Michael Georgieff

Evaluation of three risk scores to predict postoperative nausea and vomiting

Background: So far there are three different scores to predict postoperative vomiting (PV: Apfel et al., 1998) or postoperative nausea and vomiting (PONV: Koivuranta et al., 1997; Palazzo and Evans, 1993). All three scores used logistic regression analysis to identify and create weights for the risk factors for PV or PONV. In short, these were sex, age, history of previous PONV, motion sickness, duration of anaesthesia, and use of postoperative opioids. However, an external evaluation and a comparison of these scores has not been performed so far.

Cardiovascular Effects of Xenon in Isoflurane-anesthetized Dogs with Dilated Cardiomyopathy

Background Clinical interest in xenon has been rekindled recently by new recycling systems that have decreased its relative cost. The cardiovascular effects of xenon were examined in isoflurane‐anesthetized dogs before and after the development of rapid left ventricular (LV) pacing‐induced cardiomyopathy. Methods Dogs (n = 10) were chronically instrumented to measure aortic and LV pressure, LV subendocardial segment length, and aortic blood flow. Hemodynamics were recorded, and indices of LV systolic and diastolic function and afterload were determined in the conscious state and during 1.5 minimum alveolar concentration isoflurane anesthesia alone and combined with 0.25, 0.42, and 0.55 minimum alveolar concentration xenon in dogs with and without cardiomyopathy. Results Administration of xenon to healthy dogs anesthetized with isoflurane decreased heart rate and increased the time constant [small tau, Greek] of isovolumic relaxation but did not alter arterial and LV pressures, preload recruitable stroke work slope, and indices of LV afterload. Chronic rapid LV pacing increased the baseline heart rate and LV end‐diastolic pressure, decreased arterial and LV systolic pressures, and produced LV systolic and diastolic dysfunction. Administration of xenon to isoflurane‐anesthetized, cardiomyopathic dogs did not alter heart rate, arterial and LV pressures, myocardial contractility, and indices of early LV filling and regional chamber stiffness. More pronounced increases in [small tau, Greek] were accompanied by increases in total arterial resistance during administration of xenon to isoflurane‐anesthetized cardiomyopathic compared with healthy dogs. Conclusions The results indicate that xenon produces minimal cardiovascular actions in the presence of isoflurane in dogs with and without experimental dilated cardiomyopathy.

Xenon Does Not Alter Cardiac Function or Major Cation Currents in Isolated Guinea Pig Hearts or Myocytes

Background The noble gas xenon (Xe) has been used as an inhalational anesthetic agent in clinical trials with little or no physiologic side effects. Like nitrous oxide, Xe is believed to exert minimal unwanted cardiovascular effects, and like nitrous oxide, the vapor concentration to achieve 1 minimum alveolar concentration (MAC) for Xe in humans is high, i.e., 70–80%. In the current study, concentrations of up to 80% Xe were examined for possible myocardial effects in isolated, erythrocyte-perfused guinea pig hearts and for possible effects on altering major cation currents in isolated guinea pig cardiomyocytes. Methods Isolated guinea pigs hearts were perfused at 70 mmHg via the Langendorff technique initially with a salt solution at 37°C. Hearts were then perfused with fresh filtered (40-&mgr;m pore) and washed canine erythrocytes diluted in the salt solution equilibrated with 20% O2 in nitrogen (control), with 20% O2, 40% Xe, and 40% N2, (0.5 MAC), or with 20% O2 and 80% Xe (1 MAC), respectively. Hearts were perfused with 80% Xe for 15 min, and bradykinin was injected into the blood perfusate to test endothelium-dependent vasodilatory responses. Using the whole-cell patch-clamp technique, 80% Xe was tested for effects on the cardiac ion currents, the Na+, the L-type Ca2+, and the inward-rectifier K+ channel, in guinea pig myocytes suffused with a salt solution equilibrated with the same combinations of Xe, oxygen, and nitrogen as above. Results In isolated hearts, heart rate, atrioventricular conduction time, left ventricular pressure, coronary flow, oxygen extraction, oxygen consumption, cardiac efficiency, and flow responses to bradykinin were not significantly (repeated measures analysis of variance, P > 0.05) altered by 40% or 80% Xe compared with controls. In isolated cardiomyocytes, the amplitudes of the Na+, the L-type Ca2+, and the inward-rectifier K+ channel over a range of voltages also were not altered by 80% Xe compared with controls. Conclusions Unlike hydrocarbon-based gaseous anesthetics, Xe does not significantly alter any measured electrical, mechanical, or metabolic factors, or the nitric oxide–dependent flow response in isolated hearts, at least partly because Xe does not alter the major cation currents as shown here for cardiac myocytes. The authors’ results indicate that Xe, at approximately 1 MAC for humans, has no physiologically important effects on the guinea pig heart.

Task2 potassium channels set central respiratory CO2 and O2 sensitivity

Task2 K+ channel expression in the central nervous system is surprisingly restricted to a few brainstem nuclei, including the retrotrapezoid (RTN) region. All Task2-positive RTN neurons were lost in mice bearing a Phox2b mutation that causes the human congenital central hypoventilation syndrome. In plethysmography, Task2−/− mice showed disturbed chemosensory function with hypersensitivity to low CO2 concentrations, leading to hyperventilation. Task2 probably is needed to stabilize the membrane potential of chemoreceptive cells. In addition, Task2−/− mice lost the long-term hypoxia-induced respiratory decrease whereas the acute carotid-body-mediated increase was maintained. The lack of anoxia-induced respiratory depression in the isolated brainstem–spinal cord preparation suggested a central origin of the phenotype. Task2 activation by reactive oxygen species generated during hypoxia could silence RTN neurons, thus contributing to respiratory depression. These data identify Task2 as a determinant of central O2 chemoreception and demonstrate that this phenomenon is due to the activity of a small number of neurons located at the ventral medullary surface.

Incidence and prognostic impact of new-onset atrial fibrillation in patients with septic shock: a prospective observational study

IntroductionSince data regarding new-onset atrial fibrillation (AF) in septic shock patients are scarce, the purpose of the present study was to evaluate the incidence and prognostic impact of new-onset AF in this patient group.MethodsWe prospectively studied all patients with new-onset AF and all patients suffering from septic shock in a non-cardiac surgical intensive care unit (ICU) during a 13 month period.ResultsDuring the study period, 687 patients were admitted to the ICU, of which 58 patients were excluded from further analysis due to pre-existing chronic or intermittent AF. In 49 out of the remaining 629 patients (7.8%) new-onset AF occurred and 50 out of the 629 patients suffered from septic shock. 23 out of the 50 patients with septic shock (46%) developed new-onset AF. There was a steady, significant increase in C-reactive protein (CRP) levels before onset of AF in septic shock patients. ICU mortality in septic shock patients with new-onset AF was 10/23 (44%) compared with 6/27 (22%) in septic shock patients with maintained sinus rhythm (SR) (P = 0.14). During a 2-year follow-up there was a trend towards an increased mortality in septic shock patients with new-onset AF, but the difference did not reach statistical significance (P = 0.075). The median length of ICU stay among surviving patients was longer in patients with new-onset AF compared to those with maintained SR (30 versus 17 days, P = 0.017). The success rate to restore SR was 86%. Failure to restore SR was associated with increased ICU mortality (71.4% versus 21.4%, P = 0.015).ConclusionsAF is a common complication in septic shock patients and is associated with an increased length of ICU stay among surviving patients. The increase in CRP levels before onset of AF may support the hypothesis that systemic inflammation is an important trigger for AF.

Droperidol and 5‐HT3‐receptor antagonists, alone or in combination, for prophylaxis of postoperative nausea and vomiting

Background: Droperidol and 5‐HT3‐receptor antagonists are among the most potent antiemetics to prevent postoperative nausea and vomiting (PONV). Combinations of these drugs have been used to increase the efficacy of antiemetic treatment. However, so far the quantitative effect of this combination has not been evaluated systematically.

Perioperative respiratory events in smokers and nonsmokers undergoing general anaesthesia

Background: The prevalence of respiratory diseases in smokers and nonsmokers and the incidence of perioperative respiratory events (PREs) were investigated for patients undergoing general anaesthesia. The aim was to quantify well‐known problems and to identify possible new associations between smoking and PREs.

Effects of intravenous sulfide during porcine aortic occlusion-induced kidney ischemia/reperfusion injury.

In rodents, inhaled H2S and injection of H2S donors protected against kidney ischemia/reperfusion (I/R) injury. During porcine aortic occlusion, the H2S donor Na2S (sulfide) reduced energy expenditure and decreased the noradrenaline requirements needed to maintain hemodynamic targets during early reperfusion. Therefore, we tested the hypothesis whether sulfide pretreatment may also ameliorate organ function in porcine aortic occlusion-induced kidney I/R injury. Anesthetized, ventilated, and instrumented pigs randomly received either sulfide or vehicle and underwent 90 min of kidney ischemia using intraaortic balloon-occlusion, and 8 h of reperfusion. During reperfusion, noradrenaline was titrated to maintain blood pressure at baseline levels. Sulfide attenuated the fall in creatinine clearance and the rise in creatinine blood levels, whereas renal blood flow and fractional Na+ excretion were comparable. Sulfide also lowered the blood IL-6, IL-1&bgr;, and nitrite + nitrate concentrations, which coincided with reduced kidney oxidative DNA base damage and iNOS expression, and attenuated glomerular histological injury as assessed by the incidence of glomerular tubularization. While expression of heme oxygenase 1 and cleaved caspase 3 did not differ, sulfide reduced the expression Bcl-xL and increased the activation of nuclear transcription factor &kgr;B. During porcine aortic occlusion-induced kidney I/R injury, sulfide pretreatment attenuated tissue injury and organ dysfunction as a result of reduced inflammation and oxidative and nitrosative stress. The higher nuclear transcription factor &kgr;B activation was probably due to the drop in temperature.

Cardiopulmonary, histologic, and inflammatory effects of intravenous Na2S after blunt chest trauma-induced lung contusion in mice.

BACKGROUND When used as a pretreatment, hydrogen sulfide (H2S) either attenuated or aggravated lung injury. Therefore, we tested the hypothesis whether posttreatment intravenous Na2S (sulfide) may attenuate lung injury. METHODS After blast wave blunt chest trauma or sham procedure, anesthetized and instrumented mice received continuous intravenous sulfide or vehicle while being kept at 37°C or 32°C core temperature. After 4 hours of pressure-controlled, thoracopulmonary compliance-titrated, lung-protective mechanical ventilation, blood and tissue were harvested for cytokine concentrations, heme oxygenase-1, IκBα, Bcl-Xl, and pBad expression (western blotting), nuclear factor-κB activation (electrophoretic mobility shift assay), and activated caspase-3, cystathionine-β synthase and cystathionine-γ lyase (immunohistochemistry). RESULTS Hypothermia caused marked bradycardia and metabolic acidosis unaltered by sulfide. Chest trauma impaired thoracopulmonary compliance and arterial Po2, again without sulfide effect. Cytokine levels showed inconsistent response. Sulfide increased nuclear factor-κB activation during normothermia, but this effect was blunted during hypothermia. While histologic lung injury was variable, both sulfide and hypothermia attenuated the trauma-related increase in heme oxygenase-1 expression and activated caspase-3 staining, which coincided with increased Bad phosphorylation and Bcl-Xl expression. Sulfide and hypothermia also attenuated the trauma-induced cystathionine-β synthase and cystathionine-γ lyase expression. CONCLUSIONS Posttreatment sulfide infusion after blunt chest trauma did not affect the impaired lung mechanics and gas exchange but attenuated stress protein expression and apoptotic cell death. This protective effect was amplified by moderate hypothermia. The simultaneous reduction in cystathionine-β synthase and cystathionine-γ lyase expression supports the role of H2S-generating enzymes as an adaptive response during stress states.

Peri-operative tolerance to large-dose 6% HES 200/0.5 in major urological procedures compared with 5% human albumin

We studied the long‐term efficacy and safety of medium‐molecular‐weight hydroxyethyl starch (HES) administered in doses above 20 mlkg−1 during major blood replacement therapy. Blood replacement for 50 patients used 6% HES 200/0.5 (HES group) or 5% albumin (ALB group) and additional blood components according to a defined protocol. We compared safety, efficacy and costs in 4 peri‐operative days. Colloid administration on the day of surgery was 38.4 mlkg−1 (HES group) and 35.1 mlkg−1 (ALB group). Haemodynamic, coagulation and renal function parameters were similar. Although total serum protein was still different on the third postoperative day (53.45 gl−1 (HES group) and 60.6 gl−1 (ALB group) (p < 0.01)) the colloid osmotic pressure always remained above 19.5 (2.5) mmHg (HES group). Blood loss (3810 (1632) ml (HES group) and 3455 (1733) ml (ALB group)) and the requirement for blood components was comparable. Costs were reduced by 35% (p < 0.05) in the HES group. We conclude that using 6% HES 200/0.5 as the only colloid for treatment even of large blood loss is a safe and economic alternative to albumin.