Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Indication Criteria for Total Hip Arthroplasty in Patients with Hip Osteoarthritis—Recommendations from a German Consensus Initiative

Background: Osteoarthritis of the hip (hip OA) is a leading cause of pain and disability in elderly people. If non-surgical therapies become ineffective, patients may consider total hip arthroplasty (THA). The biggest challenge in recommending a THA is identifying patients for whom the benefits of this procedure outweigh the potential risks. The aim of this initiative was to develop a clinical practice guideline with accompanying algorithm to guide consultations on THA, supported by a pocket-sized checklist. Methods: The initiative “Evidence- and consensus-based indication criteria for total hip replacement (EKIT-Hip)” used a stepwise approach, starting with an inauguration workshop, where a multidisciplinary German stakeholder panel from various scientific societies agreed on the working process. A Project Coordinating Group (PCG) was formed, and it performed a comprehensive systematic literature search of guidelines and systematic reviews related to the indication criteria for THA, as well as factors influencing outcomes. Based on best-available evidence, preliminary recommendations were formulated by the PCG and discussed with the stakeholder panel during a consensus meeting. In addition, the panel was asked to assess the feasibility of an extracted algorithm and to approve a final checklist. Results: In total, 31 recommendations were approved by 29 representatives of 23 societies. These were used to underpin an algorithm (EKIT-Algorithm), which indicates the minimum requirements for a THA (confirmed diagnosis of hip OA, present and documented individual burden of illness, ineffectiveness of non-surgical therapies, and absence of any contraindications). Once these criteria are fulfilled, further considerations should encompass the medical implications of modifiable risk factors and patients’ individual treatment goals, as discussed during shared decision making. The subsequently developed checklist (EKIT-Checklist) lists relevant criteria for decision making. Conclusions: Adherence to the EKIT-Algorithm, conveniently accessed via the EKIT-Checklist, should improve the standardization of decision making leading to a recommendation for THA. By applying minimum requirements and patient-related risk factors, as well as considering patients’ individual goals, it is possible to identify patients for whom the benefits of THA may exceed the potential risks

Surveillance of multiple congenital anomalies; searching for new associations

Many human teratogens are associated with a spectrum of congenital anomalies rather than a single defect, and therefore the identification of congenital anomalies occurring together more frequently than expected may improve the detection of teratogens. Thirty-two EUROCAT congenital anomaly registries covering 6,599,765 births provided 123,566 cases with one or more major congenital anomalies (excluding chromosomal and genetic syndromes) for the birth years 2008–2016. The EUROCAT multiple congenital anomaly algorithm identified 8804 cases with two or more major congenital anomalies in different organ systems, that were not recognized as part of a syndrome or sequence. For each pair of anomalies, the odds of a case having both anomalies relative to having only one anomaly was calculated and the p value was estimated using a two-sided Fisher’s exact test. The Benjamini–Hochberg procedure adjusted p values to control the false discovery rate and pairs of anomalies with adjusted p values < 0.05 were identified. A total of 1386 combinations of two anomalies were analyzed. Out of the 31 statistically significant positive associations identified, 20 were found to be known associations or sequences already described in the literature and 11 were considered “potential new associations” by the EUROCAT Coding and Classification Committee. After a review of the literature and a detailed examination of the individual cases with the anomaly pairs, six pairs remained classified as new associations. In summary, systematically searching for congenital anomalies occurring together more frequently than expected using the EUROCAT database is worthwhile and has identified six new associations that merit further investigation.info:eu-repo/semantics/publishedVersio

Association between night-time surgery and occurrence of intraoperative adverse events and postoperative pulmonary complications

Background: The aim of this post hoc analysis of a large cohort study was to evaluate the association between night-time surgery and the occurrence of intraoperative adverse events (AEs) and postoperative pulmonary complications (PPCs). Methods: LAS VEGAS (Local Assessment of Ventilatory Management During General Anesthesia for Surgery) was a prospective international 1-week study that enrolled adult patients undergoing surgical procedures with general anaesthesia and mechanical ventilation in 146 hospitals across 29 countries. Surgeries were defined as occurring during 'daytime' when induction of anaesthesia was between 8: 00 AM and 7: 59 PM, and as 'night-time' when induction was between 8: 00 PM and 7: 59 AM. Results: Of 9861 included patients, 555 (5.6%) underwent surgery during night-time. The proportion of patients who developed intraoperative AEs was higher during night-time surgery in unmatched (43.6% vs 34.1%; P<0.001) and propensity-matched analyses (43.7% vs 36.8%; P = 0.029). PPCs also occurred more often in patients who underwent night-time surgery (14% vs 10%; P = 0.004) in an unmatched cohort analysis, although not in a propensity-matched analysis (13.8% vs 11.8%; P = 0.39). In a multivariable regression model, including patient characteristics and types of surgery and anaesthesia, night-time surgery was independently associated with a higher incidence of intraoperative AEs (odds ratio: 1.44; 95% confidence interval: 1.09-1.90; P = 0.01), but not with a higher incidence of PPCs (odds ratio: 1.32; 95% confidence interval: 0.89-1.90; P = 0.15). Conclusions: Intraoperative adverse events and postoperative pulmonary complications occurred more often in patients undergoing night-time surgery. Imbalances in patients' clinical characteristics, types of surgery, and intraoperative management at night-time partially explained the higher incidence of postoperative pulmonary complications, but not the higher incidence of adverse events

Intraoperative ventilator settings and their association with postoperative pulmonary complications in neurosurgical patients: post-hoc analysis of LAS VEGAS study

Background: Limited information is available regarding intraoperative ventilator settings and the incidence of postoperative pulmonary complications (PPCs) in patients undergoing neurosurgical procedures. The aim of this post-hoc analysis of the 'Multicentre Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study was to examine the ventilator settings of patients undergoing neurosurgical procedures, and to explore the association between perioperative variables and the development of PPCs in neurosurgical patients. Methods: Post-hoc analysis of LAS VEGAS study, restricted to patients undergoing neurosurgery. Patients were stratified into groups based on the type of surgery (brain and spine), the occurrence of PPCs and the assess respiratory risk in surgical patients in Catalonia (ARISCAT) score risk for PPCs. Results: Seven hundred eighty-four patients were included in the analysis; 408 patients (52%) underwent spine surgery and 376 patients (48%) brain surgery. Median tidal volume (VT) was 8 ml [Interquartile Range, IQR = 7.3-9] per predicted body weight; median positive end-expiratory pressure (PEEP) was 5 [3 to 5] cmH20. Planned recruitment manoeuvres were used in the 6.9% of patients. No differences in ventilator settings were found among the sub-groups. PPCs occurred in 81 patients (10.3%). Duration of anaesthesia (odds ratio, 1.295 [95% confidence interval 1.067 to 1.572]; p = 0.009) and higher age for the brain group (odds ratio, 0.000 [0.000 to 0.189]; p = 0.031), but not intraoperative ventilator settings were independently associated with development of PPCs. Conclusions: Neurosurgical patients are ventilated with low VT and low PEEP, while recruitment manoeuvres are seldom applied. Intraoperative ventilator settings are not associated with PPCs

Intraoperative ventilator settings and their association with postoperative pulmonary complications in neurosurgical patients: Post-hoc analysis of LAS VEGAS study

Background: Limited information is available regarding intraoperative ventilator settings and the incidence of postoperative pulmonary complications (PPCs) in patients undergoing neurosurgical procedures. The aim of this post-hoc analysis of the 'Multicentre Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study was to examine the ventilator settings of patients undergoing neurosurgical procedures, and to explore the association between perioperative variables and the development of PPCs in neurosurgical patients. Methods: Post-hoc analysis of LAS VEGAS study, restricted to patients undergoing neurosurgery. Patients were stratified into groups based on the type of surgery (brain and spine), the occurrence of PPCs and the assess respiratory risk in surgical patients in Catalonia (ARISCAT) score risk for PPCs. Results: Seven hundred eighty-four patients were included in the analysis; 408 patients (52%) underwent spine surgery and 376 patients (48%) brain surgery. Median tidal volume (VT) was 8 ml [Interquartile Range, IQR = 7.3-9] per predicted body weight; median positive end-expiratory pressure (PEEP) was 5 [3 to 5] cmH20. Planned recruitment manoeuvres were used in the 6.9% of patients. No differences in ventilator settings were found among the sub-groups. PPCs occurred in 81 patients (10.3%). Duration of anaesthesia (odds ratio, 1.295 [95% confidence interval 1.067 to 1.572]; p = 0.009) and higher age for the brain group (odds ratio, 0.000 [0.000 to 0.189]; p = 0.031), but not intraoperative ventilator settings were independently associated with development of PPCs. Conclusions: Neurosurgical patients are ventilated with low VT and low PEEP, while recruitment manoeuvres are seldom applied. Intraoperative ventilator settings are not associated with PPCs