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

Age-related and depot-specific changes in white adipose tissue of growth hormone receptor-null mice

Growth hormone receptor-null (GHR(−/−)) mice are dwarf, insulin sensitive, and long-lived in spite of increased adiposity. However, their adiposity is not uniform, with select white adipose tissue (WAT) depots enlarged. To study WAT depot–specific effects on insulin sensitivity and life span, we analyzed individual WAT depots of 12- and 24-month-old GHR(−) (/−) and wild-type (WT) mice, as well as their plasma levels of selected hormones. Adipocyte sizes and plasma insulin, leptin, and adiponectin levels decreased with age in both GHR(−) (/−) and WT mice. Two-dimensional gel electrophoresis proteomes of WAT depots were similar among groups, but several proteins involved in endocytosis and/or cytoskeletal organization (Ehd2, S100A10, actin), anticoagulation (S100A10, annexin A5), and age-related conditions (alpha2-macroglobulin, apolipoprotein A-I, transthyretin) showed significant differences between genotypes. Because Ehd2 may regulate endocytosis of Glut4, we measured Glut4 levels in the WAT depots of GHR(−) (/−) and WT mice. Inguinal WAT of 12-month-old GHR(−) (/−) mice displayed lower levels of Glut4 than WT. Overall, the protein changes detected in this study offer new insights into possible mechanisms contributing to enhanced insulin sensitivity and extended life span in GHR(−) (/−) mice

The role of GH in adipose tissue:Lessons from adipose-specific GH receptor gene-disrupted mice

GH receptor (GHR) gene-disrupted mice (GHR−/−) have provided countless discoveries as to the numerous actions of GH. Many of these discoveries highlight the importance of GH in adipose tissue. For example GHR−/− mice are insulin sensitive yet obese with preferential enlargement of the sc adipose depot. GHR−/− mice also have elevated levels of leptin, resistin, and adiponectin, compared with controls leading some to suggest that GH may negatively regulate certain adipokines. To help clarify the role that GH exerts specifically on adipose tissue in vivo, we selectively disrupted GHR in adipose tissue to produce Fat GHR Knockout (FaGHRKO) mice. Surprisingly, FaGHRKOs shared only a few characteristics with global GHR−/− mice. Like the GHR−/− mice, FaGHRKO mice are obese with increased total body fat and increased adipocyte size. However, FaGHRKO mice have increases in all adipose depots with no improvements in measures of glucose homeostasis. Furthermore, resistin and adiponectin levels in FaGHRKO mice are similar to controls (or slightly decreased) unlike the increased levels found in GHR−/− mice, suggesting that GH does not regulate these adipokines directly in adipose tissue in vivo. Other features of FaGHRKO mice include decreased levels of adipsin, a near-normal GH/IGF-1 axis, and minimal changes to a large assortment of circulating factors that were measured such as IGF-binding proteins. In conclusion, specific removal of GHR in adipose tissue is sufficient to increase adipose tissue and decrease circulating adipsin. However, removal of GHR in adipose tissue alone is not sufficient to increase levels of resistin or adiponectin and does not alter glucose metabolism

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

Sex dependence of postoperative pulmonary complications – A post hoc unmatched and matched analysis of LAS VEGAS

Study objective: Male sex has inconsistently been associated with the development of postoperative pulmonary complications (PPCs). These studies were different in size, design, population and preoperative risk. We reanalysed the database of 'Local ASsessment of Ventilatory management during General Anaesthesia for Surgery study' (LAS VEGAS) to evaluate differences between females and males with respect to PPCs. Design, setting and patients: Post hoc unmatched and matched analysis of LAS VEGAS, an international observational study in patients undergoing intraoperative ventilation under general anaesthesia for surgery in 146 hospitals across 29 countries. The primary endpoint was a composite of PPCs in the first 5 postoperative days. Individual PPCs, hospital length of stay and mortality were secondary endpoints. Propensity score matching was used to create a similar cohort regarding type of surgery and epidemiological factors with a known association with development of PPCs. Main results: The unmatched cohort consisted of 9697 patients; 5342 (55.1%) females and 4355 (44.9%) males. The matched cohort consisted of 6154 patients; 3077 (50.0%) females and 3077 (50.0%) males. The incidence in PPCs was neither significant between females and males in the unmatched cohort (10.0 vs 10.7%; odds ratio (OR) 0.93 [0.81-1.06]; P = 0.255), nor in the matched cohort (10.5 vs 10.0%; OR 1.05 [0.89-1.25]; P = 0.556). New invasive ventilation occurred less often in females in the unmatched cohort. Hospital length of stay and mortality were similar between females and males in both cohorts. Conclusions: In this conveniently-sized worldwide cohort of patients receiving intraoperative ventilation under general anaesthesia for surgery, the PPC incidence was not significantly different between sexes. Registration: LAS VEGAS was registered at clinicaltrial.gov (study identifier NCT01601223)