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  • 51.
    Gudmundsson, M
    et al.
    Department of Anaesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Perchiazzi, G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Pellegrini, Mariangela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Vena, A
    Department of Emergency and Organ Transplant, Bari University, Bari, Italy.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Rylander, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Department of Anaesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Atelectasis is inversely proportional to transpulmonary pressure during weaning from ventilator support in a large animal model2018In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, no 1, p. 94-104Article in journal (Refereed)
    Abstract [en]

    Background

    In mechanically ventilated, lung injured, patients without spontaneous breathing effort, atelectasis with shunt and desaturation may appear suddenly when ventilator pressures are decreased. It is not known how such a formation of atelectasis is related to transpulmonary pressure (PL) during weaning from mechanical ventilation when the spontaneous breathing effort is increased. If the relation between PL and atelectasis were known, monitoring of PL might help to avoid formation of atelectasis and cyclic collapse during weaning. The main purpose of this study was to determine the relation between PL and atelectasis in an experimental model representing weaning from mechanical ventilation.

    Methods

    Dynamic transverse computed tomography scans were acquired in ten anaesthetized, surfactant-depleted pigs with preserved spontaneous breathing, as ventilator support was lowered by sequentially reducing inspiratory pressure and positive end expiratory pressure in steps. The volumes of gas and atelectasis in the lungs were correlated with PL obtained using oesophageal pressure recordings. Work of breathing (WOB) was assessed from Campbell diagrams.

    Results

    Gradual decrease in PL in both end-expiration and end-inspiration caused a proportional increase in atelectasis and decrease in the gas content (linear mixed model with an autoregressive correlation matrix; P < 0.001) as the WOB increased. However, cyclic alveolar collapse during tidal ventilation did not increase significantly.

    Conclusion

    We found a proportional correlation between atelectasis and PL during the ‘weaning process’ in experimental mild lung injury. If confirmed in the clinical setting, a gradual tapering of ventilator support can be recommended for weaning without risk of sudden formation of atelectasis.

  • 52. Guérin, C
    et al.
    Beuret, P
    Constantin, J M
    Bellani, G
    Garcia-Olivares, P
    Roca, O
    Meertens, J H
    Maia, P Azevedo
    Becher, T
    Peterson, J
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Gurjar, M
    Hajjej, Z
    Kovari, F
    Assiri, A H
    Mainas, E
    Hasan, M S
    Morocho-Tutillo, D R
    Baboi, L
    Chrétien, J M
    François, G
    Ayzac, L
    Chen, L
    Brochard, L
    Mercat, A
    A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study2018In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 44, no 1, p. 22-37Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low.

    AIM: This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).

    METHODS: The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles).

    RESULTS: Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).

    CONCLUSIONS: In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

  • 53.
    Hanslin, Katja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Skorup, Paul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Wilske, Frida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Perioperative Medicine and Intensive Care, Karolinska University Hospital and CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    The impact of the systemic inflammatory response on hepatic bacterial elimination in experimental abdominal sepsis2019In: Intensive Care Medicine Experimental, ISSN 2197-425X, Vol. 7, no 1, article id 52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bacterial translocation from the gut has been suggested to induce a systemic inflammatory response syndrome (SIRS) and organ dysfunction. The liver has a pivotal role in eliminating circulating bacteria entering from the gut. We investigated whether pre-existing inflammation affects hepatic bacterial elimination.

    METHODS: Fifteen anaesthetised piglets were infused with E. coli in the portal vein for 3 h. The naive group (n = 6) received the bacterial infusion without endotoxin exposure. SIRS (SIRS group, n = 6) was induced by endotoxin infusion 24 h before the bacterial infusion. For effects of anaesthesia, controls (n = 3) received saline instead of endotoxin for 24 h. Bacterial counts and endotoxin levels in the portal and hepatic veins were analysed during bacterial infusion.

    RESULTS: The bacterial killing rate was higher in the naive group compared with the SIRS group (p = 0.001). The ratio of hepatic to portal venous bacterial counts, i.e. the median bacterial influx from the splanchnic circulation, was 0.06 (IQR 0.01-0.11) in the naive group and 0.71 (0.03-1.77) in the SIRS group at 3 h, and a magnitude lower in the naive group during bacteraemia (p = 0.03). Similar results were seen for hepatic endotoxin elimination. Peak log tumour necrosis factor alpha was higher in the naive 4.84 (4.77-4.89) vs. the SIRS group 3.27 (3.26-3.32) mg/L (p < 0.001).

    CONCLUSIONS: Our results suggest that hepatic bacterial and endotoxin elimination is impaired in pigs with pre-existing SIRS while the inflammatory response to bacterial infusion is diminished. If similar mechanisms operate in human critical illness, the hepatic elimination of bacteria from the gut could be impaired by SIRS.

  • 54.
    Hedenstierna, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Hosp, Med Sci, Uppsala, Sweden.
    Lundin, S.
    Univ Hosp, Anesthesia & Intens Care, Gothenburg, Sweden.
    Pesenti, A.
    Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy.
    Chiumello, D.
    Università degli Studi di Milano, Anesthesia and Intensive Care, Milan, Italy.
    Larsson, Anders S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Stenqvist, O.
    Sahlgrens Univ Hosp, Anaesthesiol & Intens Care, Gothenburg, Sweden.
    Chest Wall Elastance During Passive Mechanical Ventilation: An Alternative Hypothesis2018In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 197Article in journal (Other academic)
  • 55.
    Hedenstierna, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Meyhoff, Christian S
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Who Can Make Sense of the WHO Guidelines to Prevent Surgical Site Infection?2017In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 126, no 5, p. 771-773Article in journal (Refereed)
  • 56.
    Hedenstierna, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Tokics, Leif
    Karolinska Hosp, Dept Anesthesia & Intens Care, Huddinge, Sweden.
    Scaramuzzo, Gaetano
    Univ Ferrara, Dept Morphol Surg & Expt Med, Sect Anesthesia & Intens Care, Ferrara, Italy.
    Rothen, Hans U.
    Univ Bern, Univ Hosp, Dept Intens Care Med, Inselspital, Bern, Switzerland.
    Edmark, Lennart
    Vasteras Hosp, Dept Anesthesia & Intens Care, Vasteras, Sweden.
    Öhrvik, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Oxygenation Impairment during Anesthesia: Influence of Age and Body Weight2019In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 131, no 1, p. 46-57Article in journal (Refereed)
    Abstract [en]

    Background: Anesthesia is increasingly common in elderly and overweight patients and prompted the current study to explore mechanisms of age- and weight-dependent worsening of arterial oxygen tension (Pao(2)). Methods: This is a primary analysis of pooled data in patients with (1) American Society of Anesthesiologists (ASA) classification of 1; (2) normal forced vital capacity; (3) preoxygenation with an inspired oxygen fraction (FIO2) more than 0.8 and ventilated with FIO2 0.3 to 0.4; (4) measurements done during anesthesia before surgery. Eighty patients (21 women and 59 men, aged 19 to 69 yr, body mass index up to 30 kg/m(2)) were studied with multiple inert gas elimination technique to assess shunt and perfusion of poorly ventilated regions (low ventilation/perfusion ratio [(V) over dot(A)/Q]) and computed tomography to assess atelectasis. Results: Pao(2) /FIO2 was lower during anesthesia than awake (368; 291 to 470 [median; quartiles] vs. 441; 397 to 462 mm Hg; P = 0.003) and fell with increasing age and body mass index. Log shunt was best related to a quadratic function of age with largest shunt at 45 yr (r(2) = 0.17, P = 0.001). Log shunt was linearly related to body mass index (r(2) = 0.15, P < 0.001). A multiple regression analysis including age, age(2), and body mass index strengthened the association further (r(2) = 0.27). Shunt was highly associated to atelectasis (r(2) = 0.58, P < 0.001). Log low (V) over dot(A)/Q showed a linear relation to age (r(2) = 0.14, P = 0.001). Conclusions: Pao(2)/FIO2 ratio was impaired during anesthesia, and the impairment increased with age and body mass index. Shunt was related to atelectasis and was a more important cause of oxygenation impairment in middle-aged patients, whereas low (V) over dot(A)/Q, likely caused by airway closure, was more important in elderly patients. Shunt but not low (V) over dot(A)/Q increased with increasing body mass index. Thus, increasing age and body mass index impaired gas exchange by different mechanisms during anesthesia.

  • 57.
    Heili-Frades, Sarah
    et al.
    UAM, CIBERES, IIS Fdn Jimenez Diaz, Intermediate Resp Care Unit,Pulmonol Dept, Madrid, Spain;Inst Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Hosp Univ Princesa, Serv Med Intensiva, Madrid, Spain;Inst Carlos III, CIBER Enfermedades Resp, Madrid, Spain;Uppsala Univ Hosp, Uppsala, Sweden.
    Santos, Arnoldo
    CIBER Enfermedades Resp CIBERES, ITC, Madrid, Spain.
    Pilar Carballosa, Maria
    UAM, CIBERES, IIS Fdn Jimenez Diaz, Intermediate Resp Care Unit,Pulmonol Dept, Madrid, Spain.
    Naya-Prieto, Alba
    UAM, CIBERES, IIS Fdn Jimenez Diaz, Intermediate Resp Care Unit,Pulmonol Dept, Madrid, Spain.
    Castilla-Reparaz, Carlos
    IIS Fdn Jimenez Diaz, Dept Expt Surg, Madrid, Spain.
    Jesus Rodriguez-Nieto, Maria
    UAM, CIBERES, IIS Fdn Jimenez Diaz, Intermediate Resp Care Unit,Pulmonol Dept, Madrid, Spain;Inst Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
    Gonzalez-Mangado, Nicolas
    UAM, CIBERES, IIS Fdn Jimenez Diaz, Intermediate Resp Care Unit,Pulmonol Dept, Madrid, Spain;Inst Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
    Peces-Barba, German
    UAM, CIBERES, IIS Fdn Jimenez Diaz, Intermediate Resp Care Unit,Pulmonol Dept, Madrid, Spain;Inst Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
    Continuous monitoring of intrinsic PEEP based on expired CO2 kinetics: an experimental validation study2019In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 23, article id 192Article in journal (Refereed)
    Abstract [en]

    Background Quantification of intrinsic PEEP (PEEPi) has important implications for patients subjected to invasive mechanical ventilation. A new non-invasive breath-by-breath method (etCO(2)D) for determination of PEEPi is evaluated. MethodsIn 12 mechanically ventilated pigs, dynamic hyperinflation was induced by interposing a resistance in the endotracheal tube. Airway pressure, flow, and exhaled CO2 were measured at the airway opening. Combining different I:E ratios, respiratory rates, and tidal volumes, 52 different levels of PEEPi (range 1.8-11.7cmH(2)O; mean 8.450.32cmH(2)O) were studied. The etCO(2)D is based on the detection of the end-tidal dilution of the capnogram. This is measured at the airway opening by means of a CO2 sensor in which a 2-mm leak is added to the sensing chamber. This allows to detect a capnogram dilution with fresh air when the pressure coming from the ventilator exceeds the PEEPi. This method was compared with the occlusion method. Results The etCO(2)D method detected PEEPi step changes of 0.2cmH(2)O. Reference and etCO(2)D PEEPi presented a good correlation (R-2 0.80, P<0.0001) and good agreement, bias -0.26, and limits of agreement +/- 1.96 SD (2.23, -2.74) (P<0.0001). Conclusions The etCO(2)D method is a promising accurate simple way of continuously measure and monitor PEEPi. Its clinical validity needs, however, to be confirmed in clinical studies and in conditions with heterogeneous lung diseases.

  • 58.
    Holzgraefe, Bernhard
    et al.
    Karolinska Univ Hosp, ECMO Dept Karolinska, Huddinge, Sweden; Karolinska Univ Hosp, Dept Physiol & Pharmacol, Sect Anesthesiol & Intens Care Med, Huddinge, Sweden.
    Andersson, Christin
    Karolinska Univ Hosp, Dept Psychol, Huddinge, Sweden; Karolinska Univ Hosp, Dept Clin Neurosci, Stockholm, Sweden.
    Kalzén, Håkan
    Karolinska Univ Hosp, ECMO Dept Karolinska, Q9 00, S-17176 Stockholm, Sweden.
    von Bahr, Viktor
    Karolinska Univ Hosp, ECMO Dept Karolinska, Huddinge, Sweden; Karolinska Univ Hosp, Dept Physiol & Pharmacol, Sect Anesthesiol & Intens Care Med, Huddinge, Sweden.
    Mosskin, Mikael
    Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Palmér, Kenneth
    Karolinska Univ Hosp, ECMO Dept Karolinska, Q9 00, S-17176 Stockholm, Sweden.
    Frenckner, Björn
    Karolinska Univ Hosp, ECMO Dept Karolinska, Q9 00, S-17176 Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Does permissive hypoxaemia during extracorporeal membrane oxygenation cause long-term neurological impairment?: A study in patients with H1N1-induced severe respiratory failure2017In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 34, no 2, p. 98-103Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Extracorporeal Life Support Organisation accepts permissive hypoxaemia in adult patients during extracorporeal membrane oxygenation (ECMO). The neurological long-term outcome of this approach has not yet been studied.

    OBJECTIVES: We investigated the prevalence of brain lesions and cognitive dysfunction in survivors from the Influenza A/H1N1 2009 pandemic treated with permissive hypoxaemia during ECMO for severe acute respiratory distress syndrome (ARDS). Our hypothesis was that this method is reasonable if tissue hypoxia is avoided.

    DESIGN: Long-term follow-up study after ECMO.

    SETTING: Karolinska University Hospital, Sweden, from October 2012 to July 2013.

    PATIENTS: Seven patients treated with ECMO for severe influenza A/H1N1-induced ARDS were studied 3.2 years after treatment. Blood lactate concentrations were used as a surrogate for tissue oxygenation.

    INTERVENTIONS: Neurocognitive outcome was studied with standardised cognitive tests and MRI of the brain.

    MAIN OUTCOME MEASURES: Cognitive functioning and hypoxic brain lesions after permissive hypoxaemia during ECMO. The observation period was the first 10 days of ECMO or the entire treatment period if shorter than 10 days.

    RESULTS: Eleven of 13 patients were still alive 3 years after ECMO. We were able to contact seven of these patients (mean age 31 years), who all agreed to participate in this study. Mean +/- SD peripherally measured arterial saturation during the observation period was 79 +/- 10%. Full-scale Intelligence Quotient was within one standard deviation or above from the mean of a healthy population in five patients, and was 1.5 SD below the mean in one patient. In one other patient, it could not be determined because of a lack of formal education. Memory functioning was normal in all patients. MRI showed no changes related to cerebral hypoxia.

    CONCLUSIONS: Permissive hypoxaemia during ECMO might not negatively affect long-term cognitive outcome if adequate organ perfusion is maintained.

  • 59.
    Holzgraefe, Bernhard
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Arvika Community Hosp, Cty Council Varmland, Dept Anaesthesia Surg Serv & Intens Care Med, Arvika, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    von Kobyletzki, Laura
    Lund Univ, Skane Univ Hosp, Dept Dermatol, Malmo, Sweden.;Karlstad Univ, Dept Publ Hlth Sci, Karlstad, Sweden..
    Do we have scientific evidence about the effect of hypoxaemia on cognitive outcome in adult patients with severe acute respiratory failure?2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 68-70Article in journal (Refereed)
  • 60.
    Horst, Sandra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Kawati, Rafael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Rasmusson, J
    Department of Anesthesiology and Intensive Care, Gävle County Hospital, Gävle, Sweden.
    Pikwer, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Castegren, M
    Perioperative Medicine and Intensive Care, Karolinska University Hospital and CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Impact of resuscitation fluid bag size availability on volume of fluid administration in the intensive care unit2018In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, no 9, p. 1261-1266Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Iatrogenic fluid overload is associated with increased mortality in the intensive care unit (ICU). Decisions on fluid therapy may, at times, be based on other factors than physiological endpoints. We hypothesized that because of psychological factors volume of available fluid bags would affect the amount of resuscitation fluid administered to ICU patients.

    METHODS: We performed a prospective intervention cross-over study at 3 Swedish ICUs by replacing the standard resuscitation fluid bag of Ringer's Acetate 1000 mL with 500 mL bags (intervention group) for 5 separate months and then compared it with the standard bag size for 5 months (control group). Primary endpoint was the amount of Ringer's Acetate per patient during ICU stay. Secondary endpoints were differences between the groups in cumulative fluid balance and change in body weight, hemoglobin and creatinine levels, urine output, acute kidney failure (measured as the need for renal replacement therapy, RRT) and 90-day mortality.

    RESULTS: Six hundred and thirty-five ICU patients were included (291 in the intervention group, 344 in the control group). There was no difference in the amount of resuscitation fluid per patient during the ICU stay (2200 mL [1000-4500 median IQR] vs 2245 mL [1000-5630 median IQR]), RRT rate (11 vs 9%), 90-day mortality (11 vs 10%) or total fluid balance between the groups. The daily amount of Ringer's acetate administered per day was lower in the intervention group (1040 (280-2000) vs 1520 (460-3000) mL; P = .03).

    CONCLUSIONS: The amount of resuscitation fluid administered to ICU patients was not affected by the size of the available fluid bags. However, altering fluid bag size could have influenced fluid prescription behavior.

  • 61.
    Hurtado, Daniel E.
    et al.
    Pontificia Univ Catolica Chile, Sch Engn, Dept Struct & Geotech Engn, Santiago, Chile.;Pontificia Univ Catolica Chile, Inst Biol & Med Engn, Sch Engn, Vicuna Mackenna 4860, Santiago, Chile.;Pontificia Univ Catolica Chile, Inst Biol & Med Engn, Sch Med, Vicuna Mackenna 4860, Santiago, Chile.;Pontificia Univ Catolica Chile, Inst Biol & Med Engn, Sch Biol Sci, Vicuna Mackenna 4860, Santiago, Chile..
    Villarroel, Nicolas
    Pontificia Univ Catolica Chile, Sch Engn, Dept Struct & Geotech Engn, Santiago, Chile..
    Andrade, Carlos
    Pontificia Univ Catolica Chile, Sch Engn, Dept Struct & Geotech Engn, Santiago, Chile..
    Retamal, Jaime
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Pontificia Univ Catolica Chile, Fac Med, Dept Med Intensiva, Marcoleta 367, Santiago, Chile.
    Bugedo, Guillermo
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intensiva, Marcoleta 367, Santiago, Chile..
    Bruhn, Alejandro
    Pontificia Univ Catolica Chile, Fac Med, Dept Med Intensiva, Marcoleta 367, Santiago, Chile..
    Spatial patterns and frequency distributions of regional deformation in the healthy human lung2017In: Biomechanics and Modeling in Mechanobiology, ISSN 1617-7959, E-ISSN 1617-7940, Vol. 16, no 4, p. 1413-1423Article in journal (Refereed)
    Abstract [en]

    Understanding regional deformation in the lung has long attracted the medical community, as parenchymal deformation plays a key role in respiratory physiology. Recent advances in image registration make it possible to noninvasively study regional deformation, showing that volumetric deformation in healthy lungs follows complex spatial patterns not necessarily shared by all subjects, and that deformation can be highly anisotropic. In this work, we systematically study the regional deformation in the lungs of eleven human subjects by means of in vivo image-based biomechanical analysis. Regional deformation is quantified in terms of 3D maps of the invariants of the right stretch tensor, which are related to regional changes in length, surface and volume. Based on the histograms of individual lungs, we show that log-normal distributions adequately represent the frequency distribution of deformation invariants in the lung, which naturally motivates the normalization of the invariant fields in terms of the log-normal score. Normalized maps of deformation invariants allow for a direct intersubject comparison, as they display spatial patterns of deformation in a range that is common to all subjects. For the population studied, we find that lungs in supine position display a marked gradient along the gravitational direction not only for volumetric but also for length and surface regional deformation, highlighting the role of gravity in the regional deformation of normal lungs under spontaneous breathing.

  • 62.
    Hällsjö Sander, Caroline
    et al.
    Karolinska Univ Hosp, Dept Anaesthesiol Surg Serv & Intens Care Med, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Sigmundsson, Thorir
    Karolinska Univ Hosp, Dept Anaesthesiol Surg Serv & Intens Care Med, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Hallbäck, Magnus
    Maquet Crit Care AB, Solna, Sweden..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Carlos III, CIBER Enfermedades Resp CIBERES, Madrid, Spain..
    Wallin, Mats
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Maquet Crit Care AB, Solna, Sweden..
    Oldner, Anders
    Karolinska Univ Hosp, Dept Anaesthesiol Surg Serv & Intens Care Med, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Björne, Hakan
    Karolinska Univ Hosp, Dept Anaesthesiol Surg Serv & Intens Care Med, S-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    A modified breathing pattern improves the performance of a continuous capnodynamic method for estimation of effective pulmonary blood flow2017In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 31, no 4, p. 717-725Article in journal (Refereed)
    Abstract [en]

    In a previous study a new capnodynamic method for estimation of effective pulmonary blood flow (COEPBF) presented a good trending ability but a poor agreement with a reference cardiac output (CO) measurement at high levels of PEEP. In this study we aimed at evaluating the agreement and trending ability of a modified COEPBF algorithm that uses expiratory instead of inspiratory holds during CO and ventilatory manipulations. COEPBF was evaluated in a porcine model at different PEEP levels, tidal volumes and CO manipulations (N = 8). An ultrasonic flow probe placed around the pulmonary trunk was used for CO measurement. We tested the COEPBF algorithm using a modified breathing pattern that introduces cyclic end-expiratory time pauses. The subsequent changes in mean alveolar fraction of carbon dioxide were integrated into a capnodynamic equation and effective pulmonary blood flow, i.e. non-shunted CO, was calculated continuously breath by breath. The overall agreement between COEPBF and the reference method during all interventions was good with bias (limits of agreement) 0.05 (-1.1 to 1.2) L/min and percentage error of 36 %. The overall trending ability as assessed by the four-quadrant and the polar plot methodology was high with a concordance rate of 93 and 94 % respectively. The mean polar angle was 0.4 (95 % CI -3.7 to 4.5)A degrees. A ventilatory pattern recurrently introducing end-expiratory pauses maintains a good agreement between COEPBF and the reference CO method while preserving its trending ability during CO and ventilatory alterations.

  • 63.
    Höstman, Staffan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Ahlgren, Kerstin M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Engström, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    THAM reduces CO2-associated increase in pulmonary vascular resistance: an experimental study in lung-injured piglets2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, article id 331Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Low tidal volume (VT) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO2), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl)aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR.

    METHODS: A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with VT of 6 ml/kg to maintain normocapnia, VT was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment.

    RESULTS: In the controls, the decrease in VT from 6 to 3 ml/kg increased PaCO2 from 6.0±0.5 to 13.8±1.5 kPa and lowered pH from 7.40±0.01 to 7.12±0.06, whereas base excess (BE) remained stable at 2.7±2.3 mEq/L to 3.4±3.2 mEq/L. In the THAM groups, PaCO2 decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO2 increased above the corresponding level of the controls (15.2±1.7 kPa and 22.6±3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8±3.5 and 31.2±2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329±77 dyn∙s/m(5) and 255±43 dyn∙s/m(5) in the 1-h and 3-h groups, respectively, compared with 450±141 dyn∙s/m(5) in the controls), as were pulmonary arterial pressures.

    CONCLUSIONS: The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO2 after stopping the THAM infusion, possibly by intracellular release of CO2. Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia.

  • 64.
    Höstman, Staffan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Kawati, Rafael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    THAM administration reduces pulmonary carbon dioxide elimination, causing rebound in arterial carbon dioxide tension: An experimental study in hypoventilated pigsManuscript (preprint) (Other academic)
  • 65.
    Höstman, Staffan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Kawati, Rafael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    THAM administration reduces pulmonary carbon dioxide elimination in hypercapnia: an experimental porcine study2018In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, no 6, p. 820-828Article in journal (Refereed)
    Abstract [en]

    Background: In a previous study, we found a rebound of arterial carbon dioxide tension (PaCO2) after stopping THAM buffer administration. We hypothesized that this was due to reduced pulmonary CO2 elimination during THAM administration. The aim of this study was to investigate this hypothesis in an experimental porcine hypercapnic model.

    Methods: In seven, initially normoventilated, anesthetized pigs (22-27 kg) minute ventilation was reduced by 66% for 7 h. Two hours after commencing hypoventilation, THAM was infused IV for 3 h in a dose targeting a pH of 7.35 followed by a 2 h observation period. Acid-base status, blood-gas content and exhaled CO2 were measured.

    Results: THAM raised pH (7.07 0.04 to 7.41 +/- 0.04, P < 0.05) and lowered PaCO2 (15.2 +/- 1.4 to 12.2 +/- 1.1 kPa, P < 0.05). After the infusion, pH decreased and PaCO2 increased again. At the end of the observation period, pH and PaCO2 were 7.24 +/- 0.03 and 16.6 +/- 1.2 kPa, respectively (P < 0.05). Pulmonary CO2 excretion decreased from 109 +/- 12 to 74 +/- 12 ml/min (P < 0.05) during the THAM infusion but returned at the end of the observation period to 111 +/- 15 ml/min (P < 0.05). The estimated reduction of pulmonary CO2 elimination during the infusion was 5800 ml.

    Conclusions: In this respiratory acidosis model, THAM reduced PaCO2, but seemed not to increase the total CO2 elimination due to decreased pulmonary CO2 excretion(,) suggesting only cautious use of THAM in hypercapnic acidosis.

  • 66. Karagiannidis, C.
    et al.
    Kampe, K. Aufm
    Sipmann, F. Suarez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Görna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Windisch, W.
    Mueller, T.
    Pathophysiology and technical Prerequisites of veno-venous extracorporal C0(2) Elimination(ECCO2R) to the treatment of difficult respiratory Acidosis2015In: MEDIZINISCHE KLINIK-INTENSIVMEDIZIN UND NOTFALLMEDIZIN, ISSN 2193-6218, Vol. 110, no 4, p. 311-311Article in journal (Other academic)
  • 67. Karagiannidis, Christian
    et al.
    Kampe, Kristin Aufm
    Sipmann, Fernando Suarez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Windisch, Wolfram
    Mueller, Thomas
    Veno-venous extracorporeal CO2 removal for the treatment of severe respiratory acidosis: pathophysiological and technical considerations2014In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 18, no 3, p. R124-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    While non-invasive ventilation aimed at avoiding intubation has become the modality of choice to treat mild to moderate acute respiratory acidosis, many severely acidotic patients (pH <7.20) still need intubation. Extracorporeal veno-venous CO2 removal (ECCO2R) could prove to be an alternative. The present animal study tested in a systematic fashion technical requirements for successful ECCO2R in terms of cannula size, blood and sweep gas flow.

    METHODS:

    ECCO2R with a 0.98 m2 surface oxygenator was performed in six acidotic (pH <7.20) pigs using either a 14.5 French (Fr) or a 19Fr catheter, with sweep gas flow rates of 8 and 16 L/minute, respectively. During each experiment the blood flow was incrementally increased to a maximum of 400 mL/minute (14.5Fr catheter) and 1000 mL/minute (19Fr catheter).

    RESULTS:

    Amelioration of severe respiratory acidosis was only feasible when blood flow rates of 750 to 1000 mL/minute (19Fr catheter) were used. Maximal CO2-elimination was 146.1 ± 22.6 mL/minute, while pH increased from 7.13 ± 0.08 to 7.41 ± 0.07 (blood flow of 1000 mL/minute; sweep gas flow 16 L/minute). Accordingly, a sweep gas flow of 8 L/minute resulted in a maximal CO2-elimination rate of 138.0 ± 16.9 mL/minute. The 14.5Fr catheter allowed a maximum CO2 elimination rate of 77.9 mL/minute, which did not result in the normalization of pH.

    CONCLUSIONS:

    Veno-venous ECCO2R may serve as a treatment option for severe respiratory acidosis. In this porcine model, ECCO2R was most effective when using blood flow rates ranging between 750 and 1000 mL/minute, while an increase in sweep gas flow from 8 to 16 L/minute had less impact on ECCO2R in this setting.

  • 68. Karagiannidis, Christian
    et al.
    Strassmann, Stephan
    Brodie, Daniel
    Ritter, Philine
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Borchardt, Ralf
    Windisch, Wolfram
    Impact of membrane lung surface area and blood flow on extracorporeal CO2 removal during severe respiratory acidosis2017In: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 5, article id 34Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Veno-venous extracorporeal CO2 removal (vv-ECCO2R) is increasingly being used in the setting of acute respiratory failure. Blood flow rates through the device range from 200 ml/min to more than 1500 ml/min, and the membrane surface areas range from 0.35 to 1.3 m2. The present study in an animal model with similar CO2 production as an adult patient was aimed at determining the optimal membrane lung surface area and technical requirements for successful vv-ECCO2R.

    METHODS: Four different membrane lungs, with varying lung surface areas of 0.4, 0.8, 1.0, and 1.3m2 were used to perform vv-ECCO2R in seven anesthetized, mechanically ventilated, pigs with experimentally induced severe respiratory acidosis (pH 7.0-7.1) using a 20Fr double-lumen catheter with a sweep gas flow rate of 8 L/min. During each experiment, the blood flow was increased stepwise from 250 to 1000 ml/min.

    RESULTS: Amelioration of severe respiratory acidosis was only feasible when blood flow rates from 750 to 1000 ml/min were used with a membrane lung surface area of at least 0.8 m2. Maximal CO2 elimination was 150.8 ml/min, with pH increasing from 7.01 to 7.30 (blood flow 1000 ml/min; membrane lung 1.3 m2). The membrane lung with a surface of 0.4 m2 allowed a maximum CO2 elimination rate of 71.7 mL/min, which did not result in the normalization of pH, even with a blood flow rate of 1000 ml/min. Also of note, an increase of the surface area above 1.0 m2 did not result in substantially higher CO2 elimination rates. The pressure drop across the oxygenator was considerably lower (<10 mmHg) in the largest membrane lung, whereas the smallest revealed a pressure drop of more than 50 mmHg with 1000 ml blood flow/min.

    CONCLUSIONS: In this porcine model, vv-ECCO2R was most effective when using blood flow rates ranging between 750 and 1000 ml/min, with a membrane lung surface of at least 0.8 m2. In contrast, low blood flow rates (250-500 ml/min) were not sufficient to completely correct severe respiratory acidosis, irrespective of the surface area of the membrane lung being used. The converse was also true, low surface membrane lungs (0.4 m2) were not capable of completely correcting severe respiratory acidosis across the range of blood flows used in this study.

  • 69.
    Karbing, D. S.
    et al.
    Aalborg Univ, Dept Hlth Sci & Technol, Resp & Crit Care Rcare, Aalborg, Denmark.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Rees, S. E.
    Aalborg Univ, Dept Hlth Sci & Technol, Resp & Crit Care Rcare, Aalborg, Denmark.
    Jaffe, M. B.
    Cardioresp Consulting LLC, Cheshire, CT USA.
    Journal of Clinical Monitoring and Computing 2017 end of year summary: respiration2018In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 32, no 2, p. 197-205Article, review/survey (Refereed)
    Abstract [en]

    This paper reviews 32 papers or commentaries published in Journal of Clinical Monitoring and Computing in 2016, within the field of respiration. Papers were published covering airway management, ventilation and respiratory rate monitoring, lung mechanics and gas exchange monitoring, in vitro monitoring of lung mechanics, CO2 monitoring, and respiratory and metabolic monitoring techniques.

  • 70.
    Klarin, Bengt
    et al.
    Lund Univ, Dept Anaesthesiol & Intens Care, Lund, Sweden; Skåne Univ Hosp, Lund, Sweden.
    Adolfsson, Anne
    Lund Univ, Dept Anaesthesiol & Intens Care, Lund, Sweden; Skåne Univ Hosp, Lund, Sweden.
    Torstensson, Anders
    Cty Hosp, Dept Anaesthesiol, Halmstad, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Can probiotics be an alternative to chlorhexidine for oral care in the mechanically ventilated patient? A multicentre, prospective, randomised controlled open trial2018In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 22, article id 272Article in journal (Refereed)
    Abstract [en]

    Background: Pathogenic enteric bacteria aspirated from the oropharynx are the main cause of ventilator-associated pneumonia (VAP). Using chlorhexidine (CHX) orally or selective decontamination has been shown to reduce VAP. In a pilot study we found that oral care with the probiotic bacterium Lactobacillus plantarum 299 (Lp299) was as effective as CHX in reducing enteric bacteria in the oropharynx. To confirm those results, in this expanded study with an identical protocol we increased the number of patients and participating centres.

    Methods: One hundred and fifty critically ill patients on mechanical ventilation were randomised to oral care with either standard 0.1% CHX solution (control group) or a procedure comprising final application of an emulsion of Lp299. Samples for microbiological analyses were taken from the oropharynx and trachea at inclusion and subsequently at defined intervals.

    Student’s t test was used for comparisons of parameters recorded daily and Fisher’s exact test was used to compare the results of microbiological cultures.

    Results: Potentially pathogenic enteric bacteria not present at inclusion were identified in oropharyngeal samples from 29 patients in the CHX group and in 31 samples in the probiotic group. Considering cultures of tracheal secretions, enteric bacteria were found in 17 and 19 samples, respectively. Risk ratios show a difference in favour of the Lp group for fungi in oropharyngeal cultures. VAP was diagnosed in seven patients in the Lp group and in 10 patients among the controls.

    Conclusions: In this multicentre study, we could not demonstrate any difference between Lp299 and CHX used in oral care procedures regarding their impact on colonisation with emerging potentially pathogenic enteric bacteria in the oropharynx and trachea.

    Trial registration: ClinicalTrials.gov, NCT01105819. Registered on 9 April 2010. First part: Current Controlled Trials, ISRCTN00472141. Registered on 22 November 2007 (published Critical Care 2008, 12:R136).

  • 71.
    Knudsen, Kati
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Högman, Marieann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Nilsson, Ulrica
    The best method to predict easy intubation: a quasi-experimental pilot study2014In: Journal of Perianesthesia Nursing, ISSN 1089-9472, E-ISSN 1532-8473, Vol. 29, no 4, p. 292-297Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To facilitate evaluation of the airway before endotracheal intubation, different scores have been developed, mainly to predict difficult airways. However, in anesthesia clinical practice in Sweden, scores would be more useful if they could also predict an easy airway, so that the correct category of anesthesia personnel can be allocated. Therefore, we evaluated whether scoring systems commonly used to predict difficult airways could also predict easy endotracheal intubation.

    DESIGN:

    This prospective observational study included patients who were scheduled for general anesthesia and required endotracheal intubation.

    METHODS:

    Airways were evaluated preoperatively by two independent variables, namely Mallampati classification and thyromental distance. After anesthesia induction, the Cormack and Lehane grade was assessed.

    FINDING:

    Mallampati scores yielded the highest specificity in predicting easy intubation, and Cormack and Lehane grades yielded the highest positive predictive value for predicting easy intubation.

    CONCLUSIONS:

    Mallampati classification is an appropriate screening test for predicting easy intubation.

  • 72.
    Kostic, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lo Mauro, Antonella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Politecn Milan, TBM Lab, Dipartimento Elettron Informaz & Bioingn, Pzza L da Vinci 32, I-20133 Milan, Italy.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Aliverti, A
    Politecn Milan, TBM Lab, Dipartimento Elettron Informaz & Bioingn, Pzza L da Vinci 32, I-20133 Milan, Italy.
    Specific anesthesia-induced lung volume changes from induction to emergence: a pilot study.2018In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, no 3, p. 282-292Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Studies aimed at maintaining intraoperative lung volume to reduce post-operative pulmonary complications have been inconclusive because they mixed up the effect of general anesthesia and the surgical procedure. Our aims were to study: (1) lung volume during the entire course of anesthesia without the confounding effects of surgical procedures; (2) the combination of three interventions to maintain lung volume; and (3) the emergence phase with focus on the restored activation of the respiratory muscles.

    METHODS: Eighteen ASA I-II patients undergoing ENT surgery under general anesthesia without muscle relaxants were randomized to an intervention group, receiving lung recruitment maneuver (LRM) after induction, 7 cmH2 O positive end-expiratory pressure (PEEP) during anesthesia and continuous positive airway pressure (CPAP) during emergence with 0.4 inspired oxygen fraction (FiO2 ) or a control group, ventilated without LRM, with 0 cmH2 O PEEP, and 1.0 FiO2 during emergence without CPAP application. End-expiratory lung volume (EELV) was continuously estimated by opto-electronic plethysmography. Inspiratory and expiratory ribcage muscles electromyography was measured in a subset of seven patients.

    RESULTS: End-expiratory lung volume decreased after induction in both groups. It remained low in the control group and further decreased at emergence, because of active expiratory muscle contraction. In the intervention group, EELV increased after LRM and remained high after extubation.

    CONCLUSION: A combined intervention consisting of LRM, PEEP and CPAP during emergence may effectively maintain EELV during anesthesia and even after extubation. An unexpected finding was that the activation of the expiratory muscles may contribute to EELV reduction during the emergence phase.

  • 73.
    Kostic, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lo Mauro, Antonella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Pedotti, Antonio
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Aliverti, Andrea
    Active expiration may contribute to the reduction in end-expiratory volume during emergence from anesthesia and in the immediate post-operative period.Manuscript (preprint) (Other academic)
  • 74.
    Kostic, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Milesi, Ilaria
    Zannin, Emanuela
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Frykholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Dellaca, Raffaele L
    The application of forced oscillation technique and self-mixing laser interferometers during anesthesia and mechanical ventilation.Manuscript (preprint) (Other academic)
  • 75.
    Kozian, Alf
    et al.
    Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Kretzschmar, Moritz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Baumgardner, James E.
    Oscillogy ® LLC, Folsom, PA, USA.
    Schreiber, Jens
    Department of Pneumology, Otto-von-Guericke-University Magdeburg, Germany.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hachenberg, Thomas
    Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Schilling, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke-University Magdeburg, Germany.
    Effects of methacholine infusion on desflurane pharmacokinetics in piglets2015In: Data in brief, ISSN 2352-3409, Vol. 5, p. 939-947Article in journal (Refereed)
    Abstract [en]

    The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V̇A/Q̇) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) [1]. The objective of the present data is to determine V̇A/Q̇ matching by Multiple Inert Gas Elimination Technique (MIGET) in piglets before and during methacholine- (MCh-) induced bronchoconstriction, induced by MCh infusion, and to assess the blood concentration profiles for desflurane (DES) by Micropore Membrane Inlet Mass Spectrometry (MMIMS). Healthy piglets (n=4) under general anesthesia were instrumented with arterial, central venous, and pulmonary artery lines. The airway was secured via median tracheostomy with an endotracheal tube, and animals were mechanically ventilated with intermittent positive pressure ventilation (IPPV) with a FiO2 of 0.4, tidal volume (V T)=10 ml/kg and PEEP of 5cmH2O using an open system. The determination of V.A/Q. was done by MIGET: before desflurane application and at plateau in both healthy state and during MCh infusion. Arterial blood was sampled at 0, 1, 2, 5, 10, 20, and 30 min during wash-in and washout, respectively. Bronchoconstriction was established by MCH infusion aiming at doubling the peak airway pressure, after which wash-in and washout of the anesthetic gas was repeated. Anesthesia gas concentrations were measured by MMIMS. Data were analyzed by ANOVA, paired t-test, and by nonparametric Friedman׳s test and Wilcoxon׳s matched pairs test. We measured airway pressures, pulmonary resistance, and mean paO2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and pulmonary perfusion in relation to the V.A/Q. compartments, data of logSDQ̇ and logSDV̇ (the second moments describing global dispersion, i.e. heterogeneity of distribution) were estimated prior to and after MCh infusion. The uptake and elimination of desflurane was determined by MMIMS.

  • 76.
    Kretzschmar, Moritz A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Magdeburg, Dept Anaesthesiol & Intens Care Med, Leipziger Str 44, D-39120 Magdeburg, Germany..
    Hachenberg, Thomas
    Univ Magdeburg, Dept Anaesthesiol & Intens Care Med, Leipziger Str 44, D-39120 Magdeburg, Germany..
    Thoracic anaesthesia 20162016In: Current Opinion in Anaesthesiology, ISSN 0952-7907, E-ISSN 1473-6500, Vol. 29, no 1, p. 1-1Article in journal (Other academic)
  • 77.
    Kretzschmar, Moritz A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hachenberg, Thomas
    Thoracic anesthesia2015In: Current Opinion in Anaesthesiology, ISSN 0952-7907, E-ISSN 1473-6500, Vol. 28, no 1, p. 1-1Article in journal (Other academic)
  • 78.
    Kretzschmar, Moritz Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Ventilation/Perfusion Matching and its Effect on Volatile Pharmacokinetics2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The mismatching of alveolar ventilation and perfusion (VA/Q) is the major determinant of impaired gas exchange. The gold standard for analyzing VA/Q distribution is the multiple inert gas elimination technique (MIGET), conventionally based on gas chromatography (GC), and, although simple in principle, a technically demanding procedure limiting its use. A new technique based on micropore membrane inlet mass spectrometry (MMIMS) combined MIGET with mass spectrometry, simplifying the sample handling process, and potentially providing VA/Q distributions for a general clinical approach.

    The kinetics of volatile anesthetics are well known in patients with healthy lungs. The uptake and distribution of inhaled anesthetics have usually been modeled by physiologic models. However, these models have limitations, and they do not consider ventilation/perfusion matching. Respiratory diseases account for a large part of morbidity and mortality and are associated with pulmonary VA/Q mismatch that may affect uptake and elimination of volatile anesthetics.

    The objectives of the studies were firstly to investigate assessment of VA/Q mismatch by MMIMS and secondly to investigate the effects of asthma-like VA/Q mismatch on the kinetics of volatile anesthetics in an experimental porcine model.

    Anesthetized and mechanically ventilated piglets were studied.

    In study I, a direct comparison of MIGET by MMIMS with the conventional MIGET by GC in three animal models that covered a wide range of VA/Q distributions was preformed. The two methods agreed well, and parameters derived from both methods showed good agreement with externally measured references.

    In studies II–IV, a stable method of inducing and maintaining asthma-like VA/Q mismatch with methacholine (MCh) administration was established, and the effect of VA/Q mismatch on the pharmacokinetics of desflurane and isoflurane was investigated. The present model of bronchoconstriction demonstrates a delay in volatile anesthetic uptake and elimination, related to the heterogeneity of MCh-inhalation induced ventilation. The difference in solubility of volatile anesthetics has a significant influence on their uptake and elimination under VA/Q mismatch. The higher blood soluble isoflurane is affected to a lesser degree than the fairly insoluble desflurane.

    List of papers
    1. Multiple inert gas elimination technique by micropore membrane inlet mass spectrometry-a comparison with reference gas chromatography
    Open this publication in new window or tab >>Multiple inert gas elimination technique by micropore membrane inlet mass spectrometry-a comparison with reference gas chromatography
    Show others...
    2013 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, no 8, p. 1107-1118Article in journal (Refereed) Published
    Abstract [en]

    The mismatching of alveolar ventilation and perfusion (V-A/Q) is the major determinant of impaired gas exchange. The gold standard for measuring V-A/Q distributions is based on measurements of the elimination and retention of infused inert gases. Conventional multiple inert gas elimination technique (MIGET) uses gas chromatography (GC) to measure the inert gas partial pressures, which requires tonometry of blood samples with a gas that can then be injected into the chromatograph. The method is laborious and requires meticulous care. A new technique based on micropore membrane inlet mass spectrometry (MMIMS) facilitates the handling of blood and gas samples and provides nearly real-time analysis. In this study we compared MIGET by GC and MMIMS in 10 piglets: 1) 3 with healthy lungs; 2) 4 with oleic acid injury; and 3) 3 with isolated left lower lobe ventilation. The different protocols ensured a large range of normal and abnormal V-A/Q distributions. Eight inert gases (SF6, krypton, ethane, cyclopropane, desflurane, enflurane, diethyl ether, and acetone) were infused; six of these gases were measured with MMIMS, and six were measured with GC. We found close agreement of retention and excretion of the gases and the constructed V-A/Q distributions between GC and MMIMS, and predicted Pa-O2 from both methods compared well with measured Pa-O2. V-A/Q by GC produced more widely dispersed modes than MMIMS, explained in part by differences in the algorithms used to calculate V-A/Q distributions. In conclusion, MMIMS enables faster measurement of V-A/Q, is less demanding than GC, and produces comparable results.

    Keywords
    MIGET, ventilation/perfusion distributions, inert gases, mass spectrometry, membrane inlet, gas chromatography
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-210589 (URN)10.1152/japplphysiol.00072.2013 (DOI)000325869400001 ()
    Available from: 2013-11-11 Created: 2013-11-11 Last updated: 2017-12-06Bibliographically approved
    2. Effects of methacholine infusion on desflurane pharmacokinetics in piglets
    Open this publication in new window or tab >>Effects of methacholine infusion on desflurane pharmacokinetics in piglets
    Show others...
    2015 (English)In: Data in brief, ISSN 2352-3409, Vol. 5, p. 939-947Article in journal (Refereed) Published
    Abstract [en]

    The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V̇A/Q̇) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) [1]. The objective of the present data is to determine V̇A/Q̇ matching by Multiple Inert Gas Elimination Technique (MIGET) in piglets before and during methacholine- (MCh-) induced bronchoconstriction, induced by MCh infusion, and to assess the blood concentration profiles for desflurane (DES) by Micropore Membrane Inlet Mass Spectrometry (MMIMS). Healthy piglets (n=4) under general anesthesia were instrumented with arterial, central venous, and pulmonary artery lines. The airway was secured via median tracheostomy with an endotracheal tube, and animals were mechanically ventilated with intermittent positive pressure ventilation (IPPV) with a FiO2 of 0.4, tidal volume (V T)=10 ml/kg and PEEP of 5cmH2O using an open system. The determination of V.A/Q. was done by MIGET: before desflurane application and at plateau in both healthy state and during MCh infusion. Arterial blood was sampled at 0, 1, 2, 5, 10, 20, and 30 min during wash-in and washout, respectively. Bronchoconstriction was established by MCH infusion aiming at doubling the peak airway pressure, after which wash-in and washout of the anesthetic gas was repeated. Anesthesia gas concentrations were measured by MMIMS. Data were analyzed by ANOVA, paired t-test, and by nonparametric Friedman׳s test and Wilcoxon׳s matched pairs test. We measured airway pressures, pulmonary resistance, and mean paO2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and pulmonary perfusion in relation to the V.A/Q. compartments, data of logSDQ̇ and logSDV̇ (the second moments describing global dispersion, i.e. heterogeneity of distribution) were estimated prior to and after MCh infusion. The uptake and elimination of desflurane was determined by MMIMS.

    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:uu:diva-275036 (URN)10.1016/j.dib.2015.11.002 (DOI)26702425 (PubMedID)
    Note

    Alf Kozian, Moritz Kretzschmar and Thomas Schilling were equally involved in processing the experiments, in analyzing the data, and in preparing of themanuscript.

    Available from: 2016-01-28 Created: 2016-01-28 Last updated: 2016-12-08Bibliographically approved
    3. Bronchoconstriction induced by inhaled methacholine delays desflurane uptake and elimination in a piglet model
    Open this publication in new window or tab >>Bronchoconstriction induced by inhaled methacholine delays desflurane uptake and elimination in a piglet model
    Show others...
    2016 (English)In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 220, p. 88-94Article in journal (Refereed) Published
    Abstract [en]

    Bronchoconstriction is a hallmark of asthma and impairs gas exchange. We hypothesized that pharmacokinetics of volatile anesthetics would be affected by bronchoconstriction. Ventilation/perfusion (V̇A/Q̇) ratios and pharmacokinetics of desflurane in both healthy state and during inhalational administration of methacholine (MCh) to double peak airway pressure were studied in a piglet model. In piglets, MCh administration by inhalation (100μg/ml, n=6) increased respiratory resistance, impaired V̇A/Q̇ distribution, increased shunt, and decreased paO2 in all animals. The uptake and elimination of desflurane in arterial blood was delayed by nebulization of MCh, as determined by Micropore Membrane Inlet Mass Spectrometry (wash-in time to P50, healthy vs. inhalation: 0.5min vs. 1.1min, to P90: 4.0min vs. 14.8min). Volatile elimination was accordingly delayed. Inhaled methacholine induced severe bronchoconstriction and marked inhomogeneous V̇A/Q̇ distribution in pigs, which is similar to findings in human asthma exacerbation. Furthermore, MCh-induced bronchoconstriction delayed both uptake and elimination of desflurane. These findings might be considered when administering inhalational anesthesia to asthmatic patients.

    National Category
    Physiology Respiratory Medicine and Allergy Medical and Health Sciences
    Research subject
    Physiology
    Identifiers
    urn:nbn:se:uu:diva-264207 (URN)10.1016/j.resp.2015.09.014 (DOI)000368045500012 ()26440992 (PubMedID)
    Funder
    Swedish Research Council, 5315 X2015-99x-22731-01-04Swedish Heart Lung Foundation
    Available from: 2015-10-07 Created: 2015-10-07 Last updated: 2018-01-11Bibliographically approved
    4. Effect of Bronchoconstriction-induced Ventilation-Perfusion Mismatch on Uptake and Elimination of Isoflurane and Desflurane
    Open this publication in new window or tab >>Effect of Bronchoconstriction-induced Ventilation-Perfusion Mismatch on Uptake and Elimination of Isoflurane and Desflurane
    Show others...
    2017 (English)In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 127, no 5, p. 800-812Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Increasing numbers of patients with obstructive lung diseases need anesthesia for surgery. These conditions are associated with pulmonary ventilation/perfusion (VA/Q) mismatch affecting kinetics of volatile anesthetics. Pure shunt might delay uptake of less soluble anesthetic agents but other forms of VA/Q scatter have not yet been examined. Volatile anesthetics with higher blood solubility would be less affected by VA/Q mismatch. We therefore compared uptake and elimination of higher soluble isoflurane and less soluble desflurane in a piglet model.

    METHODS: Juvenile piglets (26.7 ± 1.5 kg) received either isoflurane (n = 7) or desflurane (n = 7). Arterial and mixed venous blood samples were obtained during wash-in and wash-out of volatile anesthetics before and during bronchoconstriction by methacholine inhalation (100 μg/ml). Total uptake and elimination were calculated based on partial pressure measurements by micropore membrane inlet mass spectrometry and literature-derived partition coefficients and assumed end-expired to arterial gradients to be negligible. VA/Q distribution was assessed by the multiple inert gas elimination technique.

    RESULTS: Before methacholine inhalation, isoflurane arterial partial pressures reached 90% of final plateau within 16 min and decreased to 10% after 28 min. By methacholine nebulization, arterial uptake and elimination delayed to 35 and 44 min. Desflurane needed 4 min during wash-in and 6 min during wash-out, but with bronchoconstriction 90% of both uptake and elimination was reached within 15 min.

    CONCLUSIONS: Inhaled methacholine induced bronchoconstriction and inhomogeneous VA/Q distribution. Solubility of inhalational anesthetics significantly influenced pharmacokinetics: higher soluble isoflurane is less affected than fairly insoluble desflurane, indicating different uptake and elimination during bronchoconstriction.

    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-334179 (URN)10.1097/ALN.0000000000001847 (DOI)000414634700010 ()28857808 (PubMedID)
    Funder
    Swedish Research Council, X2015-99x-22731-01-04
    Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2018-02-16Bibliographically approved
  • 79.
    Kretzschmar, Moritz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Otto von Guericke Univ, Dept Anesthesia & Intens Care Med, Magdeburg, Germany.
    Kozian, Alf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Otto von Guericke Univ, Dept Anesthesia & Intens Care Med, Magdeburg, Germany.
    Baumgardner, James E
    Oscill LLC, Pittsburgh, PA USA; Univ Pittsburgh, Med Ctr, Dept Anesthesiol, Pittsburgh, PA USA.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hachenberg, Thomas
    Otto von Guericke Univ, Dept Anesthesia & Intens Care Med, Magdeburg, Germany.
    Schilling, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Otto von Guericke Univ, Dept Anesthesia & Intens Care Med, Magdeburg, Germany.
    Effect of Bronchoconstriction-induced Ventilation-Perfusion Mismatch on Uptake and Elimination of Isoflurane and Desflurane2017In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 127, no 5, p. 800-812Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Increasing numbers of patients with obstructive lung diseases need anesthesia for surgery. These conditions are associated with pulmonary ventilation/perfusion (VA/Q) mismatch affecting kinetics of volatile anesthetics. Pure shunt might delay uptake of less soluble anesthetic agents but other forms of VA/Q scatter have not yet been examined. Volatile anesthetics with higher blood solubility would be less affected by VA/Q mismatch. We therefore compared uptake and elimination of higher soluble isoflurane and less soluble desflurane in a piglet model.

    METHODS: Juvenile piglets (26.7 ± 1.5 kg) received either isoflurane (n = 7) or desflurane (n = 7). Arterial and mixed venous blood samples were obtained during wash-in and wash-out of volatile anesthetics before and during bronchoconstriction by methacholine inhalation (100 μg/ml). Total uptake and elimination were calculated based on partial pressure measurements by micropore membrane inlet mass spectrometry and literature-derived partition coefficients and assumed end-expired to arterial gradients to be negligible. VA/Q distribution was assessed by the multiple inert gas elimination technique.

    RESULTS: Before methacholine inhalation, isoflurane arterial partial pressures reached 90% of final plateau within 16 min and decreased to 10% after 28 min. By methacholine nebulization, arterial uptake and elimination delayed to 35 and 44 min. Desflurane needed 4 min during wash-in and 6 min during wash-out, but with bronchoconstriction 90% of both uptake and elimination was reached within 15 min.

    CONCLUSIONS: Inhaled methacholine induced bronchoconstriction and inhomogeneous VA/Q distribution. Solubility of inhalational anesthetics significantly influenced pharmacokinetics: higher soluble isoflurane is less affected than fairly insoluble desflurane, indicating different uptake and elimination during bronchoconstriction.

  • 80.
    Kretzschmar, Moritz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Kozian, Alf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Baumgardner, James E
    Schreiber, Jens
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hachenberg, Thomas
    Schilling, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bronchoconstriction induced by inhaled methacholine delays desflurane uptake and elimination in a piglet model2016In: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 220, p. 88-94Article in journal (Refereed)
    Abstract [en]

    Bronchoconstriction is a hallmark of asthma and impairs gas exchange. We hypothesized that pharmacokinetics of volatile anesthetics would be affected by bronchoconstriction. Ventilation/perfusion (V̇A/Q̇) ratios and pharmacokinetics of desflurane in both healthy state and during inhalational administration of methacholine (MCh) to double peak airway pressure were studied in a piglet model. In piglets, MCh administration by inhalation (100μg/ml, n=6) increased respiratory resistance, impaired V̇A/Q̇ distribution, increased shunt, and decreased paO2 in all animals. The uptake and elimination of desflurane in arterial blood was delayed by nebulization of MCh, as determined by Micropore Membrane Inlet Mass Spectrometry (wash-in time to P50, healthy vs. inhalation: 0.5min vs. 1.1min, to P90: 4.0min vs. 14.8min). Volatile elimination was accordingly delayed. Inhaled methacholine induced severe bronchoconstriction and marked inhomogeneous V̇A/Q̇ distribution in pigs, which is similar to findings in human asthma exacerbation. Furthermore, MCh-induced bronchoconstriction delayed both uptake and elimination of desflurane. These findings might be considered when administering inhalational anesthesia to asthmatic patients.

  • 81.
    Laake, J. H.
    et al.
    Oslo Univ Hosp, Div Crit Care & Emergencies, Dept Anaesthesiol, Oslo, Norway.
    Tonnessen, T. I.
    Oslo Univ Hosp, Div Crit Care & Emergencies, Dept Anaesthesiol, Oslo, Norway.
    Chew, M. S.
    Linkoping Univ, Dept Anaesthesia & Intens Care, Med & Hlth Sci, Linkoping, Sweden.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hjelmqvist, H.
    Orebro Univ, Sch Med Sci, Dept Anaesthesia & Intens Care, Orebro, Sweden;Univ Hosp, Orebro, Sweden.
    Wilkman, E.
    Univ Helsinki, Dept Anaesthesiol Intens Care & Pain Med, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Pettilae, V.
    Univ Helsinki, Dept Anaesthesiol Intens Care & Pain Med, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Hoffmann-Petersen, J.
    Odense Univ Hosp, Dept Anaesthesiol & Intens Care, Odense, Denmark.
    Moller, M. H.
    Copenhagen Univ Hosp, Rigshospi, Dept Intens Care, Copenhagen, Denmark.
    The SSAI fully supports the suspension of hydroxyethyl-starch solutions commissioned by the European Medicines Agency2018In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, no 6, p. 874-875Article in journal (Other academic)
  • 82. Laffey, John G
    et al.
    Bellani, Giacomo
    Pham, Tài
    Fan, Eddy
    Madotto, Fabiana
    Bajwa, Ednan K
    Brochard, Laurent
    Clarkson, Kevin
    Esteban, Andres
    Gattinoni, Luciano
    van Haren, Frank
    Heunks, Leo M
    Kurahashi, Kiyoyasu
    Laake, Jon Henrik
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    McAuley, Daniel F
    McNamee, Lia
    Nin, Nicolas
    Qiu, Haibo
    Ranieri, Marco
    Rubenfeld, Gordon D
    Thompson, B Taylor
    Wrigge, Hermann
    Slutsky, Arthur S
    Pesenti, Antonio
    Correction to: Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome2018In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 44, no 1, p. 157-165Article in journal (Refereed)
    Abstract [en]

    Correction to: Intensive Care Med (2016) 42:1865-1876 DOI 10.1007/s00134-016-4571-5.

  • 83. Laffey, John G
    et al.
    Bellani, Giacomo
    Pham, Tài
    Fan, Eddy
    Madotto, Fabiana
    Bajwa, Ednan K
    Brochard, Laurent
    Clarkson, Kevin
    Esteban, Andres
    Gattinoni, Luciano
    van Haren, Frank
    Heunks, Leo M
    Kurahashi, Kiyoyasu
    Laake, Jon Henrik
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    McAuley, Daniel F
    McNamee, Lia
    Nin, Nicolas
    Qiu, Haibo
    Ranieri, Marco
    Rubenfeld, Gordon D
    Thompson, B Taylor
    Wrigge, Hermann
    Slutsky, Arthur S
    Pesenti, Antonio
    Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study2016In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 42, no 12, p. 1865-1876Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality.

    METHODS: The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1-2 who received invasive mechanical ventilation.

    RESULTS: 2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO2/FiO2 ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores.

    CONCLUSIONS: Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT02010073.

  • 84.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Karlsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Rapid testing of red blood cell parameters in primary care patients using HemoScreen™ point of care instrument2019In: BMC Family Practice, ISSN 1471-2296, E-ISSN 1471-2296, Vol. 20, no 1, article id 77Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with anemia are frequently encountered in primary care. Once anemia is detected, it is essential to define the type and identify the underlying cause prior to initiation of treatment. In most cases, the cause can be determined using information from the patient history, physical exam, and complete blood counts (CBC). Point of care testing of blood cell counts would speed up the work up of anemia patients. The aim of the present study was to evaluate if the HemoScreen™ instrument (PixCell Medical, Yokneam Ilit, Israel) could be used for primary care samples. It is a POCT instrument that utilizes single sample cuvettes and image analysis of full blood count including RBC, Hemoglobin, MCV, MCH, platelets, WBC, and WBC 5-part differential.

    METHODS: We compared the HemoScreen™ and the Sysmex XN instrument results of 100 primary care patient samples focusing on the total white blood cells, red blood cell parameters RBC, Hemoglobin, MCH, MCV and platelets.

    RESULTS: Deming correlations between the HemoScreen™ and the Sysmex XN instruments for the CBC were WBCHemoScreen™ = 1.016* WBCSysmex + 0.34; r = 0.981, RBCHemoScreen™ = 0.988* RBCSysmex + 0.015; r = 0.974, HemoglobinHemoScreen™ = 1.081* HemoglobinSysmex - 11.25; r = 0.964, MCHHemoScreen™ = 0.978* MCHSysmex + 0.78; r = 0.939, MCVHemoScreen™ = 0.963* MCVSysmex + 8.68; r = 0.946, PlateletsHemoScreen™ = 0.964* PlateletsSysmex + 25.7; r = 0.953.

    CONCLUSION: The HemoScreen™ instrument could provide rapid and accurate test results for evaluation of the red blood cell parameters in primary care. This new technology is interesting as it allows the analysis red blood cell parameters also at small primary care centers.

  • 85.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Dhonneur, Gilles
    Videolaryngoscopy: towards a new standard method for tracheal intubation in the ICU?2013In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 39, no 12, p. 2220-2222Article in journal (Other academic)
  • 86.