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  • 1.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Torkzad, Michael R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bergman, Antonina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pulmonary influences on early postoperative recovery in patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy treatment2011In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598Article in journal (Other academic)
  • 2.
    Björnsson, Marcus A
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Norberg, Åke
    Kalman, Sigridur
    Simonsson, Ulrika S H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    A Recirculatory Model for Pharmacokinetics and the Effects on Bispectral Index After Intravenous Infusion of the Sedative and Anesthetic AZD3043 in Healthy Volunteers2015In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 121, no 4, 904-913 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: AZD3043 is a positive allosteric modulator of the γ-aminobutyric acid type A receptor, with sedative and anesthetic properties. We describe a population pharmacokinetic (PK) model of arterial and venous concentrations of AZD3043 and the pharmacodynamic effects on bispectral index (BIS) in healthy volunteers.

    METHODS: Arterial and venous plasma concentrations of AZD3043 and BIS were measured in 2 clinical studies in 125 healthy volunteers, where AZD3043 was given as a 1-minute bolus (1-6 mg/kg), a 30-minute infusion (1-81 mg/kg/h), or 0.8 + 10, 1 + 15, 3 + 30, and 4 + 40 (mg/kg bolus + mg/kg/h infusion for 30 minutes). Population PK/pharmacodynamic analysis was performed with NONMEM.

    RESULTS: A recirculatory model, comprising a series of 5 compartments for the transit of drug between venous and arterial plasma, 2 peripheral distribution compartments, and 1 compartment for the nondistributive transit of drug from arterial to venous plasma, described the PK of AZD3043. Systemic clearance was high (2.2 L/min; 95% confidence interval, 2.12-2.25), and apparent volumes of distribution were low, leading to a short elimination half-life. The apparent volumes of distribution of the arterial and peripheral compartments increased with increasing administered dose, giving a total apparent volume of distribution of 15 L after the lowest dose and 37 L after the greatest dose. A sigmoid maximum effect (Emax) model with an EC50 of 15.6 µg/mL and a γ of 1.7 described the relationship between AZD3043 effect-site concentrations and BIS. The between-subject variability in EC50 was 37%. An effect compartment model, with a half-life of the equilibration rate constant ke0 of 1.1 min, described the delay in effect in relation to the arterial plasma concentrations.

    CONCLUSIONS: AZD3043 had a high clearance and a low apparent volume of distribution, leading to a short half-life. However, the apparent volume of distribution was dose dependent (P < 0.001), leading to an increased half-life with increasing dose. The distribution to the effect site was fast and together with the short plasma half-life led to a fast onset and offset of effects.

  • 3. Cunha-Goncalves, Doris
    et al.
    Perez-de-Sa, Valeria
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Thörne, Johan
    Blomquist, Sten
    Inotropic support during experimental endotoxemic shock: part II. A comparison of levosimendan with dobutamine2009In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 109, no 5, 1576-83 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We compared the association of levosimendan or dobutamine with norepinephrine for the maintenance of systemic and hepatosplanchnic perfusion during early endotoxemic shock. METHODS: Twenty anesthetized pigs (26.8 +/- 0.5 kg) were instrumented with flow probes and catheters to monitor systemic and regional perfusion as described in our companion article in this issue of the journal. Two animals were excluded because of surgical complications. Oxygen consumption (VO(2)) was measured by indirect calorimetry. Starting 1 h after instrumentation, an endotoxin infusion (Escherichia coli lipopolysaccharide, 2 microg x kg(-1) x h(-1)) was administered for 300 min. Sixty minutes after the start of endotoxin, the animals were fluid resuscitated (20 mL/kg dextran 70); at 120 min, they were randomized into three groups of six animals each: levosimendan (25-50 microg x kg(-1) x h(-1)), dobutamine (10-20 microg x kg(-1) x min(-1)), and control. In the first two groups, norepinephrine (0.5-2 microg x kg(-1) x min(-1)) was added when mean arterial blood pressure (MAP) or= baseline. The data were divided into two subsets: before (0-120 min, all animals) and after (120-300 min, three groups) randomization, and analyzed by analysis of variance. P < 0.05 was considered significant. RESULTS: At 120 min, cardiac output was 15% higher (P < 0.001), systemic vascular resistance was 30% lower (P < 0.001), and MAP decreased 12.5% (P = 0.004); blood flow in the hepatic artery, superior mesenteric artery, and portal vein had increased by 100% (P = 0.004), 60% (P < 0.001), and 20% (P < 0.001), respectively. Between 120 and 300 min, cardiac output and systemic oxygen delivery decreased 50% in control animals (P < 0.05), remained unchanged in the levosimendan group, and increased 60% with dobutamine (P = 0.05). MAP (P = 0.043) and VO(2) (P = 0.001) decreased 20% in the control group. Portal vein flow decreased in the control (50%) and levosimendan (30%) groups (P < 0.001) and was therefore higher in the dobutamine group (P = 0.003) at 300 min. Hepatic and gut oxygen deliveries decreased in the levosimendan (50%, and 30%, respectively, P < 0.001) and control groups (70% and 45%, respectively, P < 0.05); thus, regional oxygen deliveries were greater in the dobutamine group (P < 0.05). In this group, mixed venous and hepatic vein oxygen saturation were maintained; the latter variable was higher than in the other groups (P < 0.05). Although unchanged with dobutamine, arterial (P = 0.020), portal (P = 0.020), and hepatic vein (P = 0.034) lactate concentrations increased twofold with levosimendan. CONCLUSION: In volume-resuscitated endotoxemic pigs, the association of either levosimendan or dobutamine with norepinephrine preserved systemic blood flow, oxygen delivery, and VO(2). However, only dobutamine-norepinephrine maintained portal blood flow, which was associated with preservation of splanchnic and hepatic oxygen homeostasis and stable lactate concentrations.

  • 4. Ekman, A.
    et al.
    Stålberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Sundman, E.
    Eriksson, L.I.
    Brudin, L.
    Sandin, R.
    The effect of neuromuscular block and noxious stimulation on hypnosis monitoring during sevoflurane anesthesia2007In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 105, no 3, 688-695 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There are conflicting results on the influence of neuromuscular block (NMB) on the bispectral index (BIS). We investigated the influence of two degrees of NMB on BIS, Alaris auditory-evoked potential index (AAI), and the electromyogram (EMG) obtained with needle electrodes from the frontal and temporal muscles, immediately adjacent to the BIS-sensor. METHODS: Twenty patients were anesthetized with sevoflurane, titrated for 30 min to an end-tidal concentration of 1.2% (baseline). Rocuronium was infused to 50% (partial) and 95% (profound) depression of the first twitch in a train-of-four response, the order being randomly chosen. Noxious tetanic electrical stimulation was applied at four occasions: 1) at baseline (control measurement), 2 and 3) at each degree of NMB, and 4) after neostigmine reversal. BIS, AAI, and EMG were obtained 2 min before and 2 min after each noxious stimulation. RESULTS: Median BIS and AAI at baseline were 44 (39-50) and 15 (14-16), respectively. The two degrees of NMB did not affect BIS, AAI, and EMG before noxious stimulation. In contrast, profound NMB altered the BIS and AAI responses to noxious stimulation when compared with partial NMB, (BIS P = 0.01, AAI P < 0.01), after neostigmine reversal (BIS P < 0.01, AAI P = 0.01) and compared with baseline (BIS P = 0.08, AAI P = 0.02). No significant increase in EMG was found. CONCLUSION: BIS and AAI responses to noxious tetanic electrical stimulation are affected by the degree of NMB during sevoflurane anesthesia whereas NMB does not affect BIS or AAI in the absence of noxious stimulation.

  • 5. Garcia-Fernandez, Javier
    et al.
    Tusman, Gerardo
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Llorens, Julio
    Soro, Marina
    Belda, Javier F
    Programming pressure support ventilation in pediatric patients in ambulatory surgery with a laryngeal mask airway.2007In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 105, no 6, 1585-1591 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Anesthesia workstations with pressure support ventilation (PSV) are available, but there are few studies published on how to program flow-triggered PSV using a laryngeal mask airway (LMA) under general anesthesia in pediatric patients.

    METHODS: We studied 60 ASA I and II patients, from 2 mo to 14 yr, scheduled for ambulatory surgery under combined general and regional anesthesia with a LMA. Patients were classified according to their body weight as follows: Group A ≤10 kg, Group B 11–20 kg, and Group C >20 kg. All were ventilated in PSV using the following settings: positive end-expiratory pressure of 4 cm H2O, the minimum flow-trigger without provoking auto-triggering, and the minimum level of pressure support to obtain 10 mL/kg of tidal volume.

    RESULTS: The flow-trigger most frequently used in our study was 0.4 L/min, ranging from 0.2 to 0.6 L/min. We found no correlation between the flow-trigger setting and the patient’s age, weight, compliance, resistance, or respiratory rate. There was a good correlation between the level of pressure support (Group A = 15 cm H2O, Group B = 10 cm H2O and Group C = 9 cm H2O) and age (P < 0.001), weight (P < 0.001), dynamic compliance (P < 0.001), and airway resistances (P < 0.001).

    CONCLUSIONS: PSV with a Proseal™ LMA in outpatient pediatric anesthesia can be programmed simply using the common clinical noninvasive variables studied. However, more studies are needed to estimate the level of pressure support that may be required in other clinical situations (respiratory pathology, endotracheal tubes, or other types of surgeries) or with other anesthesia workstations.

    IMPLICATIONS: This study evaluates the ability to administer positive pressure support ventilation through a laryngeal mask airway to anesthetized, spontaneously breathing children.

  • 6.
    Karlsson, Victoria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Sporre, Bengt
    Univ Uppsala Hosp, Unit Pediat Anesthesia, Uppsala, Sweden..
    Ågren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Transcutaneous Pco(2) Monitoring in. Newborn Infants During General Anesthesia Is Technically Feasible2016In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 123, no 4, 1004-1007 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Transcutaneous (TC) measurement of Pco(2) (TC Pco(2)) is a well-established method to monitor assisted ventilation in neonatal intensive care, but its use in the operating room is limited, and the data regarding its performance during general anesthesia of the newborn are lacking. The aim of this study is to evaluate the performance of continuous TC Pco(2) monitoring during general anesthesia in newborn infants. METHODS: Infants (n = 25) with a gestational age of 23 to 41 weeks and a birth weight of 548 to 4114 g were prospectively enrolled. During general anesthesia and surgery, TC Pco(2) was measured continuously and recorded at 1-minute intervals. Five-minute mean values were compared with simultaneously obtained blood gas (BG) analyses of Pco(2). Only the first paired TC and BG samples were used in this analysis. We defined precision as 2.1 times the standard deviation of the difference of the 2 samples. P < .01 was considered statistically significant. RESULTS: We obtained samples from 25 infants. The difference between TC and BG was 0.3 +/- 0.7 kPa (mean +/- standard deviation) giving a precision of 1.47 kPa. Nineteen of twenty-five (76%) sample pairs displayed a difference of <1 kPa (99% confidence interval, 48%-92%, P = .016). The difference in paired samples was similar for different gestational and postnatal ages and did not appear to be affected by electrocautery. CONCLUSIONS: In this small study, we did not demonstrate that TC CO2 monitoring was accurate at P < .01. This partly reflects the small size of the study, resulting in wide 99% confidence bounds.

  • 7.
    Kawati, Rafael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Vimlati, Laszlo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Guttmann, Josef
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Sjöstrand, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Schumann, Stefan
    Lichtwarck-Aschoff, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Change in expiratory flow detects partial endotracheal tube obstruction in pressure-controlled ventilation2006In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 103, no 3, 650-657 p.Article in journal (Refereed)
    Abstract [en]

    Only extreme degrees of endotracheal tube (ETT) narrowing can be detected with monitoring of tidal volume (V-T) during pressure-controlled ventilation (PCV). To assess the degree of ETT obstruction in PCV and to compare it to V,, monitoring, we produced 3 levels of partial ETT obstruction in 11 healthy anesthetized piglets using ETTs of 4 different inner diameters (IDs 9.0, 8.0, 7.0, and 6.0 mm). An expiratory flow over volume (<(V)over dot >(e)-V) curve was plotted and the time constant (tau(e)) at 15% of expiration time (T-e) was calculated. We also calculated the fractional volume expired during the first 15% of T-e (V-ex (fract, 15)) and compared those variables to full expiratory V, for each of the 3 obstructions. V-T monitoring failed to detect ETT narrowing. By contrast, V-ex (fract,15) decreased and tau(e)e increased significantly with increasing ETT narrowing (for IDs 9.0, 8.0, 7.0, and 6.0, mean V-ex (fract,15) was 195, 180, 146, and 134 mL respectively and mean tau(e) was 380, 491, 635, 794 ms for IDs 9.0, 8.0, 7.0, and 6.0 respectively). We conclude that when the elastic recoil that drives <(V)over dot >(e) is appropriately considered, analysis of <(V)over dot >(e) and V-ex (fract,15) detects partial ETT obstruction during PCV.

  • 8.
    Lipcsey, Miklos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Einarsson, Roland
    Abdul Qadhr, Goran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    The brain is a source of S100B increase during endotoxemia in the pig2010In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 110, no 1, 174-180 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Cerebral dysfunction frequently complicates septic shock. A marker of cerebral dysfunction could be of significant value in managing sedated septic patients. Plasma S100 (S100B) proteins increase in sepsis. S100B is present not only in the brain but also in other tissues. The source of this protein has not been investigated in sepsis. Our aim in this study was to determine whether the brain is an important source of S100B in an experimental sepsis model.

    METHODS:

    Twenty-seven pigs were anesthetized and randomized to either infusion of endotoxin at the rate of 1 µg · kg-1 · h-1 (n = 19) or saline (n = 8). Catheters were inserted into a cervical artery and the superior sagittal sinus. Blood samples were collected from both sites and physiologic data were registered before the start of the endotoxin infusion and hourly during the experiment. After 6 h, the animals were killed and brain tissue samples were taken from the left hemisphere. S100B in plasma was measured by enzyme-linked immunosorbent assay. Brain tissue samples were stained with biotinylated S100B antibodies.

    RESULTS:

    In the endotoxemic animals, the arterial S100B concentration increased to 442 ± 33 and 421 ± 24 ng/L at 1 and 2 h, respectively, vs 306 ± 28 and 261 ± 25 ng/L in controls (P = 0.018 and 0.00053, respectively). Mean superior sagittal sinus S100B concentrations were higher than mean arterial concentrations at all time points in the endotoxemic animals; however, significance was only reached at 2 h (P = 0.033). The focal glial S100B expression was more intense in the endotoxemic pigs than in controls (P = 0.0047).

    CONCLUSIONS:

    Our results support the hypothesis that the brain is an important source of S100B in endotoxemia even though there may be other sources. These findings make S100B a candidate as a marker of cerebral dysfunction in septic shock.

  • 9. Nisula, Sara
    et al.
    Yang, Runkuan
    Kaukonen, Kirsi-Maija
    Vaara, Suvi T.
    Kuitunen, Anne
    Tenhunen, Jyrki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Pettila, Ville
    Korhonen, Anna-Maija
    The Urine Protein NGAL Predicts Renal Replacement Therapy, but Not Acute Kidney Injury or 90-Day Mortality in Critically III Adult Patients2014In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 119, no 1, 95-102 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Urine neutrophil gelatinase-associated lipocalin (uNGAL) is increasingly used as a biomarker for acute kidney injury (AKI). However, the clinical value of uNGAL with respect to AKI, renal replacement therapy (RRT), or 90-day mortality in critically ill patients is unclear. Accordingly, we tested the hypothesis that uNGAL is a clinically relevant biomarker for these end points in a large, nonselected cohort of critically ill adult patients. METHODS: We prospectively obtained urine samples from 1042 adult patients admitted to 15 Finnish intensive care units. We analyzed 3 samples (on admission, at 12 hours, and at 24 hours) with NGAL ELISA Rapid Kits (BioPorto (R) Diagnostics, Gentofte, Denmark). We chose the highest uNGAL (uNGAL24) for statistical analyses. We calculated the areas under receiver operating characteristics curves (AUC) with 95% confidence intervals (95% CIs), the best cutoff points with the Youden index, positive likelihood ratios (LR+), continuous net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). We performed sensitivity analyses excluding patients with AKI or RRT on day 1, sepsis, or with missing baseline serum creatinine concentration. RESULTS: In this study population, the AUG of uNGAL24 (95% CI) for development of AKI (defined by the Kidney Disease: Improving Global Outcomes [KDIGO] criteria) was 0.733(0.701-0.765), and the continuous NRI for AKI was 56.9%. For RRT, the AUG of uNGAL24 (95% CI) was 0.839 (0.797-0.880), and NRI 56.3%. For 90-day mortality, the AUG of uNGAL24 (95% CI) was 0.634 (0.593 to 0.675), and NRI 15.3%. The LR+ (95% CI) for RRT was 3.81 (3.26-4.47). CONCLUSION: In this study, we found that uNGAL associated well with the initiation of RRT but did not provide additional predictive value regarding AKI or 90-day mortality in critically ill patients.

  • 10. Rudin, Åsa
    et al.
    Lundberg, Johan F.
    Hammarlund-Udenaes, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Flisberg, Per
    Werner, Mads U.
    Morphine metabolism after major liver surgery2007In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 104, no 6, 1409-1414 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Impaired metabolism of morphine may lead to an increase in sedation and respiratory depression. METHODS: In the present study we investigated morphine pharmacokinetics in patients who had undergone liver resection (n = 15) compared to a control group undergoing colon resection (n = 15). Morphine was administered IV by patient-controlled analgesia. Plasma concentrations of morphine, morphine-6-glucuronide, and morphine-3-glucuronide were measured 2-3 times daily for the first two postoperative days. Pain intensity scores were assessed three times daily and respiratory rate and sedation scores every third hour. RESULTS: There were no differences in morphine requirements 1.1 (0.8-2.5 [median, interquartile range]) mg/h (liver resection) and 1.5 (1.1-1.7) mg/h (colon resection) [P = 0.84]) or in pain intensity scores (P > 0.3) between the groups. Plasma morphine concentrations were higher in patients undergoing liver resection than in the control group (P < 0.01) reflecting a lower rate of morphine metabolism. Plasma morphine concentrations were correlated with the volume of liver resection (P < 0.02). However, plasma concentrations of morphine-6-glucuronide and morphine-3-glucuronide did not differ between the groups (P = 0.62 and P = 0.48, respectively). There was a higher incidence of sedation (P = 0.02), but not respiratory depression (P = 0.48), after liver resection. CONCLUSION: The study demonstrates that plasma concentrations of morphine are higher in patients undergoing liver resection compared with patients undergoing colon resection. Sedation scores were higher in patients undergoing liver resection. Caution is therefore recommended when administering morphine to this patient group.

  • 11. Schilling, Thomas
    et al.
    Kozian, Alf
    Huth, Christof
    Bühling, Frank
    Kretzschmar, Moritz
    Welte, Tobias
    Hachenberg, Thomas
    The pulmonary immune effects of mechanical ventilation in patients undergoing thoracic surgery2005In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 101, no 4, 957-965 p.Article in journal (Refereed)
    Abstract [en]

    Mechanical ventilation (MV) may induce an inflammatory alveolar response. One-lung ventilation (OLV) with tidal volumes (Vt) as used during two-lung ventilation is a suggested algorithm but may impose mechanical stress of the dependent lung and potentially aggravate alveolar mediator release. We studied whether ventilation with different Vt modifies pulmonary immune function, hemodynamics, and gas exchange. Thirty-two patients undergoing open thoracic surgery were randomized to receive either MV with Vt = 10 mL/kg (n = 16) or Vt = 5 mL/kg (n = 16) adjusted to normal Pa(CO2) during and after OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed, and cells, protein, tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, soluble intercellular adhesion molecule (sICAM)-1, IL-10, and elastase were determined in the bronchoalveolar lavage. Data were analyzed by parametric or nonparametric tests, as indicated. In all patients, an increase of proinflammatory variables was found. The time courses of intra-alveolar cells, protein, albumin, IL-8, elastase, and IL-10 did not differ between the groups after OLV and postoperatively. TNF-alpha (8.4 versus 5.0 microg/mL) and sICAM-1 (52.7 versus 27.5 microg/mL) concentrations were significantly smaller after OLV with Vt = 5 mL/kg. These results indicate that MV may induce epithelial damage and a proinflammatory response in the ventilated lung. Reduction of tidal volume during OLV may reduce alveolar concentrations of TNF-alpha and of sICAM-1. IMPLICATIONS: Reductions of tidal volume, with subsequently decreased peak airway pressures, may reduce some alveolar inflammatory responses seen with mechanical ventilation.

  • 12. Tusman, Gerardo
    et al.
    Bohm, Stephan H.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Scandurra, Adriana
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lung recruitment and positive end-expiratory pressure have different effects on CO2 elimination in healthy and sick lungs2010In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 111, no 4, 968-977 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We studied the effects that the lung recruitment maneuver (RM) and positive end-expiratory pressure (PEEP) have on the elimination of CO(2) per breath (Vtco(2,br)). METHODS: In 7 healthy and 7 lung-lavaged pigs at constant ventilation, PEEP was increased from 0 to 18 cm H(2)O and then decreased to 0 in steps of 6 cm H(2)O every 10 minutes. Cycling RMs with plateau pressure/PEEP of 40/20 (healthy) and 50/25 (lavaged) cm H(2)O were applied for 2 minutes between 18-PEEP steps. Volumetric capnography, respiratory mechanics, blood gas, and hemodynamic data were recorded. RESULTS: In healthy lungs before the RM, Vtco(2,br) was inversely proportional to PEEP decreasing from 4.0 (3.6-4.4) mL (median and interquartile range) at 0-PEEP to 3.1 (2.8-3.4) mL at 18-PEEP (P < 0.05). After the RM, Vtco(2,br) increased from 3.3 (3-3.6) mL at 18-PEEP to 4.0 (3.5-4.5) mL at 0-PEEP (P < 0.05). In lavaged lungs before the RM, Vtco(2,br) increased initially from 2.0 (1.7-2.3) mL at 0-PEEP to 2.6 (2.2-3) mL at 12-PEEP (P < 0.05) but then decreased to 2.4 (2-2.8) mL when PEEP was increased further to 18 cm H(2)O (P < 0.05). After the RM, the highest Vtco(2,br) of 2.9 (2.1-3.7) mL was observed at 12-PEEP and then decreased to 2.5 (1.9-3.1) mL at 0-PEEP (P < 0.05). Vtco(2,br) was directly related to changes in lung perfusion, the area of gas exchange, and alveolar ventilation but inversely related to changes in dead space. CONCLUSIONS: CO(2) elimination by the lungs was dependent on PEEP and recruitment and showed major differences between healthy and lavaged lungs.

  • 13. Tusman, Gerardo
    et al.
    Groisman, Ivan
    Fiolo, Felipe E.
    Scandurra, Adriana
    Martinez Arca, Jorge
    Krumrick, Gustavo
    Bohm, Stephan H.
    Suarez Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Noninvasive Monitoring of Lung Recruitment Maneuvers in Morbidly Obese Patients: The Role of Pulse Oximetry and Volumetric Capnography2014In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 118, no 1, 137-144 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We conducted this study to determine whether pulse oximetry and volumetric capnography (VCap) can determine the opening and closing pressures of lungs of anesthetized morbidly obese patients. METHODS: Twenty morbidly obese patients undergoing laparoscopic bariatric surgery with capnoperitoneum were studied. A lung recruitment maneuver was performed in pressure control ventilation as follows: (1) During an ascending limb, the lungs' opening pressure was detected. After increasing positive end-expiratory pressure (PEEP) from 8 to 16 cm H2O, fraction of inspired oxygen (Fio(2)) was decreased until pulse oximetric arterial saturation (Spo(2)) was <92%. Thereafter, end-inspiratory pressure was increased in steps of 2 cm H2O, from 36 to a maximum of 50 cm H2O. The opening pressure was attained when Spo(2) exceeded 97%. (2) During a subsequent decreasing limb, the lungs' closing pressure was identified. PEEP was decreased from 22 to 10 cm H2O in steps of 2 cm H2O. The closing pressure was determined as the PEEP value at which respiratory compliance decreased from its maximum value. We continuously recorded lung mechanics, Spo(2), and VCap. RESULTS: The lungs' opening pressures were detected at 44 (4) cm H2O (median and interquartile range) and the closing pressure at 14 (2) cm H2O. Therefore, the level of PEEP that kept the lungs without collapse was found to be 16 (3) cm H2O. Using respiratory compliance as a reference, receiver operating characteristic analysis showed that Spo(2) (area under the curve [AUC] 0.80 [SE 0.07], sensitivity 0.65, and specificity 0.94), the elimination of CO2 per breath (AUC 0.91 [SE 0.05], sensitivity 0.85, and specificity 0.98), and Bohr's dead space (AUC 0.83 [SE 0.06], sensitivity 0.70, and specificity 0.95] were relatively accurate for detecting lung collapse during the decreasing limb of a recruitment maneuver. CONCLUSIONS: Lung recruitment in morbidly obese patients could be effectively monitored by combining noninvasive pulse oximetry and VCap. Spo(2), the elimination of CO2, and Bohr's dead space detected the individual's opening and closing pressures.

  • 14.
    Tusman, Gerardo
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Mar Del Plata, Buenos Aires, Argentina..
    Groisman, Ivan
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Mar Del Plata, Buenos Aires, Argentina..
    Maidana, Gustavo A.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Mar Del Plata, Buenos Aires, Argentina..
    Scandurra, Adriana
    Univ Mar del Plata, Sch Engn, Dept Elect, Bioengn Lab, Mar Del Plata, Buenos Aires, Argentina..
    Martinez Arca, Jorge
    Univ Mar del Plata, Sch Engn, Dept Elect, Bioengn Lab, Mar Del Plata, Buenos Aires, Argentina..
    Bohm, Stephan H.
    Swisstom AG, Landquart, Switzerland..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Inst Salud Carlos III, CIBERES, CIBER Enfermedades Resp, Madrid, Spain..
    The Sensitivity and Specificity of Pulmonary Carbon Dioxide Elimination for Noninvasive Assessment of Fluid Responsiveness2016In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 122, no 5, 1404-1411 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We sought to determine whether the response of pulmonary elimination of CO2 (Vco(2)) to a sudden increase in positive end-expiratory pressure (PEEP) could predict fluid responsiveness and serve as a noninvasive surrogate for cardiac index (CI). METHODS: Fifty-two patients undergoing cardiovascular surgery were included in this study. By using a constant-flow ventilation mode, we performed a PEEP challenge of 1-minute increase in PEEP from 5 to 10 cm H2O. At PEEP of 5 cm H2O, patients were preloaded with 500 mL IV saline solution after which a second PEEP challenge was performed. Patients in whom fluid administration increased CI by >= 15% from the individual baseline value were defined as volume responders. Beat-by-beat CI was derived from arterial pulse contour analysis, and breath-by-breath Vco(2) data were collected during the protocol. The sensitivity and specificity of Vco(2) for detecting the fluid responders according to CI was performed by the receiver operating characteristic curves. RESULTS: Twenty-one of 52 patients were identified as fluid responders (40%). The PEEP maneuver before fluid administration decreased CI from 2.65 +/- 0.34 to 2.21 +/- 0.32 L/min/m(2) (P = 0.0011) and Vco(2) from 150 +/- 23 to 123 +/- 23 mL/min (P = 0.0036) in responders, whereas the changes in CI and Vco(2) were not significant in nonresponders. The PEEP challenge after fluid administration induced no significant changes in CI and Vco(2), in neither responders nor nonresponders. PEEP-induced decreases in CI and Vco(2) before fluid administration were well correlated (r(2) = 0.75, P < 0.0001) but not thereafter. The area under the receiver operating characteristic curves for a PEEP-induced decrease in Delta CI and Delta Vco(2) was 0.99, with a 95% confidence interval from 0.96 to 0.99 for Delta CI and from 0.97 to 0.99 for Delta Vco(2). During the PEEP challenge, a decrease in Vco(2) by 11% predicted fluid responsiveness with a sensitivity of 0.90 (95% confidence interval, 0.87-0.93) and a specificity of 0.95 (95% confidence interval, 0.92-0.98). CONCLUSIONS: PEEP-induced changes in Vco(2) predicted fluid responsiveness with accuracy in patients undergoing cardiac surgery.

  • 15. Tusman, Gerardo
    et al.
    Sipmann, Fernando Suarez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bohm, Stephan H.
    Rationale of Dead Space Measurement by Volumetric Capnography2012In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 114, no 4, 866-874 p.Article in journal (Refereed)
    Abstract [en]

    Dead space is the portion of a tidal volume that does not participate in gas exchange because it does not get in contact with blood flowing through the pulmonary capillaries. It is commonly calculated using volumetric capnography, the plot of expired carbon dioxide (CO2) versus tidal volume, which is an easy bedside assessment of the inefficiency of a particular ventilatory setting. Today, Bohr's original dead space can be calculated in an entirely noninvasive and breath-by-breath manner as the mean alveolar partial pressure of CO2 (PAco(2)) which can now be determined directly from the capnogram. The value derived from Enghoff's modification of Bohr's formula (using Paco(2) instead of PAco(2)) is a global index of the inefficiency of gas exchange rather than a true "dead space" because it is influenced by all causes of ventilation/perfusion mismatching, from real dead space to shunt. Therefore, the results obtained by Bohr's and Enghoff's formulas have different physiological meanings and clinicians must be conscious of such differences when interpreting patient data. In this article, we describe the rationale of dead space measurements by volumetric capnography and discuss its main clinical implications and the misconceptions surrounding it.

  • 16. Tusman, Gerardo
    et al.
    Suarez Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bohm, Stephan H.
    Bohr Dead Space Calculation In Response2012In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 115, no 6, 1472-1473 p.Article in journal (Refereed)
  • 17.
    Tusman, Gerardo
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Mar Del Plata, Buenos Aires, Argentina..
    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.
    Confusion Between Integration and Receiver Operator Curves?: Response2016In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 123, no 5, 1332-1333 p.Article in journal (Refereed)
  • 18.
    Vimlati, Laszlo
    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.
    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.
    Lichtwarck-Aschoff, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Spontaneous Breathing Improves Shunt Fraction and Oxygenation in Comparison with Controlled Ventilation at a Similar Amount of Lung Collapse2011In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 113, no 5, 1089-1095 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Spontaneous breathing (SB), when allowed during mechanical ventilation (MV), improves oxygenation in different models of acute lung injury. However, it is not known whether oxygenation is improved during mechanically unsupported SB. Therefore, we compared SB without any support with controlled MV at identical tidal volume (V(T)) and respiratory rate (RR) without positive end-expiratory pressure in a porcine lung collapse model.

    METHODS: In 25 anesthetized piglets, stable lung collapse was induced by application of negative pressure, and animals were randomized to either resume SB or to be kept on MV at identical VT (5 mL/kg; 95% confidence interval: 3.8 to 6.4) and RR (65 per minute [57 to 73]) as had been measured during an initial SB period. Oxygenation was assessed by blood gas analysis (n = 15) completed by multiple inert gas elimination technique (n = 8 of the 15) for shunt measurement. In addition, possible lung recruitment was studied with computed tomography of the chest (n = 10).

    RESULTS: After induction of lung collapse, PaO(2)/FIO(2) decreased to 90 mm Hg (76 to 103). With SB, PaO(2)/FIO(2) increased to 235 mm Hg (177 to 293) within 15 minutes, whereas MV at identical VT and RR did not cause any improvement in oxygenation. Intrapulmonary shunt by 45 minutes after induction of lung collapse was lower during SB (SB: 27% [24 to 30] versus MV: 41% [28 to 55]; P = 0.017). Neither SB nor MV reduced collapsed lung areas on computed tomography.

    CONCLUSIONS: SB without any support improves oxygenation and reduces shunt in comparison with MV at identical settings. This seems to be achieved without any major signs of recruitment of collapsed lung regions.

1 - 18 of 18
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