Dose-dependent relationship between intra-procedural hypoxaemia or hypocapnia and postoperative delirium in older patients.

BACKGROUND: Previous studies indicated an association between impaired cerebral perfusion and post-procedural neurological disorders. We investigated whether intra-procedural hypoxaemia or hypocapnia are associated with delirium after surgery. METHODS: Inpatients ≥60 yr of age undergoing anaesthesia for surgical or interventional procedures between 2009 and 2020 at an academic healthcare network in the USA (Massachusetts) were included in this hospital registry study. The primary exposure was intra-procedural hypoxaemia, defined as peripheral oxygen saturation <90% for >2 cohering min. The co-primary exposure was hypocapnia during general anaesthesia, defined as end-tidal carbon dioxide pressure ≤25 mm Hg for >5 cohering min. The primary outcome was delirium within 7 days after surgery. RESULTS: Of 71 717 included patients, 1702 (2.4%) developed postoperative delirium, and hypoxaemia was detected in 2532 (3.5%). Of 42 894 patients undergoing general anaesthesia, 532 (1.2%) experienced hypocapnia. The occurrence of either hypoxaemia (adjusted odds ratio [ORadj]=1.71; 95% confidence interval [CI], 1.40-2.07; P<0.001) or hypocapnia (ORadj=1.77; 95% CI, 1.30-2.41; P<0.001) was associated with a higher risk of delirium within 7 days. Both associations were dependent on the magnitude, and increased with event duration (ORadj=1.03; 95% CI, 1.02-1.04; P<0.001 and ORadj=1.01; 95% CI, 1.00-1.01; P=0.005, for each minute increase in the longest continuous episode, respectively). There was no association between occurrence of hypercapnia and postoperative delirium (ORadj=1.24; 95% CI, 0.90-1.71; P=0.181). CONCLUSIONS: Intra-procedural hypoxaemia and hypocapnia were dose-dependently associated with a higher risk of postoperative delirium. These findings support maintaining normal gas exchange to avoid postoperative neurological disorders.

Cycling under the influence of alcohol-criminal offenses in a German metropolis.

INTRODUCTION: Real or simulated cycling tests under the influence of alcohol might be biased by laboratory settings. Accident analyses consider incidents with injuries only. Herein, criminal offenses consisting of drunk cycling are evaluated in detail to fill this gap. MATERIAL AND METHODS: All police-recorded cases of cycling under the influence of alcohol that took place in Düsseldorf, Germany, from 2009 to 2018 were identified. A total of 388 respective prosecutor's files were available for analyses. RESULTS: Mean blood alcohol concentrations were approximately 2 g/kg in both men and women. Men were overrepresented (6:1). Almost 60% of the cases were recorded between Friday and Sunday (the "weekend"). The average blood alcohol concentration (BAC) at night (01:00-05:59) was 0.39 g/kg lower than that during the day (06:00-17:59). Drinking after cycling allegations appear almost irrelevant among (German) cyclists. On average, the legal outcomes show 33 daily rates (median: 30). Additionally, the presented data raise doubts about whether the utilized medical tests or the ways in which they are carried out reliably discriminate between different grades of intoxication. Negative tests did not exclude high BACs, nor did positive tests correlate well with BACs. DISCUSSION/CONCLUSION: In practice, CUI is seen with BACs above 1.60 g/kg in most cases. BACs below 1.60 g/kg either seem to be a minor problem or they have been incompletely addressed thus far. In summary, to be prosecuted, drunk cyclists have to ride their bikes in either a highly insecure or rude manner or they must cause an accident.

[Update on PONV-What is new in prophylaxis and treatment of postoperative nausea and vomiting? : Summary of recent consensus recommendations and Cochrane reviews on prophylaxis and treatment of postoperative nausea and vomiting]. / Update PONV ­ Was gibt es Neues bei der Prophylaxe und Therapie von postoperativer Übelkeit und postoperativem Erbrechen? : Zusammenfassung rezenter Konsensusempfehlungen sowie Cochrane-Reviews zu Prophylaxe und Therapie postoperativer Übelkeit und postoperativen Erbrechens.

The prophylaxis and treatment of postoperative pain to enhance patient comfort has been a primary goal of anesthesiologists for the last decades; however, avoiding postoperative nausea and vomiting (PONV) is, from a patient's perspective, a highly relevant and equally important goal of anesthesia. Recent consensus-based guidelines suggest the assessment of risk factors including female gender, postoperative opioid administration, non-smoking status, a history of PONV or motion sickness, young patient age, longer duration of anesthesia, volatile anesthetics and the type of surgery and reducing the patient's baseline risk (e.g. through the use of regional anesthesia and administration of non-opioid analgesics as part of a multimodal approach). In general, a liberal PONV prophylaxis is encouraged for adult patients and children, which should also be administered when no risk assessment is made. The basis for every adult patient should be a standard prophylaxis with two antiemetics, such as dexamethasone in combination with a 5-HT3 receptor antagonist. In patients at high risk, this should be supplemented by a third and potentially a fourth antiemetic prophylaxis with a different mechanism of action. A recently published comprehensive Cochrane meta-analysis comparing available antiemetic prophylaxes reported the highest effectiveness to prevent PONV for the NK1 receptor antagonist aprepitant (relative risk, RR 0.26), followed by ramosetron (RR 0.44), granisetron (RR 0.45), dexamethasone (RR 0.51) and ondansetron (RR 0.55), thereby revising the dogma that every antiemetic is equally effective. Adverse events of antiemetics were generally rare and reported in less than half of the included studies, yielding a low quality of evidence for these end points. In general, combinations of different antiemetics were more effective than single prophylaxes. In children above 3 years of age, the same principles should be applied as in adults. For these patients, there is a high degree of evidence for the combination of dexamethasone and 5­HT3 receptor antagonists. When PONV occurs, the consensus guidelines suggest that antiemetics from a class different than given as prophylaxis should be administered. To decrease the incidence of PONV and increase the quality of care, the importance of the implementation of institutional-level guidelines and protocols as well as assessment of PONV prophylaxis and PONV incidence is highly recommended.

Sublingual microcirculation predicts survival after out-of-hospital cardiac arrest.

BACKGROUND: Despite successful resuscitation with return of spontaneous circulation (ROSC), the prediction of survival in patients suffering out-of-hospital cardiac arrest (OHCA) remains difficult. Several studies have shown alterations in sublingual microcirculation in the critical ill. We hypothesized that early alterations in sublingual microcirculation may predict short-term survival after OHCA. METHODS: We prospectively included all adults admitted to our university hospital between April and September 2019 with ROSC following OHCA. Sidestream dark-field microscopy to obtain sublingual microcirculation was performed at admission and after 6, 12 and 24 hours. Primary outcome was survival until discharge. RESULTS: Twenty-five patients were included. Six hours after ROSC, the proportion of perfused small vessels (PPVsmall ) was lower in non-survivors than in survivors (85 ± 7.9 vs. 75 ± 6.6%; p = .01). PPVsmall did not correlate with serum lactate. Stratification for survival with cutoff values >78.4% for PPVsmall 6 h post-admission and <5.15 mmol/l for initial serum lactate as suggested by ROC-Analyses results in a positive predictive value of 100% and a negative one of 67% for our study population. CONCLUSION: Estimating short-term prognosis of OHCA patients with ROSC may be supported by measuring the PPVsmall at the sublingual microcirculation 6 hours after admission.

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.

Succinylcholine and postoperative pulmonary complications: a retrospective cohort study using registry data from two hospital networks.

BACKGROUND: Neuromuscular blocking agents (NMBAs) with a non-depolarising mechanism of action carry the risk of postoperative residual paralysis and are associated with postoperative pulmonary complications (POPC). Owing to the shorter duration of action, the depolarising NMBA succinylcholine may be associated with less postoperative residual paralysis, and hence fewer POPC. We tested the association of succinylcholine administration during anaesthesia and POPC. METHODS: In a retrospective cohort study of registry data from two large US academic medical centres, 244 850 adult noncardiac surgical patients undergoing general anaesthesia were included. The primary outcome was POPC, defined as post-extubation haemoglobin oxygen de-saturation to <90%, or re-intubation requiring intensive care unit admission within 7 days after surgery. The association between succinylcholine and POPC and its dose-dependency were tested in a hierarchical fashion using a multivariable logistic regression model. RESULTS: A total of 13 206 patients (5.4%) experienced POPC. Use of succinylcholine was associated with increased risk of POPC (adjusted odds ratio [ORAdj]=1.11; 95% confidence interval [CI], 1.06-1.16; P<0.001; adjusted risk=5.18%; 95% CI, 5.06-5.30 without and 5.69%; 95% CI, 5.53-5.85 with succinylcholine), with a dose-dependent relationship (ORAdj=1.08; 95% CI, 1.05-1.11 per mg kg-1; P<0.001). In patients receiving non-depolarising NMBAs, succinylcholine further increased the risk of POPC (ORAdj=1.08; 95% CI, 1.03-1.14; P=0.001). The association between succinylcholine and POPC was modified (P=0.03 for interaction) by the duration of surgery with higher odds of POPC in patients undergoing surgeries of <2 vs ≥2 h (ORAdj=1.24; 95% CI, 1.15-1.33 and 1.05; 95% CI, 1.00-1.10, respectively). CONCLUSIONS: In contrast to our prediction, succinylcholine administration was associated with an increased risk of POPC. This association was dose-dependent and magnified in surgeries of shorter duration.

Association between propofol dose and 1-year mortality in patients with or without a diagnosis of solid cancer.

BACKGROUND: Preclinical data suggest suppression of cancer proliferation by propofol, and retrospective studies suggest improved survival after cancer surgery with propofol-based anaesthesia. METHODS: To determine whether propofol dose administered for anaesthesia is associated with 1-yr mortality in patients with and without a diagnosis of solid cancer, we analysed adult patients undergoing monitored anaesthesia care or general anaesthesia at two academic medical centres in Boston, MA, USA. Logistic regression with interaction term analysis was applied with propofol dose (mg kg-1) as primary and diagnosis of solid cancer as co-primary exposure, and 1-yr mortality as the primary outcome. RESULTS: Of 280 081 patient cases, 10 744 (3.8%) died within 1 yr. Increasing propofol dose was associated with reduced odds of 1-yr mortality (adjusted odds ratio [aOR] 0.93 per 10 mg kg-1; 95% confidence interval [CI]: 0.89-0.98; absolute risk reduction fifth vs first quintile 0.5%; 95% CI: 0.2-0.7). This association was modified by a diagnosis of solid cancer (P<0.001 for interaction). Increasing propofol dose was associated with reduced odds of 1-yr mortality in patients without solid cancer (aOR: 0.78; 95% CI: 0.71-0.85), but not in patients with solid cancer (0.99; 0.94-1.04), a finding that was replicated when examining 5-yr mortality. CONCLUSIONS: Increasing propofol dose is associated with lower 1-yr mortality in patients without, but not in patients with, a diagnosis of solid cancer. We found evidence for competing effects, modifying the association between propofol dose and mortality.

Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: a network meta-analysis.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause of patient dissatisfaction and may lead to prolonged hospital stay and higher costs of care along with more severe complications. Many antiemetic drugs are available for prophylaxis. They have various mechanisms of action and side effects, but there is still uncertainty about which drugs are most effective with the fewest side effects. OBJECTIVES: • To compare the efficacy and safety of different prophylactic pharmacologic interventions (antiemetic drugs) against no treatment, against placebo, or against each other (as monotherapy or combination prophylaxis) for prevention of postoperative nausea and vomiting in adults undergoing any type of surgery under general anaesthesia • To generate a clinically useful ranking of antiemetic drugs (monotherapy and combination prophylaxis) based on efficacy and safety • To identify the best dose or dose range of antiemetic drugs in terms of efficacy and safety SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and reference lists of relevant systematic reviews. The first search was performed in November 2017 and was updated in April 2020. In the update of the search, 39 eligible studies were found that were not included in the analysis (listed as awaiting classification). SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing effectiveness or side effects of single antiemetic drugs in any dose or combination against each other or against an inactive control in adults undergoing any type of surgery under general anaesthesia. All antiemetic drugs belonged to one of the following substance classes: 5-HT3 receptor antagonists, D2 receptor antagonists, NK1 receptor antagonists, corticosteroids, antihistamines, and anticholinergics. No language restrictions were applied. Abstract publications were excluded. DATA COLLECTION AND ANALYSIS: A review team of 11 authors independently assessed trials for inclusion and risk of bias and subsequently extracted data. We performed pair-wise meta-analyses for drugs of direct interest (amisulpride, aprepitant, casopitant, dexamethasone, dimenhydrinate, dolasetron, droperidol, fosaprepitant, granisetron, haloperidol, meclizine, methylprednisolone, metoclopramide, ondansetron, palonosetron, perphenazine, promethazine, ramosetron, rolapitant, scopolamine, and tropisetron) compared to placebo (inactive control). We performed network meta-analyses (NMAs) to estimate the relative effects and ranking (with placebo as reference) of all available single drugs and combinations. Primary outcomes were vomiting within 24 hours postoperatively, serious adverse events (SAEs), and any adverse event (AE). Secondary outcomes were drug class-specific side effects (e.g. headache), mortality, early and late vomiting, nausea, and complete response. We performed subgroup network meta-analysis with dose of drugs as a moderator variable using dose ranges based on previous consensus recommendations. We assessed certainty of evidence of NMA treatment effects for all primary outcomes and drug class-specific side effects according to GRADE (CINeMA, Confidence in Network Meta-Analysis). We restricted GRADE assessment to single drugs of direct interest compared to placebo. MAIN RESULTS: We included 585 studies (97,516 randomized participants). Most of these studies were small (median sample size of 100); they were published between 1965 and 2017 and were primarily conducted in Asia (51%), Europe (25%), and North America (16%). Mean age of the overall population was 42 years. Most participants were women (83%), had American Society of Anesthesiologists (ASA) physical status I and II (70%), received perioperative opioids (88%), and underwent gynaecologic (32%) or gastrointestinal surgery (19%) under general anaesthesia using volatile anaesthetics (88%). In this review, 44 single drugs and 51 drug combinations were compared. Most studies investigated only single drugs (72%) and included an inactive control arm (66%). The three most investigated single drugs in this review were ondansetron (246 studies), dexamethasone (120 studies), and droperidol (97 studies). Almost all studies (89%) reported at least one efficacy outcome relevant for this review. However, only 56% reported at least one relevant safety outcome. Altogether, 157 studies (27%) were assessed as having overall low risk of bias, 101 studies (17%) overall high risk of bias, and 327 studies (56%) overall unclear risk of bias. Vomiting within 24 hours postoperatively Relative effects from NMA for vomiting within 24 hours (282 RCTs, 50,812 participants, 28 single drugs, and 36 drug combinations) suggest that 29 out of 36 drug combinations and 10 out of 28 single drugs showed a clinically important benefit (defined as the upper end of the 95% confidence interval (CI) below a risk ratio (RR) of 0.8) compared to placebo. Combinations of drugs were generally more effective than single drugs in preventing vomiting. However, single NK1 receptor antagonists showed treatment effects similar to most of the drug combinations. High-certainty evidence suggests that the following single drugs reduce vomiting (ordered by decreasing efficacy): aprepitant (RR 0.26, 95% CI 0.18 to 0.38, high certainty, rank 3/28 of single drugs); ramosetron (RR 0.44, 95% CI 0.32 to 0.59, high certainty, rank 5/28); granisetron (RR 0.45, 95% CI 0.38 to 0.54, high certainty, rank 6/28); dexamethasone (RR 0.51, 95% CI 0.44 to 0.57, high certainty, rank 8/28); and ondansetron (RR 0.55, 95% CI 0.51 to 0.60, high certainty, rank 13/28). Moderate-certainty evidence suggests that the following single drugs probably reduce vomiting: fosaprepitant (RR 0.06, 95% CI 0.02 to 0.21, moderate certainty, rank 1/28) and droperidol (RR 0.61, 95% CI 0.54 to 0.69, moderate certainty, rank 20/28). Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol showed clinically important benefit, but low doses showed no clinically important benefit. Aprepitant was used mainly at high doses, ramosetron at recommended doses, and fosaprepitant at doses of 150 mg (with no dose recommendation available). Frequency of SAEs Twenty-eight RCTs were included in the NMA for SAEs (10,766 participants, 13 single drugs, and eight drug combinations). The certainty of evidence for SAEs when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to low. Droperidol (RR 0.88, 95% CI 0.08 to 9.71, low certainty, rank 6/13) may reduce SAEs. We are uncertain about the effects of aprepitant (RR 1.39, 95% CI 0.26 to 7.36, very low certainty, rank 11/13), ramosetron (RR 0.89, 95% CI 0.05 to 15.74, very low certainty, rank 7/13), granisetron (RR 1.21, 95% CI 0.11 to 13.15, very low certainty, rank 10/13), dexamethasone (RR 1.16, 95% CI 0.28 to 4.85, very low certainty, rank 9/13), and ondansetron (RR 1.62, 95% CI 0.32 to 8.10, very low certainty, rank 12/13). No studies reporting SAEs were available for fosaprepitant. Frequency of any AE Sixty-one RCTs were included in the NMA for any AE (19,423 participants, 15 single drugs, and 11 drug combinations). The certainty of evidence for any AE when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to moderate. Granisetron (RR 0.92, 95% CI 0.80 to 1.05, moderate certainty, rank 7/15) probably has no or little effect on any AE. Dexamethasone (RR 0.77, 95% CI 0.55 to 1.08, low certainty, rank 2/15) and droperidol (RR 0.89, 95% CI 0.81 to 0.98, low certainty, rank 6/15) may reduce any AE. Ondansetron (RR 0.95, 95% CI 0.88 to 1.01, low certainty, rank 9/15) may have little or no effect on any AE. We are uncertain about the effects of aprepitant (RR 0.87, 95% CI 0.78 to 0.97, very low certainty, rank 3/15) and ramosetron (RR 1.00, 95% CI 0.65 to 1.54, very low certainty, rank 11/15) on any AE. No studies reporting any AE were available for fosaprepitant. Class-specific side effects For class-specific side effects (headache, constipation, wound infection, extrapyramidal symptoms, sedation, arrhythmia, and QT prolongation) of relevant substances, the certainty of evidence for the best and most reliable anti-vomiting drugs mostly ranged from very low to low. Exceptions were that ondansetron probably increases headache (RR 1.16, 95% CI 1.06 to 1.28, moderate certainty, rank 18/23) and probably reduces sedation (RR 0.87, 95% CI 0.79 to 0.96, moderate certainty, rank 5/24) compared to placebo. The latter effect is limited to recommended and high doses of ondansetron. Droperidol probably reduces headache (RR 0.76, 95% CI 0.67 to 0.86, moderate certainty, rank 5/23) compared to placebo. We have high-certainty evidence that dexamethasone (RR 1.00, 95% CI 0.91 to 1.09, high certainty, rank 16/24) has no effect on sedation compared to placebo. No studies assessed substance class-specific side effects for fosaprepitant. Direction and magnitude of network effect estimates together with level of evidence certainty are graphically summarized for all pre-defined GRADE-relevant outcomes and all drugs of direct interest compared to placebo in http://doi.org/10.5281/zenodo.4066353. AUTHORS' CONCLUSIONS: We found high-certainty evidence that five single drugs (aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron) reduce vomiting, and moderate-certainty evidence that two other single drugs (fosaprepitant and droperidol) probably reducevomiting, compared to placebo. Four of the six substance classes (5-HT3 receptor antagonists, D2 receptor antagonists, NK1 receptor antagonists, and corticosteroids) were thus represented by at least one drug with important benefit for prevention of vomiting. Combinations of drugs were generally more effective than the corresponding single drugs in preventing vomiting. NK1 receptor antagonists were the most effective drug class and had comparable efficacy to most of the drug combinations. 5-HT3 receptor antagonists were the best studied substance class. For most of the single drugs of direct interest, we found only very low to low certainty evidence for safety outcomes such as occurrence of SAEs, any AE, and substance class-specific side effects. Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol were more effective than low doses for prevention of vomiting. Dose dependency of side effects was rarely found due to the limited number of studies, except for the less sedating effect of recommended and high doses of ondansetron. The results of the review are transferable mainly to patients at higher risk of nausea and vomiting (i.e. healthy women undergoing inhalational anaesthesia and receiving perioperative opioids). Overall study quality was limited, but certainty assessments of effect estimates consider this limitation. No further efficacy studies are needed as there is evidence of moderate to high certainty for seven single drugs with relevant benefit for prevention of vomiting. However, additional studies are needed to investigate potential side effects of these drugs and to examine higher-risk patient populations (e.g. individuals with diabetes and heart disease).

The Effect of Xenon-Based Anesthesia on Somatosensory-Evoked Potentials in Patients Undergoing Carotid Endarterectomy.

OBJECTIVES: The aim of this study was to investigate the influence of xenon-based anesthesia on somatosensory-evoked potentials. DESIGN: Observational cohort study. SETTING: University hospital. PARTICIPANTS: Twenty subsequent adult patients undergoing elective carotid endarterectomy. INTERVENTIONS: Xenon-based anesthesia. MEASUREMENTS AND MAIN RESULTS: Cortical-evoked responses to median nerve stimulation were quantified by measurement of the amplitude and latency of the N20 wave, which are typically assessed during carotid surgery to detect intraoperative cerebral hypoperfusion and ischemia. Primary (N20 amplitude and latency) and secondary (mean arterial pressure, norepinephrine requirements and depth of anesthesia) were assessed during (1) propofol/remifentanil and (2) subsequent xenon/remifentanil anesthesia. Xenon at an inspiratory fraction of 62.5 ± 7% decreased norepinephrine requirement (0.067 ± 0.04 v 0.028 ± 0.02 µg/kg/min, p < 0.001), and mean arterial pressure was unchanged (90.6 ± 15.0 v 93.1 ± 9.6 mmHg, p = 0.40). Somatosensory-evoked potentials were available in all patients during xenon/remifentanil. Despite similar depth of anesthesia (Narcotrend index 38.4 ± 6.2 v 38.5 ± 5.8) during propofol and xenon, N20 amplitude was reduced after xenon wash-in from 3.7 ± 1.7 to 1.4 ± 2.8 µV, p < 0.001 on the surgical and 3.6 ± 1.6 to 1.4 ± 0.6 µV, p < 0.001 on the contralateral side. N20 latency remained unchanged during xenon (22.9 ± 2.1 v 22.5 ± 2.8 ms, p = 0.34 and 22.9 ± 2.0 v 22.9 ± 3.0, p = 0.97). CONCLUSIONS: Xenon influences somatosensory-evoked potentials measurement by reducing N20 wave amplitude but not latency. When xenon is considered as an anesthetic for carotid endarterectomy, wash-in needs to be completed before carotid surgery is commenced to provide stable baseline somatosensory-evoked potential measurement.

A rapid positive influence of S-ketamine on the anxiety of patients in palliative care: a retrospective pilot study.

BACKGROUND: Patients in palliative care need rapid-acting pharmacological options for psychological distress. N-methyl-D-aspartate antagonist ketamine is known to have a fast onset of anti-depressant and anxiolytic action. Its S-enantiomer S-ketamine (or esketamine) is an analgesic used as a routine treatment for refractory pain as an intravenous infusion (0.25 mg/kg over 45 min). This study investigates whether S-ketamine pain therapy has a positive impact on psychological distress caused by anxiety and depression in palliative care. METHODS: Patient routine data from a palliative care unit of a tertiary care hospital were used in a retrospective analysis after positive ethics approval. Eight patients, who received analgesic S-ketamine treatment, were compared to a control group matched by gender and age. The main analysis was conducted using three-way mixed MANOVA followed by two-way mixed ANOVA. Target variables were the values for anxiety and depression in the state-trait anxiety-depression inventory STADI. The predictor variables were the time of measurement before (T1) and after (T2) S-ketamine application and group membership. RESULTS: Comparison of the S-ketamine group (n = 8; 4 male, 4 female; average age 52 years) with the control group (n = 8; 3 male, 5 female; average age 55 years) revealed a significant multivariate effect on anxiety and depression F(1, 14) = 4.78; p = 0.046; r = 0.50. The univariate comparisons showed a significant reduction of the anxiety scores from T1 to T2 in the S-ketamine group compared to the control group F(1, 14) = 10.14; p = 0.007; r = 0.65. With regard to depression, there was no significant reduction from T1 to T2 in the group comparison F(1, 14) = 1.60; p = 0.23; r = 0.32. No long-lasting effects on pain were found. CONCLUSIONS: Our findings show that psychological distress of patients in palliative care may improve after a single administration of S-ketamine, which mainly alleviates anxiety in those patients. Limitations of this study arise from non-randomization, retrospective analysis and low sample size. Therefore, further prospective and ideally randomized studies are necessary.

[Management of patients with MELAS syndrome : A case report and general characteristics from an anesthesiological perspective]. / Management von Patienten mit MELAS-Syndrom : Ein Fallbericht und allgemeine Besonderheiten aus anästhesiologischer Sicht.

BACKGROUND: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare progressive disease with acute neurological episodes caused by a mitochondriopathy. Due to a defect of oxidative phosphorylation in the respiratory chain, there is impaired mitochondrial energy production with subsequent lactic acidosis, especially in situations with increased stress. Due to the high risk of metabolic derailment MELAS syndrome is a great challenge with respect to the perioperative management of anesthesia. OBJECTIVE: This article gives a general overview of the special features of anesthesia management in patients with MELAS syndrome. A case report is presented in order to demonstrate how intraoperative parenteral nutrition can possibly be used to counteract the formation of lactic acidosis. MATERIAL AND METHODS: A systematic review of the literature was performed. As only very few reports on MELAS syndrome are available, a case report was also integrated into this overview article for illustration purposes. RESULTS AND CONCLUSION: Patients with MELAS syndrome represent a challenging cohort with respect to management of anesthesia and an intensive monitoring of the metabolic status is crucial. In cases of increasing lactate values, the administration of intraoperative parenteral nutrition seems to be a suitable approach to avoid lactic acidosis and to improve the perioperative treatment of patients with MELAS syndrome in the future.

Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study.

BACKGROUND: The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. METHODS: We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. RESULTS: A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10- 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10- 5 from the GWAS. CONCLUSIONS: We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

Temporal Changes in Ventilator Settings in Patients With Uninjured Lungs: A Systematic Review.

In patients with uninjured lungs, increasing evidence indicates that tidal volume (VT) reduction improves outcomes in the intensive care unit (ICU) and in the operating room (OR). However, the degree to which this evidence has translated to clinical changes in ventilator settings for patients with uninjured lungs is unknown. To clarify whether ventilator settings have changed, we searched MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science for publications on invasive ventilation in ICUs or ORs, excluding those on patients <18 years of age or those with >25% of patients with acute respiratory distress syndrome (ARDS). Our primary end point was temporal change in VT over time. Secondary end points were changes in maximum airway pressure, mean airway pressure, positive end-expiratory pressure, inspiratory oxygen fraction, development of ARDS (ICU studies only), and postoperative pulmonary complications (OR studies only) determined using correlation analysis and linear regression. We identified 96 ICU and 96 OR studies comprising 130,316 patients from 1975 to 2014 and observed that in the ICU, VT size decreased annually by 0.16 mL/kg (-0.19 to -0.12 mL/kg) (P < .001), while positive end-expiratory pressure increased by an average of 0.1 mbar/y (0.02-0.17 mbar/y) (P = .017). In the OR, VT size decreased by 0.09 mL/kg per year (-0.14 to -0.04 mL/kg per year) (P < .001). The change in VTs leveled off in 1995. Other intraoperative ventilator settings did not change in the study period. Incidences of ARDS (ICU studies) and postoperative pulmonary complications (OR studies) also did not change over time. We found that, during a 39-year period, from 1975 to 2014, VTs in clinical studies on mechanical ventilation have decreased significantly in the ICU and in the OR.

Effect of iloprost inhalation on postoperative outcome in high-risk cardiac surgical patients: a prospective randomized-controlled multicentre trial (ILOCARD).

PURPOSE: Perioperative right ventricular (RV) failure due to pressure overload from pulmonary hypertension (PH) worsens postoperative outcomes after cardiac surgery. Inhaled iloprost is a potent pulmonary vasodilator improving RV performance, ameliorating myocardial and pulmonary ischemia-reperfusion injury and attenuating inflammation. We hypothesized that the prophylactic inhalation of iloprost would reduce postoperative ventilation times after cardiac surgery. METHODS: In this phase III, multicentre, randomized, double-blind, placebo-controlled trial, we randomly assigned 253 cardiac surgical patients at high risk of perioperative RV failure to the prophylactic inhalation of 20 µg iloprost or placebo before and during weaning from extracorporeal circulation. The primary endpoint was the duration of postoperative ventilation. Secondary endpoints included perioperative hemodynamics, intensive care unit and hospital length of stay, and 90-day mortality. Safety was assessed by the incidence of adverse events. RESULTS: Iloprost had no significant effect on the median [interquartile range] duration of postoperative ventilation compared with placebo (720 [470-1170] min vs 778 [541-1219] min, respectively; median decrease, 65 min; 95% confidence interval [CI], - 77 to 210; P = 0.37). While the nebulization of iloprost decreased RV afterload and improved cardiac index, major secondary endpoints were not significantly affected. Ninety-day mortality occurred in 14% of the iloprost patients compared with 14% of the placebo patients (hazard ratio, 0.97; 95% CI, 0.50 to 1.89; P = 0.93). The incidence of adverse events was comparable in both groups. CONCLUSIONS: The prophylactic inhalation of iloprost did not meaningfully improve the outcome in high-risk cardiac surgical patients. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT00927654); registered 25 June, 2009.

RéSUMé: OBJECTIF: L'insuffisance cardiaque droite périopératoire due à une surcharge de pression provoquée par l'hypertension pulmonaire (HP) a un impact négatif sur le pronostic postopératoire après une chirurgie cardiaque. L'iloprost administré par inhalation est un vasodilatateur pulmonaire puissant qui améliore la performance du ventricule droit (VD), réduisant ainsi la lésion d'ischémie-reperfusion myocardique et pulmonaire et atténuant l'inflammation. Nous avons émis l'hypothèse qu'une inhalation prophylactique d'iloprost réduirait les temps de ventilation postopératoire après une chirurgie cardiaque. MéTHODE: Dans cette étude multicentrique de phase III, contrôlée par placebo, à double insu et randomisée, nous avons distribué aléatoirement 253 patients chirurgicaux courant un risque élevé d'insuffisance cardiaque droite périopératoire à une prophylaxie de 20 µg d'iloprost ou d'un placebo par inhalation avant et pendant le sevrage de la circulation extracorporelle. Le critère d'évaluation principal était la durée de ventilation postopératoire. Les critères d'évaluation secondaires étaient les données hémodynamiques périopératoires, la durée de séjour à l'unité de soins intensifs et à l'hôpital, et la mortalité à 90 jours. L'innocuité a été évaluée en fonction de l'incidence d'événements indésirables. RéSULTATS: L'iloprost n'a pas eu d'effet significatif sur la durée médiane [écart interquartile] de ventilation postopératoire par rapport au placebo (720 [470­1170] min vs 778 [541­1219] min, respectivement; réduction médiane, 65 min; intervalle de confiance [IC] 95 %, − 77 à 210; P = 0,37). Bien que la nébulisation d'iloprost ait réduit la post-charge du VD et amélioré l'index cardiaque, cette manœuvre n'a pas eu d'impact significatif sur les critères d'évaluation secondaires majeurs. Une mortalité à 90 jours a été observée chez 14 % des patients ayant reçu de l'iloprost, comparativement à 14 % des patients ayant reçu un placebo (rapport de risque, 0,97; IC 95 %, 0,50 à 1,89; P = 0,93). L'incidence d'événements indésirables était comparable dans les deux groupes. CONCLUSION: L'inhalation prophylactique d'iloprost n'a pas amélioré le pronostic des patients de chirurgie cardiaque à haut risque. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT00927654); enregistrée le 25 juin 2009.

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery.

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. METHODS: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. RESULTS: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed. CONCLUSIONS: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.).

Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry - a prospectively controlled randomized double-blind clinical trial.

BACKGROUND: Argatroban or lepirudin anticoagulation therapy in patients with heparin induced thrombocytopenia (HIT) or HIT suspect is typically monitored using the activated partial thromboplastin time (aPTT). Although aPTT correlates well with plasma levels of argatroban and lepirudin in healthy volunteers, it might not be the method of choice in critically ill patients. However, in-vivo data is lacking for this patient population. Therefore, we studied in vivo whether ROTEM or global clotting times would provide an alternative for monitoring the anticoagulant intensity effects in critically ill patients. METHODS: This study was part of the double-blind randomized trial "Argatroban versus Lepirudin in critically ill patients (ALicia)", which compared critically ill patients treated with argatroban or lepirudin. Following institutional review board approval and written informed consent, for this sub-study blood of 35 critically ill patients was analysed. Before as well as 12, 24, 48 and 72 h after initiation of argatroban or lepirudin infusion, blood was analysed for aPTT, aPTT ratios, thrombin time (TT), INTEM CT,INTEM CT ratios, EXTEM CT, EXTEM CT ratios and maximum clot firmness (MCF) and correlated with the corresponding plasma concentrations of the direct thrombin inhibitor. RESULTS: To reach a target aPTT of 1.5 to 2 times baseline, median [IQR] plasma concentrations of 0.35 [0.01-1.2] µg/ml argatroban and 0.17 [0.1-0.32] µg/ml lepirudin were required. For both drugs, there was no significant correlation between aPTT and aPTT ratios and plasma concentrations. INTEM CT, INTEM CT ratios, EXTEM CT, EXTEM CT ratios, TT and TT ratios correlated significantly with plasma concentrations of both drugs. Additionally, agreement between argatroban plasma levels and EXTEM CT and EXTEM CT ratios were superior to agreement between argatroban plasma levels and aPTT in the Bland Altman analysis. MCF remained unchanged during therapy with both drugs. CONCLUSION: In critically ill patients, TT and ROTEM parameters may provide better correlation to argatroban and lepirudin plasma concentrations than aPTT. TRIAL REGISTRATION: ClinicalTrials.gov , NCT00798525 , registered on 25 Nov 2008.

Total intravenous anesthesia vs single pharmacological prophylaxis to prevent postoperative vomiting in children: A systematic review and meta-analysis.

BACKGROUND: Postoperative nausea and postoperative vomiting are frequent but often missed complications after general anesthesia in pediatric patients. Because inhaled anesthetics are known to trigger postoperative vomiting, total intravenous anesthesia is often administered in high-risk children to avoid the use of inhalational anesthesia. Since inhalational anesthesia might be advantageous in some situations, the question is raised whether administration of pharmacological prophylaxis offers equal protection from postoperative vomiting compared with total intravenous anesthesia alone. AIM: The aim of this systematic review was to compare total intravenous anesthesia with single-drug pharmacological prophylaxis for the protection of postoperative vomiting in pediatric patients. METHODS: We conducted a systematic review (EMBASE, MEDLINE, and CENTRAL) with meta-analysis on randomized controlled trials including patients <18 years of age undergoing general anesthesia, with one group receiving propofol-based total intravenous anesthesia and another group receiving inhalational anesthesia with single pharmacological prophylaxis. Primary outcome was the overall incidence for postoperative vomiting. Secondary outcomes included early and late postoperative vomiting, the need for postoperative antiemetic medication, time to first oral intake, duration of stay in the postanesthesia care unit, and any adverse events defined as such by the respective authors. Risk ratios (RR) or mean differences (MD) with 95% confidence intervals (95% CI) were calculated using a random effects model with inverse variance weighting. RESULTS: Four randomized controlled trials including 558 children were included in the final analysis. All patients underwent strabismus surgery. Total intravenous anesthesia and single pharmacological prophylaxis were equally effective in preventing overall postoperative vomiting (RR 0.99 [95% CI 0.77; 1.27]; 4 trials), as well as vomiting in the early (1.48 [0.78; 2.83]; 4 trials) and late (0.89 [0.56;1.42]; 2 trials) postoperative period. There was no difference in the need for postoperative antiemetic medication. Although patients resumed drinking and eating significantly earlier following total intravenous anesthesia (MD -1.40 hours [-2.01; -0.80], P < .001), the duration of PACU stay did not differ between groups. The incidence of intraoperative oculocardiac reflex was the only reported adverse event, which was more likely to occur after total intravenous anesthesia (1.86 [1.01; 3.41]). CONCLUSION: Single pharmacological prophylaxis appears equally effective compared with total intravenous anesthesia in preventing postoperative vomiting in pediatric patients. However, during strabismus surgery, total intravenous anesthesia increases the risk for bradycardia due to oculocardiac reflex. Thus, when anesthesia is maintained with inhalational anesthetics, its emetogenic effects can sufficiently be compensated by the addition of a single prophylactic antiemetic medication.

Dipyrone (metamizole) markedly interferes with platelet inhibition by aspirin in patients with acute and chronic pain: A case-control study.

BACKGROUND: Nonopioid analgesic drugs may interfere with platelet inhibition by aspirin. Recent in vitro and clinical studies in patients with cardiovascular disease have suggested that this pharmacodynamic interaction may also occur with dipyrone, a nonopioid analgesic popular in Europe, Asia and South America. OBJECTIVE: Dipyrone is used extensively in acute and chronic pain. This study was undertaken to provide clinical data, so far missing, on its interactions in this group of patients. DESIGN: A case-control study. SETTING: Primary care in one European university hospital centre. PATIENTS: In total, 27 patients with stable cardiovascular, cerebrovascular or peripheral arterial disease and acute or chronic pain were identified and given dipyrone for at least 5 days in combination with low-dose aspirin. In total, 10 comparable patients on low-dose aspirin alone served as controls. MAIN OUTCOME MEASURES: Platelet-rich plasma was prepared to determine arachidonic acid-induced aggregation (aggregometry) and thromboxane formation (immunoassay). Platelet sensitivity to aspirin was examined in vitro. The presence of dipyrone (metabolites) in plasma was confirmed by HPLC. Additional in vitro measurements examined the aspirin/dipyrone interaction in healthy donors. RESULTS: Inhibition of aggregation was observed in only six of 27 patients receiving aspirin with dipyrone, with absence of complete inhibition by antiplatelet therapy showing in 78% of patients. In contrast, aggregation was completely inhibited in nine of 10 control patients (P < 0.001). Platelet thromboxane synthesis was higher in patients receiving dipyrone + aspirin compared with controls (387 ±â€Š89 vs. 7 ±â€Š1 ng ml, P < 0.001). Aspirin added in vitro failed to inhibit aggregation and thromboxane synthesis in platelet-rich plasma from dipyrone-treated patients. In vitro measurements with blood from healthy individuals confirmed that dipyrone dramatically reduces inhibition of platelet thromboxane synthesis by aspirin. CONCLUSIONS: Dipyrone given for 5 days or longer blunts platelet inhibition by low-dose aspirin in the majority of recipients. TRIAL REGISTRATION: German Clinical Trials Register: DRKS ID DRKS00000204. Universal Trial Number (UTN): U1111-1113-3946.

Ventilation with high versus low peep levels during general anaesthesia for open abdominal surgery does not affect postoperative spirometry: A randomised clinical trial.

BACKGROUND: Invasive mechanical ventilation during general anaesthesia for surgery typically causes atelectasis and impairs postoperative lung function. OBJECTIVE: We investigated the effect of intraoperative ventilation with high positive end-expiratory pressure (PEEP) and recruitment manoeuvres (RMs) on postoperative spirometry. DESIGN: This was a preplanned, single-centre substudy of an international multicentre randomised controlled trial, the PROVHILO trial. SETTING: University hospital from November 2011 to January 2013. PATIENTS: Nonobese patients scheduled for major abdominal surgery at a high risk of postoperative pulmonary complications (PPCs). INTERVENTION: Intraoperative low tidal volume ventilation with PEEP levels of 12 cmH2O and RM (the high PEEP group) or with PEEP levels of 2 cmH2O or less without RM (the low PEEP group). MAIN OUTCOME MEASURES: Time-weighted averages (TWAs) of the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) up to postoperative day five. RESULTS: Thirty-one patients were allocated to the high PEEP group and 32 to the low PEEP group. No postoperative spirometry test results were available for 6 patients. In both groups, TWA of FEV1 and FVC until postoperative day five were lower than preoperative values. Postoperative spirometry test results were not different between the high and low PEEP group; Data are median [interquartile range], TWA FVC 1.8 [1.6 to 2.4] versus 1.7 [1.2 to 2.4] l (P = NS) and TWA FEV1 1.2 [1.1 to 2.5] versus 1.2 [0.9 to 1.9] l (P = NS). Patients who developed PPCs had lower FEV1 and FVC on postoperative day five; 1.1 [0.9 to 1.6] versus 1.6 [1.4 to 1.9] l (P = 0.001) and 1.6 [1.2 to 2.6] versus 2.3 [1.7 to 2.6] l (P = 0.036), respectively. CONCLUSION: Postoperative spirometry is not affected by PEEP and RM during intraoperative ventilation for open abdominal surgery in nonobese patients at a high risk of PPCs, but rather is associated with the development of PPCs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01441791.