The effects of sugammadex vs. neostigmine on postoperative respiratory complications and advanced healthcare utilisation: a multicentre retrospective cohort study.

Reversing neuromuscular blockade with sugammadex can eliminate residual paralysis, which has been associated with postoperative respiratory complications. There are equivocal data on whether sugammadex reduces these when compared with neostigmine. We investigated the association of the choice of reversal drug with postoperative respiratory complications and advanced healthcare utilisation. We included adult patients who underwent surgery and received general anaesthesia with sugammadex or neostigmine reversal at two academic healthcare networks between January 2016 and June 2021. The primary outcome was postoperative respiratory complications, defined as post-extubation oxygen saturation < 90%, respiratory failure requiring non-invasive ventilation, or tracheal re-intubation within 7 days. Our main secondary outcome was advanced healthcare utilisation, a composite outcome including: 7-day unplanned intensive care unit admission; 30-day hospital readmission; or non-home discharge. In total, 5746 (6.9%) of 83,250 included patients experienced postoperative respiratory complications. This was not associated with the reversal drug (adjusted OR (95%CI) 1.01 (0.94-1.08); p = 0.76). After excluding patients admitted from skilled nursing facilities, 8372 (10.5%) patients required advanced healthcare utilisation, which was not associated with the choice of reversal (adjusted OR (95%CI) 0.95 (0.89-1.01); p = 0.11). Equivalence testing supported an equivalent effect size of sugammadex and neostigmine on both outcomes, and neostigmine was non-inferior to sugammadex with regard to postoperative respiratory complications or advanced healthcare utilisation. Finally, there was no association between the reversal drug and major adverse cardiovascular events (adjusted OR 1.07 (0.94-1.21); p = 0.32). Compared with neostigmine, reversal of neuromuscular blockade with sugammadex was not associated with a reduction in postoperative respiratory complications or post-procedural advanced healthcare utilisation.

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

Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti-emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta-analyses to compare, and rank in terms of efficacy and safety, single anti-emetic drugs and their combinations, including 5-hydroxytryptamine3 , dopamine-2 and neurokinin-1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo-controlled and head-to-head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta-Analysis (CINeMA) approaches for vomiting within 24 h postoperatively, serious adverse events, any adverse event and drug class-specific side-effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin-1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18-0.38); ramosetron, 0.44 (0.32-0.59); granisetron, 0.45 (0.38-0.54); dexamethasone, 0.51 (0.44-0.57); and ondansetron, 0.55 (0.51-0.60). It was moderate for fosaprepitant, 0.06 (0.02-0.21) and droperidol, 0.61 (0.54-0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side-effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.

Influence of xenon on pulmonary mechanics and lung aeration in patients with healthy lungs.

BACKGROUND: The anaesthetic xenon shows potent organ-protective properties. Due to high density and dynamic viscosity, peak inspiratory pressure (Pmax) increases during xenon application. Thus, barotrauma may counteract organ protection. Accordingly, we investigated the influence of xenon on lung mechanics and lung aeration in patients with normal and reduced thoracic wall compliance. METHODS: After registration and ethical approval, 20 patients free of pulmonary disease undergoing routine xenon-based anaesthesia were mechanically ventilated. The primary outcome variable transpulmonary pressure (Ptp) was determined from plateau pressure and intraoesophageal pressure before and after xenon wash-in. We recorded Pmax, and calculated airway resistance (RAW), and static (Cstat) and dynamic (Cdyn) respiratory compliances. Finally, lung aeration was quantified by electrical impedance tomography-derived centre of ventilation index (CVI) and global inhomogeneity index (GI) in the awake state, before and during xenon. RESULTS: Xenon increased Pmax [20.8 (SD 3) vs 22.6 (3) cm H2O, P<0.001] and RAW [0.9 (0.2) vs 1.4 (0.3) cm H2O litre-1 s, P<0.001], without affecting Ptp [1.5 (4) vs 2.0 (4) cm H2O, P=0.15]. While Cstat remained unchanged, Cdyn was reduced [33.9 (7) vs 31.2 (6) ml (cm H2O)-1, P<0.001). A ventral tidal volume shift after anaesthesia induction [CVI 0.53 (0.03) vs 0.59 (0.04), P<0.001] was unaltered during xenon [CVI 0.59 (0.04), P=0.29]. Homogeneity of lung aeration was also unchanged during xenon [GI 0.37 (0.03) vs 0.37 (0.03), P=0.99]. There were no clinically meaningful differential BMI-related effects. CONCLUSIONS: Xenon increases calculated airway resistance and peak inspiratory pressure without affecting transpulmonary pressure, independent of BMI. CLINICAL TRIAL REGISTRATION: NCT02682758.

The hip fracture surgery in elderly patients (HIPELD) study to evaluate xenon anaesthesia for the prevention of postoperative delirium: a multicentre, randomized clinical trial.

BACKGROUND: Postoperative delirium occurs frequently in elderly hip fracture surgery patients and is associated with poorer overall outcomes. Because xenon anaesthesia has neuroprotective properties, we evaluated its effect on the incidence of delirium and other outcomes after hip fracture surgery. METHODS: This was a phase II, multicentre, randomized, double-blind, parallel-group, controlled clinical trial conducted in hospitals in six European countries (September 2010 to October 2014). Elderly (≥75yr-old) and mentally functional hip fracture patients were randomly assigned 1:1 to receive either xenon- or sevoflurane-based general anaesthesia during surgery. The primary outcome was postoperative delirium diagnosed through postoperative day 4. Secondary outcomes were delirium diagnosed anytime after surgery, postoperative sequential organ failure assessment (SOFA) scores, and adverse events (AEs). RESULTS: Of 256 enrolled patients, 124 were treated with xenon and 132 with sevoflurane. The incidence of delirium with xenon (9.7% [95% CI: 4.5 -14.9]) or with sevoflurane (13.6% [95% CI: 7.8 -19.5]) were not significantly different (P=0.33). Overall SOFA scores were significantly lower with xenon (least-squares mean difference: -0.33 [95% CI: -0.60 to -0.06]; P=0.017). For xenon and sevoflurane, the incidence of serious AEs and fatal AEs was 8.0% vs 15.9% (P=0.05) and 0% vs 3.8% (P=0.06), respectively. CONCLUSIONS: Xenon anaesthesia did not significantly reduce the incidence of postoperative delirium after hip fracture surgery. Nevertheless, exploratory observations concerning postoperative SOFA-scores, serious AEs, and deaths warrant further study of the potential benefits of xenon anaesthesia in elderly hip fracture surgery patients. CLINICAL TRIAL REGISTRATION: EudraCT 2009-017153-35; ClinicalTrials.gov NCT01199276.

[Integration of palliative care into intensive care : Systematic review]. / Integration der Palliativmedizin in die Intensivmedizin : Systematische Übersichtsarbeit.

BACKGROUND: One of the prime aims of intensive care is to cure patients or at least to extend life duration, sometimes to the extent of losing quality of life. Palliative care aims to improve the quality of life of patients with life-limiting conditions; however, some patients need both intensive and palliative care. About 5-10% of all deaths in Germany and 20% of all deaths in the USA occur in an intensive care unit (ICU) and many of those as well as other patients may benefit from palliative care consultation. Palliative care consultations are increasingly available for intensive care patients but are still infrequently used. OBJECTIVES: We aimed to determine the current situation of palliative patients in ICU settings: what is the impact of palliative care interventions on the quality of care of ICU patients? To what extent is palliative care support at ICUs available and to what extent is it used? Which factors trigger palliative care consultations? METHOD: We set out with a search of PubMed, Scopus and other databases in English and on a) the impact of palliative care interventions on the quality of care of ICU patients, b) the utilization of palliative care support in ICUs and c) the factors which trigger palliative care consultations. We included both quantitative and qualitative studies to reflect the views of all parties involved. To emphasize the situation in German-speaking countries we also searched Google Scholar with search terms in German and added those results to the review. Additionally, hand-searched studies in English and in German were included. RESULTS: We screened 695 abstracts and identified 18 relevant articles of which 15 were from the USA and Great Britain, 1 each was from Austria, Germany and Switzerland. Palliative care is a meaningful addition to ICU standard treatment: it can improve quality of care and helps reduce length of stay in an ICU. It is unclear if the reduced length of stay leads to economic benefits; however, the utilization of palliative care is inconsistent and infrequent as is its acceptance among ICU physicians. Trigger factors can be used to improve the integration of palliative care support in ICUs and point out patients' unmet palliative needs. DISCUSSION: Trigger factors can reduce barriers which hold back the integration of palliative care in ICUs. Early integration of palliative care can improve quality of care by offering psychological support to patients and their families and by providing collegial consultation. An ongoing prospective study is investigating the acceptance of trigger factors in the daily routine among ICU physicians in Germany.

Predictors for postoperative nausea and vomiting after xenon-based anaesthesia.

BACKGROUND: In contrast to volatile anaesthetics, xenon acts by antagonism at N-methyl-d-aspartate receptors and antagonizes 5-hydroxytryptamine type 3 receptors that mediate nausea and vomiting. Therefore, it is unknown whether the same risk factors for postoperative nausea and vomiting (PONV) after volatile anaesthetics apply to xenon-based anaesthesia. METHODS: With ethics committee approval and written informed consent, 502 consecutive patients undergoing xenon-based anaesthesia were included in a multicentre prospective observational study. Antiemetic prophylaxis was administered at the discretion of the attending anaesthetists. Postoperative nausea and vomiting and need for antiemetic rescue medication were assessed for 24 h after anaesthesia. Multivariate logistic regression analysis was performed to quantify risk factors for PONV and need for rescue medication. RESULTS: Four hundred and eighty-eight subjects were available for the final analysis. The incidence of PONV in subjects without prophylaxis was lower than expected according to the Apfel Score (28% observed; 42% expected, P<0.001). Independent predictors for PONV were (adjusted odds ratio; 95% confidence interval) female sex (1.76; 1.08-2.89), younger patient age (0.82 per 10 yr; 0.69-0.97), and longer duration of anaesthesia (1.36 per hour; 1.17-1.59). CONCLUSIONS: The incidence of PONV was significantly lower than predicted by the Apfel Score. Female sex, younger age, and longer duration of anaesthesia are risk factors for PONV after xenon-based anaesthesia. CLINICAL TRIAL REGISTRATION: German Federal Institute for Drugs and Medical Devices number AL-PMS-01/07GER.

Cardiovascular stability and unchanged muscle sympathetic activity during xenon anaesthesia: role of norepinephrine uptake inhibition.

BACKGROUND: Intraoperative hypotension is associated with increased risk of perioperative complications. The N-methyl-d-aspartate (NMDA) receptor (NMDA-R) antagonist xenon (Xe) induces general anaesthesia without impairment of cardiac output and vascular resistance. Mechanisms involved in cardiovascular stability have not been identified. METHODS: Muscle sympathetic activity (MSA) (microneurography), sympathetic baroreflex gain, norepinephrine (NE) plasma concentration (high-performance liquid chromatography), anaesthetic depth (Narcotrend(®) EEG monitoring), and vital parameters were analysed in vivo during Xe mono-anaesthesia in human volunteers (n=8). In vitro, NE transporter (NET) expressing HEK293 cells and SH-SY5Y neuroblastoma cells were pre-treated with ketamine, MK-801, NMDA/glycine, or vehicle. Subsequently, cells were incubated with or without Xe (65%). NE uptake was measured by using a fluorescent NET substrate (n=4) or [(3)H]NE (n=6). RESULTS: In vivo, Xe anaesthesia increased mean (standard deviation) arterial pressure from 93 (4) to 107 (6) mm Hg and NE plasma concentration from 156 (55) to 292 (106) pg ml(-1), P<0.01. MSA and baroreflex gain were unaltered. In vitro, ketamine decreased NET activity (P<0.01) in NET-expressing HEK293 cells, while Xe, MK-801, and NMDA/glycine did not. Xe reduced uptake in SH-SY5Y cells expressing NET and NMDA-Rs (P<0.01). MK-801 (P<0.01) and ketamine (P<0.01) also reduced NET activity, but NMDA/glycine blocked the effect of Xe on [(3)H]NE uptake. CONCLUSIONS: In vivo, Xe anaesthesia does not alter sympathetic activity and baroreflex gain, despite increased mean arterial pressure. In vitro, Xe decreases the uptake of NE in neuronal cells by the inhibition of NET. This inhibition might be related to NMDA-R antagonism and explain increased NE concentrations at the synaptic cleft and in plasma, contributing to cardiovascular stability during Xe anaesthesia.

Ventilation with low tidal volumes during upper abdominal surgery does not improve postoperative lung function.

BACKGROUND: Prolonged postoperative decrease in lung function is common after major upper abdominal surgery. Evidence suggests that ventilation with low tidal volumes may limit the damage during mechanical ventilation. We compared postoperative lung function of patients undergoing upper abdominal surgery, mechanically ventilated with high or low tidal volumes. METHODS: This was a double-blind, prospective, randomized controlled clinical trial. One hundred and one patients (age ≥ 50 yr, ASA ≥ II, duration of surgery ≥ 3 h) were ventilated with: (i) high [12 ml kg(-1) predicted body weight (PBW)] or (ii) low (6 ml kg(-1) PBW) tidal volumes intraoperatively. The positive end-expiratory pressure was 5 cm H(2)O in both groups and breathing frequency adjusted to normocapnia. Time-weighted averages (TWAs) of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) until 120 h after operation were compared (P<0.025 considered statistically significant). Secondary outcomes were oxygenation, respiratory and non-respiratory complications, length of stay and mortality. RESULTS: The mean (sd) values of TWAs of FVC and FEV(1) were similar in both groups: FVC: 6 ml group 1.8 (0.7) litre vs 12 ml group 1.6 (0.5) litre (P=0.12); FEV(1): 6 ml group 1.4 (0.5) litre vs 12 ml group 1.2 (0.4) litre (P=0.15). FVC and FEV(1) at any single time point and secondary outcomes did not differ significantly between groups. CONCLUSIONS: Prolonged impaired lung function after major abdominal surgery is not ameliorated by low tidal volume ventilation.

Brief communication: foramen magnum-carotid foramina relationship: is it useful for species designation?

The anterior placement of the foramen magnum is often used to indicate bipedalism and therefore to distinguish hominid from nonhominid fossils. Often, only fragmentary cranial remains are found, and the placement of the foramen magnum must be determined by its relationship to another landmark. The purpose of this study was to test if hominid crania could be distinguished from nonhominid crania based on the relationship between the foramen magnum and the carotid foramina, and therefore to determine if the carotid foramina can be used to determine the anteriorness of the foramen magnum. The samples consisted of 16 modern human crania and 19 modern chimpanzee (Pan troglodytes) crania. Linear measurements were taken of (1) the distance from the anterior border of the foramen magnum to a chord connecting the carotid foramina and (2) total cranial length. An index of the distance of the foramen magnum from the bicarotid chord as a proportion of total cranial length was calculated to control for differences due to body size. Results indicate that on average, human crania can be distinguished from chimpanzee crania by using either (1) the distance of the foramen magnum from the bicarotid chord as a linear measurement or (2) this linear measurement as a proportion of total cranial length. Both measures are significantly smaller in the human sample; however, there was considerable overlap between species, indicating that the distance of the foramen magnum from the bicarotid chord is not a certain indicator for individual specimens.