ICU- and ventilator-free days with isoflurane or propofol as a primary sedative - A post- hoc analysis of a randomized controlled trial.

PURPOSE: To compare ICU-free (ICU-FD) and ventilator-free days (VFD) in the 30 days after randomization in patients that received isoflurane or propofol without receiving the other sedative. MATERIALS AND METHODS: A recent randomized controlled trial (RCT) compared inhaled isoflurane via the Sedaconda® anaesthetic conserving device (ACD) with intravenous propofol for up to 54 h (Meiser et al. 2021). After end of study treatment, continued sedation was locally determined. Patients were eligible for this post-hoc analysis only if they had available 30-day follow-up data and never converted to the other drug in the 30 days from randomization. Data on ventilator use, ICU stay, concomitant sedative use, renal replacement therapy (RRT) and mortality were collected. RESULTS: Sixty-nine of 150 patients randomized to isoflurane and 109 of 151 patients randomized to propofol were eligible. After adjusting for potential confounders, the isoflurane group had more ICU-FD than the propofol group (17.3 vs 13.8 days, p = 0.028). VFD for the isoflurane and propofol groups were 19.8 and 18.5 respectively (p = 0.454). Other sedatives were used more frequently (p < 0.0001) and RRT started in a greater proportion of patients in the propofol group (p = 0.011). CONCLUSIONS: Isoflurane via the ACD was not associated with more VFD but with more ICU-FD and less concomitant sedative use.

Isoflurane vs. propofol for sedation in invasively ventilated patients with acute hypoxemic respiratory failure: an a priori hypothesis substudy of a randomized controlled trial.

BACKGROUND: Acute hypoxemic respiratory failure (AHRF) is a leading concern in critically ill patients. Experimental and clinical data suggest that early sedation with volatile anesthestics may improve arterial oxygenation and reduce the plasma and alveolar levels of markers of alveolar epithelial injury and of proinflammatory cytokines. METHODS: An a priori hypothesis substudy of a multicenter randomized controlled trial (The Sedaconda trial, EUDRA CT Number 2016-004551-67). In the Sedaconda trial, 301 patients on invasive mechanical ventilation were randomized to 48 h of sedation with isoflurane or propofol in a 1:1 ratio. For the present substudy, patients with a ratio of arterial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2), PaO2/FiO2, of ≤ 300 mmHg at baseline were included (n = 162). The primary endpoint was the change in PaO2/FiO2 between baseline and the end of study sedation. A subgroup analysis in patients with PaO2/FiO2 ≤ 200 mmHg was performed (n = 82). RESULTS: Between baseline and the end of study sedation (48 h), oxygenation improved to a similar extent in the isoflurane vs. the propofol group (isoflurane: 199 ± 58 to 219 ± 76 mmHg (n = 70), propofol: 202 ± 62 to 236 ± 77 mmHg (n = 89); p = 0.185). On day seven after randomization, PaO2/FiO2 was 210 ± 79 mmHg in the isoflurane group (n = 41) and 185 ± 87 mmHg in the propofol group (n = 44; p = 0.411). In the subgroup of patients with PaO2/FiO2 ≤ 200 mmHg, PaO2/FiO2 increase between baseline and end of study sedation was 152 ± 33 to 186 ± 54 mmHg for isoflurane (n = 37), and 150 ± 38 to 214 ± 85 mmHg for propofol (n = 45; p = 0.029). On day seven, PaO2/FiO2 was 198 ± 69 mmHg in patients randomized to isoflurane (n = 20) and 174 ± 106 mmHg in patients randomized to propofol (n = 20; p = 0.933). Both for the whole study population and for the subgroup with PaO2/FiO2 ≤ 200 mmHg, no significant between-group differences were observed for PaCO2, pH and tidal volume as well as 30-day mortality and ventilator-free days alive. CONCLUSIONS: In patients with AHRF, inhaled sedation with isoflurane for a duration of up to 48 h did not lead to improved oxygenation in comparison to intravenous sedation with propofol. Trial registration The main study was registered in the European Medicines Agency's EU Clinical Trial register (EudraCT), 2016-004551-67, before including the first patient. The present substudy was registered at German Clinical Trials Register (DRKS, ID: DRKS00018959) on January 7th, 2020, before opening the main study data base and obtaining access to study results.

SARS-CoV-2 Infects Red Blood Cell Progenitors and Dysregulates Hemoglobin and Iron Metabolism.

BACKGROUND: SARS-CoV-2 infection causes acute respiratory distress, which may progress to multiorgan failure and death. Severe COVID-19 disease is accompanied by reduced erythrocyte turnover, low hemoglobin levels along with increased total bilirubin and ferritin serum concentrations. Moreover, expansion of erythroid progenitors in peripheral blood together with hypoxia, anemia, and coagulopathies highly correlates with severity and mortality. We demonstrate that SARS-CoV-2 directly infects erythroid precursor cells, impairs hemoglobin homeostasis and aggravates COVID-19 disease. METHODS: Erythroid precursor cells derived from peripheral CD34+ blood stem cells of healthy donors were infected in vitro with SARS-CoV-2 alpha variant and differentiated into red blood cells (RBCs). Hemoglobin and iron metabolism in hospitalized COVID-19 patients and controls were analyzed in plasma-depleted whole blood samples. Raman trapping spectroscopy rapidly identified diseased cells. RESULTS: RBC precursors express ACE2 receptor and CD147 at day 5 of differentiation, which makes them susceptible to SARS-CoV-2 infection. qPCR analysis of differentiated RBCs revealed increased HAMP mRNA expression levels, encoding for hepcidin, which inhibits iron uptake. COVID-19 patients showed impaired hemoglobin biosynthesis, enhanced formation of zinc-protoporphyrine IX, heme-CO2, and CO-hemoglobin as well as degradation of Fe-heme. Moreover, significant iron dysmetablolism with high serum ferritin and low serum iron and transferrin levels occurred, explaining disturbances of oxygen-binding capacity in severely ill COVID-19 patients. CONCLUSIONS: Our data identify RBC precursors as a direct target of SARS-CoV-2 and suggest that SARS-CoV-2 induced dysregulation in hemoglobin- and iron-metabolism contributes to the severe systemic course of COVID-19. This opens the door for new diagnostic and therapeutic strategies.

Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial.

BACKGROUND: Previous studies indicate that isoflurane could be useful for the sedation of patients in the intensive care unit (ICU), but prospective studies evaluating isoflurane's efficacy have been small. The aim of this study was to test whether the sedation with isoflurane was non-inferior to sedation with propofol. METHODS: This phase 3, randomised, controlled, open-label non-inferiority trial evaluated the efficacy and safety of up to 54 h of isoflurane compared with propofol in adults (aged ≥18 years) who were invasively ventilated in ICUs in Germany (21 sites) and Slovenia (three sites). Patients were randomly assigned (1:1) to isoflurane inhalation via the Sedaconda anaesthetic conserving device (ACD; Sedana Medical AB, Danderyd, Sweden; ACD-L [dead space 100 mL] or ACD-S [dead space 50 mL]) or intravenous propofol infusion (20 mg/mL) for 48 h (range 42-54) using permuted block randomisation with a centralised electronic randomisation system. The primary endpoint was percentage of time in Richmond Agitation-Sedation Scale (RASS) range -1 to -4, assessed in eligible participants with at least 12 h sedation (the per-protocol population), five or more RASS measurements, and no major protocol violations, with a non-inferiority margin of 15%. Key secondary endpoints were opioid requirements, spontaneous breathing, time to wake-up and extubation, and adverse events. Safety was assessed in all patients who received at least one dose. The trial is complete and registered with EudraCT, 2016-004551-67. FINDINGS: Between July 2, 2017, and Jan 12, 2020, 338 patients were enrolled and 301 (89%) were randomly assigned to isoflurane (n=150) or propofol (n=151). 146 patients (97%) in each group completed the 24-h follow-up. 146 (97%) patients in the isoflurane group and 148 (98%) of patients in the propofol group were included in the per-protocol analysis of the primary endpoint. Least-squares mean percentage of time in RASS target range was 90·7% (95% CI 86·8-94·6) for isoflurane and 91·1% (87·2-95·1) for propofol. With isoflurane sedation, opioid dose intensity was 29% lower than with propofol for the overall sedation period (0·22 [0·12-0·34] vs 0·32 [0·21-0·42] mg/kg per h morphine equivalent dose, p=0·0036) and spontaneous breathing was more frequent on day 1 (odds ratio [OR] 1·72 [1·12-2·64], generalised mixed linear model p=0·013, with estimated rates of 50% of observations with isoflurane vs 37% with propofol). Extubation times were short and median wake-up was significantly faster after isoflurane on day 2 (20 min [IQR 10-30] vs 30 min [11-120]; Cox regression p=0·0011). The most common adverse events by treatment group (isoflurane vs propofol) were: hypertension (ten [7%] of 150 vs two [1%] of 151), delirium (eight [5%] vs seven [5%]), oliguria (seven [5%] vs six [4%]), and atrial fibrillation (five [3%] vs four [3%]). INTERPRETATION: These results support the use of isoflurane in invasively ventilated patients who have a clinical need for sedation. FUNDING: Sedana Medical AB.

Treatment of spinal anaesthesia-induced hypotension with cafedrine/theodrenaline versus ephedrine during caesarean section: Results from HYPOTENS, a national, multicentre, prospective, noninterventional study.

BACKGROUND: In Germany, hypotension induced by spinal anaesthesia is commonly treated with a combination of cafedrine hydrochloride (C, 200 mg) and theodrenaline hydrochloride (T, 10 mg) in 2 ml. We compared the effectiveness of C/T with ephedrine. OBJECTIVES: The primary objectives were to assess the speed of onset and the ability to restore blood pressure without an increase in heart rate. Secondary objectives were to evaluate maternal/foetal outcomes and the number of required additional boluses or other additional measures. DESIGN: HYPOTENS was a national, multicentre, prospective, open-label, two-armed, noninterventional study comparing C/T with ephedrine in two prospectively defined cohorts. This study relates to the cohort of patients receiving spinal anaesthesia for caesarean section. SETTING: German hospitals using either C/T or ephedrine in their routine clinical practice. PATIENTS: Women aged at least 18 years receiving spinal anaesthesia for caesarean section. INTERVENTIONS: Bolus administration of C/T or ephedrine at the discretion of the attending anaesthesiologist. MAIN OUTCOME MEASURES: Endpoints within 15 min after initial administration of C/T or ephedrine were area under the curve between the observed SBP and the minimum target SBP; and incidence of newly occurring heart rate of at least 100 beats min-1. RESULTS: Although effective blood pressure stabilisation was achieved with both treatments, this effect was faster and more pronounced with C/T (P < 0.0001). The incidence of tachycardia and changes in heart rate were higher with ephedrine (P < 0.01). Fewer additional boluses (P < 0.01) were required with C/T. Although favourable neonatal outcomes were reported in both groups, base deficit and lactate values were greater with ephedrine (P < 0.01). Physician satisfaction was higher with C/T. CONCLUSIONS: After C/T, tachycardia was not a problem, providing an advantage over ephedrine. Fewer additional boluses were required with C/T, suggesting greater effectiveness. An increased base deficit with ephedrine suggests reduced oxygen supply or increased demands in foetal circulation. TRIALS REGISTRATION: Clinicaltrials.gov: NCT02893241, German Clinical Trials Register: DRKS00010740.

Amisulpride Prevents Postoperative Nausea and Vomiting in Patients at High Risk: A Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Postoperative nausea and vomiting causes distress for patients and can prolong care requirements. Consensus guidelines recommend use of multiple antiemetics from different mechanistic classes as prophylaxis in patients at high risk of postoperative nausea and vomiting. The prophylactic efficacy of the dopamine D2/D3 antagonist amisulpride in combination with other antiemetics was investigated. METHODS: This double-blind, randomized, placebo-controlled, international, multicenter trial was conducted in 1,147 adult surgical patients having three or four postoperative nausea and vomiting risk factors. Patients were randomized to receive either intravenous amisulpride (5 mg) or matching placebo at induction of general anesthesia, in addition to one standard, nondopaminergic antiemetic, most commonly ondansetron or dexamethasone. Vomiting/retching, nausea, and use of rescue medication were recorded for 24 h after wound closure. The primary endpoint was complete response, defined as no emesis or rescue medication use in the 24-h postoperative period. RESULTS: Complete response occurred in 330 of 572 (57.7%) of the amisulpride group and 268 of 575 (46.6%) of the control group (difference 11.1 percentage points; 95% CI, 5.3 to 16.8; P < 0.001). The incidences of emesis (13.8% vs. 20.0%, P = 0.003), any nausea (50.0% vs. 58.3%, P = 0.002), significant nausea (37.1% vs. 47.7%, P < 0.001), and rescue medication use (40.9% vs. 49.4%, P = 0.002) were significantly lower in the amisulpride group. Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently with amisulpride than with placebo. CONCLUSIONS: Intravenous amisulpride was safe and effective as prophylaxis of postoperative nausea and vomiting when given in combination with an antiemetic from another class to adult patients at high risk for suffering postoperative nausea and vomiting undergoing elective surgery under inhalational general anesthesia. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B727.

Geburtshilfe: kombinierte Spinal-Epidural-Analgesie (CSE).

Due to intrathecal application, CSE combines rapid response with adequate analgesia with the possibility of providing unlimited neuraxial obstetrical pain relief via the indwelling epidural catheter. The superiority of CSE over EDA lies above all in its rapid action, excellent analgesia, lack of motor blockade after a single intrathecal opioid administration, lower rate of unilateral blockages and less need for subsequent epidural injections. The most common side effect is pruritus, which is harmless and usually does not require any therapeutic intervention. Even if no effect on rate of C-sections and APGAR values have been observed, the increased rate of fetal bradycardia after CSE must be kept in mind. A reduction of these fetal bradycardias and after intrathecal administration, prolongation of analgesia by means of appropriate drug combinations or additives should be the subject of future research.

Propofol versus flunitrazepam for inducing and maintaining sleep in postoperative ICU patients.

CONTEXT: Sleep deprivation is a common problem on intensive care units (ICUs) influencing not only cognition, but also cellular functions. An appropriate sleep-wake cycle should therefore be maintained to improve patients' outcome. Multiple disruptive factors on ICUs necessitate the administration of sedating and sleep-promoting drugs for patients who are not analgo-sedated. AIMS: The objective of the present study was to evaluate sleep quantity and sleep quality in ICU patients receiving either propofol or flunitrazepam. SETTINGS AND DESIGN: Monocentric, randomized, double-blinded trial. MATERIALS AND METHODS: A total of 66 ICU patients were enrolled in the study (flunitrazepam n = 32, propofol n = 34). Propofol was injected continuously (2 mg/kg/h), flunitrazepam as a bolus dose (0.015 mg/kg). Differences between groups were evaluated using a standardized sleep diary and the bispectral index (BIS). STATISTICAL ANALYSIS USED: Group comparisons were performed by Mann-Whitney U-Test. P < 0.05 was considered to be statistically significant. RESULTS: Sleep quality and the frequency of awakenings were significantly better in the propofol group (Pg). In the same group lower BIS values were recorded (median BIS propofol 74.05, flunitrazepam 78.7 [P = 0.016]). BIS values had to be classified predominantly to slow-wave sleep under propofol and light sleep after administration of flunitrazepam. Sleep quality improved in the Pg with decreasing frequency of awakenings and in the flunitrazepam group with increasing sleep duration. CONCLUSIONS: Continuous low-dose injection of propofol for promoting and maintaining night sleep in ICU patients who are not analgo-sedated was superior to flunitrazepam regarding sleep quality and sleep structure.

Intravenous buspirone for the prevention of postoperative nausea and vomiting.

RATIONALE: Buspirone, a partial 5HT(1A) agonist and D2 and D3 antagonist, has shown promising antiemetic efficacy when given parenterally in animal models, but its efficacy for the prevention of postoperative nausea and vomiting (PONV) is unknown. OBJECTIVE: To study the efficacy and dose-responsiveness of intravenous buspirone for the prevention of PONV. METHODS: A randomised, double-blind, placebo-controlled study was performed in adults at moderate to high PONV risk undergoing surgery with a general anaesthetic. Patients were randomised to receive an intravenous dose of buspirone (0.3, 1.0, 2.0, 3.0 mg) or placebo at the end of surgery. The primary endpoint was the cumulative 24-h PONV incidence (i.e. any nausea and/or vomiting). Vomiting included retching. Nausea was defined as a score of ≥ 4 on an 11-point verbal rating scale running from zero (no nausea) to ten (the worst nausea imaginable). RESULTS: A total of 257 patients received the study drug and fulfilled the criteria for inclusion in the primary efficacy and safety analyses. With placebo, the mean 24-h PONV incidence was 49.0 % (90 % confidence interval [CI] 37.5-60.5 %). With buspirone, that incidence ranged from a mean of 40.8 % (29.3-52.4 %) in the 1 mg arm to 58.0 % (46.5-69.5 %) in the 0.3 mg arm (P > 0.05 for all comparisons). There was no difference between placebo and buspirone at any dose for any other efficacy endpoint, nor in the number or severity of adverse events or any other safety measures. CONCLUSION: We were unable to show that intravenous single-dose buspirone, at the tested dose-range, was effective at preventing PONV in surgical adult patients. The present study emphasises the difficulty in extrapolating from animal models of emesis to clinical efficacy in PONV.

[Postoperative nausea and vomiting (PONV) - recommendations for risk assessment, prophylaxis and therapy - results of an expert panel meeting]. / Übelkeit und Erbrechen nach Operationen in Allgemeinanästhesie - Empfehlungen zur Risikoeinschätzung, Prophylaxe und Therapie.

BACKGROUND: The aim was to update recommendations concerning the management of postoperative nausea and vomiting (PONV) for German speaking countries. METHODS: An expert panel produced evidence-based, consented statements graded according to the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: Relevant risk factors for PONV include female gender, non-smoking status, history of PONV, history of motion sickness, use of intra- and postoperative opioids, volatile anesthetics and nitrous oxide. PONV scoring systems allow for an approximative risk assessment as a basis for a risk adapted approach. Since a risk-adapted prophylaxis vs. a risk-independent, fixed (combined) prophylaxis has not yet proven superior and because of inherent limitations of PONV scoring systems a fixed prophylaxis may be favourable. Regardless of the strategy for prophylaxis of PONV, high risk patients must be given a multimodal prophylaxis by avoiding known risk factors and applying multiple validated and effective antiemetic interventions. In the case of PONV immediate treatment is indicated due to its relevance for patients as well as the economic and medicolegal implications PONV may have. CONCLUSIONS: Given the impact of PONV on patient satisfaction and the availability of effective and safe measures to prevent and treat PONV, further efforts should be taken to actually implement present evidence in order to improve patient?s outcome following surgical procedures.

Nausea and vomiting after surgery under general anesthesia: an evidence-based review concerning risk assessment, prevention, and treatment.

BACKGROUND: The German-language recommendations for the management of postoperative nausea and vomiting (PONV) have been revised by an expert committee. Major aspects of this revision are presented here in the form of an evidence-based review article. METHODS: The literature was systematically reviewed with the goal of revising the existing recommendations. New evidence-based recommendations for the management of PONV were developed, approved by consensus, and graded according to the scheme of the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: The relevant risk factors for PONV include female sex, nonsmoker status, prior history of PONV, motion sickness, use of opioids during and after surgery, use of inhalational anesthetics and nitrous oxide, and the duration of anesthesia. PONV scoring systems provide a rough assessment of risk that can serve as the basis for a risk-adapted approach. Risk-adapted prophylaxis, however, has not been shown to provide any greater benefit than fixed (combination) prophylaxis, and PONV risk scores have inherent limitations; thus, fixed prophylaxis may be advantageous. Whichever of these two approaches to manage PONV is chosen, high-risk patients must be given multimodal prophylaxis, involving both the avoidance of known risk factors and the application of multiple validated and effective antiemetic interventions. PONV should be treated as soon as it arises, to minimize patient discomfort, the risk of medical complications, and the costs involved. CONCLUSION: PONV lowers patient satisfaction but is treatable. The effective, evidence-based measures of preventing and treating it should be implemented in routine practice.

Do variations in the 5-HT3A and 5-HT3B serotonin receptor genes (HTR3A and HTR3B) influence the occurrence of postoperative vomiting?

BACKGROUND: Postoperative nausea and vomiting are unpleasant side effects of general anesthesia. Besides known risk factors (female gender, nonsmoker, history, and opioids), a genetic influence of the serotonin receptor system on the development of nausea and vomiting has repeatedly been proposed. In this pilot study, we therefore investigated the genes of the serotonin receptor subunits A and B (HTR3A and HTR3B) for genetic variants. METHODS: We included 95 patients who had suffered from postoperative vomiting (POV) after general anesthesia and 94 control patients. After DNA isolation, the entire HTR3A and HTR3B coding regions, the 5' flanking regions, and exon/intron boundaries were screened for genetic variants. Correlation of identified genetic variants with POV was determined by logistic regression. RESULTS: We identified 16 different variants in the HTR3A gene and 19 in the HTR3B gene. By using a multivariate logistic regression model that also included classical risk factors, the HTR3A variant c1377A>G was associated with a significantly higher risk (odds ratio [OR] 2.972; 95% confidence interval [CI] 1.466-6.021; P = 0.003) and the HTR3B variants c5+201_+202delCA (OR 0.421; 95% CI 0.257-0.69; P = 0.001) and c6-137C>T (OR 0.034; 95% CI 0.003-0.332; P = 0.004) were associated with a lower risk for POV. However, all significant genetic variants were located in noncoding regions of their gene. CONCLUSIONS: Genetic variations in the HTR3A and HTR3B gene seem to be associated with the individual risk of developing POV. How strong their influence is within the multifactorial genesis of POV needs to be investigated in additional studies with an appropriate sample size.

[Postoperative nausea and vomiting--what's new in anti-emetic pharmacotherapy?]. / Alles beim Alten in der Pharmakotherapie von PONV?

Neurokinin-1 receptor antagonists represent a new approach in the prevention of postoperative nausea and vomiting (PONV) and show an efficacy comparable with those of common antiemetics with some evidence for superiority with regard to vomiting. Currently, only aprepitant is available as an oral preparation. Palonosetron is a new representative of the serotonin-3 receptor antagonists but without the hoped for superiority on the 2nd and 3rd postoperative days. However, available data do suggest that palanosetron does not prolong the OT (c) interval. When using 5-HT (3)-receptor antagonists for the prevention of PONV, anaesthetists should be aware of negative interactions with analgesics. Low-dose droperidol has regained approval and should be considered as first choice among the current available neuroleptics.

Effects of clonidine and superficial cervical plexus block on hemodynamic stability after carotid endarterectomy.

OBJECTIVES: To evaluate the effects of 2 interventions (intravenous clonidine and superficial cervical block) on hemodynamic stability after carotid endarterectomy and to identify variables associated with hemodynamic instability. DESIGN: Prospective, observational study, sequential enrollment. SETTING: University hospital. PARTICIPANTS: Two hundred seventy-five patients undergoing elective carotid endarterectomy under general anesthesia. INTERVENTIONS: Group NN (n = 50) received no intervention. In group CN (n = 85), 3 mug/kg of clonidine were administered intravenously 30 minutes before the end of the operation. Group CB (n = 140) additionally received a superficial cervical plexus block (SCB) with 20 mL of naropine 0.5% before the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Clonidine alone (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.45-3.76) and clonidine combined with an SCB (OR, 4.99; 95% CI, 3.19-7.82) resulted in a significant increase in hemodynamic stability after CEA (p < 0.001) from 53.3% (NN) to 70.0% (CN) and 83.3% (CB), respectively. The need for rescue medication decreased from 40.0% to 17.6% and 13.6% (p < 0.001). Both interventions significantly reduced the need for postoperative opioid analgesics (p < 0.01). Logistic regression analysis showed preoperative systolic blood pressure values greater than 170 mmHg (OR, 3.23; 95% CI, 1.76-5.93), previous cardiac interventions (OR, 3.3; 95% CI, 1.54-7.11), and the need for rescue medication in the awakening period (OR, 5.8; 95% CI, 2.88-11.52) to be independent risk factors for postoperative hemodynamic instability (p < or = 0.002). CONCLUSIONS: Intravenous clonidine and superficial cervical block significantly improve cardiovascular stability after carotid endarterectomy. Patients with pre-existing excessive hypertension and previous coronary interventions must be considered a high-risk group.

The impact of isoflurane, desflurane, or sevoflurane on the frequency and severity of postoperative nausea and vomiting after lumbar disc surgery.

STUDY OBJECTIVE: To test the hypothesis that anesthesia with the low-soluble inhalation anesthetics, sevoflurane, and desflurane, may result in a lower frequency and severity of postoperative nausea and vomiting (PONV) than anesthesia with isoflurane. DESIGN: Prospective, observational study. SETTING: Postoperative care unit and neurosurgical ward at a university hospital. PATIENTS: 625 ASA physical status I, II, and III patients undergoing elective lumbar disc surgery with general anesthesia were included in this study. INTERVENTIONS: Patients were enrolled sequentially to receive either 0.7%-1.2% isoflurane (year 2002), 3.5%-5.5% desflurane (year 2003), or 1.2%-1.9% sevoflurane (year 2004) for maintenance of anesthesia without nitrous oxide. Study personnel, general anesthesia management, and surgical technique remained unchanged over the three-year study period. MEASUREMENTS: Occurrence of PONV within 24 hours of the end of surgery was recorded. Secondary outcome measures were occurrence of multiple PONV episodes, maximum severity, time to the first PONV event, need for rescue medication, difference between the occurrence of PONV (indicator variable) and the expected risk of PONV (based on the Apfel score). MAIN RESULTS: Type of inhalation anesthetic had no influence on PONV frequency (9.3%, 11.2%, and 10.8% after isoflurane, desflurane, and sevoflurane, respectively; P = 0.8) or its severity (numerical rating scale, 4.5 +/- 2.0, 4.4 +/- 2.4, and 4.2 +/- 2.1; P = 0.9). Patients who received isoflurane experienced fewer early events but had a late peak of PONV frequency (P = 0.031). For every 10 minutes by which the total duration of the anesthesia exceeded the net time between incision and suture, the risk of PONV increased by a factor of 1.36 (95% confidence interval, 1.15-1.61; P < 0.001). CONCLUSIONS: There is no difference between the three inhalation anesthetics currently used with regard to frequency or severity of postoperative nausea, vomiting, or both.

Comparative evaluation of Bispectral Index and Narcotrend Index in children below 5 years of age.

BACKGROUND: The use of electroencephalogram (EEG) monitoring devices for assessing the depth of hypnosis is most difficult in children under 5 years of age. METHODS: Forty five children aged 0-60 months were included in a prospective observational study. A direct comparison of the processed EEG variables Bispectral Index (BIS, version 3.4) and Narcotrend Index (NI, version 2.0AF) was to be achieved by simultaneous recording. The ability of these parameters to differentiate between various clinical states was evaluated by using the prediction probability (P(k)). Age-related effects on the BIS and NI were analyzed by dividing the children into three age groups: 0-6, 7-18 and 19-60 months. RESULTS: The preanesthesia, conscious children were differentiated from anesthetized patients by the BIS and NI with no overlap (P(k) = 1.0). In the awake period the BIS was superior to the NI (P(k) to differentiate 'end of anesthesia' from 'awakening' was 0.97 vs 0.73 respectively; P = 0.002). Patients aged 7-18 months showed higher BIS and NI values in the course of anesthesia than the younger and older children (P = 0.001). On awakening, children aged 0-6 months showed the lowest mean BIS (n.s.) and NI (P = 0.006) values. CONCLUSIONS: The BIS currently seems to be superior to the NI, but age-related processing algorithms of the raw EEG must be implemented in both BIS and NI in order to be useful in children younger than 5 years of age.