (15.4% vs 8.0%, P = 0.011). With regard to specific diagnoses, significantly higher mortality rates were recorded in hyperglycemic patients with acute respiratory tract infections (28% vs 8%, P = 0.011) and malaria (21.4% vs 5.0%, P = 0.006) than in their normoglycemic counterparts. Conclusions Hyperglycemia is common in ill children admitted to the emergency rooms and is associated with 2 to 4 times higher mortality in common childhood diseases encountered. Blood glucose determination is important in all acutely ill children at presentation. The practice of empirical administration of intravenous glucose in some resource-constrained facilities where blood glucose testing facilities are not readily available should be discouraged.

  • 315.
    Palmgren, Ingrid
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Transesophageal Echocardiography in Patients Undergoing Elective Coronary Artery Bypass Surgery2002Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Transesophageal echocardiography (TEE) has become a useful tool in monitoring the heart in patients during open-heart surgery. This study was undertaken to evaluate whether it is feasible to use TEE to assess left ventricular myocardial viability in anesthetized patients scheduled for coronary artery bypass grafting (CABG).

    A total of 84 patients were studied. To test myocardial viability, TEE and a low-dose dobutamine stress regimen were used. Echocardiographic data were analyzed off-line using a visual or semiautomatic analysis of segmental left ventricular wall motion (LVWM). Visual assessment was performed by readers blinded to the sequence of events. The agreement between readers in visual analysis of segmental LVWM in the transgastric short-axis view was 73% or higher. Segmental LVWM assessed by TEE was compared to hemodynamic data obtained by thermodilution pulmonary artery catheter (PAC) and coronary angiographic data. Also, using the same low-dose dobutamine stress regimen, TEE findings in the anesthetized patient perioperatively were compared with preoperative transthoracic echocardiography (TTE) findings in the awake patient.

    TEE was found to be feasible and adequate for testing left segmental ventricular viability. A concomitant increase in stroke volume assessed by PAC and decrease in LVWM-score assessed by TEE was found with dobutamine stimulation. Abnormal segmental LVWM corresponded to angiographically stenosed supplying coronary artery vessels. During dobutamine stimulation, 69% of the corresponding segments responded which is a sign of viability. The LVWM response to preoperative TTE and perioperative TEE dobutamine stress was comparable except for a significant difference in the apical segments.

    This study showed that perioperative TEE dobutamine stress could be used to test left ventricular viability and was also a valuable supplement to PAC, angiography and TTE. The acquired knowledge is important and suggest that further development of transesophageal ultrasound technology is warranted.

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  • 316.
    Parenmark, Fredric
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Gavle Cent Hosp, Dept Anaesthesia & Intens Care, Gavle, Sweden;Linkoping Univ, Fac Heath Sci, Dept Med & Heath Sci, Linkoping, Sweden.
    Karlstrom, Goran
    Swedish Intens Care Registry, Karlstad, Sweden.
    Nolin, Thomas
    Cent Hosp Kristianstad, Dept Anaesthesia & Intens Care, Kristianstad, Sweden.
    Fredrikson, Mats
    Linkoping Univ, Fac Med, Dept Clin & Expt Med, Div Occupat & Environm Med, Linkoping, Sweden;Linkoping Univ, Fac Med, Forum Ostergotland, Linkoping, Sweden.
    Walther, Sten M.
    Linkoping Univ, Fac Heath Sci, Dept Med & Heath Sci, Linkoping, Sweden;Linkoping Univ Hosp, Dept Cardiothorac Anaesthesia & Intens Care, Linkoping, Sweden.
    Reducing night-time discharge from intensive care. A nationwide improvement project with public display of ICU outcomes2019Ingår i: Journal of critical care, ISSN 0883-9441, E-ISSN 1557-8615, Vol. 49, s. 7-13Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Discharge from an intensive care unit (ICU) during the night is an independent risk factor for adverse outcomes. A quality improvement project was conducted with the aim of reducing the incidence and the associated mortality after night-time discharge. Materials and methods: ICUs that submitted data to the Swedish Intensive Care Registry (SIR) agreed to appoint night-time discharge as a national quality indicator with detailed public display on the internet of various discharge proportions and outcomes. The registry was then examined for trends during a 10-year period with use of multilevel mixed-effects models. Results: We analysed 163,371 patients who were discharged alive from 70 ICUs to a general ward within the same hospital during 2006-2015. The prevalence of night-time discharge fell from 7.0% (95% CI: 52 to 8.7%) in 2006 to 4.9% (95% CI: 43 to 5.5%) in 2015 (P = .035 for trend). The original increased risk of death within 30 days after night-time discharge in 2006-2010, OR 1.20 (95% CI: 1.01 to 1.42), disappeared in 2011-2015, OR 1.06 (95% CI: 0.96 to 1.17). Conclusions: During the 10-year period of the quality improvement project, the annual prevalence and risk of death within 30-days after night-time discharge were reduced. The public display and feedback of audit data could have helped in achieving this.

  • 317.
    Partanen, Mikko
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Anestesidjup med hjälp av Bispectral Index: litteraturstudie2012Självständigt arbete på avancerad nivå (magisterexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
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  • 318.
    Pellegrini, Mariangela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Regional Lung Mechanics and Influence of an Active Diaphragm in Experimental Lung Injury2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Despite being an essential life-support strategy in severe respiratory failure, mechanical ventilation can, if not optimally set and monitored, lead to injury of the lung parenchyma and diaphragm. These conditions are called ventilator-induced lung injury and ventilator-induced diaphragmatic dysfunction (VIDD), respectively. Although substantial progress has been made in the ventilator management of severely lung-injured patients, we are still far from a fully protective mechanical ventilation. In consideration of this gap of knowledge, this doctoral thesis aimed at investigating regional lung mechanics during both inspiration and expiration, in both controlled and assisted ventilation. Particular emphasis was placed on the expiratory phase, which is involved in expiratory flow limitation, airway closure and atelectasis formation, although commonly considered non-harmful.

    A novel methodological approach has been the fundamental basis for this research project. The combination of respiratory mechanics, diaphragmatic electromyographic activity and lung imaging enabled a breath-by-breath analysis at high temporal and spatial resolution.

    In Study I, the gravitational field affected the distribution of gas and transpulmonary pressures, as previously shown. This effect differed between healthy and injured lungs. Moreover, lung injury induced a heterogeneous distribution of gas within the lungs, as well as an increased gravitational gradient in transpulmonary pressure. Study I was mainly aimed at testing the new methodological approach centred on the investigation of regional lung mechanics.

    In Study II, the focus was on assisted ventilation and the phenomenon of gas redistribution within the lungs. Large pendelluft events had been demonstrated in disproportionate inspiratory efforts. In Study II, we showed that large pendelluft resulting from pathological respiratory drive could be attenuated by high positive end expiratory pressure (PEEP). Moreover, we showed that transient and widespread small gas redistribution events occur at all times during inspiration. Assisted ventilation and high PEEP reduced the size of gas redistribution as compared with controlled ventilation and low PEEP.

    In Study III, we demonstrated a diaphragmatic expiratory contraction in lungs prone to collapse, serving to brake the expiratory flow. It preserved end expiratory lung volume (EELV) and counteracted tidal atelectasis. However, the expiratory brake induced by diaphragmatic contraction is a known cause of VIDD.

    In Study IV, we tested the effects of external expiratory resistances (ExpR). We showed that, by applying ExpR, an expiratory brake was induced. The beneficial effects on EELV were retained, while the diaphragm could quickly relax during the expiration, thus reducing the risk of VIDD.

    Delarbeten
    1. Effects of superimposed tissue weight on regional compliance of injured lungs
    Öppna denna publikation i ny flik eller fönster >>Effects of superimposed tissue weight on regional compliance of injured lungs
    Visa övriga...
    2016 (Engelska)Ingår i: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 228, s. 16-24Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Computed tomography (CT), together with image analysis technologies, enable the construction of regional volume (V-REG) and local transpulmonary pressure (P-TP,P-REG) maps of the lung. Purpose of this study is to assess the distribution of V-REG vs P-TP,P-REG along the gravitational axis in healthy (HL) and experimental acute lung injury conditions (eALI) at various positive end-expiratory pressures (PEEPS) and inflation volumes. Mechanically ventilated pigs underwent inspiratory hold maneuvers at increasing volumes simultaneously with lung CT scans. eALI was induced via the iv administration of oleic acid. We computed voxel-level V-REG vs P-TP,P-REG curves into eleven isogravitational planes by applying polynomial regressions. Via F-test, we determined that V-REG vs P-TP,P-REG curves derived from different anatomical planes (p-values < 1.4E-3), exposed to different PEEPs (p-values < 1.5E-5) or subtending different lung status (p-values < 3E-3) were statistically different (except for two cases of adjacent planes). Lung parenchyma exhibits different elastic behaviors based on its position and the density of superimposed tissue which can increase during lung injury.

    Nyckelord
    Lung compliance, Computed tomography, Acute lung injury, Image registration, Mechanical ventilation, Gravity
    Nationell ämneskategori
    Lungmedicin och allergi
    Identifikatorer
    urn:nbn:se:uu:diva-298837 (URN)10.1016/j.resp.2016.03.005 (DOI)000376832900003 ()26976688 (PubMedID)
    Forskningsfinansiär
    Hjärt-Lungfonden
    Tillgänglig från: 2016-07-11 Skapad: 2016-07-11 Senast uppdaterad: 2019-10-07Bibliografiskt granskad
    2. Transients of Air‐Redistribution Characterize Both Spontaneous Breathing and Mechanical Ventilation
    Öppna denna publikation i ny flik eller fönster >>Transients of Air‐Redistribution Characterize Both Spontaneous Breathing and Mechanical Ventilation
    (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-394304 (URN)
    Tillgänglig från: 2019-10-07 Skapad: 2019-10-07 Senast uppdaterad: 2019-10-07
    3. The Diaphragm Acts as a Brake During Expiration to Prevent Lung Collapse
    Öppna denna publikation i ny flik eller fönster >>The Diaphragm Acts as a Brake During Expiration to Prevent Lung Collapse
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    2017 (Engelska)Ingår i: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195, nr 12, s. 1608-1616Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Rationale: The diaphragm is the major inspiratory muscle and is assumed to relax during expiration. However, electrical postinspiratory activity has been observed. Whether there is an expiratory diaphragmatic contraction that preserves lung patency has yet to be explored.

    Objectives: We hypothesized the occurrence of an expiratory diaphragmatic contraction directed at stabilizing peripheral airways and preventing or reducing cyclic expiratory lung collapse.

    Methods: Mild acute respiratory distress syndrome was induced in 10 anesthetized, spontaneously breathing pigs. Lung volume was decreased by lowering end-expiratory airway pressure in a stepwise manner. We recorded the diaphragmatic electric activity during expiration, dynamic computed tomographic scans, and respiratory mechanics. In five pigs, the same protocol was repeated during mechanical ventilation after muscle paralysis.

    Measurements and Main Results: Diaphragmatic electric activity during expiration increased by decreasing end-expiratory lung volume during spontaneous breathing. This enhanced the diaphragm muscle force, to a greater extent with lower lung volume, indicating a diaphragmatic electromechanical coupling during spontaneous expiration. In turn, the resulting diaphragmatic contraction delayed and reduced the expiratory collapse and increased lung aeration compared with mechanical ventilation with muscle paralysis and absence of diaphragmatic activity.

    Conclusions: The diaphragm is an important regulator of expiration. Its expiratory activity seems to preserve lung volume and to protect against lung collapse. The loss of diaphragmatic expiratory contraction during mechanical ventilation and muscle paralysis may be a contributing factor to unsuccessful respiratory support.

    Nationell ämneskategori
    Kirurgi
    Identifikatorer
    urn:nbn:se:uu:diva-312488 (URN)10.1164/rccm.201605-0992OC (DOI)000403383600015 ()27922742 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, X2015-99x-22731-01-4Hjärt-Lungfonden
    Tillgänglig från: 2017-01-10 Skapad: 2017-01-10 Senast uppdaterad: 2019-10-07Bibliografiskt granskad
    4. Expiratory Resistance Prevents Eccentric Diaphragm Contraction, Flow Limitation andLung Collapse
    Öppna denna publikation i ny flik eller fönster >>Expiratory Resistance Prevents Eccentric Diaphragm Contraction, Flow Limitation andLung Collapse
    Visa övriga...
    (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-394303 (URN)
    Tillgänglig från: 2019-10-07 Skapad: 2019-10-07 Senast uppdaterad: 2019-10-07
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    presentationsbild
  • 319.
    Pellegrini, Mariangela
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Gudmundsson, Magni
    Bencze, Reka
    Segelsjö, Monica
    Freden, Filip
    Rylander, Christian
    Hedenstierna, Göran
    Larsson, Anders Sune
    Perchiazzi, Gaetano
    Expiratory Resistance Prevents Eccentric Diaphragm Contraction, Flow Limitation andLung CollapseIngår i: Artikel i tidskrift (Refereegranskat)
  • 320.
    Pellegrini, Mariangela
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Hedenstierna, Göran
    Larsson, Anders Sune
    Perchiazzi, Gaetano
    Transients of Air‐Redistribution Characterize Both Spontaneous Breathing and Mechanical VentilationIngår i: Artikel i tidskrift (Refereegranskat)
  • 321.
    Pelosi, Paolo
    et al.
    Univ Genoa, Dept Surg Sci & Integrated Diagnost, IRCCS AOU San Martino IST, Genoa, Italy.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Ball, Lorenzo
    Univ Genoa, Dept Surg Sci & Integrated Diagnost, IRCCS AOU San Martino IST, Genoa, Italy.
    Edmark, Lennart
    Vasteras Hosp, Dept Anesthesia & Intens Care, Vasteras, Sweden.
    Bignami, Elena
    IRCCS, San Raffaele Sci Inst, Dept Anesthesia & Intens Care, Via Olgettina 60, I-20132 Milan, Italy.
    The real role of the PEEP in operating room: pros & cons2018Ingår i: Minerva Anestesiologica, ISSN 0375-9393, E-ISSN 1827-1596, Vol. 84, nr 2, s. 229-235Artikel i tidskrift (Refereegranskat)
  • 322.
    Peng, Di
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Cupples, Claire
    Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC, Canada..
    Cupples, Will
    Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC, Canada..
    Mitrou, Nicholas
    Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC, Canada..
    Macrophage infiltration in the kidney after prolonged surgery with anesthesia2017Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, nr 8, s. 1010-1011Artikel i tidskrift (Övrigt vetenskapligt)
  • 323.
    Perchiazzi, Gaetano
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wrigge, Hermann
    Univ Hosp Leipzig, Dept Anesthesiol & Intens Care Med, D-04103 Leipzig, Germany;Bergmannstrost Hosp Halle, Dept Anesthesiol Intens Care & Emergency Med Pain, D-06112 Halle, Germany.
    Acute Respiratory Distress Syndrome (ARDS): Pathophysiological Insights and Lung Imaging2019Ingår i: JOURNAL OF CLINICAL MEDICINE, ISSN 2077-0383, Vol. 8, nr 12, artikel-id 2171Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Acute respiratory distress syndrome (ARDS) is in the center of the scientific debate both for its complex pathophysiology and for the discussion about the remedies that could contribute to its healing. The intricate interplay of different body systems that characterizes ARDS is mirrored by two main research threads, one centered on the pathophysiological mechanisms of the disease and the other on the new approaches to lung imaging. In this Special Issue of the Journal of Clinical Medicine are presented studies using imaging technologies based on electrical impedance tomography, synchrotron radiation computed tomography and intravital probe-based confocal laser endomicroscopy. The studies on the pathophysiological mechanisms pertain to the evaluation of the biomarkers of the disease and the platelet disfunction during extracorporeal membrane oxygenation. These contributions witness the intensity of ARDS research as many of the key problems of the disease are only in part resolved.

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    FULLTEXT01
  • 324. Perner, Anders
    et al.
    Haase, Nicolai
    Winkel, Per
    Guttormsen, Anne B.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Klemenzson, Gudmundur
    Muller, Rasmus G.
    Aneman, Anders
    Wetterslev, Jorn
    Long-term outcomes in patients with severe sepsis randomised to resuscitation with hydroxyethyl starch 130/0.42 or Ringer's acetate2014Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 40, nr 7, s. 927-934Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We assessed long-term mortality and hospitalisation in patients with severe sepsis resuscitated with hydroxyethyl starch (HES) or Ringer's acetate. This was an investigator-initiated, parallel-grouped, blinded randomised trial using computer-generated allocation sequence and centralised allocation data that included 804 patients with severe sepsis needing fluid resuscitation in 26 general intensive care units (ICUs) in Scandinavia. Patients were allocated to fluid resuscitation using either 6 % HES 130/0.42 or Ringer's acetate during ICU admission. We assessed mortality rates at 6 months, 1 year and at the time of longest follow-up and days alive and out of hospital at 1 year. The vital status of all patients was obtained at a median of 22 (range 13-36) months after randomisation. Mortality rates in the HES versus Ringer's groups at 6 months were 53.3 (212/398 patients) versus 47.5 % (190/400) [relative risk 1.12; 95 % confidence interval (CI) 0.98-1.29; P = 0.10], respectively; at 1 year, 56.0 (223/398) versus 51.5 % (206/400) (1.09; 95 % CI 0.96-1.24; P = 0.20), respectively; at the time of longest follow-up, 59.8 (238/398) versus 56.3 % (225/400) (1.06; 95 % CI 0.94-1.20; P = 0.31), respectively. Percentage of days alive and out of hospital at 1 year in the HES versus Ringer's groups was 24 (0-87 days) versus 63 % (0-90) (P = 0.07). The long-term mortality rates did not differ in patients with severe sepsis assigned to HES 130/0.42 versus Ringer's acetate, but we could not reject a 24 % relative increased or a 4 % relative decreased mortality at 1 year with HES at the 95 % confidence level.

  • 325.
    Petersson, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Quantification of lipid accumulation in the diaphragm after mechanical ventilation2013Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    During mechanical ventilation the diaphragm experiences an extreme case of muscleunloading. In many cases this results in respiratory muscle dysfunctions making it difficult towean the patient off the ventilator. One component in this dysfunction is the accumulation ofintramyocellular lipids (IMCL) in the diaphragm muscle fibres. Using Oil Red O stainingsand confocal microscopy on rat diaphragm sections we have quantified this process. Theresults show a sudden increase in IMCL contents between 18 and 24 hours. No significantdifference between fibre types could be seen.

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    fulltext
  • 326.
    Pikwer, Andreas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Mälarsjukhuset.
    Castegren, Markus
    Karolinska Univ Hosp, Perioperat Med & Intens Care PMI, Stockholm, Sweden.;Karolinska Inst, Clintec, Stockholm, Sweden..
    Namdar, Sijal
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Mälarsjukhuset.
    Blennow, Kaj
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden..
    Zetterberg, Henrik
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden.;UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England..
    Mattsson, Niklas
    Lund Univ, Clin Memory Res Unit, Fac Med, Lund, Sweden.;Skane Univ Hosp, Dept Neurol, Lund, Sweden..
    Effects of surgery and propofol-remifentanil total intravenous anesthesia on cerebrospinal fluid biomarkers of inflammation, Alzheimer's disease, and neuronal injury in humans: a cohort study2017Ingår i: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 14, artikel-id 193Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Surgery and anesthesia have been linked to postoperative cognitive disturbance and increased risk of Alzheimer's disease. It is not clear by which mechanisms this increased risk for cognitive disease is mediated. Further, amyloid beta production has been suggested to depend on the sleep-wake cycle and neuronal activity. The aim of the present study was to examine if cerebrospinal fluid (CSF) concentrations of a number of biomarkers for Alzheimer's disease-related processes, including amyloid beta, neuronal injury, and inflammation, changed over time during intravenous anesthesia in surgical patients. Methods: We included patients scheduled for hysterectomy via laparotomy during general anesthesia with intravenous propofol and remifentanil. CSF samples were obtained before, during, and after surgery (5 h after induction) and tested for 27 biomarkers. Changes over time were tested with linear mixed effects models. Results: A total of 22 patients, all females, were included. The mean age was 50 years (+/- 9 SD). The mean duration of the anesthesia was 145 min (+/- 40 SD). Interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, and vascular endothelial growth factor A increased over time. IL-15 and IL-7 decreased slightly over time. Macrophage inflammatory protein 1 beta and placental growth factor also changed significantly. There were no significant effects on amyloid beta (A beta) or tau biomarkers. Conclusions: Surgery and general anesthesia with intravenous propofol and remifentanil induce, during and in the short term after the procedure, a neuroinflammatory response which is dominated by monocyte attractants, without biomarker signs of the effects on Alzheimer's disease pathology or neuronal injury.

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    fulltext
  • 327.
    Pino, Fabio
    et al.
    Univ Genoa, Dept Surg Sci & Integrated Diagnost, Genoa, Italy..
    Ball, Lorenzo
    Univ Genoa, Dept Surg Sci & Integrated Diagnost, Genoa, Italy..
    Scaramuzzo, Gaetano
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Univ Genoa, Dept Surg Sci & Integrated Diagnost, Genoa, Italy.;Hosp La Fe, Valencia, Spain.; Univ Sao Paulo, Hosp Clin, Sao Paulo, Brazil.;Hop Croix Rousse, Lyon, France.;Bari Univ, Bari, Italy..
    Pinol Ribas, Miquel
    Hosp La Fe, Valencia, Spain..
    Pelosi, Paolo
    Univ Genoa, Dept Surg Sci & Integrated Diagnost, Genoa, Italy..
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Borges, Joao Batista
    Univ Genoa, Dept Surg Sci & Integrated Diagnost, Genoa, Italy.;Univ Sao Paulo, Hosp Clin, Sao Paulo, Brazil..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Guerin, Claude
    Hop Croix Rousse, Lyon, France..
    Perchiazzi, Gaetano
    Bari Univ, Bari, Italy..
    A comparison between PEEP titration methods in a porcine ARDS model2017Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, nr 8, s. 1024-1025Artikel i tidskrift (Övrigt vetenskapligt)
  • 328.
    Pontén, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Neonatal Exposure to Anaesthesia and Adjuvants: Acute Effects on Cerebral Apoptosis and Neuroproteins, and Late  Behavioural Aberrations in Mice2012Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    During a finite developmental phase – the brain growth spurt – the brain grows and matures at an accelerated rate. During this period the brain is more sensitive to harmful substances such as ethanol and environmental toxins than before or after. This period extends from the last trimester to the second year in humans and occurs postnatally in the mice used for these studies.

    The aims of this thesis were; to investigate common anaesthetics ability to promote acute apoptosis and late persistant behavioural aberrations measured with spontaneous behaviour in a novel home environment, learning in a radial arm maze and anxiety-like behaviour in an elevated plus maze, to measure alterations in BDNF, CaMKII, GAP-43, synaptophysin and tau after anaesthesia exposure, to evaluate clonidine as a potentially protecting agent and examine if theophylline, a chemically unrelated compound, causes similar effects as anaesthetics.

    Some of the results are: combinations of anaesthetics acting on the GABAA receptor (propofol or pentothal) and NMDA receptor (ketamine) exhibit more apoptosis and behavioural alterations than single anaesthetics. Ketamine, but not propofol, alters the content of CaMKII and GAP-43 proteins important in brain development. Propofol exposure alters the content of BDNF (brain derived neurotrophic factor) in hippocampus, frontal and parietal cortex. Neonatal propofol exposure leads to less sensitiveness to diazepam in adult age as measured with induced spontaneous behaviour and an elevated plus maze. Clonidine, an alpha2 adrenergic agonist does not cause any aberrations and appears to prevent apoptosis and behavioural alterations after ketamine. Theophylline, used as apnoea treatment in neonates, also increases apoptosis and alters normal behaviour.

    Thus, alterations both in neuronal survival, function and protein expression is apparent after neonatal exposure to anaesthetics. This is also shown in studies of Rhesus monkeys. However, it is still difficult to assess how these findings should extrapolate to humans. Epidemiological studies give conflicting results.

    Insufficient anaesthesia is not a solution as pain and stress cause even more pronounced problems. Minimizing anaesthetic exposure, delaying procedures until after the sensitive phase and finding protective agents, such as clonidine, are possible strategies. Evaluation of other substances that infants are exposed to is needed.

    Delarbeten
    1. Neonatal exposure to a combination of N-Methyl-D-aspartate and γ-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits
    Öppna denna publikation i ny flik eller fönster >>Neonatal exposure to a combination of N-Methyl-D-aspartate and γ-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits
    2007 (Engelska)Ingår i: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 107, nr 3, s. 427-436Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: During the brain growth spurt, the brain develops and modifies rapidly. In rodents this period is neonatal, spanning the first weeks of life, whereas in humans it begins during the third trimester and continues 2 yr. This study examined whether different anesthetic agents, alone and in combination, administered to neonate mice, can trigger apoptosis and whether behavioral deficits occur later in adulthood.

    Methods: Ten-day-old mice were injected subcutaneously with ketamine (25 mg/kg), thiopental (5 mg/kg or 25 mg/kg), propofol (10 mg/kg or 60 mg/kg), a combination of ketamine (25 mg/kg) and thiopental (5 mg/kg), a combination of ketamine (25 mg/kg) and propofol (10 mg/kg), or control (saline). Fluoro-Jade staining revealed neurodegeneration 24 h after treatment. The behavioral tests-spontaneous behavior, radial arm maze, and elevated plus maze (before and after anxiolytic)-were conducted on mice aged 55-70 days.

    Results: Coadministration of ketamine plus propofol or ketamine plus thiopental or a high dose of propofol alone significantly triggered apoptosis. Mice exposed to a combination of anesthetic agents or ketamine alone displayed disrupted spontaneous activity and learning. The anxiolytic action of diazepam was less effective when given to adult mice that were neonatally exposed to propofol.

    Conclusion: This study shows that both a γ-aminobutyric acid type A agonist (thiopental or propofol) and an N-methyl-d-aspartate antagonist (ketamine) during a critical stage of brain development potentiated neonatal brain cell death and resulted in functional deficits in adulthood. The use of thiopental, propofol, and ketamine individually elicited no or only minor changes.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-11526 (URN)10.1097/01.anes.0000278892.62305.9c (DOI)000249297200011 ()17721245 (PubMedID)
    Tillgänglig från: 2008-05-15 Skapad: 2008-05-15 Senast uppdaterad: 2017-12-11Bibliografiskt granskad
    2. Neonatal ketamine exposure results in changes in biochemical substrates of neuronal growth and synaptogenesis, and alters adult behavior irreversibly
    Öppna denna publikation i ny flik eller fönster >>Neonatal ketamine exposure results in changes in biochemical substrates of neuronal growth and synaptogenesis, and alters adult behavior irreversibly
    Visa övriga...
    2008 (Engelska)Ingår i: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 249, nr 2-3, s. 153-9Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Ketamine, an anaesthetic agent used in newborns and toddlers, has been shown to induce neurodegeneration and alter adult behavior in mice, when administered during the neonatal period. Mammals have a marked period of rapid brain growth and development (BGS), which is postnatal in mice and rats, spanning the first 3-4 weeks of life and reaching its peak around postnatal day 10. CaMKII and GAP-43 play important roles during the BGS in mammals. In the present study, 10 days old mice were exposed to 5-25 mg ketamine/kg bw and 24 h later brains were analyzed for calcium/calmodulin-dependent protein kinase II (CaMKII) and growth associated protein-43 (GAP-43) and at an age of 2 and 4 months the animals were tested for spontaneous behavior. The protein analysis showed that CaMKII increased significantly in hippocampus, but not in cortex, in animals 24h after exposure to ketamine. GAP-43 showed a significant increase in hippocampus, but a significant decrease in cortex for the highest ketamine dose. When looking at the adult behavior it was clear that neonatal ketamine exposure affected spontaneous behavior and habituation in a dose-response-related manner and that these behavioral disturbances were not transient but still persisted 2 months later. Taken together, this shows that ketamine affects important proteins involved in normal maturation of the brain and induce functional deficits in the adult individual, which further strengthen our findings concerning ketamine as a developmental neurotoxicological agent.

    Nyckelord
    Ketamine, Neonatal, Neurotoxicity, CaMKII, GAP-43, Behavior
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-87826 (URN)10.1016/j.tox.2008.04.019 (DOI)000258242100010 ()18550250 (PubMedID)
    Tillgänglig från: 2009-01-14 Skapad: 2009-01-14 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    3. Neonatal exposure to propofol affects BDNF but not CaMKII, GAP-43, synaptophysin and tau in the neonatal brain and causes an altered behavioural response to diazepam in the adult mouse brain
    Öppna denna publikation i ny flik eller fönster >>Neonatal exposure to propofol affects BDNF but not CaMKII, GAP-43, synaptophysin and tau in the neonatal brain and causes an altered behavioural response to diazepam in the adult mouse brain
    Visa övriga...
    2011 (Engelska)Ingår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 223, nr 1, s. 75-80Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Animal studies have shown that neonatal anaesthesia is associated with acute signs of neurodegeneration and later behavioural changes in adult animals. The anaesthetic effect of propofol is thought to be mediated by gamma-amino butyric acid (GABA)(A) receptors. The present study investigated the effects on proteins important for normal neonatal brain development (i.e. BDNF, CaMKII, GAP-43, synaptophysin and tau), and adult spontaneous motor and anxiety-like behaviours in response to diazepam, after neonatal exposure to propofol. Ten-day-old mice were exposed to 0, 10 or 60 mg/kg bodyweight propofol. Neonatal propofol exposure changed the levels of BDNF in the brain, 24h after exposure, but did not alter any of the other proteins. Neonatal propofol exposure significantly changed the adult response to the GABA-mimetic drug diazepam, manifest as no change in spontaneous motor activity and/or reduced sedative effect and an extinguished effect on the reduction of anxiety-like behaviours in an elevated plus maze. Although no adult spontaneous behavioural changes were detected after neonatal propofol exposure, the exposure caused an adult dose-dependent decrease in the response to the GABA-mimetic drug diazepam. These changes may be due to neonatal alterations in BDNF levels.

    Nyckelord
    Propofol, BDNF, Behaviour
    Nationell ämneskategori
    Anestesi och intensivvård Farmakologi och toxikologi
    Identifikatorer
    urn:nbn:se:uu:diva-156580 (URN)10.1016/j.bbr.2011.04.019 (DOI)000292587700012 ()
    Tillgänglig från: 2011-08-07 Skapad: 2011-08-04 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
    4. Clonidine abolishes the adverse effects on apoptosis and behaviour after neonatal ketamine exposure in mice
    Öppna denna publikation i ny flik eller fönster >>Clonidine abolishes the adverse effects on apoptosis and behaviour after neonatal ketamine exposure in mice
    Visa övriga...
    2012 (Engelska)Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 56, nr 8, s. 1058-1065Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background

    An increasing amount of both experimental and epidemiological data indicates that neonatal anaesthesia causes disruption of normal brain development in rodents and primates, as manifested by acute increased apoptosis and long-lasting altered behaviour and learning. It is necessary to seek strategies that avoid the possible adverse effects after anaesthesia. Our purpose is to show that increased apoptosis and behavioural alterations after ketamine exposure during this period may be prevented by clonidine, a compound already used by paediatric anaesthetists for sedation.

    Methods

    To investigate the protective properties of clonidine pre-treatment, five groups of 10-day-old mice were injected with either ketamine 50 mg/kg, clonidine 40 μg/kg, ketamine 50 mg/kg 30 min after 10 μg/kg clonidine, ketamine 50 mg/kg 30 min after 40 μg/kg clonidine or saline (control). Apoptosis was measured 24 h after treatment using Flouro-Jade staining. Spontaneous activity in a novel environment was tested at an age of 55 days.

    Results

    Pre-treatment with 40 μg/kg clonidine, but not 10 μg/kg clonidine, 30 min before ketamine exposure abolished ketamine-induced apoptosis and the behavioural changes observed in the young adult mice. The mice exposed to clonidine alone showed no differences from the saline-treated (control) mice.

    Conclusion

    The administration of clonidine eliminated the adverse effects of ketamine in this mouse model, suggesting a possible strategy for protection. Alone, clonidine did not cause any adverse effects in these tests.

    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-173406 (URN)10.1111/j.1399-6576.2012.02722.x (DOI)000307437600016 ()
    Tillgänglig från: 2012-05-07 Skapad: 2012-04-23 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    5. Theophylline causes dose dependent persistent behavioural changes in neonatal mice
    Öppna denna publikation i ny flik eller fönster >>Theophylline causes dose dependent persistent behavioural changes in neonatal mice
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Abstract

    Background

    Theophylline is used in clinic to promote breathing in premature infants and in neonates. Caffeine, a compound also belonging to the group of xanthenes, is known to increase apoptosis and to cause behavioural defects. The present study was conducted to investigate whether theophylline can induce neuronal death and behavioural disturbances when administered to neonatal mice during a period of brain growth corresponding to premature infants and an approximately week 13 to 24.

    Methods

    Neonatal mice, three days old, were exposed to theophylline at doses 1, 5, or 25 mg/kg body weight twice daily for five consecutive days. Controls received in the same manner the vehicle, saline. Neuronal death was assessed in whole brain sections by Fluoro Jade 24 hours after the last exposure to theophylline. Adult mice, age 55 to 63 days old, were observed for spontaneous behavior in a novel home environment, learning and memory in a radial arm maze and for anxiety-like behavior in an elevated plus maze.

    Results

    Adult mice neonatally exposed to theophylline showed significant dose-response changes in all three behavioural tests. The lowest dose to induce any behavioral defects was 5 mg/kg body weight. No significant alterations in neuronal death were observed in the neonatal brains.

    Conclusion

    The present study shows that neonatal exposure to theophylline can cause behavioural defects related to learning and memory impairments and reduced cognitive function in young adult mice.

     

    Nyckelord
    neonatal, apoptosis, theophylline, behaviour, mice, learning
    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Medicin
    Identifikatorer
    urn:nbn:se:uu:diva-173786 (URN)
    Tillgänglig från: 2012-05-07 Skapad: 2012-05-07 Senast uppdaterad: 2012-06-08
    Ladda ner fulltext (pdf)
    fulltext
  • 329.
    Pontén, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Ekotoxikologi.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Fredriksson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Ulleråker, Akademiska sjukhuset.
    Theophylline causes dose dependent persistent behavioural changes in neonatal miceManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Abstract

    Background

    Theophylline is used in clinic to promote breathing in premature infants and in neonates. Caffeine, a compound also belonging to the group of xanthenes, is known to increase apoptosis and to cause behavioural defects. The present study was conducted to investigate whether theophylline can induce neuronal death and behavioural disturbances when administered to neonatal mice during a period of brain growth corresponding to premature infants and an approximately week 13 to 24.

    Methods

    Neonatal mice, three days old, were exposed to theophylline at doses 1, 5, or 25 mg/kg body weight twice daily for five consecutive days. Controls received in the same manner the vehicle, saline. Neuronal death was assessed in whole brain sections by Fluoro Jade 24 hours after the last exposure to theophylline. Adult mice, age 55 to 63 days old, were observed for spontaneous behavior in a novel home environment, learning and memory in a radial arm maze and for anxiety-like behavior in an elevated plus maze.

    Results

    Adult mice neonatally exposed to theophylline showed significant dose-response changes in all three behavioural tests. The lowest dose to induce any behavioral defects was 5 mg/kg body weight. No significant alterations in neuronal death were observed in the neonatal brains.

    Conclusion

    The present study shows that neonatal exposure to theophylline can cause behavioural defects related to learning and memory impairments and reduced cognitive function in young adult mice.

     

  • 330.
    Pontén, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Fredriksson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Ekotoxikologi.
    Viberg, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Ekotoxikologi.
    Neonatal exposure to propofol affects BDNF but not CaMKII, GAP-43, synaptophysin and tau in the neonatal brain and causes an altered behavioural response to diazepam in the adult mouse brain2011Ingår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 223, nr 1, s. 75-80Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Animal studies have shown that neonatal anaesthesia is associated with acute signs of neurodegeneration and later behavioural changes in adult animals. The anaesthetic effect of propofol is thought to be mediated by gamma-amino butyric acid (GABA)(A) receptors. The present study investigated the effects on proteins important for normal neonatal brain development (i.e. BDNF, CaMKII, GAP-43, synaptophysin and tau), and adult spontaneous motor and anxiety-like behaviours in response to diazepam, after neonatal exposure to propofol. Ten-day-old mice were exposed to 0, 10 or 60 mg/kg bodyweight propofol. Neonatal propofol exposure changed the levels of BDNF in the brain, 24h after exposure, but did not alter any of the other proteins. Neonatal propofol exposure significantly changed the adult response to the GABA-mimetic drug diazepam, manifest as no change in spontaneous motor activity and/or reduced sedative effect and an extinguished effect on the reduction of anxiety-like behaviours in an elevated plus maze. Although no adult spontaneous behavioural changes were detected after neonatal propofol exposure, the exposure caused an adult dose-dependent decrease in the response to the GABA-mimetic drug diazepam. These changes may be due to neonatal alterations in BDNF levels.

  • 331.
    Pontén, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Viberg, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Ekotoxikologi.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Ekotoxikologi.
    Fredriksson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Ulleråker, Akademiska sjukhuset.
    Clonidine abolishes the adverse effects on apoptosis and behaviour after neonatal ketamine exposure in mice2012Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 56, nr 8, s. 1058-1065Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    An increasing amount of both experimental and epidemiological data indicates that neonatal anaesthesia causes disruption of normal brain development in rodents and primates, as manifested by acute increased apoptosis and long-lasting altered behaviour and learning. It is necessary to seek strategies that avoid the possible adverse effects after anaesthesia. Our purpose is to show that increased apoptosis and behavioural alterations after ketamine exposure during this period may be prevented by clonidine, a compound already used by paediatric anaesthetists for sedation.

    Methods

    To investigate the protective properties of clonidine pre-treatment, five groups of 10-day-old mice were injected with either ketamine 50 mg/kg, clonidine 40 μg/kg, ketamine 50 mg/kg 30 min after 10 μg/kg clonidine, ketamine 50 mg/kg 30 min after 40 μg/kg clonidine or saline (control). Apoptosis was measured 24 h after treatment using Flouro-Jade staining. Spontaneous activity in a novel environment was tested at an age of 55 days.

    Results

    Pre-treatment with 40 μg/kg clonidine, but not 10 μg/kg clonidine, 30 min before ketamine exposure abolished ketamine-induced apoptosis and the behavioural changes observed in the young adult mice. The mice exposed to clonidine alone showed no differences from the saline-treated (control) mice.

    Conclusion

    The administration of clonidine eliminated the adverse effects of ketamine in this mouse model, suggesting a possible strategy for protection. Alone, clonidine did not cause any adverse effects in these tests.

  • 332.
    Purins, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Brain Tissue Oxygenation in Traumatic Brain Injury: Experimental and Clinical Studies2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Traumatic brain injury (TBI) is a major cause of death and disability. TBI is frequently followed by cerebral ischemia which is a great contributor to secondary brain damage. The main causes of cerebral ischemia are pathophysiological changes in cerebral blood flow and metabolism. Treatment of TBI patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted treatment protocols. However, ICP and CPP alone do not provide information of the oxygen availability in the brain. Monitoring of brain tissue oxygenation (BtipO2) may give additional and valuable information about the risk for development of ischemia in TBI patients.

    The aims of this thesis were to study BtipO2 monitoring devices in-vitro regarding accuracy and stability, to detect threshold level of cerebral ischemia in-vivo and finally to examine the cerebral oxygen levels and cerebral metabolism in TBI patients.

    The BtipO2 probes performed with high accuracy and stability at different clinically relevant oxygen concentrations.

    A pig TBI model was developed by step-wise intracranial volume/pressure increase. Volume increase resulted in a gradual increased ICP, decreased CPP, intracranial compliance and BtipO2, respectively. Brain death (BD) was confirmed by negative CPP and negligible amount of previously injected microspheres in the brain tissue. The model simulated the clinical development of BD in humans with a classical pressure-volume response and systemic cardiovascular reactions. The model should be suitable for studies of brain injury mechanisms.

    From the same in-vivo model it was also possible to detect the threshold level of cerebral ischemia in the pig, where BtipO2 below 10 mmHg and CPP below 30 mmHg was associated with an impaired cerebral metabolism (microdialysis lactate to pyruvate ratio >30).

    BtipO2 together with cerebral microdialysis were studied in 23 severe TBI patients. We observed different patterns of changes in BtipO2 and cerebral microdialysis biomarkers in focal and diffuse TBI.  Increased cerebral microdialysis levels of glutamate, glycerol or the lactate/pyruvate ratio were observed at BtipO2 < 5 mmHg, indicating increased vulnerability of the brain at this critical level of tissue oxygenation in TBI patients.

    Delarbeten
    1. Brain tissue oxygen monitoring: a study of in vitro accuracy and stability of Neurovent-PTO and Licox sensors
    Öppna denna publikation i ny flik eller fönster >>Brain tissue oxygen monitoring: a study of in vitro accuracy and stability of Neurovent-PTO and Licox sensors
    2010 (Engelska)Ingår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 152, nr 4, s. 681-688Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECT: Periods of brain tissue ischemia are common after severe head injury, and their occurrence and duration are negatively correlated with outcome. Accurate and reliable measurement of brain tissue oxygenation (B(ti) pO(2)) may be a key to improve patient outcome after severe head injury. Knowledge of stability and accuracy of the B(ti) pO(2) systems is crucial. We have therefore conducted a bench test study of new Neurovent-PTO(R) (NV) and Licox(R) (LX) oxygen tension catheters to evaluate the sensor accuracy, response time to different oxygen tensions, response to temperature changes and long-term stability. METHODS: For all experiments five new fluorescent NV sensors and five new electrochemical LX sensors were used. The catheter probes were placed into a container filled with a buffer solution. The solution was equilibrated with five high precision calibration gases. The accuracy of the probes was recorded after an equilibration period of 20 min in O(2) concentrations of 5, 10, 20, 30 and 40 mmHg at 37.0 +/- 0.2 degrees C. The probe response to an increase in temperature from 37.0 degrees C to 38.5 degrees C to 40.0 degrees C in two different gases with O(2) concentrations of 10 and 20 mmHg were analysed. We also recorded the time for reaching 90% of a new oxygen concentration level when switching from one concentration to another. Finally, to test if there was a time-dependant drift in pO(2) recordings, all sensors were left in 10 mmHg O(2) solution for 10 days, and recordings were taken every 24 h. RESULTS: In all gas concentrations, NV and LX sensors measured pO(2) with high accuracy and stability in vitro (mean differences from calculated values were for NV 0.76-1.6 mmHg and for LX -0.46-0.26 mmHg). Both sensors showed a shorter response time to pO(2) increase (for NV 56 +/- 22 s and for LX 78 +/- 21 s) compared to pO(2) decrease (for NV 131 +/- 42 s and for LX 215 +/- 63 s). NV pO(2) values were more stable for changes in temperature, while LX sensors showed larger standard deviations with increasing temperature (the difference from the calculated values in 19.7 mmHg O(2) at 40 degrees C were for NV probes between 0.5 and 1.7 mmHg and LX between -2.3 and 1.9 mmHg). Both sensors gave stable results with low standard deviations during long-term (10 days) use, but with a slight elevation of measured pO(2) levels by time. CONCLUSIONS: Both NV and LX were accurate in detecting different oxygen tensions, and they did not deviate over longer recording times. However, LX needed a significantly longer time to detect changes in pO(2) levels compared to NV. Furthermore, LX probes showed an increased standard deviation with higher temperatures.

    Nyckelord
    Licox, Neurovent-PTO, Brain tissue oxygenation, Accuracy, Neurointensive care, Traumatic brain injury
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-110760 (URN)10.1007/s00701-009-0532-x (DOI)000275945600017 ()19826757 (PubMedID)
    Tillgänglig från: 2009-11-24 Skapad: 2009-11-24 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
    2. Standardized experimental brain death model for studies of intracranial dynamics, organ preservation, and organ transplantation in the pig
    Öppna denna publikation i ny flik eller fönster >>Standardized experimental brain death model for studies of intracranial dynamics, organ preservation, and organ transplantation in the pig
    Visa övriga...
    2011 (Engelska)Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 39, nr 3, s. 512-517Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECTIVES:: Brain death impairs organ function and outcome after transplantation. There is a need for a brain death model to allow studies of organ viability and preservation. For neurointensive care research, it is also of interest to have a relevant brain death model for studies of intracranial dynamics and evaluation of cerebral monitoring devices. Therefore, the objective was to develop a standardized clinically relevant brain death model. METHODS:: Six pigs of both sexes (10-12 wks old; mean weight, 24.5 ± 1.4 kg) were included. Mean arterial blood pressure, heart rate, intracranial pressure, intracranial compliance, cerebral perfusion pressure, and brain tissue oxygenation (BtiPo2) were recorded during stepwise elevation of intracranial pressure by inflation of an epidural balloon catheter with saline (1 mL/20 mins). Brain death criteria were decided to be reached when cerebral perfusion pressure was <0 mm Hg for 60 mins and at least 10 mL saline was inflated epidurally. BtiPo2 and arterial injections of microspheres were used for confirmation of brain death. RESULTS:: A gradual volume-dependent elevation of intracranial pressure was observed. After 10 mL of balloon infusion, mean intracranial pressure was 89.8 ± 9.7 (sd) mm Hg. Intracranial compliance decreased from 0.137 ± 0.069 mL/mm Hg to 0.007 ± 0.001 mL/mm Hg. The mean arterial pressure decreased and the heart rate increased when the intracranial volume was increased to between 5 and 6 mL. All animals showed cerebral perfusion pressure ≤0 after 7 to 10 mL of infusion. In all animals, the criteria for brain death with negative cerebral perfusion pressure and BtiPo2 ∼0 mm Hg were achieved. Only a negligible amount of microspheres were found in the cerebrum, confirming brain death. The kidneys showed small foci of acute tubular necrosis. CONCLUSIONS:: The standardized brain death model designed in pigs simulates the clinical development of brain death in humans with a classic pressure-volume response and systemic cardiovascular reactions. Brain death was convincingly confirmed.

    Nyckelord
    brain death, experimental animal model, intracranial pressure, cerebral perfusion pressure, brain tissue oxygenation, organ preservation
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-143532 (URN)10.1097/CCM.0b013e318206b824 (DOI)000287480000013 ()21187748 (PubMedID)
    Tillgänglig från: 2011-01-21 Skapad: 2011-01-21 Senast uppdaterad: 2017-12-11Bibliografiskt granskad
    3. Brain Tissue Oxygenation and Cerebral Perfusion Pressure Thresholds of Ischemia in a Standardized Pig Brain Death Model
    Öppna denna publikation i ny flik eller fönster >>Brain Tissue Oxygenation and Cerebral Perfusion Pressure Thresholds of Ischemia in a Standardized Pig Brain Death Model
    2012 (Engelska)Ingår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 16, nr 3, s. 462-469Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND:

    Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. Monitoring brain tissue oxygenation (B(ti)pO(2)) is of considerable clinical interest, but the exact threshold level of ischemia has been difficult to establish due to the complexity of the clinical situation. The objective of this study was to use the Neurovent-PTO (NV) probe, and to define critical cerebral oxygenation- and CPP threshold levels of cerebral ischemia in a standardized brain death model caused by increasing the ICP in pig. Ischemia was defined by a severe increase of cerebral microdialysis (MD) lactate/pyruvate ratio (L/P ratio > 30).

    METHODS:

    B(ti)pO(2), L/P ratio, Glucose, Glutamate, Glycerol and CPP were recorded using NV and MD probes during gradual increase of ICP by inflation of an epidural balloon catheter with saline until brain death was achieved.

    RESULTS:

    Baseline level of B(ti)pO(2) was 22.9 ± 6.2 mmHg, the L/P ratio 17.7 ± 6.1 and CPP 73 ± 17 mmHg. B(ti)pO(2) and CPP decreased when intracranial volume was added. The L/P ratio increased above its ischemic levels, (>30) when CPP decreased below 30 mmHg and B(ti)pO(2) to <10 mmHg.

    CONCLUSIONS:

    A severe increase of ICP leading to CPP below 30 mmHg and B(ti)pO(2) below 10 mmHg is associated with an increase of the L/P ratio, thus seems to be critical thresholds for cerebral ischemia under these conditions.

    Nyckelord
    Brain tissue oxygenation, Cerebral perfusion pressure, Microdialysis, Threshold levels, Traumatic brain injury
    Nationell ämneskategori
    Neurovetenskaper
    Forskningsämne
    Neurokirurgi; Neurovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-170951 (URN)10.1007/s12028-012-9675-3 (DOI)000304619000019 ()
    Tillgänglig från: 2012-03-16 Skapad: 2012-03-14 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
    4. Brain tissue oxygenation and cerebral metabolic patterns in focal and diffuse traumatic brain injury
    Öppna denna publikation i ny flik eller fönster >>Brain tissue oxygenation and cerebral metabolic patterns in focal and diffuse traumatic brain injury
    Visa övriga...
    2014 (Engelska)Ingår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, artikel-id 64Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Introduction: Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. There are reasons to believe that knowledge of brain tissue oxygenation (BtipO2) would add information with the potential of improving patient outcome. The aim of this study was to examine BtipO2 and cerebral metabolism using the Neurovent-PTO probe and cerebral microdialysis (MD) in TBI patients.

    Methods: Twenty-three severe TBI patients with monitoring of physiological parameters, ICP, CPP, BtipO2, and MD for biomarkers of energy metabolism (glucose, lactate, and pyruvate) and cellular distress (glutamate, glycerol) were included. Patients were grouped according to injury type (focal/diffuse) and placement of the Neurovent-PTO probe and MD catheter (injured/non-injured hemisphere).

    Results: We observed different patterns in BtipO2 and MD biomarkers in diffuse and focal injury where placement of the probe also influenced the results (ipsilateral/contralateral). In all groups, despite fairly normal levels of ICP and CPP, increased MD levels of glutamate, glycerol, or the L/P ratio were observed at BtipO2 <5 mmHg, indicating increased vulnerability of the brain at this level.

    Conclusion: Monitoring of BtipO2 adds important information in addition to traditional ICP and CPP surveillance. Because of the different metabolic responses to very low BtipO2 in the individual patient groups we submit that brain tissue oximetry is a complementary tool rather than an alternative to MD monitoring.

    Nyckelord
    brain tissue oxygenation, cerebral metabolism, traumatic brain injury, cerebral ischemia, Neurovent-PTO
    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Neurokirurgi
    Identifikatorer
    urn:nbn:se:uu:diva-194684 (URN)10.3389/fneur.2014.00064 (DOI)000209629300064 ()24817863 (PubMedID)
    Forskningsfinansiär
    VetenskapsrådetHjärnfonden
    Tillgänglig från: 2013-02-18 Skapad: 2013-02-18 Senast uppdaterad: 2017-12-06Bibliografiskt granskad
    Ladda ner fulltext (pdf)
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  • 333.
    Purins, Karlis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Howells, Timothy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Brain tissue oxygenation and cerebral metabolic patterns in focal and diffuse traumatic brain injury2014Ingår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, artikel-id 64Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. There are reasons to believe that knowledge of brain tissue oxygenation (BtipO2) would add information with the potential of improving patient outcome. The aim of this study was to examine BtipO2 and cerebral metabolism using the Neurovent-PTO probe and cerebral microdialysis (MD) in TBI patients.

    Methods: Twenty-three severe TBI patients with monitoring of physiological parameters, ICP, CPP, BtipO2, and MD for biomarkers of energy metabolism (glucose, lactate, and pyruvate) and cellular distress (glutamate, glycerol) were included. Patients were grouped according to injury type (focal/diffuse) and placement of the Neurovent-PTO probe and MD catheter (injured/non-injured hemisphere).

    Results: We observed different patterns in BtipO2 and MD biomarkers in diffuse and focal injury where placement of the probe also influenced the results (ipsilateral/contralateral). In all groups, despite fairly normal levels of ICP and CPP, increased MD levels of glutamate, glycerol, or the L/P ratio were observed at BtipO2 <5 mmHg, indicating increased vulnerability of the brain at this level.

    Conclusion: Monitoring of BtipO2 adds important information in addition to traditional ICP and CPP surveillance. Because of the different metabolic responses to very low BtipO2 in the individual patient groups we submit that brain tissue oximetry is a complementary tool rather than an alternative to MD monitoring.

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  • 334.
    Ravn, Bo
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Sect Anaesthesia & Intens Care Med, S-17176 Stockholm, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Mårtensson, Johan
    Karolinska Inst, Dept Physiol & Pharmacol, Sect Anaesthesia & Intens Care Med, S-17176 Stockholm, Sweden; Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia.
    Martling, Claes-Roland
    Karolinska Inst, Dept Physiol & Pharmacol, Sect Anaesthesia & Intens Care Med, S-17176 Stockholm, Sweden.
    Bell, Max
    Karolinska Inst, Dept Physiol & Pharmacol, Sect Anaesthesia & Intens Care Med, S-17176 Stockholm, Sweden.
    Intra-day variability of cystatin C, creatinine and estimated GFR in intensive care patients2016Ingår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 460, s. 1-4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Markers of renal function are widely used in intensive care and sudden changes are important indicators of acute kidney injury. The problem is to distinguish between disease progression/improvement from the natural variation in the patient. The aim of the present study was thus to study the normal intraday variation in ICU patients.

    METHODS: We studied the intra-day variation of creatinine, cystatin C and estimated GFR based on these two markers in 28 clinically stable ICU patients.

    RESULTS: The median diurnal coefficient of variation sCV) for creatinine was 3.70% (1.92-9.25%) while the median CV for cystatin C was 3.66% (1.36-8.11%). The corresponding CVs for the estimated GFRs were 2.00% (0.89-9.82%) for eGFRcreatinine and 4.60% (1.65-10.24%) for eGFRcystc.

    CONCLUSIONS: The eGFRcreatinine values in individual patients were clearly higher than the eGFRcystc values. The median CV for creatinine, cystatin C and the eGFR measurements were below 5% which means that 95% of the test results will vary by <10% between sampling times in stable ICU patients. Differences >10% between sampling times are thus likely to be an indication of changes in biomarker levels due to the disease/treatment.

  • 335.
    Ravn, Bo
    et al.
    Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 76 Stockholm, Sweden..
    Rimes-Stigare, Claire
    Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 76 Stockholm, Sweden..
    Bell, Max
    Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 76 Stockholm, Sweden..
    Hansson, Magnus
    Department of Laboratory Medicine (LABMED), H5, Division of Clinical Chemistry, C1 74 Karolinska Universitetssjukhuset Huddinge, 14186 Stockholm, Sweden..
    Hansson, Lars-Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Martling, Claes-Roland
    Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 76 Stockholm, Sweden..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Mårtensson, Johan
    Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 76 Stockholm, Sweden..
    Creatinine versus cystatin C based glomerular filtration rate in critically ill patients2019Ingår i: Journal of critical care, ISSN 0883-9441, E-ISSN 1557-8615, Vol. 52, s. 136-140Artikel i tidskrift (Refereegranskat)
  • 336.
    Reinius, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Open lung concept in high risk anaesthesia: Optimizing mechanical ventilation in morbidly obese patients and during one lung ventilation with capnothorax2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Formation of atelectasis, defined as reversible collapse of aerated lung, often occurs after induction of anaesthesia with mechanical ventilation. As a consequence, there is a risk for hypoxemia, altered hemodynamics and impaired respiratory system mechanics. In certain situations, the risk for atelectasis formation is increased and its consequences may also be more difficult to manage. Anesthesia for bariatric surgery in morbidly obese patients and surgery requiring one-lung ventilation (OLV) with capnothorax are examples of such situations.

    In Paper I (30 patients with BMI > 40 kg/m2 scheduled for bariatric surgery) a recruit­ment maneuver followed by positive end-expiratory pressure (PEEP) re­duced the amount of atelectasis and improved oxygenation for a prolonged period of time. PEEP or a recruitment maneuver alone did not reduce the amount of atelectasis.

    In paper II we investigated whether it is possible to predict respiratory function impairment in morbidly obese patients without pulmonary disease from a preoperative lung function test. Patients with mild signs of airway obstruction (reduced end-expiratory flow) in the preoperative spirometry developed less atelectasis during anaesthesia.

    In paper III we developed an experimental model of sequential OLV with capnothorax using electrical impedance tomography (EIT) that in real-time detected lung separation and dynamic changes in pulmonary ventilation and perfusion distributions. OLV to the left side caused a decrease in cardiac output, arterial oxygenation and mixed venous saturation.

    In paper IV we used our model of OLV with capnothorax and applied a CO2-insufflation pressure of 16 cm H2O. We demonstrated that a PEEP level of 12-16 cm H2O is needed for optimal oxygenation and lowest possible driving pressure without compromising hemodynamic variables. Thus, the optimal PEEP was closely related to the level of the capnothorax insufflation pressure. With insufficient PEEP, ventilation/perfusion mismatch in the ventilated lung and redistribution of blood flow to the non-ventilated lung occurred.

    Delarbeten
    1. Prevention of atelectasis in morbidly obese patients during general anesthesia and paralysis: a computerized tomography study
    Öppna denna publikation i ny flik eller fönster >>Prevention of atelectasis in morbidly obese patients during general anesthesia and paralysis: a computerized tomography study
    Visa övriga...
    2009 (Engelska)Ingår i: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 111, nr 5, s. 979-987Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: Morbidly obese patients show impaired pulmonary function during anesthesia and paralysis, partly due to formation of atelectasis. This study analyzed the effect of general anesthesia and three different ventilatory strategies to reduce the amount of atelectasis and improve respiratory function. METHODS: Thirty patients (body mass index 45 +/- 4 kg/m) scheduled for gastric bypass surgery were prospectively randomized into three groups: (1) positive end-expiratory pressure of 10 cm H2O (PEEP), (2) a recruitment maneuver with 55 cm H2O for 10 s followed by zero end-expiratory pressure, (3) a recruitment maneuver followed by PEEP. Transverse lung computerized tomography scans and blood gas analysis were recorded: awake, 5 min after induction of anesthesia and paralysis at zero end-expiratory pressure, and 5 min and 20 min after intervention. In addition, spiral computerized tomography scans were performed at two occasions in 23 of the patients. RESULTS: After induction of anesthesia, atelectasis increased from 1 +/- 0.5% to 11 +/- 6% of total lung volume (P < 0.0001). End-expiratory lung volume decreased from 1,387 +/- 581 ml to 697 +/- 157 ml (P = 0.0014). A recruitment maneuver + PEEP reduced atelectasis to 3 +/- 4% (P = 0.0002), increased end-expiratory lung volume and increased Pao2/Fio2 from 266 +/- 70 mmHg to 412 +/- 99 mmHg (P < 0.0001). PEEP alone did not reduce the amount of atelectasis or improve oxygenation. A recruitment maneuver + zero end-expiratory pressure had a transient positive effect on respiratory function. All values are presented as mean +/- SD. CONCLUSIONS: A recruitment maneuver followed by PEEP reduced atelectasis and improved oxygenation in morbidly obese patients, whereas PEEP or a recruitment maneuver alone did not.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-113069 (URN)10.1097/ALN.0b013e3181b87edb (DOI)000271172500009 ()19809292 (PubMedID)
    Tillgänglig från: 2010-01-25 Skapad: 2010-01-25 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
    2. Preoperative lung function tests as a predictor for atelectasis in morbidly obese patients during anesthesia
    Öppna denna publikation i ny flik eller fönster >>Preoperative lung function tests as a predictor for atelectasis in morbidly obese patients during anesthesia
    Visa övriga...
    (Engelska)Artikel i tidskrift (Övrigt vetenskapligt) Submitted
    Abstract [en]

    Rationale: Pulmonary function is regularly impaired during general anesthesia and paralysis in morbidly obese patients. The aim of this study was to compare preoperative lung function with the alterations in respiratory function after induction of anesthesia in patients with BMI > 40 kg/m2.

    Methods: 23 women and 7 men (38 ± 9 years, (mean ± SD)), with a body mass index of 45 ± 4 kg/m2 were studied. 20 patients were active smokers (20 ± 12 pack years). All patients underwent preoperative lung functiontests. Arterial blood gases were collected before and after induction of anesthesia and either a single slice CT or a spiral CT was made for assessment of the amount of lung collapse. Respiratory system compliance was measured during anesthesia.

    Results: Lung volumes were within normal limits, however forced expiratory gas flow was reduced during the latter part of expiration. The arterial oxygen tension divided by the inspired O2 fraction (PaO2/FIO2 ratio) decreased from 409 ± 47 mmHg awake to 238 ± 80 mmHg after induction of anesthesia. The higher FEV1 was, the larger was the fall in oxygenation during anesthesia. At 5 min after induction, atelectasis in a CT cut 1 cm above the diaphragm was 7 ± 2 % of the lung area. The amount of atelectasis during anesthesia correlated with FEF75 in a regression analysis (p = 0.03).

    Conclusion: In morbidly obese patients without clinical signs of pulmonary disease a preoperative spirometry with mild signs of airway obstruction (reduced late expiratory flow) may predict reduced formation of atelectasis during anesthesia.

    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Anestesiologi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-268621 (URN)
    Tillgänglig från: 2015-12-08 Skapad: 2015-12-08 Senast uppdaterad: 2018-05-18
    3. Real-time ventilation and perfusion distributions by electrical impedance tomography during one-lung ventilation with capnothorax
    Öppna denna publikation i ny flik eller fönster >>Real-time ventilation and perfusion distributions by electrical impedance tomography during one-lung ventilation with capnothorax
    Visa övriga...
    2015 (Engelska)Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, nr 3, s. 354-368Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Carbon dioxide insufflation into the pleural cavity, capnothorax, with one-lung ventilation (OLV) may entail respiratory and hemodynamic impairments. We investigated the online physiological effects of OLV/capnothorax by electrical impedance tomography (EIT) in a porcine model mimicking the clinical setting.

    Methods: Five anesthetized, muscle-relaxed piglets were subjected to first right and then left capnothorax with an intra-pleural pressure of 19cm H2O. The contra-lateral lung was mechanically ventilated with a double-lumen tube at positive end-expiratory pressure 5 and subsequently 10cm H2O. Regional lung perfusion and ventilation were assessed by EIT. Hemodynamics, cerebral tissue oxygenation and lung gas exchange were also measured.

    Results: During right-sided capnothorax, mixed venous oxygen saturation (P=0.018), as well as a tissue oxygenation index (P=0.038) decreased. There was also an increase in central venous pressure (P=0.006), and a decrease in mean arterial pressure (P=0.045) and cardiac output (P=0.017). During the left-sided capnothorax, the hemodynamic impairment was less than during the right side. EIT revealed that during the first period of OLV/capnothorax, no or very minor ventilation on the right side could be seen (33% vs. 97 +/- 3%, right vs. left, P=0.007), perfusion decreased in the non-ventilated and increased in the ventilated lung (18 +/- 2% vs. 82 +/- 2%, right vs. left, P=0.03). During the second OLV/capnothorax period, a similar distribution of perfusion was seen in the animals with successful separation (84 +/- 4% vs. 16 +/- 4%, right vs. left).

    Conclusion: EIT detected in real-time dynamic changes in pulmonary ventilation and perfusion distributions. OLV to the left lung with right-sided capnothorax caused a decrease in cardiac output, arterial oxygenation and mixed venous saturation.

    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-248178 (URN)10.1111/aas.12455 (DOI)000349604000010 ()25556329 (PubMedID)
    Anmärkning

    De 2 första författarna delar förstaförfattarskapet.

    Tillgänglig från: 2015-04-12 Skapad: 2015-03-30 Senast uppdaterad: 2017-12-04Bibliografiskt granskad
    4. Optimal PEEP during one-lung ventilation with capnothorax: An experimental study
    Öppna denna publikation i ny flik eller fönster >>Optimal PEEP during one-lung ventilation with capnothorax: An experimental study
    Visa övriga...
    2019 (Engelska)Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 63, nr 2, s. 222-231Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: One‐lung ventilation (OLV) with induced capnothorax carries the risk of severely impaired ventilation and circulation. Optimal PEEP may mitigate the physiological perturbations during these conditions.

    Methods: Right‐sided OLV with capnothorax (16 cm H2O) on the left side was initiated in eight anesthetized, muscle‐relaxed piglets. A recruitment maneuver and a decremental PEEP titration from PEEP 20 cm H2O to zero end‐expiratory pressure (ZEEP) was performed. Regional ventilation and perfusion were studied with electrical impedance tomography and computer tomography of the chest was used. End‐expiratory lung volume and hemodynamics were recorded and.

    Results: PaO2 peaked at PEEP 12 cm H2O (49 ± 14 kPa) and decreased to 11 ± 5 kPa at ZEEP (P < 0.001). PaCO2 was 9.5 ± 1.3 kPa at 20 cm H2O PEEP and did not change when PEEP step‐wise was reduced to 12 cm H2O PaCO2. At lower PEEP, PaCO2 increased markedly. The ventilatory driving pressure was lowest at PEEP 14 cm H2O (19.6 ± 5.8 cm H2O) and increased to 38.3 ± 6.1 cm H2O at ZEEP (P < 0.001). When reducing PEEP below 12‐14 cm H2O ventilation shifted from the dependent to the nondependent regions of the ventilated lung (P = 0.003), and perfusion shifted from the ventilated to the nonventilated lung (P = 0.02).

    Conclusion: Optimal PEEP was 12‐18 cm H2O and probably relates to capnothorax insufflation pressure. With suboptimal PEEP, ventilation/perfusion mismatch in the ventilated lung and redistribution of blood flow to the nonventilated lung occurred.

    Nyckelord
    anesthesia, capnothorax, cardio-thoracic surgery, one lung ventilation, optimal PEEP, PEEP titration
    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Anestesiologi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-268620 (URN)10.1111/aas.13247 (DOI)000454814700012 ()30132806 (PubMedID)
    Forskningsfinansiär
    Hjärt-Lungfonden
    Anmärkning

    Title in thesis list of papers: Optimal PEEP during one lung ventilation with capnothorax. An experimental study

    Tillgänglig från: 2015-12-08 Skapad: 2015-12-08 Senast uppdaterad: 2019-01-31Bibliografiskt granskad
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  • 337.
    Reinius, Henrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Batista Borges, João
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Laboratório de Pneumologia LIM–09, Disciplina de Pneumologia, Heart Institute (Incor) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
    Engström, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Ahlgren, Oskar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lennmyr, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Fredén, Filip
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Optimal PEEP during one-lung ventilation with capnothorax: An experimental study2019Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 63, nr 2, s. 222-231Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: One‐lung ventilation (OLV) with induced capnothorax carries the risk of severely impaired ventilation and circulation. Optimal PEEP may mitigate the physiological perturbations during these conditions.

    Methods: Right‐sided OLV with capnothorax (16 cm H2O) on the left side was initiated in eight anesthetized, muscle‐relaxed piglets. A recruitment maneuver and a decremental PEEP titration from PEEP 20 cm H2O to zero end‐expiratory pressure (ZEEP) was performed. Regional ventilation and perfusion were studied with electrical impedance tomography and computer tomography of the chest was used. End‐expiratory lung volume and hemodynamics were recorded and.

    Results: PaO2 peaked at PEEP 12 cm H2O (49 ± 14 kPa) and decreased to 11 ± 5 kPa at ZEEP (P < 0.001). PaCO2 was 9.5 ± 1.3 kPa at 20 cm H2O PEEP and did not change when PEEP step‐wise was reduced to 12 cm H2O PaCO2. At lower PEEP, PaCO2 increased markedly. The ventilatory driving pressure was lowest at PEEP 14 cm H2O (19.6 ± 5.8 cm H2O) and increased to 38.3 ± 6.1 cm H2O at ZEEP (P < 0.001). When reducing PEEP below 12‐14 cm H2O ventilation shifted from the dependent to the nondependent regions of the ventilated lung (P = 0.003), and perfusion shifted from the ventilated to the nonventilated lung (P = 0.02).

    Conclusion: Optimal PEEP was 12‐18 cm H2O and probably relates to capnothorax insufflation pressure. With suboptimal PEEP, ventilation/perfusion mismatch in the ventilated lung and redistribution of blood flow to the nonventilated lung occurred.

  • 338.
    Reinius, Henrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Borges, João Batista
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Fredén, Filip
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Jideus, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi.
    Camargo, E. D. L. B.
    Amato, M. B. P.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Lennmyr, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Real-time ventilation and perfusion distributions by electrical impedance tomography during one-lung ventilation with capnothorax2015Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, nr 3, s. 354-368Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Carbon dioxide insufflation into the pleural cavity, capnothorax, with one-lung ventilation (OLV) may entail respiratory and hemodynamic impairments. We investigated the online physiological effects of OLV/capnothorax by electrical impedance tomography (EIT) in a porcine model mimicking the clinical setting.

    Methods: Five anesthetized, muscle-relaxed piglets were subjected to first right and then left capnothorax with an intra-pleural pressure of 19cm H2O. The contra-lateral lung was mechanically ventilated with a double-lumen tube at positive end-expiratory pressure 5 and subsequently 10cm H2O. Regional lung perfusion and ventilation were assessed by EIT. Hemodynamics, cerebral tissue oxygenation and lung gas exchange were also measured.

    Results: During right-sided capnothorax, mixed venous oxygen saturation (P=0.018), as well as a tissue oxygenation index (P=0.038) decreased. There was also an increase in central venous pressure (P=0.006), and a decrease in mean arterial pressure (P=0.045) and cardiac output (P=0.017). During the left-sided capnothorax, the hemodynamic impairment was less than during the right side. EIT revealed that during the first period of OLV/capnothorax, no or very minor ventilation on the right side could be seen (33% vs. 97 +/- 3%, right vs. left, P=0.007), perfusion decreased in the non-ventilated and increased in the ventilated lung (18 +/- 2% vs. 82 +/- 2%, right vs. left, P=0.03). During the second OLV/capnothorax period, a similar distribution of perfusion was seen in the animals with successful separation (84 +/- 4% vs. 16 +/- 4%, right vs. left).

    Conclusion: EIT detected in real-time dynamic changes in pulmonary ventilation and perfusion distributions. OLV to the left lung with right-sided capnothorax caused a decrease in cardiac output, arterial oxygenation and mixed venous saturation.

  • 339.
    Reinius, Henrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hedenström, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Fredén, Filip
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Preoperative lung function tests as a predictor for atelectasis in morbidly obese patients during anesthesiaArtikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Rationale: Pulmonary function is regularly impaired during general anesthesia and paralysis in morbidly obese patients. The aim of this study was to compare preoperative lung function with the alterations in respiratory function after induction of anesthesia in patients with BMI > 40 kg/m2.

    Methods: 23 women and 7 men (38 ± 9 years, (mean ± SD)), with a body mass index of 45 ± 4 kg/m2 were studied. 20 patients were active smokers (20 ± 12 pack years). All patients underwent preoperative lung functiontests. Arterial blood gases were collected before and after induction of anesthesia and either a single slice CT or a spiral CT was made for assessment of the amount of lung collapse. Respiratory system compliance was measured during anesthesia.

    Results: Lung volumes were within normal limits, however forced expiratory gas flow was reduced during the latter part of expiration. The arterial oxygen tension divided by the inspired O2 fraction (PaO2/FIO2 ratio) decreased from 409 ± 47 mmHg awake to 238 ± 80 mmHg after induction of anesthesia. The higher FEV1 was, the larger was the fall in oxygenation during anesthesia. At 5 min after induction, atelectasis in a CT cut 1 cm above the diaphragm was 7 ± 2 % of the lung area. The amount of atelectasis during anesthesia correlated with FEF75 in a regression analysis (p = 0.03).

    Conclusion: In morbidly obese patients without clinical signs of pulmonary disease a preoperative spirometry with mild signs of airway obstruction (reduced late expiratory flow) may predict reduced formation of atelectasis during anesthesia.

  • 340.
    Retamal, Jaime
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Borges, Joao Batista
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Bruhn, A
    Cao, Xiaofang
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Feinstein, R
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Johansson, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Suarez-Sipmann, Fernando
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    High respiratory rate is associated with early reduction of lung edema clearance in an experimental model of ARDS2016Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, nr 1, s. 79-92Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The independent impact of respiratory rate on ventilator-induced lung injury has not been fully elucidated. The aim of this study was to investigate the effects of two clinically relevant respiratory rates on early ventilator-induced lung injury evolution and lung edema during the protective ARDSNet strategy. We hypothesized that the use of a higher respiratory rate during a protective ARDSNet ventilation strategy increases lung inflammation and, in addition, lung edema associated to strain-induced activation of transforming growth factor beta (TGF-β) in the lung epithelium.

    METHODS: Twelve healthy piglets were submitted to a two-hit lung injury model and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated during 6 h according to the ARDSNet strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, the lungs were excised and wet/dry ratio, TGF-β pathway markers, regional histology, and cytokines were evaluated.

    RESULTS: No differences in oxygenation, PaCO2 levels, systemic and pulmonary arterial pressures were observed during the study. Respiratory system compliance and mean airway pressure were lower in LRR group. A decrease in EVLW over time occurred only in the LRR group (P < 0.05). Wet/dry ratio was higher in the HRR group (P < 0.05), as well as TGF-β pathway activation. Histological findings suggestive of inflammation and inflammatory tissue cytokines were higher in LRR.

    CONCLUSION: HRR was associated with more pulmonary edema and higher activation of the TGF-β pathway. In contrast with our hypothesis, HRR was associated with less lung inflammation.

  • 341.
    Retamal, Jaime
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Pontificia Univ Catolica Chile, Dept Med Intensiva, Fac Med, Santiago, Chile..
    Bugedo, G.
    Pontificia Univ Catolica Chile, Dept Med Intensiva, Fac Med, Santiago, Chile..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Bruhn, A.
    Pontificia Univ Catolica Chile, Dept Med Intensiva, Fac Med, Santiago, Chile..
    High PEEP levels are associated with overdistension and tidal recruitment/derecruitment in ARDS patients2015Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, nr 9, s. 1161-1169Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundPositive end-expiratory pressure (PEEP) improves gas exchange and respiratory mechanics, and it may decrease tissue injury and inflammation. The mechanisms of this protective effect are not fully elucidated. Our aim was to determine the intrinsic effects of moderate and higher levels of PEEP on tidal recruitment/derecruitment, hyperinflation, and lung mechanics, in patients with acute respiratory distress syndrome (ARDS). MethodsNine patients with ARDS of mainly pulmonary origin were ventilated sequential and randomly using two levels of PEEP: 9 and 15cmH(2)O, and studied with dynamic computed tomography at a fix transversal lung region. Tidal recruitment/derecruitment and hyperinflation were determined as non-aerated tissue and hyperinflated tissue variation between inspiration and expiration, expressed as percentage of total weight. We also assessed the maximal amount of non-aerated and hyperinflated tissue weight. ResultsPEEP 15cmH(2)O was associated with decrease in non-aerated tissue in all the patients (P<0.01). However, PEEP 15cmH(2)O did not decrease tidal recruitment/derecruitment compared to PEEP 9cmH(2)O (P=1). In addition, PEEP 15cmH(2)O markedly increased maximal hyperinflation (P<0.01) and tidal hyperinflation (P<0.05). Lung compliance decreased with PEEP 15cmH(2)O (P<0.001). ConclusionIn this series of patients with ARDS of mainly pulmonary origin, application of high levels of PEEP did not decrease tidal recruitment/derecruitment, but instead consistently increased tidal and maximal hyperinflation.

  • 342.
    Retamal, Jaime
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hurtado, Daniel
    Villarroel, Nicolas
    Bruhn, Alejandro
    Bugedo, Guillermo
    Amato, Marcelo
    Costa, Eduardo
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Borges, Joao Batista
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Regional pulmonary deformation is positively correlated with regional lung inflammation assessed by 18F-FDG positron emission tomography / computed tomographyManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Objective: Lung deformation beyond of physiological capacity is associated with cell death and inflammation. Lung strain has been estimated as a global strain, but uneven strain distribution may lead to regional stress concentrations and lung damage. Local lung inflammation can be estimated using PET imaging of [18F]fluoro-2-deoxy-D-glucose. We hypothesized that local lung deformation correlates well with local inflammation. The aim of this study was to assess local tidal deformations by using a new mathematical model of finite-elements to analyze CT images, and to correlate them with local inflammation in a porcine experimental model of early acute respiratory distress syndrome.

    Design: Retrospective images analysis, laboratory investigation.

    Setting: University animal research laboratory.

    Subjects: Seven piglets submitted to experimental ventilator-induced lung injury and five healthy ventilated controls.

    Intervention: Lung injury was induced by repeated lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [18F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration. Then maps of deformation were constructed and regional deformation was estimated. We divided the lung parenchyma in 10 horizontal ROIs, and correlations of local volumetric strain and [18F]fluoro-2-deoxy-D-glucose uptake were analyzed in each ROI.

    Measurements and Main Results: The deformation maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions. We found a strong correlation between local strain and inflammation (R2 > 0.5) for the whole lung, when we eliminate the 3/10 dorsal ROIs R2 increased until>0.8.

    Conclusion: the present findings suggest that the greater local stretches were mainly concentrated in the intermediate gravitational zones of injured heterogeneous lungs. Additionally, local lung deformations correlated well with local inflammation in this experimental model of VILI. And the new proposed image-based estimation of regional volumetric strain based on finite element interpolations has the potential to give new insights of local pathogenic mechanisms of VILI and how best design protective-ventilations strategies.

  • 343.
    Retamal, Jaime
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
    Hurtado, Daniel
    Villarroel, Nicolás
    Bruhn, Alejandro
    Bugedo, Guillermo
    Amato, Marcelo Britto Passos
    Costa, Eduardo Leite Vieira
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Batista Borges, João
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Pulmonary Division, Heart Institute (InCor), Hospital das Clinicas, University of São Paulo, São Paulo, Brazil.
    Does Regional Lung Strain Correlate With Regional Inflammation in Acute Respiratory Distress Syndrome During Nonprotective Ventilation?: An Experimental Porcine Study2018Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 46, nr 6, s. e591-e599Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: It is known that ventilator-induced lung injury causes increased pulmonary inflammation. It has been suggested that one of the underlying mechanisms may be strain. The aim of this study was to investigate whether lung regional strain correlates with regional inflammation in a porcine model of acute respiratory distress syndrome.

    DESIGN: Retrospective analysis of CT images and positron emission tomography images using [18F]fluoro-2-deoxy-D-glucose.

    SETTING: University animal research laboratory.

    SUBJECTS: Seven piglets subjected to experimental acute respiratory distress syndrome and five ventilated controls.

    INTERVENTIONS: Acute respiratory distress syndrome was induced by repeated lung lavages, followed by 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressures (mean, 4 cm H2O) and high inspiratory pressures (mean plateau pressure, 45 cm H2O). All animals were subsequently studied with CT scans acquired at end-expiration and end-inspiration, to obtain maps of volumetric strain (inspiratory volume - expiratory volume)/expiratory volume, and dynamic positron emission tomography imaging. Strain maps and positron emission tomography images were divided into 10 isogravitational horizontal regions-of-interest, from which spatial correlation was calculated for each animal.

    MEASUREMENTS AND MAIN RESULTS: The acute respiratory distress syndrome model resulted in a decrease in respiratory system compliance (20.3 ± 3.4 to 14.0 ± 4.9 mL/cm H2O; p < 0.05) and oxygenation (PaO2/FIO2, 489 ± 80 to 92 ± 59; p < 0.05), whereas the control animals did not exhibit changes. In the acute respiratory distress syndrome group, strain maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions, which was similar to the distribution of [18F]fluoro-2-deoxy-D-glucose uptake observed in the positron emission tomography images, resulting in a positive spatial correlation between both variables (median R2 = 0.71 [0.02-0.84]; p < 0.05 in five of seven animals), which was not observed in the control animals.

    CONCLUSION: In this porcine acute respiratory distress syndrome model, regional lung strain was spatially correlated with regional inflammation, supporting that strain is a relevant and prominent determinant of ventilator-induced lung injury.

  • 344.
    Retamal Montes, Jaime
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Aspects on ventilation induced stress and strain on regional and global inflammation in experimental acute respiratory distress syndrome2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Mechanical ventilation (MV) is a life-saving therapy in acute respiratory distress syndrome (ARDS), a condition that affects 3000 patients/year in Sweden with a mortality rate of about 40%. However, MV may induce or worsen lung injury causing “ventilator-induced lung injury (VILI)”. From a mechanical perspective strain (deformation, or relative change in lung volume) and stress (tension) have been postulated as main determinants of VILI. High respiratory rate is potentially another factor that may exacerbate VILI by amplifying the total energy transmitted to the lungs during MV. In this thesis in animal ARDS models the hypotheses were that 1) lung parenchyma inhomogeneities concentrate stress and amplify lung damage and inflammation, 2) higher respiratory rates increase lung inflammation and lung edema in heterogeneous ARDS, and 3) local lung deformation is related to local inflammation.

    First, in a rat model the effect on inflammation and structural damage of regional lung collapse on the healthy surrounding lung tissue was assessed. Second, in porcine models the effect of respiratory rate on lung edema and inflammation was studied during two ventilatory modes; a) a permissive collapse mode and b) a homogenized lung parenchyma mode. Finally, lung deformation was correlated with lung inflammation assessed by positron emission tomography using 18F-FDG uptake.

    It was found that; 1) local inhomogeneities can act as stress amplifiers, increasing lung tissue inflammation and damage in the healthy surrounded lung. 2) high respiratory rate increases lung edema but decreases lung inflammation when permissive lung collapse is used and that these effects are prevented with lung parenchyma homogenization; 3) local lung deformation and inflammation are well correlated.

    In conclusion, lung inhomogeneities may aggravate VILI, respiratory rate may affect in different ways VILI progression depending on the ventilatory strategy, and finally, lung deformation is closely related to lung inflammation. With the caveat that the studies are performed in animal models, the results suggest that using ventilator strategies that homogenize the lungs, i.e., open collapsed lung regions and prevent re-collapse in ARDS will reduce VILI and in the end may decrease morbidity and the high mortality in this condition.

    Delarbeten
    1. Non-lobar atelectasis generates inflammation and structural alveolar injury in the surrounding healthy tissue during mechanical ventilation
    Öppna denna publikation i ny flik eller fönster >>Non-lobar atelectasis generates inflammation and structural alveolar injury in the surrounding healthy tissue during mechanical ventilation
    Visa övriga...
    2014 (Engelska)Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 18, nr 5, s. 505-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Introduction

    When alveoli collapse the traction forces exerted on their walls by adjacent expanded units may increase and concentrate. These forces may promote its re-expansion at the expense of potentially injurious stresses at the interface between the collapsed and the expanded units. We developed an experimental model to test the hypothesis that a local non-lobar atelectasis can act as a stress concentrator, contributing to inflammation and structural alveolar injury in the surrounding healthy lung tissue during mechanical ventilation.

    Methods

    A total of 35 rats were anesthetized, paralyzed and mechanically ventilated. Atelectasis was induced by bronchial blocking: after five minutes of stabilization and pre-oxygenation with FIO2 = 1.0, a silicon cylinder blocker was wedged in the terminal bronchial tree. Afterwards, the animals were randomized between two groups: 1) Tidal volume (VT) = 10 ml/kg and positive end-expiratory pressure (PEEP) = 3 cmH2O (VT10/PEEP3); and 2) VT = 20 ml/kg and PEEP = 0 cmH2O (VT20/zero end-expiratory pressure (ZEEP)). The animals were then ventilated during 180 minutes. Three series of experiments were performed: histological (n = 12); tissue cytokines (n = 12); and micro-computed tomography (microCT; n = 2). An additional six, non-ventilated, healthy animals were used as controls.

    Results

    Atelectasis was successfully induced in the basal region of the lung of 26 out of 29 animals. The microCT of two animals revealed that the volume of the atelectasis was 0.12 and 0.21 cm3. There were more alveolar disruption and neutrophilic infiltration in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. Edema was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in the VT20/ZEEP than VT10/PEEP3 group. The volume-to-surface ratio was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. We did not find statistical difference in tissue interleukin-1β and cytokine-induced neutrophil chemoattractant-1 between regions.

    Conclusions

    The present findings suggest that a local non-lobar atelectasis acts as a stress concentrator, generating structural alveolar injury and inflammation in the surrounding lung tissue.

    Nationell ämneskategori
    Klinisk medicin
    Forskningsämne
    Klinisk fysiologi
    Identifikatorer
    urn:nbn:se:uu:diva-233429 (URN)10.1186/s13054-014-0505-1 (DOI)000351850600024 ()25200702 (PubMedID)
    Tillgänglig från: 2014-10-03 Skapad: 2014-10-03 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
    2. High respiratory rate is associated with early reduction of lung edema clearance in an experimental model of ARDS
    Öppna denna publikation i ny flik eller fönster >>High respiratory rate is associated with early reduction of lung edema clearance in an experimental model of ARDS
    Visa övriga...
    2016 (Engelska)Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, nr 1, s. 79-92Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: The independent impact of respiratory rate on ventilator-induced lung injury has not been fully elucidated. The aim of this study was to investigate the effects of two clinically relevant respiratory rates on early ventilator-induced lung injury evolution and lung edema during the protective ARDSNet strategy. We hypothesized that the use of a higher respiratory rate during a protective ARDSNet ventilation strategy increases lung inflammation and, in addition, lung edema associated to strain-induced activation of transforming growth factor beta (TGF-β) in the lung epithelium.

    METHODS: Twelve healthy piglets were submitted to a two-hit lung injury model and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated during 6 h according to the ARDSNet strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, the lungs were excised and wet/dry ratio, TGF-β pathway markers, regional histology, and cytokines were evaluated.

    RESULTS: No differences in oxygenation, PaCO2 levels, systemic and pulmonary arterial pressures were observed during the study. Respiratory system compliance and mean airway pressure were lower in LRR group. A decrease in EVLW over time occurred only in the LRR group (P < 0.05). Wet/dry ratio was higher in the HRR group (P < 0.05), as well as TGF-β pathway activation. Histological findings suggestive of inflammation and inflammatory tissue cytokines were higher in LRR.

    CONCLUSION: HRR was associated with more pulmonary edema and higher activation of the TGF-β pathway. In contrast with our hypothesis, HRR was associated with less lung inflammation.

    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Anestesiologi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-264211 (URN)10.1111/aas.12596 (DOI)000368139400010 ()26256848 (PubMedID)
    Forskningsfinansiär
    Hjärt-LungfondenVetenskapsrådet, K2015-99X-22731-01-4
    Tillgänglig från: 2015-10-07 Skapad: 2015-10-07 Senast uppdaterad: 2017-12-01Bibliografiskt granskad
    3. Open lung approach ventilation abolishes the negative effects of respiratory rate in experimental lung injury
    Öppna denna publikation i ny flik eller fönster >>Open lung approach ventilation abolishes the negative effects of respiratory rate in experimental lung injury
    Visa övriga...
    2016 (Engelska)Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, nr 8, s. 1131-1141Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: We recently reported that a high respiratory rate was associated with less inflammation than a low respiratory rate, but caused more pulmonary edema in a model of ARDS when an ARDSNet ventilatory strategy was used. We hypothesized that an open lung approach (OLA) strategy would neutralize the independent effects of respiratory rate on lung inflammation and edema. This hypothesis was tested in an ARDS model using two clinically relevant respiratory rates during OLA strategy.

    METHODS: Twelve piglets were subjected to an experimental model of ARDS and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated for 6 h according to an OLA strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, wet/dry ratio, regional histology, and cytokines were evaluated.

    RESULTS: After the ARDS model was established, Cdyn,rs decreased from 21 ± 3.3 to 9.0 ± 1.8 ml/cmH2 O (P < 0.0001). After the lung recruitment maneuver, Cdyn,rs increased to the pre-injury value. During OLA ventilation, no differences in respiratory mechanics, hemodynamics, or EVLW were observed between groups. Wet/dry ratio and histological scores were not different between groups. Cytokine quantification was similar and showed a homogeneous distribution throughout the lung in both groups.

    CONCLUSION: Contrary to previous findings with the ARDSNet strategy, respiratory rate did not influence lung inflammatory response or pulmonary edema during OLA ventilation in experimental ARDS. This indicates that changing the respiratory rate when OLA ventilation is used will not exacerbate lung injury.

    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-296932 (URN)10.1111/aas.12735 (DOI)000380960400012 ()27110871 (PubMedID)
    Forskningsfinansiär
    Hjärt-LungfondenVetenskapsrådet, K2015-99X-22731-01-4
    Tillgänglig från: 2016-06-20 Skapad: 2016-06-20 Senast uppdaterad: 2018-11-12Bibliografiskt granskad
    4. Regional pulmonary deformation is positively correlated with regional lung inflammation assessed by 18F-FDG positron emission tomography / computed tomography
    Öppna denna publikation i ny flik eller fönster >>Regional pulmonary deformation is positively correlated with regional lung inflammation assessed by 18F-FDG positron emission tomography / computed tomography
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Objective: Lung deformation beyond of physiological capacity is associated with cell death and inflammation. Lung strain has been estimated as a global strain, but uneven strain distribution may lead to regional stress concentrations and lung damage. Local lung inflammation can be estimated using PET imaging of [18F]fluoro-2-deoxy-D-glucose. We hypothesized that local lung deformation correlates well with local inflammation. The aim of this study was to assess local tidal deformations by using a new mathematical model of finite-elements to analyze CT images, and to correlate them with local inflammation in a porcine experimental model of early acute respiratory distress syndrome.

    Design: Retrospective images analysis, laboratory investigation.

    Setting: University animal research laboratory.

    Subjects: Seven piglets submitted to experimental ventilator-induced lung injury and five healthy ventilated controls.

    Intervention: Lung injury was induced by repeated lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [18F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration. Then maps of deformation were constructed and regional deformation was estimated. We divided the lung parenchyma in 10 horizontal ROIs, and correlations of local volumetric strain and [18F]fluoro-2-deoxy-D-glucose uptake were analyzed in each ROI.

    Measurements and Main Results: The deformation maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions. We found a strong correlation between local strain and inflammation (R2 > 0.5) for the whole lung, when we eliminate the 3/10 dorsal ROIs R2 increased until>0.8.

    Conclusion: the present findings suggest that the greater local stretches were mainly concentrated in the intermediate gravitational zones of injured heterogeneous lungs. Additionally, local lung deformations correlated well with local inflammation in this experimental model of VILI. And the new proposed image-based estimation of regional volumetric strain based on finite element interpolations has the potential to give new insights of local pathogenic mechanisms of VILI and how best design protective-ventilations strategies.

    Nationell ämneskategori
    Anestesi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-296945 (URN)
    Tillgänglig från: 2016-06-20 Skapad: 2016-06-20 Senast uppdaterad: 2016-08-25Bibliografiskt granskad
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  • 345.
    Retamal Montes, Jaime
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Pontificia Univ Catolica Chile, Dept Med Intens, Santiago, Chile.
    Borges, João Batista
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Univ Sao Paulo, Cardiopulm Dept, Pulm Div, Heart Inst Incor, Sao Paulo, Brazil.
    Bruhn, Alejandro
    Pontificia Univ Catolica Chile, Dept Med Intens, Santiago, Chile.
    Feinstein, Ricardo
    Natl Vet Inst, Dept Pathol & Wildlife Dis, Uppsala, Sweden.
    Hedenstierna, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Suarez-Sipmann, Fernando
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Open lung approach ventilation abolishes the negative effects of respiratory rate in experimental lung injury2016Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, nr 8, s. 1131-1141Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: We recently reported that a high respiratory rate was associated with less inflammation than a low respiratory rate, but caused more pulmonary edema in a model of ARDS when an ARDSNet ventilatory strategy was used. We hypothesized that an open lung approach (OLA) strategy would neutralize the independent effects of respiratory rate on lung inflammation and edema. This hypothesis was tested in an ARDS model using two clinically relevant respiratory rates during OLA strategy.

    METHODS: Twelve piglets were subjected to an experimental model of ARDS and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated for 6 h according to an OLA strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, wet/dry ratio, regional histology, and cytokines were evaluated.

    RESULTS: After the ARDS model was established, Cdyn,rs decreased from 21 ± 3.3 to 9.0 ± 1.8 ml/cmH2 O (P < 0.0001). After the lung recruitment maneuver, Cdyn,rs increased to the pre-injury value. During OLA ventilation, no differences in respiratory mechanics, hemodynamics, or EVLW were observed between groups. Wet/dry ratio and histological scores were not different between groups. Cytokine quantification was similar and showed a homogeneous distribution throughout the lung in both groups.

    CONCLUSION: Contrary to previous findings with the ARDSNet strategy, respiratory rate did not influence lung inflammatory response or pulmonary edema during OLA ventilation in experimental ARDS. This indicates that changing the respiratory rate when OLA ventilation is used will not exacerbate lung injury.

  • 346.
    Rhodin, Annica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Long-term Effects of Opioids in the Treatment of Chronic Pain: Investigation of Problems and Hazards on Clinical, Biochemical, Cellular and Genetic Levels2010Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    After two decades of liberal prescribing of opioids, there has been an increasing recognition of problems connected to the prolonged use of opioids for chronic pain.

    The aim of my thesis was to explore some consequences of long-term opioid treatment for chronic pain such as problematic opioid use, endocrine disorders, tolerance and genetic variations in pain and opioid response.

    Sixty patients with severe pain and problematic opioid use were treated with a structured methadone programme. Risk factors were musculoskeletal pain, psychiatric co-morbidity and previous addiction. Treatment resulted in good pain relief and improved quality of life, but function was impaired by side effects indicating endocrine dysregulation.

    The possibility of opioid-induced endocrine dysfunction was explored in the second paper, where 40 pain patients treated with strong opioids and 20 pain patients without treatment of strong opioids were investigated. The opioid-treated patients had significantly higher incidence of endocrine disturbance affecting gonadal and adrenal function and prolactin levels.

    The functionality of the μ-receptor after long-term treatment with morphine, saline and naloxone was explored in a cell-line expressing the μ-receptor. After one and four weeks of treatment the binding was tested with morphine, methadone, fentanyl and DAMGO and function measured by GTP γ-assay. The binding of DAMGO was significantly diminished after 4 weeks in cells treated with morphine compared with saline and naloxone.

    Genetic variation in three genes with functional impact on opioid response and pain sensitivity was investigated in 80 patients with chronic low-back pain and differential opioid sensitivity and in 56 healthy controls. The results indicated a higher incidence of opioid-related side effects and gender differences in patients with the minor allele of the ABCB1 gene, a correlation between increased opioid sensitivity and the major CACNA2D2 allele and a possible relationship between intrinsic protection against chronic pain and the minor allele of OPRM1.

    Delarbeten
    1. Methadone treatment of chronic non-malignant pain and opioid dependence - A long-term follow-up.
    Öppna denna publikation i ny flik eller fönster >>Methadone treatment of chronic non-malignant pain and opioid dependence - A long-term follow-up.
    2006 (Engelska)Ingår i: European Journal of Pain, ISSN 1090-3801, Vol. 10, nr 3, s. 271-8Artikel i tidskrift (Refereegranskat) Published
    Identifikatorer
    urn:nbn:se:uu:diva-78409 (URN)15972261 (PubMedID)
    Tillgänglig från: 2008-06-29 Skapad: 2008-06-29 Senast uppdaterad: 2011-01-14
    2. Combined analysis of circulating β-endorphin with gene polymorphisms in OPRM1, CACNAD2 and ABCB1 reveals correlation with pain, opioid sensitivity and opioid-related side effects
    Öppna denna publikation i ny flik eller fönster >>Combined analysis of circulating β-endorphin with gene polymorphisms in OPRM1, CACNAD2 and ABCB1 reveals correlation with pain, opioid sensitivity and opioid-related side effects
    Visa övriga...
    2013 (Engelska)Ingår i: Molecular Brain, ISSN 1756-6606, Vol. 6, s. 8-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background

    Opioids are associated with wide inter-individual variability in the analgesic response and a narrow therapeutic index. This may be partly explained by the presence of single nucleotide polymorphisms (SNPs) in genes encoding molecular entities involved in opioid metabolism and receptor activation. This paper describes the investigation of SNPs in three genes that have a functional impact on the opioid response: OPRM1, which codes for the μ-opioid receptor; ABCB1 for the ATP-binding cassette B1 transporter enzyme; and the calcium channel complex subunit CACNA2D2. The genotyping was combined with an analysis of plasma levels of the opioid peptide β-endorphin in 80 well-defined patients with chronic low back pain scheduled for spinal fusion surgery, and with differential sensitivity to the opioid analgesic remifentanil. This patient group was compared with 56 healthy controls.

    Results

    The plasma β-endorphin levels were significantly higher in controls than in pain patients.

    A higher incidence of opioid-related side effects and sex differences was found in patients with the minor allele of the ABCB1 gene. Further, a correlation between increased opioid sensitivity and the major CACNA2D2 allele was confirmed. A tendency of a relationship between opioid sensitivity and the minor allele of OPRM1 was also found.

    Conclusions

    Although the sample cohort in this study was limited to 80 patients it appears that it was possible to observe significant correlations between polymorphism in relevant genes and various items related to pain sensitivity and opioid response. Of particular interest is the new finding of a correlation between increased opioid sensitivity and the major CACNA2D2 allele. These observations may open for improved strategies in the clinical treatment of chronic pain with opioids.

    Nyckelord
    chronic pain, opioid sensitivity, beta-endorphin, mu-1-opioid receptor (OPRM1), calcium channel subunit 2 (CACNA2D2), ATP-binding cassette B1 (ABCB1)
    Nationell ämneskategori
    Anestesi och intensivvård Medicin och hälsovetenskap Neurovetenskaper
    Forskningsämne
    Anestesiologi
    Identifikatorer
    urn:nbn:se:uu:diva-129623 (URN)10.1186/1756-6606-6-8 (DOI)000316319900001 ()23402298 (PubMedID)
    Tillgänglig från: 2010-08-19 Skapad: 2010-08-19 Senast uppdaterad: 2018-01-12
    3. The effects of long-term morphine oncbinding and functionality of different opioids in C-6 cells expressing the OPRM-1 receptor
    Öppna denna publikation i ny flik eller fönster >>The effects of long-term morphine oncbinding and functionality of different opioids in C-6 cells expressing the OPRM-1 receptor
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    lontg-term morphine, OPRM 1-receptor, receptor functionality, [35 S] GTPg-assay
    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Anestesiologi
    Identifikatorer
    urn:nbn:se:uu:diva-129619 (URN)
    Tillgänglig från: 2010-08-19 Skapad: 2010-08-19 Senast uppdaterad: 2011-01-14
    4. Opioid endocrinopathy: a clinical problem in patients with chronic pain and long-term opioid treatment
    Öppna denna publikation i ny flik eller fönster >>Opioid endocrinopathy: a clinical problem in patients with chronic pain and long-term opioid treatment
    2010 (Engelska)Ingår i: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 26, nr 5, s. 374-380Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background:

    The use of strong opioids for treatment of noncancer chronic pain has increased. However, strong evidence for sustained pain relief and improved function is lacking. Controversy prevails, whether hormonal changes are induced by long-term treatment with opioids. The purpose of this study was to investigate the occurrence of endocrine dysfunction in chronic pain patients on long-term opioid treatment.

    Methods:

    A study group of 39 chronic pain patients treated with strong oral opioids for more than 1 year was compared with a control group of 20 chronic pain patients without opioid treatment. Basic levels of prolactin and function of the hypothalamic-pituitary-thyroid-, hypothalamic-pituitary-adrenal-axis, and hypothalamic-pituitary-growth-hormone - and hypothalamic-pituitary-gonadal-axis were measured. Quality-of-life and side effects were estimated with EORTC-QLQ-C30.

    Results:

    In the opioid-treated group, the patients had signs of pituitary dysfunction affecting all axes. Significant differences were shown in hypofunction of the hypothalamic-pituitary-gonadal -axis, hyperfunction of the hypothalamic-pituitary-adrenal -axis, and higher prolactin levels in the opioid-treated group, compared with the control group. The degree of pain was rated the same in both groups, but the opioid-treated group reported more side effects and lower quality of life.

    Conclusions:

    Long-term treatment of chronic pain with strong opioids causes side effects that can be attributed to hormonal abnormalities caused by opioid-induced inhibition of hypothalamic-pituitary function. Hormone substitution can be indicated to treat symptoms. Decreasing the opioid dose or stopping the opioid treatment can reverse endocrine dysfunction. This needs to be recognized by all practitioners treating chronic pain patients with opioids.

    Nyckelord
    oral opioid treatment, chronic pain, pituitary dysfunction, opioid endocrinopathy
    Nationell ämneskategori
    Anestesi och intensivvård
    Forskningsämne
    Anestesiologi och intensivvård
    Identifikatorer
    urn:nbn:se:uu:diva-129512 (URN)10.1097/AJP.0b013e3181d1059d (DOI)000278073100003 ()20473043 (PubMedID)
    Projekt
    Long-term effects of opioids
    Tillgänglig från: 2010-08-19 Skapad: 2010-08-17 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
    Ladda ner fulltext (pdf)
    FULLTEXT01
  • 347.
    Rhodin, Annica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet.
    Grönbladh, Alfhild
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet.
    Nyberg, Fred
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet.
    Hallberg, Mathias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet.
    The effects of long-term morphine oncbinding and functionality of different opioids in C-6 cells expressing the OPRM-1 receptorManuskript (preprint) (Övrigt vetenskapligt)
  • 348.
    Rhodin, Annica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Gröndbladh, Alfhild
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet.
    Ginya, Harumi
    Precision System Science Japan.
    NIlsson, Kent W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Rosenblad, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Zhou, Qin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Enlund, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Hallberg, Mathias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Division of Biological Research on Drug Dependence.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Nyberg, Fred
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Combined analysis of circulating β-endorphin with gene polymorphisms in OPRM1, CACNAD2 and ABCB1 reveals correlation with pain, opioid sensitivity and opioid-related side effects2013Ingår i: Molecular Brain, ISSN 1756-6606, Vol. 6, s. 8-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Opioids are associated with wide inter-individual variability in the analgesic response and a narrow therapeutic index. This may be partly explained by the presence of single nucleotide polymorphisms (SNPs) in genes encoding molecular entities involved in opioid metabolism and receptor activation. This paper describes the investigation of SNPs in three genes that have a functional impact on the opioid response: OPRM1, which codes for the μ-opioid receptor; ABCB1 for the ATP-binding cassette B1 transporter enzyme; and the calcium channel complex subunit CACNA2D2. The genotyping was combined with an analysis of plasma levels of the opioid peptide β-endorphin in 80 well-defined patients with chronic low back pain scheduled for spinal fusion surgery, and with differential sensitivity to the opioid analgesic remifentanil. This patient group was compared with 56 healthy controls.

    Results

    The plasma β-endorphin levels were significantly higher in controls than in pain patients.

    A higher incidence of opioid-related side effects and sex differences was found in patients with the minor allele of the ABCB1 gene. Further, a correlation between increased opioid sensitivity and the major CACNA2D2 allele was confirmed. A tendency of a relationship between opioid sensitivity and the minor allele of OPRM1 was also found.

    Conclusions

    Although the sample cohort in this study was limited to 80 patients it appears that it was possible to observe significant correlations between polymorphism in relevant genes and various items related to pain sensitivity and opioid response. Of particular interest is the new finding of a correlation between increased opioid sensitivity and the major CACNA2D2 allele. These observations may open for improved strategies in the clinical treatment of chronic pain with opioids.

  • 349.
    Rhodin, Annica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Stridsberg, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Gordh, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Opioid endocrinopathy: a clinical problem in patients with chronic pain and long-term opioid treatment2010Ingår i: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 26, nr 5, s. 374-380Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:

    The use of strong opioids for treatment of noncancer chronic pain has increased. However, strong evidence for sustained pain relief and improved function is lacking. Controversy prevails, whether hormonal changes are induced by long-term treatment with opioids. The purpose of this study was to investigate the occurrence of endocrine dysfunction in chronic pain patients on long-term opioid treatment.

    Methods:

    A study group of 39 chronic pain patients treated with strong oral opioids for more than 1 year was compared with a control group of 20 chronic pain patients without opioid treatment. Basic levels of prolactin and function of the hypothalamic-pituitary-thyroid-, hypothalamic-pituitary-adrenal-axis, and hypothalamic-pituitary-growth-hormone - and hypothalamic-pituitary-gonadal-axis were measured. Quality-of-life and side effects were estimated with EORTC-QLQ-C30.

    Results:

    In the opioid-treated group, the patients had signs of pituitary dysfunction affecting all axes. Significant differences were shown in hypofunction of the hypothalamic-pituitary-gonadal -axis, hyperfunction of the hypothalamic-pituitary-adrenal -axis, and higher prolactin levels in the opioid-treated group, compared with the control group. The degree of pain was rated the same in both groups, but the opioid-treated group reported more side effects and lower quality of life.

    Conclusions:

    Long-term treatment of chronic pain with strong opioids causes side effects that can be attributed to hormonal abnormalities caused by opioid-induced inhibition of hypothalamic-pituitary function. Hormone substitution can be indicated to treat symptoms. Decreasing the opioid dose or stopping the opioid treatment can reverse endocrine dysfunction. This needs to be recognized by all practitioners treating chronic pain patients with opioids.

  • 350.