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  • 1.
    Boström, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Hammarlund-Udenaes, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Simonsson, Ulrika S. H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Blood–Brain Barrier Transport Helps to Explain Discrepancies in In Vivo Potency between Oxycodone and Morphine2008In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 108, no 3, p. 495-505Article in journal (Refereed)
    Abstract [en]

    Background The objective of this study was to evaluate the brain pharmacokinetic-pharmacodynamic relations of un-bound oxycodone and morphine to investigate the influence of blood-brain barrier transport on differences in potency between these drugs. Methods: Microdialysis was used to obtain unbound concentrations in brain and blood. The antinociceptive effect of each drug was assessed using the hot water tail-flick method. Population pharmacokinetic modeling was used to describe the bloodbrain barrier transport of morphine as the rate (Cl.) and extent (K-p,K-uu) of equilibration, where CLin is the influx clearance across the blood-brain barrier and Kp,,,, is the ratio of the unbound concentration in brain to that in blood at steady state. Results: The six-fold difference in K-p,K-uu between oxycodone and morphine implies that, for the same unbound concentration in blood, the concentrations of unbound oxycodone in brain will be six times higher than those of morphine. A joint pharmacokinetic-pharmacodynamic model of oxycodone and morphine based on unbound brain concentrations was developed and used as a statistical tool to evaluate differences in the pharmacodynamic parameters of the drugs. A power model using Effect = Baseline + Slope center dot C-gamma best described the data. Drug-specific slope and gamma parameters made the relative potency of the drugs concentration dependent. Conclusions: For centrally acting drugs such as opioids, pharmacokinetic-pharmacodynamic relations describing the interaction with the receptor are better obtained by correlating the effects to concentrations of unbound drug in the tissue of interest rather than to blood concentrations.

  • 2.
    Buratovic, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Stenerlöw, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sundell-Bergman, Synnöve
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Ketamine interacts with low dose ionizing radiaiton during brain development to impair cognitive function in mouse2016In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175Article in journal (Refereed)
  • 3.
    Cereda, Maurizio
    et al.
    Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA;Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
    Xin, Yi
    Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA;Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
    Goffi, Alberto
    Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada;Univ Toronto, Dept Med, Toronto, ON, Canada.
    Herrmann, Jacob
    Kaczka, David W.
    Univ Iowa, Dept Anesthesia & Biomed Engn, Iowa City, IA USA;Univ Iowa, Dept Anesthesia Radiol & Biomed Engn, Iowa City, IA USA.
    Kavanagh, Brian P.
    Univ Toronto, Hosp Sick Children, Toronto, ON, Canada.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Yoshida, Takeshi
    Univ Toronto, Hosp Sick Children, Toronto, ON, Canada.
    Rizi, Rahim R.
    Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA;Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
    Imaging the Injured Lung: Mechanisms of Action and Clinical Use2019In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 131, no 3, p. 716-749Article, review/survey (Refereed)
    Abstract [en]

    Acute respiratory distress syndrome (ARDS) consists of acute hypoxemic respiratory failure characterized by massive and heterogeneously distributed loss of lung aeration caused by diffuse inflammation and edema present in interstitial and alveolar spaces. It is defined by consensus criteria, which include diffuse infiltrates on chest imaging-either plain radiography or computed tomography. This review will summarize how imaging sciences can inform modern respiratory management of ARDS and continue to increase the understanding of the acutely injured lung. This review also describes newer imaging methodologies that are likely to inform future clinical decision-making and potentially improve outcome. For each imaging modality, this review systematically describes the underlying principles, technology involved, measurements obtained, insights gained by the technique, emerging approaches, limitations, and future developments. Finally, integrated approaches are considered whereby multimodal imaging may impact management of ARDS.

  • 4. Ebo, Didier G.
    et al.
    Venemalm, Lennart
    Bridts, Chris H.
    Degerbeck, Frederik
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    De Clerck, Luc S.
    Stevens, Wim J.
    Immunoglobulin E antibodies to rocuronium: a new diagnostic tool2007In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 107, no 2, p. 253-259Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Diagnosis of allergy from neuromuscular blocking agents is not always straightforward. The objectives of the current study were to investigate the value of quantification of immunoglobulin E (IgE) by ImmunoCAP (Phadia AB, Uppsala, Sweden) in the diagnosis of rocuronium allergy and to study whether IgE inhibition tests can predict clinical cross-reactivity between neuromuscular blocking agents. METHODS: Twenty-five rocuronium-allergic patients and 30 control individuals exposed to rocuronium during uneventful anesthesia were included. Thirty-two sera (total IgE > 1,500 kU/l) were analyzed for potential interference of elevated total IgE titers. Results were compared with quantification of IgE for suxamethonium, morphine, and pholcodine. Cross-reactivity between drugs was assessed by IgE inhibition and skin tests. RESULTS: Sensitivity of IgE for rocuronium, suxamethonium, morphine, and pholcodine was 68, 60, 88, and 86%, respectively. Specificity was 100% for suxamethonium, morphine, and pholcodine IgE and 93% for rocuronium IgE. ROC analysis between patients and control individuals changed the threshold to 0.13 kUa/l for rocuronium, 0.11 kUa/l for suxamethonium, 0.36 kUa/l for morphine, and 0.43 kUa/l for pholcodine. Corresponding sensitivity was 92, 72, 88, and 86%, respectively. Specificity was unaltered. Interference of elevated total IgE with quantification of IgE was demonstrated by the analysis in sera with a total IgE greater than 1,500 kU/l. IgE inhibition did not predict clinical relevant cross-reactivity. CONCLUSIONS: The rocuronium ImmunoCAP constitutes a reliable technique to diagnose rocuronium allergy, provided an assay-specific decision threshold is applied. IgE assays based on compounds bearing ammonium epitopes are confirmed to represent reliable tools to diagnose rocuronium allergy. High total IgE titers were observed to affect specificity of the assays.

  • 5.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Kostova-Aherdan, Kamelia
    Enlund, Mats
    Department of Anesthesiology and Intensive Care, Central Hospital, Västerås, Sweden.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Optimal Oxygen Concentration during Induction of General Anesthesia2003In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 98, no 1, p. 28-33Article in journal (Other academic)
    Abstract [en]

    BACKGROUND:

    The use of 100% oxygen during induction of anesthesia may produce atelectasis. The authors investigated how different oxygen concentrations affect the formation of atelectasis and the fall in arterial oxygen saturation during apnea.

    METHODS:

    Thirty-six healthy, nonsmoking women were randomized to breathe 100, 80, or 60% oxygen for 5 min during the induction of general anesthesia. Ventilation was then withheld until the oxygen saturation, assessed by pulse oximetry, decreased to 90%. Atelectasis formation was studied with computed tomography.

    RESULTS:

    Atelectasis in a transverse scan near the diaphragm after induction of anesthesia and apnea was 9.8 +/- 5.2 cm2 (5.6 +/- 3.4% of the total lung area; mean +/- SD), 1.3 +/- 1.2 cm2 (0.6 +/- 0.7%), and 0.3 +/- 0.3 cm2 (0.2 +/- 0.2%) in the groups breathing 100, 80, and 60% oxygen, respectively (P < 0.01). The corresponding times to reach 90% oxygen saturation were 411 +/- 84, 303 +/- 59, and 213 +/- 69 s, respectively (P < 0.01).

    CONCLUSION:

    During routine induction of general anesthesia, 80% oxygen for oxygenation caused minimal atelectasis, but the time margin before unacceptable desaturation occurred was significantly shortened compared with 100% oxygen.

  • 6.
    Fredriksson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Pontén, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology.
    Neonatal exposure to a combination of N-Methyl-D-aspartate and γ-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits2007In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 107, no 3, p. 427-436Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 7.
    Gordh, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gordh, Torsten E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lindqvist, Kjell
    Lidocaine: The Origin of a Modern Local Anesthetic2010In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 113, no 6, p. 1433-1437Article in journal (Refereed)
    Abstract [en]

    Before the introduction of lidocaine, the choice of local anesthetics was limited Procaine was most commonly used and offered less toxicity than cocaine, but it had a short duration faction Tetracaine had substantial systemic toxicity, limiting its use largely to spinal anesthesia An agent with low toxicity, a quick onset, and a longer duration of action was needed This article reports the initial clinical trials with the newly synthesized lidocaine The first trials were wheal tests on the forearms of human volunteers Lidocaine anesthesia duration was markedly longer than that produced by procaine Lidocaine was first tested for infiltration anesthesia in many short procedures performed in the emergency department, followed by major procedures, including those for goiter and hernia in the operating room Consistent success was observed in both environments Lidocaine was then tested for conduction anesthesia using brachial plexus and mandibular, sacral, and paravertebral blocks Its onset as again substantially faster and longer lasting than that of procaine Lidocaine also provided good spinal and surface anesthesia of the cornea

  • 8. Hambraeus-Jonzon, Kristina
    et al.
    Chen, Luni
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Freden, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wiklund, Peter
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pulmonary Vasoconstriction during Regional Nitric Oxide Inhalation: Evidence of a Blood-borne Regulator of Nitric Oxide Synthase Activity2001In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 95, no 1, p. 102-112Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Inhaled nitric oxide (INO) is thought to cause selective pulmonary vasodilation of ventilated areas. The authors previously showed that INO to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow, but only if the opposite lung is hypoxic, indicating a more complex mechanism of action for NO. The authors hypothesized that regional hypoxia increases NO production and that INO to hyperoxic lung regions (HL) can inhibit this production by distant effect.

    METHODS: Nitric oxide concentration was measured in exhaled air (NO(E)), NO synthase (NOS) activity in lung tissue, and regional pulmonary blood flow in anesthetized pigs with regional left lower lobar (LLL) hypoxia (fraction of inspired oxygen [FIO2] = 0.05), with and without INO to HL (FIO2 = 0.8), and during cross-circulation of blood from pigs with and without INO.

    RESULTS: Left lower lobar hypoxia increased exhaled NO from the LLL (NO(E)LLL) from a mean (SD) of 1.3 (0.6) to 2.2 (0.9) parts per billion (ppb) (P < 0.001), and Ca2+-dependent NOS activity was higher in hypoxic than in hyperoxic lung tissue (197 [86] vs. 162 [96] pmol x g(-1) x min(-1), P < 0.05). INO to HL decreased the Ca2+-dependent NOS activity in hypoxic tissue to 49 [56] pmol x g(-1) x min(-1) (P < 0.01), and NO(E)LLL to 2.0 [0.8] ppb (P < 0.05). When open-chest pigs with LLL hypoxia received blood from closed-chest pigs with INO, NO(E)LLL decreased from 2.0 (0.6) to 1.5 (0.4) ppb (P < 0.001), and the Ca2+-dependent NOS activity in hypoxic tissue decreased from 152 (55) to 98 (34) pmol x g(-1) x min(-1) (P = 0.07). Pulmonary vascular resistance increased by 32 (21)% (P < 0.05), but more so in hypoxic (P < 0.01) than in hyperoxic (P < 0.05) lung regions, resulting in a further redistribution (P < 0.05) of pulmonary blood flow away from hypoxic to hyperoxic lung regions.

    CONCLUSIONS: Inhaled nitric oxide downregulates endogenous NO production in other, predominantly hypoxic, lung regions. This distant effect is blood-mediated and causes vasoconstriction in lung regions that do not receive INO.

  • 9.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Small Tidal Volumes, Positive End-expiratory Pressure, and Lung Recruitment Maneuvers during Anesthesia: Good or Bad?2015In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 123, no 3, p. 501-503Article in journal (Refereed)
  • 10.
    Hedenstierna, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Edmark, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Does high oxygen concentration reduce postoperative infection?2014In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 120, no 4, p. 1050-1050Article in journal (Refereed)
  • 11.
    Hedenstierna, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Edmark, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    In reply to: Calculating Ideal Body Weight: Keep It Simple Reply2017In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 127, no 1, p. 204-204Article in journal (Other academic)
  • 12.
    Hedenstierna, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Edmark, Lennart
    Vasteras Hosp, Dept Anesthesia & Intens Care, Vasteras, Sweden..
    Protective Ventilation during Anesthesia Is It Meaningful?2016In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 125, no 6, p. 1079-1082Article in journal (Refereed)
  • 13.
    Hedenstierna, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Meyhoff, Christian S.
    Univ Copenhagen, Bispebjerg & Frederiksberg Hosp, Dept Anaesthesia & Intens Care, Copenhagen, Denmark.
    Perchiazzi, Gaetano
    Uppsala Univ, Dept Surg Sci, Hedenstierna Lab, Uppsala, Sweden.
    Larsson, Anders
    Uppsala Univ, Dept Surg Sci, Hedenstierna Lab, Uppsala, Sweden.
    Wetterslev, Jörn
    Copenhagen Univ Hosp, Rigshosp, Ctr Clin Intervent Res, Copenhagen Trial Unit, Copenhagen, Denmark.
    Rasmussen, Lars S.
    Univ Copenhagen, Rigshosp, Dept Anesthesia, Copenhagen, Denmark.
    Modification of the World Health Organization Global Guidelines for Prevention of Surgical Site Infection Is Needed2019In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 131, no 4, p. 765-768Article in journal (Other academic)
  • 14.
    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)
  • 15.
    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.

  • 16.
    Jalde, Francesca Campoccia
    et al.
    Karolinska Univ Hosp, Perioperat Med & Intens Care Med, Solna, Sweden;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Jalde, Fredrik
    Maquet Crit Care, Solna, Sweden.
    Wallin, Mats K. E. B.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden;Maquet Crit Care, Solna, Sweden.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Hosp Univ & Politecn, Dept Intens Care Med, Valencia, Spain;Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
    Radell, Peter J.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Nelson, David
    Karolinska Univ Hosp, Perioperat Med & Intens Care Med, Solna, Sweden;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Eksborg, Staffan
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Sackey, Peter V.
    Karolinska Univ Hosp, Perioperat Med & Intens Care Med, Solna, Sweden;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Standardized Unloading of Respiratory Muscles during Neurally Adjusted Ventilatory Assist: A Randomized Crossover Pilot Study2018In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 129, no 4, p. 769-777Article in journal (Refereed)
    Abstract [en]

    Background: Currently, there is no standardized method to set the support level in neurally adjusted ventilatory assist (NAVA). The primary aim was to explore the feasibility of titrating NAVA to specific diaphragm unloading targets, based on the neuroventilatory efficiency (NVE) index. The secondary outcome was to investigate the effect of reduced diaphragm unloading on distribution of lung ventilation. Methods: This is a randomized crossover study between pressure support and NAVA at different diaphragm unloading at a single neurointensive care unit. Ten adult patients who had started weaning from mechanical ventilation completed the study. Two unloading targets were used: 40 and 60%. The NVE index was used to guide the titration of the assist in NAVA. Electrical impedance tomography data, blood-gas samples, and ventilatory parameters were collected. Results: The median unloading was 43% (interquartile range 32, 60) for 40% unloading target and 60% (interquartile range 47, 69) for 60% unloading target. NAVA with 40% unloading led to more dorsal ventilation (center of ventilation at 55% [51, 56]) compared with pressure support (52% [49, 56]; P = 0.019). No differences were found in oxygenation, CO2, and respiratory parameters. The electrical activity of the diaphragm was higher during NAVA with 40% unloading than in pressure support. Conclusions: In this pilot study, NAVA could be titrated to different diaphragm unloading levels based on the NVE index. Less unloading was associated with greater diaphragm activity and improved ventilation of the dependent lung regions.

  • 17.
    Juul, Rasmus Vestergaard
    et al.
    Univ Copenhagen, Dept Drug Design & Pharmacol, DK-2100 Copenhagen, Denmark..
    Rasmussen, Sten
    Aalborg Univ Hosp, Orthopaed Surg Res Unit, Aalborg, Denmark.;Aalborg Univ Hosp, Dept Clin Med, Aalborg, Denmark..
    Kreilgaard, Mads
    Univ Copenhagen, Dept Drug Design & Pharmacol, DK-2100 Copenhagen, Denmark..
    Christrup, Lona Louring
    Univ Copenhagen, Dept Drug Design & Pharmacol, DK-2100 Copenhagen, Denmark..
    Simonsson, Ulrika S. H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Lund, Trine Meldgaard
    Univ Copenhagen, Dept Drug Design & Pharmacol, DK-2100 Copenhagen, Denmark..
    Repeated Time-to-event Analysis of Consecutive Analgesic Events in Postoperative Pain2015In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 123, no 6, p. 1411-1419Article in journal (Refereed)
    Abstract [en]

    Background: Reduction in consumption of opioid rescue medication is often used as an endpoint when investigating analgesic efficacy of drugs by adjunct treatment, but appropriate methods are needed to analyze analgesic consumption in time. Repeated time-to-event (RTTE) modeling is proposed as a way to describe analgesic consumption by analyzing the timing of consecutive analgesic events. Methods: Retrospective data were obtained from 63 patients receiving standard analgesic treatment including morphine on request after surgery following hip fracture. Times of analgesic events up to 96 h after surgery were extracted from hospital medical records. Parametric RTTE analysis was performed with exponential, Weibull, or Gompertz distribution of analgesic events using NONMEM (R), version 7.2 (ICON Development Solutions, USA). The potential influences of night versus day, sex, and age were investigated on the probability. Results: A Gompertz distribution RTTE model described the data well. The probability of having one or more analgesic events within 24 h was 80% for the first event, 55% for the second event, 31% for the third event, and 18% for fourth or more events for a typical woman of age 80 yr. The probability of analgesic events decreased in time, was reduced to 50% after 3.3 days after surgery, and was significantly lower (32%) during night compared with day. Conclusions: RTTE modeling described analgesic consumption data well and could account for time-dependent changes in probability of analgesic events. Thus, RTTE modeling of analgesic events is proposed as a valuable tool when investigating new approaches to pain management such as opioid-sparing analgesia.

  • 18.
    Kozian, Alf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Schilling, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Schütze, Hartmut
    Senturk, Mert
    Hachenberg, Thomas
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Ventilatory Protective Strategies during Thoracic Surgery Effects of Alveolar Recruitment Maneuver and Low-tidal Volume Ventilation on Lung Density Distribution2011In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 114, no 5, p. 1025-1035Article in journal (Refereed)
    Abstract [en]

    Background: The increased tidal volume (V-T) applied to the ventilated lung during one-lung ventilation (OLV) enhances cyclic alveolar recruitment and mechanical stress. It is unknown whether alveolar recruitment maneuvers (ARMs) and reduced V-T may influence tidal recruitment and lung density. Therefore, the effects of ARM and OLV with different V-T on pulmonary gas/tissue distribution are examined. Methods: Eight anesthetized piglets were mechanically ventilated (V-T = 10 ml/kg). A defined ARM was applied to the whole lung (40 cm H2O for 10 s). Spiral computed tomographic lung scans were acquired before and after ARM. Thereafter, the lungs were separated with an endobronchial blocker. The pigs were randomized to receive OLV in the dependent lung with a V-T of either 5 or 10 ml/kg. Computed tomography was repeated during and after OLV. The voxels were categorized by density intervals (i.e., atelectasis, poorly aerated, normally aerated, or overaerated). Tidal recruitment was defined as the addition of gas to collapsed lung regions. Results: The dependent lung contained atelectatic (56 +/- 10 ml), poorly aerated (183 +/- 10 ml), and normally aerated (187 +/- 29 ml) regions before ARM. After ARM, lung volume and aeration increased (426 +/- 35 vs. 526 +/- 69 ml). Respiratory compliance enhanced, and tidal recruitment decreased(95% vs. 79% of the whole end-expiratory lung volume). OLV with 10 ml/kg further increased aeration (atelectasis, 15 +/- 2 ml; poorly aerated, 94 +/- 24 ml; normally aerated, 580 +/- 98 ml) and tidal recruitment (81% of the dependent lung). OLV with 5 ml/kg did not affect tidal recruitment or lung density distribution. (Data are given as mean +/- SD.) Conclusions: The ARM improves aeration and respiratory mechanics. In contrast to OLV with high V-T, OLV with reduced V-T does not reinforce tidal recruitment, indicating decreased mechanical stress.

  • 19.
    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.

  • 20.
    Larsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Studying tacit knowledge in anesthesiology:: a role for qualitative research2009In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 110, no 3, p. 443-4Article in journal (Refereed)
  • 21.
    Magnusson, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Zemgulis, Vitas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Tenling, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wernlund, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Tyden, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Use of a vital capacity maneuver to prevent atelectasis after cardiopulmonary bypass: an experimental study1998In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 88, no 1, p. 134-142Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Respiratory failure secondary to cardiopulmonary bypass (CPB) remains a major complication after cardiac surgery. The authors previously found that the increase in intrapulmonary shunt was well correlated with the amount of atelectasis. They tested the hypothesis that post-CPB atelectasis can be prevented by a vital capacity maneuver (VCM) performed before termination of the bypass.

    METHODS: Eighteen pigs received standard hypothermic CPB (no ventilation during bypass). The VCM was performed in two groups and consisted of inflating the lungs during 15 s to 40 cmH2O at the end of the bypass. In one group, the inspired oxygen fraction (FIO2) was then increased to 1.0. In the second group, the FIO2 was left at 0.4. In the third group, no VCM was performed (control group). Ventilation-perfusion distribution was measured with the inert gas technique and atelectasis by computed tomographic scanning.

    RESULTS: Intrapulmonary shunt increased after bypass in the control group (from 4.9 +/- 4% to 20.8 +/- 11.7%; P < 0.05) and was also increased in the vital capacity group ventilated with 100% oxygen (from 2.2 +/- 1.3% to 6.9 +/- 2.9%; P < 0.01) but was unaffected in the vital capacity group ventilated with 40% oxygen. The control pigs showed extensive atelectasis (21.3 +/- 15.8% of total lung area), which was significantly larger (P < 0.01) than the proportion of atelectasis found in the two vital capacity groups (5.7 +/- 5.7% for the vital capacity group ventilated with 100% oxygen and 2.3 +/- 2.1% for the vital capacity group ventilated with 40% oxygen.

    CONCLUSION: In this pig model, postcardiopulmonary bypass atelectasis was effectively prevented by a VCM.

  • 22.
    Magnusson, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Zemgulis, Vitas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wicky, Stephan
    Tyden, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hedenstierna, Göran
    Atelectasis is a major cause of hypoxemia and shunt after cardiopulmonary bypass: An experimental study1997In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 87, no 5, p. 1153-1163Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Respiratory failure after cardiopulmonary bypass (CPB) remains a major complication after cardiac surgery. The authors tested the hypothesis that atelectasis is an important factor responsible for the increase in intrapulmonary shunt after CPB.

    METHODS: Six pigs received standard CPB (bypass group). Six other pigs had the same surgery but without CPB (sternotomy group). Another six pigs were anesthetized for the same duration but without any surgery (control group). The ventilation-perfusion distribution was measured with the inert gases technique, extravascular lung water was quantified by the double-indicator distribution technique, and atelectasis was analyzed by computed tomography.

    RESULTS: Intrapulmonary shunt increased markedly after bypass but was unchanged over time in the control group (17.9 +/- 6.2% vs. 3.5 +/- 1.2%; P < 0.0001). Shunt also increased in the sternotomy group (10 +/- 2.6%; P < 0.01 compared with baseline) but was significantly lower than in the bypass group (P < 0.01). Extravascular lung water was not significantly altered in any group. The pigs in the bypass group showed extensive atelectasis (32.3 +/- 28.7%), which was significantly larger than in the two other groups. The pigs in the sternotomy group showed less atelectasis (4.1 +/- 1.9%) but still more (P < 0.05) than the controls (1.1 +/- 1.6%). There was good correlation between shunt and atelectasis when all data were pooled (R2 = 0.67; P < 0.0001).

    CONCLUSIONS: Atelectasis is produced to a much larger extent after CPB than after anesthesia alone or with sternotomy and it explains most of the marked post-CPB increase in shunt and hypoxemia. Surgery per se contributes to a lesser extent to postoperative atelectasis and gas exchange impairment.

  • 23. Meyhoff, Christian S.
    et al.
    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. Univ Hosp, Uppsala, Sweden.
    Perchiazzi, Gaetano
    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.
    In Reply2018In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 128, no 1, p. 222-224Article in journal (Refereed)
  • 24.
    Nyberg, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Li, Husong
    Univ Texas Med Branch Hlth, Dept Anesthesiol, Galveston, TX USA.
    Wessmark, Pehr
    Royal Inst Technol, Stockholm, Sweden.
    Winther, Viktor
    Royal Inst Technol, Stockholm, Sweden.
    Prough, Donald S.
    Univ Texas Med Branch Hlth, Dept Anesthesiol, Galveston, TX USA.
    Kinsky, Michael P.
    Univ Texas Med Branch Hlth, Dept Anesthesiol, Galveston, TX USA.
    Svensen, Christer H.
    Univ Texas Med Branch Hlth, Dept Anesthesiol, Galveston, TX USA;Soder Sjukhuset, Karolinska Inst, Dept Clin Sci & Educ, Unit Anesthesiol & Intens Care, Stockholm, Sweden.
    Population Kinetics of 0.9% Saline Distribution in Hemorrhaged Awake and Isoflurane-anesthetized Volunteers2019In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 131, no 3, p. 501-511Article in journal (Refereed)
    Abstract [en]

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

  • 25. Pham, Tai
    et al.
    Wessbergh, Joanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Persson, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Veljovic, Milic
    Outcomes of Patients Presenting with Mild Acute Respiratory Distress Syndrome: Insights from the LUNG SAFE Study2019In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 130, no 2, p. 263-283Article in journal (Refereed)
    Abstract [en]

    Background: Patients with initial mild acute respiratory distress syndrome are often underrecognized and mistakenly considered to have low disease severity and favorable outcomes. They represent a relatively poorly characterized population that was only classified as having acute respiratory distress syndrome in the most recent definition. Our primary objective was to describe the natural course and the factors associated with worsening and mortality in this population.

    Methods: This study analyzed patients from the international prospective Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) who had initial mild acute respiratory distress syndrome in the first day of inclusion. This study defined three groups based on the evolution of severity in the first week: "worsening" if moderate or severe acute respiratory distress syndrome criteria were met, "persisting" if mild acute respiratory distress syndrome criteria were the most severe category, and "improving" if patients did not fulfill acute respiratory distress syndrome criteria any more from day 2.

    Results: Among 580 patients with initial mild acute respiratory distress syndrome, 18% (103 of 580) continuously improved, 36% (210 of 580) had persisting mild acute respiratory distress syndrome, and 46% (267 of 580) worsened in the first week after acute respiratory distress syndrome onset. Global in-hospital mortality was 30% (172 of 576; specifically 10% [10 of 101], 30% [63 of 210], and 37% [99 of 265] for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively), and the median (interquartile range) duration of mechanical ventilation was 7 (4, 14) days (specifically 3 [2, 5], 7 [4, 14], and 11 [6, 18] days for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively). Admissions for trauma or pneumonia, higher nonpulmonary sequential organ failure assessment score, lower partial pressure of alveolar oxygen/fraction of inspired oxygen, and higher peak inspiratory pressure were independently associated with worsening.

    Conclusions: Most patients with initial mild acute respiratory distress syndrome continue to fulfill acute respiratory distress syndrome criteria in the first week, and nearly half worsen in severity. Their mortality is high, particularly in patients with worsening acute respiratory distress syndrome, emphasizing the need for close attention to this patient population.

  • 26.
    Reinius, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Jonsson, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gustafsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Pelosi, Paolo
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Fredén, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Prevention of atelectasis in morbidly obese patients during general anesthesia and paralysis: a computerized tomography study2009In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 111, no 5, p. 979-987Article in journal (Refereed)
    Abstract [en]

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

  • 27.
    Rothen, Hans Ulrich
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sporre, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Engberg, Greta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wegenius, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Högman, Marieann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Influence of gas composition on recurrence of atelectasis after a reexpansion maneuver during general anaesthesia1995In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 82, no 4, p. 832-842Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Atelectasis, an important cause of impaired gas exchange during general anesthesia, may be eliminated by a vital capacity maneuver. However, it is not clear whether such a maneuver will have a sustained effect. The aim of this study was to determine the impact of gas composition on reappearance of atelectasis and impairment of gas exchange after a vital capacity maneuver.

    METHODS:

    A consecutive sample of 12 adults with healthy lungs who were scheduled for elective surgery were studied. Thirty minutes after induction of anesthesia with fentanyl and propofol, the lungs were hyperinflated manually up to an airway pressure of 40 cmH2O. FIO2 was either kept at 0.4 (group 1, n = 6) or changed to 1.0 (group 2, n = 6) during the recruitment maneuver. Atelectasis was assessed by computed tomography. The amount of dense areas was measured at end-expiration in a transverse plane at the base of the lungs. The ventilation-perfusion distributions (VA/Q) were estimated with the multiple inert gas elimination technique. The static compliance of the total respiratory system (Crs) was measured with the flow interruption technique.

    RESULTS:

    In group 1 (FIO2 = 0.4), the recruitment maneuver virtually eliminated atelectasis for at least 40 min, reduced shunt (VA/Q < 0.005), and increased at the same time the relative perfusion to poorly ventilated lung units (0.005 < VA/Q < 0.1; mean values are given). The arterial oxygen tension (PaO2) increased from 137 mmHg (18.3 kPa) to 163 mmHg (21.7 kPa; before and 40 min after recruitment, respectively; P = 0.028). In contrast to these findings, atelectasis recurred within 5 min after recruitment in group 2 (FIO2 = 1.0). Comparing the values before and 40 min after recruitment, all parameters of VA/Q were unchanged. In both groups, Crs increased from 57.1/55.0 ml.cmH2O-1 (group 1/group 2) before to 70.1/67.4 ml.cmH2O-1 after the recruitment maneuver. Crs showed a slow decrease thereafter (40 min after recruitment: 61.4/60.0 ml.cmH2O-1), with no difference between the two groups.

    CONCLUSIONS:

    The composition of inspiratory gas plays an important role in the recurrence of collapse of previously reexpanded atelectatic lung tissue during general anesthesia in patients with healthy lungs. The reason for the instability of these lung units remains to be established. The change in the amount of atelectasis and shunt appears to be independent of the change in the compliance of the respiratory system.

  • 28.
    Schilling, Thomas
    et al.
    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.
    Senturk, Mert
    Huth, Christof
    Reinhold, Annegret
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hachenberg, Thomas
    Effects of volatile and intravenous anesthesia on the alveolar and systemic inflammatory response in thoracic surgical patients2011In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 115, no 1, p. 65-74Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    One-lung ventilation (OLV) results in alveolar proinflammatory effects, whereas their extent may depend on administration of anesthetic drugs. The current study evaluates the effects of different volatile anesthetics compared with an intravenous anesthetic and the relationship between pulmonary and systemic inflammation in patients undergoing open thoracic surgery.

    METHODS:

    Sixty-three patients scheduled for elective open thoracic surgery were randomized to receive anesthesia with 4 mg · kg⁻¹ · h⁻¹ propofol (n = 21), 1 minimum alveolar concentration desflurane (n = 21), or 1 minimum alveolar concentration sevoflurane (n = 21). Analgesia was provided by remifentanil (0.25 μg · kg⁻¹ · min⁻¹). After intubation, all patients received pressure-controlled mechanical ventilation with a tidal volume of approximately 7 ml · kg ideal body weight, a peak airway pressure lower than 30 cm H₂O, a respiratory rate adjusted to a Paco2 of 40 mmHg, and a fraction of inspired oxygen lower than 0.8 during OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed immediately after intubation and after surgery. The expression of inflammatory cytokines was determined in the lavage fluids and serum samples by multiplexed bead-based immunoassays.

    RESULTS:

    Proinflammatory cytokines increased in the ventilated lung after OLV. Mediator release was more enhanced during propofol anesthesia compared with desflurane or sevoflurane administration. For tumor necrosis factor-α, the values were as follows: propofol, 5.7 (8.6); desflurane, 1.6 (0.6); and sevoflurane, 1.6 (0.7). For interleukin-8, the values were as follows: propofol, 924 (1680); desflurane, 390 (813); and sevoflurane, 412 (410). (Values are given as median [interquartile range] pg · ml⁻¹). Interleukin-1β was similarly reduced during volatile anesthesia. The postoperative serum interleukin-6 concentration was increased in all patients, whereas the systemic proinflammatory response was negligible.

    CONCLUSIONS:

    OLV increases the alveolar concentrations of proinflammatory mediators in the ventilated lung. Both desflurane and sevoflurane suppress the local alveolar, but not the systemic, inflammatory responses to OLV and thoracic surgery.

  • 29.
    Schilling, Thomas
    et al.
    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.
    Senturk, Mert
    Huth, Christof
    Reinhold, Annegret
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hachenberg, Thomas
    In reply:  2012In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 116, no 2, p. 492-493Article in journal (Refereed)
  • 30. Schumann, Stefan
    et al.
    Vimlati, Laszlo
    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.
    Guttmann, Josef
    Lichtwarck-Aschoff, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Analysis of Dynamic Intratidal Compliance in a Lung Collapse Model2011In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 114, no 5, p. 1111-1117Article in journal (Refereed)
    Abstract [en]

    Background: For mechanical ventilation to be lung-protective, an accepted suggestion is to place the tidal volume (V-T) between the lower and upper inflection point of the airway pressure-volume relation. The drawback of this approach is, however, that the pressure-volume relation is assessed under quasistatic, no-flow conditions, which the lungs never experience during ventilation. Intratidal nonlinearity must be assessed under real (i.e., dynamic) conditions. With the dynamic gliding-SLICE technique that generates a high-resolution description of intratidal mechanics, the current study analyzed the profile of the compliance of the respiratory system (C-RS).

    Methods: In 12 anesthetized piglets with lung collapse, the pressure-volume relation was acquired at different levels of positive end-expiratory pressure (PEEP: 0, 5, 10, and 15 cm H2O). Lung collapse was assessed by computed tomography and the intratidal course of C-RS using the gliding-SLICE method.

    Results: Depending on PEEP, C-RS showed characteristic profiles. With low PEEP, C-RS increased up to 20% above the compliance at early inspiration, suggesting intratidal recruitment; whereas a profile of decreasing C-RS, signaling overdistension, occurred with V-T > 5 ml/kg and high PEEP levels. At the highest volume range, C-RS was up to 60% less than the maximum. With PEEP 10 cm H2O, C-RS was high and did not decrease before 5 ml/kg V-T was delivered.

    Conclusions: The profile of dynamic C-RS reflects nonlinear intratidal mechanics of the respiratory system. The SLICE analysis has the potential to detect intratidal recruitment and overdistension. This might help in finding a combination of PEEP and V-T level that is protective from a lung-mechanics perspective.

  • 31. Serpa Neto, Ary
    et al.
    Hemmes, Sabrine N T
    Barbas, Carmen S V
    Beiderlinden, Martin
    Biehl, Michelle
    Binnekade, Jan M
    Canet, Jaume
    Fernandez-Bustamante, Ana
    Futier, Emmanuel
    Gajic, Ognjen
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Hollmann, Markus W
    Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands .
    Jaber, Samir
    Kozian, Alf
    Licker, Marc
    Lin, Wen-Qian
    Maslow, Andrew D
    Memtsoudis, Stavros G
    Reis Miranda, Dinis
    Moine, Pierre
    Ng, Thomas
    Paparella, Domenico
    Putensen, Christian
    Ranieri, Marco
    Scavonetto, Federica
    Schilling, Thomas
    Schmid, Werner
    Selmo, Gabriele
    Severgnini, Paolo
    Sprung, Juraj
    Sundar, Sugantha
    Talmor, Daniel
    Treschan, Tanja
    Unzueta, Carmen
    Weingarten, Toby N
    Wolthuis, Esther K
    Wrigge, Hermann
    Gama de Abreu, Marcelo
    Pelosi, Paolo
    Schultz, Marcus J
    Protective versus Conventional Ventilation for Surgery: A Systematic Review and Individual Patient Data Meta-analysis2015In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 123, no 1, p. 66-78Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recent studies show that intraoperative mechanical ventilation using low tidal volumes (VT) can prevent postoperative pulmonary complications (PPCs). The aim of this individual patient data meta-analysis is to evaluate the individual associations between VT size and positive end-expiratory pressure (PEEP) level and occurrence of PPC.

    METHODS: Randomized controlled trials comparing protective ventilation (low VT with or without high levels of PEEP) and conventional ventilation (high VT with low PEEP) in patients undergoing general surgery. The primary outcome was development of PPC. Predefined prognostic factors were tested using multivariate logistic regression.

    RESULTS: Fifteen randomized controlled trials were included (2,127 patients). There were 97 cases of PPC in 1,118 patients (8.7%) assigned to protective ventilation and 148 cases in 1,009 patients (14.7%) assigned to conventional ventilation (adjusted relative risk, 0.64; 95% CI, 0.46 to 0.88; P < 0.01). There were 85 cases of PPC in 957 patients (8.9%) assigned to ventilation with low VT and high PEEP levels and 63 cases in 525 patients (12%) assigned to ventilation with low VT and low PEEP levels (adjusted relative risk, 0.93; 95% CI, 0.64 to 1.37; P = 0.72). A dose-response relationship was found between the appearance of PPC and VT size (R = 0.39) but not between the appearance of PPC and PEEP level (R = 0.08).

    CONCLUSIONS: These data support the beneficial effects of ventilation with use of low VT in patients undergoing surgery. Further trials are necessary to define the role of intraoperative higher PEEP to prevent PPC during nonopen abdominal surgery.

  • 32. Solomkin, Joseph
    et al.
    Egger, Matthias
    de Jonge, Stijn
    Latif, Asad
    Loke, Yoon K
    Berenholtz, Sean
    Allegranzi, Benedetta
    World Health Organization Responds to Concerns about Surgical Site Infection Prevention Recommendations.2018In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 128, no 1, p. 221-222Article in journal (Refereed)
  • 33. Söderberg, Lars
    et al.
    Dyhre, Henrik
    Roth, Bodil
    Björkman, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Ultralong peripheral nerve block by lidocaine:prilocaine 1:1 mixture in a lipid depot formulation: Comparison of in vitro, in vivo and effect kinetics2006In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 104, no 1, p. 110-121Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to develop stable and easily injectable lipid depot preparations of local anesthetics in which the drug concentration can be varied according to desired duration of action. METHODS: The formulations contained a 2.0, 5.0, 10, 20, 40, 60, 80, or 100% eutectic mixture of lidocaine and prilocaine base in medium-chain triglyceride. Duration of sciatic nerve block and local neurotoxicity was investigated in rats with 2.0% lidocaine:prilocaine HCl solution and 99.5% ethanol as controls. The rate of release of local anesthetic from the site of administration and the possibility to predict in vivo depot characteristics from in vitro release data were investigated for the 20 and 60% formulations. RESULTS: The duration of sensory sciatic block was prolonged 3 times with the 20% formulation and approximately 180 times with the 60% formulation, in comparison with the 2% aqueous solution. With the 80 and 100% formulations, all animals still showed nerve block after 2 weeks. The in vivo release of local anesthetic could be approximately predicted from in vitro data for the 20% but not for the 60% formulation. The formulations of 60% or greater and ethanol showed neurotoxic effects. CONCLUSIONS: The pharmaceutical properties of these formulations compare favorably with those of other depot preparations. The high-percentage ones showed the longest duration of action yet reported for sciatic nerve block in rats. The possibility of using a high-concentration local anesthetic depot formulation as an alternative to ethanol or phenol for long-term nerve blocks in chronic pain merits further investigation.

  • 34.
    Sütterlin, Robert
    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.
    Frykholm, Peter
    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.
    Lo Mauro, Antonella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gandolfi, Stefano
    Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.
    Priori, Rita
    Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, 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.
    Aliverti, Andrea
    Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.
    Influence of Tracheal Obstruction on the Efficacy of Superimposed High-frequency Jet Ventilation and Single-frequency Jet Ventilation2015In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 123, no 10, p. 799-809, article id doi:10.1097/ALN.0000000000000818Article in journal (Refereed)
    Abstract [en]

    Background

    Superimposed high frequency jet ventilation (SHFJV) has been used successfully in selected patients with severe central airway obstruction undergoing airway interventions.

    We sought to systematically describe the efficacy of SHFJV in relation to obstruction and the high frequency component (fHF) in a model of tracheal stenosis.

    Methods

    Ten anesthetized animals (25-31.5kg) were alternately ventilated with SHFJV (low frequency 16min-1, random fHF) at a set of different fHF from 50-600min-1. Tracheal obstruction was created using exchangeable stents with different inner diameter (2, 4, 6, 8mm) that were inserted into the trachea. Chest wall volume was measured using optoelectronic plethysmography, airway pressures were recorded and blood gases were analyzed repeatedly.

    Results

    Stent ID reduction from 8 to 2mm resulted in an increase of ∆EEVCW by up to 3x (e.g. 323 [255 - 410] ml vs 106 [81 - 138] ml at fHF=100 min-1). At the same time, VT decreased by up to 4.2x (e.g. 477 [434 – 524] ml vs 114 [79 – 165] ml). PaO2 and paCO2 remained at acceptable levels for 4-8 mm stent ID but CO2 removal became suddenly impaired at 2mm stent ID (paCO2>12 kPa). Pre-stenotic airway pressure monitoring was accurate at 8mm stent ID, but overestimation of peak inspiratory pressure (PIP) up to 2x and underestimation of PEEP up to 19x was observed at 2mm stent ID.

    Conclusion

    SHFJV was able to maintain oxygenation and carbon dioxide removal over a wide range of obstructions, despite decreasing VT and successive air trapping. At 2 mm stent ID, only carbon dioxide removal became insufficient.

  • 35.
    Sütterlin, Robert
    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.
    Lo Mauro, Antonella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.
    Gandolfi, Stefano
    Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.
    Priori, Rita
    Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.
    Aliverti, Andrea
    Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.
    Frykholm, Peter
    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.
    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.
    Efficacy of Superimposed High Frequency Jet Ventilation and High Frequency Jet Ventilation in an Animal Model of Tracheal Obstruction2014In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175Article in journal (Refereed)
    Abstract [en]

    Background

    Superimposed high frequency jet ventilation (SHFJV) and high-frequency jet ventilation (HJFV) are widely used for airway interventions using rigid bronchoscopy. SHFJV was found to provide higher lung volume and better gas exchange than HFJV in unobstructed airways.

    We hypothesized that, also in the presence of airway obstruction, SHFJV would provide higher lung volumes, better oxygenation and more effective CO2 removal than HFJV.

    Methods

    In a porcine model, we used a stent with ID 4 mm to create tracheal obstruction. The anesthetized animals (25-31.5kg) were alternately ventilated with SHFJV (low frequency 16min-1, combined with a high frequency fHF) and HFJV (solely fHF) at a set of different fHF from 50-600min-1. Chest wall volume changes were measured with opto-electronic plethysmography, airway pressures were registered continuously and arterial blood gases were obtained repeatedly.

    Results

    SHFJV provided higher ∆EEVCW than HFJV with a difference between both modes of 129 ml (fHF=50min-1) to 62 ml (fHF=400min-1). Tidal volume (VT) was always greater than 213 ml with SHFJV, but with HFJV, increasing fHF reduced VT from 112 (97-130) ml at fHF=50 min-1 to negligible values at fHF>150 min-1.

    In analogy, SHFJV provided paO2 of >30 kPa and acceptable CO2 removal for all fHF, whereas fHF>150 min-1 resulted in severe hypoxia and hypercarbia during HFJV.

    Conclusion

    SHFJV effectively increased lung volumes and maintained gas exchange compared with HFJV. SHFJV may be a safer option than HFJV in laser surgery, where low FiO2 is required. HFJV with frequencies >100-150 min-1 should not be used in severe airway obstruction.

  • 36.
    Sütterlin, Robert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    LoMauro, Antonella
    Politecn Milan, Dipartimento Elettron Informaz & Bioingn, I-20133 Milan, Italy..
    Gandolfi, Stefano
    Politecn Milan, Dipartimento Elettron Informaz & Bioingn, I-20133 Milan, Italy..
    Priori, Rita
    Politecn Milan, Dipartimento Elettron Informaz & Bioingn, I-20133 Milan, Italy..
    Aliverti, Andrea
    Politecn Milan, Dipartimento Elettron Informaz & Bioingn, I-20133 Milan, Italy..
    Frykholm, Peter
    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.
    Influence of Tracheal Obstruction on the Efficacy of Superimposed High-frequency Jet Ventilation and Single-frequency Jet Ventilation2015In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 123, no 4, p. 799-809Article in journal (Refereed)
    Abstract [en]

    Background: Both superimposed high-frequency jet ventilation (SHFJV) and single-frequency (high-frequency) jet ventilation (HFJV) have been used with success for airway surgery, but SHFJV has been found to provide higher lung volumes and better gas exchange than HFJV in unobstructed airways. The authors systematically compared the ventilation efficacy of SHFJV and HFJV at different ventilation frequencies in a model of tracheal obstruction and describe the frequency and obstruction dependence of SHFJV efficacy. Methods: Ten anesthetized animals (weight 25 to 31.5 kg) were alternately ventilated with SHFJV and HFJV at a set of different f(HF) from 50 to 600 min(-1). Obstruction was created by insertion of interchangeable stents with ID 2 to 8 mm into the trachea. Chest wall volume was measured using optoelectronic plethysmography, airway pressures were recorded, and blood gases were analyzed repeatedly. Results: SHFJV provided greater than 1.6 times higher end-expiratory chest wall volume than HFJV, and tidal volume (V-T) was always greater than 200 ml with SHFJV. Increase of f(HF) from 50 to 600 min(-1) during HFJV resulted in a more than 30-fold V-T decrease from 112 ml (97 to 130 ml) to negligible values and resulted in severe hypoxia and hypercapnia. During SHFJV, stent ID reduction from 8 to 2 mm increased end-expiratory chest wall volume by up to 3 times from approximately 100 to 300 ml and decreased V-T by up to 4.2 times from approximately 470 to 110 ml. Oxygenation and ventilation were acceptable for 4 mm ID or more, but hypercapnia occurred with the 2 mm stent. Conclusion: In this in vivo porcine model of variable severe tracheal stenosis, SHFJV effectively increased lung volumes and maintained gas exchange and may be advantageous in severe airway obstruction.

  • 37.
    Vimlati, Laszlo
    et al.
    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.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lichtwarck-Aschoff, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Pulmonary shunt is independent of decrease in cardiac output during unsupported spontaneous breathing in the pig2013In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 118, no 4, p. 914-923Article in journal (Refereed)
    Abstract [en]

    Background: During mechanical ventilation (MV), pulmonary shunt is cardiac output (CO) dependent; however, whether this relationship is valid during unsupported spontaneous breathing (SB) is unknown. The CO dependency of the calculated venous admixture was investigated, with both minor and major shunt, during unsupported SB, MV, and SB with continuous positive airway pressure (CPAP). Methods: In seven anesthetized supine piglets breathing 100% oxygen, unsupported SB, MV (with tidal volume and respiratory rate corresponding to SB), and 8 cm H2O CPAP (airway pressure corresponding to MV) were applied at random. Venous return and CO were reduced by partial balloon occlusion of the inferior vena cava. Measurements were repeated with the left main bronchus blocked, creating a nonrecruitable pulmonary shunt. Results: CO decreased from 4.2 l/min (95% CI, 3.9-4.5) to 2.5 l/min (95% CI, 2.2-2.7) with partially occluded venous return. Irrespective of whether shunt was minor or major, during unsupported SB, venous admixture was independent of CO (slope: minor shunt, 0.5; major shunt, 1.1%.min(-1).l(-1)) and mixed venous oxygen tension. During both MV and CPAP, venous admixture was dependent on CO (slope MV: minor shunt, 1.9; major shunt, 3.5; CPAP: minor shunt, 1.3; major shunt, 2.9% .min(-1).l(-1)) and mixed-venous oxygen tension (coefficient of determination 0.61-0.86 for all regressions). Conclusions: In contrast to MV and CPAP, venous admixture was independent of CO during unsupported SB, and was unaffected by mixed-venous oxygen tension, casting doubt on the role of hypoxic pulmonary vasoconstriction in pulmonary blood flow redistribution during unsupported SB.

  • 38. Wiklund, L
    et al.
    Hök, Bertil
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Jordeby-Jönsson, A
    Ståhl, K
    Post-anesthesia monitoring: More than 75% of pulse oximeter alarms are trivial1992In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 77, no A, p. 582-Article in journal (Refereed)
  • 39.
    Östberg, Erland
    et al.
    Västerås & Köping Hosp, Dept Anesthesia & Intens Care, Västerås, Sweden.
    Thorisson, Arnar
    Västerås & Köping Hosp, Dept Radiol, Västerås, Sweden.
    Enlund, Mats
    Clin Res Ctr, Västerås, Sweden.
    Zetterström, Henrik
    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.
    Edmark, Lennart
    Västerås & Köping Hosp, Dept Anesthesia & Intens Care, Västerås, Sweden.
    Positive End-expiratory Pressure Alone Minimizes Atelectasis Formation in Nonabdominal Surgery: A Randomized Controlled Trial2018In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 128, no 6, p. 1117-1124Article in journal (Refereed)
    Abstract [en]

    Background: Various methods for protective ventilation are increasingly being recommended for patients undergoing general anesthesia. However, the importance of each individual component is still unclear. In particular, the perioperative use of positive end-expiratory pressure (PEEP) remains controversial. The authors tested the hypothesis that PEEP alone would be sufficient to limit atelectasis formation during nonabdominal surgery. Methods: This was a randomized controlled evaluator-blinded study. Twenty-four healthy patients undergoing general anesthesia were randomized to receive either mechanical ventilation with PEEP 7 or 9 cm H2O depending on body mass index (n = 12) or zero PEEP (n =12). No recruitment maneuvers were used. Hie primary outcome was atelectasis area as studied by computed tomography in a transverse scan near the diaphragm, at the end of surgery, before emergence. Oxygenation was evaluated by measuring blood gases and calculating the ratio of arterial oxygen partial pressure to inspired oxygen fraction (Pao(2)/Fio(2) ratio). Results: At the end of surgery, the median (range) atelectasis area, expressed as percentage of the total lung area, was 1.8 (0.3 to 9.9) in the PEEP group and 4.6 (1.0 to 10.2) in the zero PEEP group. Tire difference in medians was 2.8% (95% CI, 1.7 to 5.7%; A = 0.002). Oxygenation and carbon dioxide elimination were maintained in the PEEP group, but both deteriorated in the zero PEEP group. Conclusions: During nonabdominal surgery, adequate PEEP is sufficient to minimize atelectasis in healthy lungs and thereby maintain oxygenation. Titus, routine recruitment maneuvers seem unnecessary, and the authors suggest that they should only be utilized when clearly indicated.

  • 40.
    Östberg, Erland
    et al.
    Vasteras Hosp, Dept Anesthesia & Intens Care, Vasteras, Sweden;Koping Cty Hosp, Dept Anesthesia & Intens Care, Koping, Sweden.
    Thorisson, Arnar
    Vasteras Hosp, Dept Radiol, Vasteras, Sweden.
    Enlund, Mats
    Vasteras Hosp, Ctr Clin Res, Vasteras, Sweden.
    Zetterström, Henrik
    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.
    Edmark, Lennart
    Vasteras Hosp, Dept Anesthesia & Intens Care, Vasteras, Sweden;Koping Cty Hosp, Dept Anesthesia & Intens Care, Koping, Sweden.
    Positive End-expiratory Pressure and Postoperative Atelectasis: A Randomized Controlled Trial2019In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 131, no 4, p. 809-817Article in journal (Refereed)
    Abstract [en]

    Background: Positive end-expiratory pressure (PEEP) increases lung volume and protects against alveolar collapse during anesthesia. During emergence, safety preoxygenation preparatory to extubation makes the lung susceptible to gas absorption and alveolar collapse, especially in dependent regions being kept open by PEEP. We hypothesized that withdrawing PEEP before starting emergence preoxygenation would limit postoperative atelectasis formation.

    Methods: This was a randomized controlled evaluator-blinded trial in 30 healthy patients undergoing nonabdominal surgery under general anesthesia and mechanical ventilation with PEEP 7 or 9 cm H2O depending on body mass index. A computed tomography scan at the end of surgery assessed baseline atelectasis. The study subjects were thereafter allocated to either maintained PEEP (n = 16) or zero PEEP (n = 14) during emergence preoxygenation. The primary outcome was change in atelectasis area as evaluated by a second computed tomography scan 30 min after extubation. Oxygenation was assessed by arterial blood gases.

    Results: Baseline atelectasis was small and increased modestly during awakening, with no statistically significant difference between groups. With PEEP applied during awakening, the increase in atelectasis area was median ( range) 1.6 (-1.1 to 12.3) cm(2) and without PEEP 2.3 (-1.6 to 7.8) cm(2). The difference was 0.7 cm(2) (95% CI, -0.8 to 2.9 cm(2); P = 0.400). Postoperative atelectasis for all patients was median 5.2 cm(2) (95% CI, 4.3 to 5.7 cm(2)), corresponding to median 2.5% of the total lung area (95% CI, 2.0 to 3.0%). Postoperative oxygenation was unchanged in both groups when compared to oxygenation in the preoperative awake state.

    Conclusions: Withdrawing PEEP before emergence preoxygenation does not reduce atelectasis formation after nonabdominal surgery. Despite using 100% oxygen during awakening, postoperative atelectasis is small and does not affect oxygenation, possibly conditional on an open lung during anesthesia, as achieved by intraoperative PEEP.

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