Trends in Racial and Ethnic Diversity in Vascular Neurology Fellowships From 2006 to 2018: A Cross-Sectional Analysis.

BACKGROUND: Workforce diversity in vascular neurology is a crucial component of reducing disparities in stroke care and outcomes. The objective of this study is to describe trends in the racial and ethnic diversity of neurology residents pursuing vascular neurology fellowship and propose an actionable plan for improvement. METHODS: This was a cross-sectional study of race/ethnicity of neurology residents and vascular neurology fellows using published Graduate Medical Education census reports from 2006, when race/ethnicity data were first included, to 2018. Percentage of trainees underrepresented in medicine are reported for 3-year epochs and were analyzed using the Cochran-Armitage test (χ2 test for trend). RESULTS: Across the study period, underrepresented in medicine representation has not changed significantly among all neurology residents and subspecialty fellows (11.9% in 2006-2009; 12.5% in 2015-2018, P=0.82) nor among neurology residents alone (12.0% in 2006-2009; 12.6% in 2015-2018, P=0.81). Among vascular neurology fellows, however, there was a significant downtrend of underrepresented in medicine representation from 16.9% in 2006 to 2009 to 9.3% in 2015 to 2018 (P=0.013). CONCLUSIONS: Racial/ethnic underrepresentation among all neurology residents as well as those pursuing vascular neurology fellowship has persisted across the study period. Concerted efforts should be pursued to increase diversity in neurology residents and vascular neurology fellowship training.

Association and predictive value of biomarkers with severe outcomes in hospitalized patients with SARS-CoV-2 infection.

This study analyzed the levels at admission of biomarkers for their association with and ability to predict risk of severe outcomes, including admission to the ICU, need for invasive mechanical ventilation (IMV), need for vasopressor use (VU), and in-hospital mortality (IHM) in 700 patients hospitalized with COVID-19. Biomarker data split by outcomes was compared using Mann-Whitney U tests; frequencies of biomarker values were compared using Chi-square tests and multivariable logistic regression analysis was performed to look at the impact of biomarkers by outcome. Patients that suffered IHM were more likely to have reduced platelet numbers and high blood urea nitrogen (BUN) levels among patients admitted to the ICU. Risk factors for mortality were related to hyper-coagulability (low platelet count and increased D-dimer) and decreased respiratory (PaO2/FiO2 ratio) and kidney function (BUN). Association with risks of other severe outcomes were as follows: ICU with hyper-inflammation (IL-6) and decreased respiratory function; IMV with low platelet count, abnormal neutrophil-lymphocyte ratio with reduced respiratory function, VU with inflammatory markers (IL-6), and low platelet count with respiratory function. Our studies confirmed the association of biomarkers of hematological, inflammatory, coagulation, pulmonary and kidney functions with disease severity. Whether these biomarkers have any mechanistic or causal role in the disease progress requires further investigation.

A case of aphemia following non-dominant sub-insular stroke: unveiling the Foix-Chavany-Marie phenomenon.

Aphemia refers to the clinical syndrome of inability to orally produce speech with intact comprehension and written expression. Aphemia has been primarily reported in dominant frontal lobe strokes resulting in apraxia of speech (AoS), and in Foix-Chavany-Marie (FCM) syndrome where bilateral opercular or sub-opercular lesions result in anarthria due to deafferentation of brainstem nuclei supplying the oro-facio-lingual and pharyngeal musculature. Aphemia is not reported in non-dominant sub-insular strokes. Here, we present a case of aphemia following non-dominant sub-insular stroke in a patient who had previously recovered from a homologous dominant sub-insular stroke without any apparent residual deficits. We discuss the accepted definitions, theories and controversies in the use of the terminology - aphemia, apraxia of speech (AoS), anarthria related to FCM syndrome, a concomitant pathology - unilateral upper motor neuron (UUMN) dysarthria, and their neuro-anatomical bases. We also highlight the importance of attributing localization value to sequential homologous lesions of the brain that can unveil symptoms due to a "loss of compensation phenomenon" that we propose be termed as "FCM phenomenon." These pathological mechanisms may alone or in certain combinations contribute to the clinical syndrome of aphemia included in the diagnostic approach proposed here. The distinction between these mechanisms requires serial careful neurological examination and detailed speech evaluation including in the recovery phase.

Outcomes and Risk Factors for Cardiovascular Events in Hospitalized COVID-19 Patients.

OBJECTIVE: To analyze outcomes and risk factors of cardiovascular events in a metropolitan coronavirus disease 2019 (COVID-19) database, and to perform a subgroup analysis in African American populations to determine whether outcomes and risk factors are influenced by race. DESIGN: Retrospective cohort analysis from March 9, 2020 to June 20, 2020. SETTING: Population-based study in Louisville, KY, USA. PARTICIPANTS: Seven hundred adult inpatients hospitalized with COVID-19. INTERVENTIONS: N/A. MEASUREMENTS AND MAIN RESULTS: This cohort consisted of 126 patients (18%) with cardiovascular events and 574 patients without cardiovascular events. Patients with cardiovascular events had a much higher mortality rate than those without cardiovascular events (45.2% v 8.7%, p < 0.001). There was no difference between African American and white patients regarding mortality (43.9% v 46.3%, p = 1) and length of stay for survivors (11 days v 9.5 days, p = 0.301). Multiple logistics regression analysis suggested that male, race, lower SaO2/FIO2, higher serum potassium, lower serum albumin, and number of cardiovascular comorbidities were highly associated with the occurrence of cardiovascular events in COVID-19 patients. Lower serum albumin and neoplastic and/or immune-compromised diseases were highly associated with cardiovascular events for African American COVID-19 patients. SaO2/FIO2 ratio and cardiovascular comorbidity count were significantly associated with cardiovascular events in white patients. CONCLUSIONS: Cardiovascular events were prevalent and associated with worse outcomes in hospitalized patients with COVID-19. Outcomes of cardiovascular events in African American and white COVID-19 patients were similar after propensity score matching analysis. There were common and unique risk factors for cardiovascular events in African American COVID-19 patients when compared with white patients.

Management of Acute Ischemic Stroke-Specific Focus on Anesthetic Management for Mechanical Thrombectomy.

Acute ischemic stroke is a neurological emergency with a high likelihood of morbidity, mortality, and long-term disability. Modern stroke care involves multidisciplinary management by neurologists, radiologists, neurosurgeons, and anesthesiologists. Current American Heart Association/American Stroke Association (AHA/ASA) guidelines recommend thrombolytic therapy with intravenous (IV) alteplase within the first 3-4.5 hours of initial stroke symptoms and endovascular mechanical thrombectomy within the first 16-24 hours depending on specific inclusion criteria. The anesthesia and critical care provider may become involved for airway management due to worsening neurologic status or to enable computerized tomography (CT) or magnetic resonance imaging (MRI) scanning, to facilitate mechanical thrombectomy, or to manage critical care of stroke patients. Existing data are unclear whether the mechanical thrombectomy procedure is best performed under general anesthesia or sedation. Retrospective cohort trials favor sedation over general anesthesia, but recent randomized controlled trials (RCT) neither suggest superiority nor inferiority of sedation over general anesthesia. Regardless of anesthesia type, a critical element of intraprocedural stroke care is tight blood pressure management. At different phases of stroke care, different blood pressure targets are recommended. This narrative review will focus on the anesthesia and critical care providers' roles in the management of both perioperative stroke and acute ischemic stroke with a focus on anesthetic management for mechanical thrombectomy.

Association of Early Oxygenation Levels with Mortality in Acute Ischemic Stroke - A Retrospective Cohort Study.

BACKGROUND: Ischemic stroke is an emergency with elevated risk for morbidity and mortality. Hypoxia is harmful in acute ischemic stroke. Recent evidence raises concerns regarding hyperoxia as well in acute illness, and for supplemental oxygen therapy when SpO2greater than 92%. Current AHA/ASA guidelines recommend maintaining SpO2greater than 94%. In this study, we aimed to assess the relationship between the oxygenation levels within the first 6-hour of ischemic stroke admission and mortality. METHODS: With the approval of the Human Studies Committee (IRB #: 13.0396), we performed a retrospective cohort study of ischemic stroke patients consecutively admitted to our hospital in the years 2013-14 and 2017-18 (n = 1479). Relationship between the first 6 hours oxygenation status and in-house mortality was assessed. SpO2/FiO2 ratio was used as the oxygenation outcome parameter. Patients who were intubated at admission were excluded. Additionally, demographics, baseline confounding factors, neurological status, and laboratory values on admission were examined for their association with mortality in a multivariate logistic regression analysis. RESULTS: Mean age of patients was 64 ± 15 years. Time interval from last seen normal to hospital admission was 7 ± 5 hours (mean ± standard deviation). NIHSS on arrival was 41-9 (median-IQR). Fourteen percent of patients received IV alteplase and 6% were treated with mechanical thrombectomy. Baseline SpO2 was 97 ± 2%, and 47% of the patients required supplemental oxygen treatment per AHA/ASA guidelines. In hospital mortality rate of this cohort was 5.7%. Lower mean SpO2 /FiO2 levels were strongly correlated with increasing mortality rates (R2 = .973). Age (1.048 [1.028-1.068]), NIHSS (1.120 [1.088-1.154]), WBC (1.116 [1.061-1.175]) and Mean SpO2/FiO2 (.995 [.992-.999]) independently risk associated with mortality. CONCLUSIONS: Baseline oxygenation varies within the acute ischemic stroke patient population. In this retrospective cohort study, we are reporting a strong association between lower SpO2/FiO2 levels in the first few hours of admission and mortality. In the light of these results, we plan to prospectively assess the role of oxygenation further in the context of recanalization status of stroke.

Perioperative Supplemental Oxygen Does Not Worsen Long-Term Mortality of Colorectal Surgery Patients.

BACKGROUND: A follow-up analysis from a large trial of oxygen and surgical-site infections reported increased long-term mortality among patients receiving supplemental oxygen, especially those having cancer surgery. Although concerning, there is no obvious mechanism linking oxygen to long-term mortality. We thus tested the hypothesis that supplemental oxygen does not increase long-term mortality in patients undergoing colorectal surgery. Secondarily, we evaluated whether the effect of supplemental oxygen on mortality depended on cancer status. METHODS: Mortality data were obtained for 927 patients who participated in 2 randomized trials evaluating the effect of supplemental oxygen on wound infection. We assessed the effect of 80% vs 30% oxygen on long-term mortality across 4 clinical sites in the 2 trials using a Cox proportional hazards regression model stratified by study and site. Kaplan-Meier survival estimates were calculated for each trial. Finally, we report site-stratified hazard ratios for patients with and without cancer at baseline. RESULTS: There was no effect of 80% vs 30% oxygen on mortality, with an overall site-stratified hazard ratio of 0.93 (95% confidence interval [CI], 0.72-1.20; P = 0.57). The treatment effect was consistent across the 2 original studies (interaction P = 0.88) and across the 4 sites (P = 0.84). There was no difference between patients with (n = 451) and without (n = 450) cancer (interaction P = 0.51), with hazard ratio of 0.85 (95% CI, 0.64-1.1) for cancer patients and 0.97 (0.53-1.8) for noncancer patients. CONCLUSIONS: In contrast to the only previous publication, we found that supplemental oxygen had no influence on long-term mortality in the overall surgical population or in patients having cancer surgery.

Teaching basic lung isolation skills on human anatomy simulator: attainment and retention of lung isolation skills.

BACKGROUND: Lung isolation skills, such as correct insertion of double lumen endobronchial tube and bronchial blocker, are essential in anesthesia training; however, how to teach novices these skills is underexplored. Our aims were to determine (1) if novices can be trained to a basic proficiency level of lung isolation skills, (2) whether video-didactic and simulation-based trainings are comparable in teaching lung isolation basic skills, and (3) whether novice learners' lung isolation skills decay over time without practice. METHODS: First, five board certified anesthesiologist with experience of more than 100 successful lung isolations were tested on Human Airway Anatomy Simulator (HAAS) to establish Expert proficiency skill level. Thirty senior medical students, who were naive to bronchoscopy and lung isolation techniques (Novice) were randomized to video-didactic and simulation-based trainings to learn lung isolation skills. Before and after training, Novices' performances were scored for correct placement using pass/fail scoring and a 5-point Global Rating Scale (GRS); and time of insertion was recorded. Fourteen novices were retested 2 months later to assess skill decay. RESULTS: Experts' and novices' double lumen endobronchial tube and bronchial blocker passing rates showed similar success rates after training (P >0.99). There were no differences between the video-didactic and simulation-based methods. Novices' time of insertion decayed within 2 months without practice. CONCLUSION: Novices could be trained to basic skill proficiency level of lung isolation. Video-didactic and simulation-based methods we utilized were found equally successful in training novices for lung isolation skills. Acquired skills partially decayed without practice.

Teaching basic fiberoptic intubation skills in a simulator: initial learning and skills decay.

PURPOSE: Generally, novices are taught fiberoptic intubation on patients by attending anesthesiologists; however, this approach raises patient safety concerns. Patient safety should improve if novice learners are trained for basic skills on simulators. In this educational study, we assessed the time and number of attempts required to train novices in fiberoptic bronchoscopy and fiberoptic intubation on simulators. Because decay in skills is inevitable, we also assessed fiberoptic bronchoscopy and fiberoptic intubation skill decay and the amount of effort required to regain fiberoptic bronchoscopy skill. METHODS: First, we established attempt- and duration-based quantitative norms for reaching skill proficiency for fiberoptic bronchoscopy and fiberoptic intubation by experienced anesthesiologists (n = 8) and prepared an 11-step checklist and a 5-point global rating scale for assessment. Novice learners (n = 15) were trained to reach the established skill proficiency in a Virtual Reality simulator for fiberoptic bronchoscopy skills and a Human Airway Anatomy Simulator for fiberoptic intubation skills. Two months later, novices were reassessed to determine decay in learned skills and the required time to retrain them to fiberoptic bronchoscopy proficiency level. RESULTS: Proficiency in fiberoptic bronchoscopy skill level was achieved with 11 ± 5 attempts and after 658 ± 351 s. After 2 months without practice, the time taken by the novices to successful fiberoptic bronchoscopy on the Virtual Reality simulator increased from 41 ± 8 to 68 ± 31 s (P = 0.0138). Time and attempts required to retrain them were 424 ± 230 s and 9.1 ± 4.6 attempts, respectively. CONCLUSION: Novices were successfully trained to proficiency skill level. Although fiberoptic bronchoscopy skills started to decay within 2 months, the re-training time was shorter.

Is video laryngoscope-assisted flexible tracheoscope intubation feasible for patients with predicted difficult airway? A prospective, randomized clinical trial.

BACKGROUND: Failed intubation may result in both increased morbidity and mortality. The combination of a video laryngoscope and a flexible tracheoscope used as a flexible video stylet may improve the success rate of securing a difficult airway. We tested the hypothesis that this combination is a feasible way to facilitate intubation in patients with a predicted difficult airway in that it will shorten intubation times and reduce the number of intubation attempts. METHODS: We conducted a randomized, prospective trial in 140 patients with anticipated difficult airways undergoing elective or urgent surgery. After insertion of video laryngoscope, patients were randomly assigned to either having their tube placed with the use of a preformed stylet (control group) or with a flexible tracheoscope (intervention group). The primary outcome measures were time to successful intubation and number of intubation attempts. RESULTS: The number of intubations requiring 2 or more intubation attempts was similar in the 2 groups (14% control vs 13% intervention, P = 1.0); the number of patients requiring 3 or more intubation attempts was not significantly different (8.6% control vs 1.4% intervention, P = 0.12). Distribution for time to intubation also did not differ between the control (median of 66 seconds, interquartile range 47-89) and the intervention group (median of 71 seconds, interquartile range 52-100; P = 0.35). In the control group, 4 patients, all with cervical spine pathology, had the trachea intubated successfully with the video laryngoscope plus flexible tracheoscope after 3 failed attempts with video laryngoscope and rigid stylet. For these 4 patients, time from the decision to change the intubation method to successful intubation with a flexible tracheoscope was 36 ± 14 seconds. Overall success probability for cervical spine patients was 100% (20/20) in the intervention group and 80% (16/20) in the control group, with an exact 95% confidence interval for the difference of 1.4% to 44%, P = 0.04. CONCLUSIONS: Flexible tracheoscope-assisted video laryngoscopic intubation is a feasible alternative to video laryngoscope only intubation in patients with predicted difficult airways. A flexible tracheoscope used in combination with video laryngoscope may also further increase the success rate of intubation in select patients with a proven difficult airway, particularly when in-line stabilization is required.

Hypercapnia and ventilator-induced diaphragmatic dysfunction.

In the previous issue of Critical Care, Jung and colleagues report on the preventive effects of hypercapnia on ventilator-induced diaphragmatic dysfunction (VIDD) under controlled ventilation. Possibly, a combination of controlled hypercapnia and allowed spontaneous breathing efforts may provide complementary protection for diaphragm and respiratory functionality during mechanical ventilation. However, further safety and efficacy studies need to be performed in various different animal models and patients before a universal application of hypercapnia in the critical care setting for the prevention of VIDD can be considered.

Bispectral index dynamics during propofol hypnosis is similar in red-haired and dark-haired subjects.

BACKGROUND: We have previously shown that red hair is associated with increased desflurane requirement for immobility, compared with dark hair. The effect of red hair on IV anesthetic requirement remains unknown. We tested the hypothesis that the propofol concentration in the effect site associated with half maximal electroencephalogram response, Ce50, is at least 50% higher in subjects with red hair. METHODS: We modeled the propofol concentration versus electroencephalogram response relationship using a 2-step approach in 29 healthy dark- and red-haired volunteers receiving a propofol infusion to produce loss of consciousness. Bispectral Index (BIS) was the measure of drug effect. The parameters of a 3-compartment pharmacokinetic model were fit to measured arterial propofol concentrations. The relationship between effect-site propofol concentration (Ce) and BIS was characterized using a sigmoid Emax model. Model performance and accuracy of the estimated parameters were evaluated using accepted metrics and bootstrap resampling. The effect of hair color on the Ce50 for BIS response in the final model was assessed using a threshold of 6.63 (P<0.01) in reduction of -2 log likelihood. The influence of body weight on the model was also assessed. RESULTS: The inclusion of hair color as a model covariate did not improve either the pharmacokinetic or the pharmacodynamic model. A separate analysis for the dark- and red-haired subjects estimated a median (95% confidence interval) Ce50 BIS of 2.71 µg/mL (2.28-3.36 µg/mL) and 2.57 µg/mL (1.68-3.60 µg/mL), respectively. Body weight was a significant covariate for the CL1 and V1. CONCLUSIONS: Red hair phenotype does not affect the pharmacokinetics or pharmacodynamics of propofol.

Nasopharyngeal Ventilation Compared to Facemask Ventilation: A Prospective, Randomized, Crossover Trial in Two Different Elective Cohorts.

BACKGROUND: Facemask ventilation is routinely used to preoxygenate patients before endotracheal intubation during anesthesia induction or to secure ventilation in patients with respiratory insufficiency. Occasionally, facemask ventilation cannot be performed adequately. The placement of a regular endotracheal tube through the nose into the hypopharynx may be a valid alternative to improve ventilation and oxygenation before endotracheal intubation (nasopharyngeal ventilation). We tested the hypothesis that nasopharyngeal ventilation is superior in its efficacy compared to traditional facemask ventilation. METHODS: In this prospective, randomized, crossover trial, we enrolled surgical patients requiring either nasal intubation (cohort #1, n = 20) or patients who met "difficult to mask ventilate" criteria (cohort #2, n = 20). Patients in each cohort were randomly assigned to receive pressure-controlled facemask ventilation followed by nasopharyngeal ventilation or vice versa. The ventilation settings were kept constant. The primary outcome was tidal volume. The secondary outcome was the difficulty of ventilation, measured using the Warters grading scale. RESULTS: Tidal volume was significantly increased by nasopharyngeal ventilation in cohort #1 (597 ± 156 ml vs.462 ± 220 ml, p = 0.019) and cohort #2 (525 ± 157 ml vs.259 ± 151 ml, p < 0.01). Warters grading scale for mask ventilation was 0.6 ± 1.4 in cohort #1, and 2.6 ± 1.5 in cohort #2. CONCLUSION: Patients at risk for difficult facemask ventilation may benefit from nasopharyngeal ventilation to maintain adequate ventilation and oxygenation before endotracheal intubation. This ventilation mode may offer another option for ventilation at induction of anesthesia and during the management of respiratory insufficiency, especially in the setting of "unexpected" ventilation difficulty.

Acute Multidisciplinary Management of Aneurysmal Subarachnoid Hemorrhage (aSAH).

Aneurysmal subarachnoid hemorrhage is a life-threatening, neurological emergency characterized by accumulation of blood in the subarachnoid space due to a ruptured aneurysm. Over the past several decades, improvements in the clinical management of aneurysmal subarachnoid hemorrhage have led to better patient outcomes. However, aneurysmal subarachnoid hemorrhage is still associated with high morbidity and mortality. During the acute phase of aneurysmal subarachnoid hemorrhage and prior to the definitive management of the aneurysm, numerous medical emergencies, such as elevated intracranial pressure and cerebral vasospasm, must be effectively managed to ensure the best possible neurological outcome. Early and rapid open communication between the clinical specialties caring for the aneurysmal subarachnoid hemorrhage patient is vital for rapid data collection, decision-making, and definitive treatment. In this narrative review, we aim to present the current guidelines for the multidisciplinary acute management of aneurysmal subarachnoid hemorrhage.

Intraoperative Fraction of Inspired Oxygen and Lung Injury in Coronary Artery Bypass Grafting: Study Protocol for a Randomised Controlled Trial.

OBJECTIVE: Postoperative pulmonary complications are a series of disorders that can contribute to respiratory distress and prolonged mechanical ventilation postoperatively. We hypothesise that a liberal oxygenation strategy during cardiac surgery leads to a higher incidence of postoperative pulmonary complications than a restrictive oxygenation strategy. METHODS: This study is a prospective, observer-blinded, centrally randomised and controlled, international multicentre clinical trial. RESULTS: After obtaining a written informed consent, 200 adult patients undergoing coronary artery bypass grafting will be enrolled and randomised to receive either restrictive or liberal oxygenation perioperatively. The liberal oxygenation group will receive 1.0 fraction of inspired oxygen throughout the intraoperative period, including during cardiopulmonary bypass. The restrictive oxygenation group will receive the lowest fraction of inspired oxygen required to maintain arterial partial pressure of oxygen between 100 and 150 mmHg during cardiopulmonary bypass and a pulse oximetry reading of 95% or greater intraoperatively, but no less than 0.3 and not higher than 0.80 (other than induction and when the oxygenation goals cannot be reached). When patients are transferred to the intensive care unit, all patients will receive an initial fraction of inspired oxygen of 0.5, and then fraction of inspired oxygen will be titrated to maintain a pulse oximetry reading of 95% or greater until extubation. The lowest postoperative arterial partial pressure of oxygen/fraction of inspired oxygen within 48 hours of intensive care unit admission will be the primary outcome. Postoperative pulmonary complications, length of mechanical ventilation, intensive care unit stay, hospital stay, and 7-day mortality after cardiac surgery will be analysed as secondary outcomes. CONCLUSION: This is one of the first randomised controlled observer-blinded trials that prospectively evaluates the influence of higher inspired oxygen fractions on early postoperative respiratory and oxygenation outcomes in cardiac surgery patients using cardiopulmonary bypass.

Benefits and harms of perioperative high fraction inspired oxygen for surgical site infection prevention: a protocol for a systematic review and meta-analysis of individual patient data of randomised controlled trials.

INTRODUCTION: The use of high fraction of inspired oxygen (FiO2) intraoperatively for the prevention of surgical site infection (SSI) remains controversial. Promising results of early randomised controlled trials (RCT) have been replicated with varying success and subsequent meta-analysis are equivocal. Recent advancements in perioperative care, including the increased use of laparoscopic surgery and pneumoperitoneum and shifts in fluid and temperature management, can affect peripheral oxygen delivery and may explain the inconsistency in reproducibility. However, the published data provides insufficient detail on the participant level to test these hypotheses. The purpose of this individual participant data meta-analysis is to assess the described benefits and harms of intraoperative high FiO2compared with regular (0.21-0.40) FiO2 and its potential effect modifiers. METHODS AND ANALYSIS: Two reviewers will search medical databases and online trial registries, including MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and WHO regional databases, for randomised and quasi-RCT comparing the effect of intraoperative high FiO2 (0.60-1.00) to regular FiO2 (0.21-0.40) on SSI within 90 days after surgery in adult patients. Secondary outcome will be all-cause mortality within the longest available follow-up. Investigators of the identified trials will be invited to collaborate. Data will be analysed with the one-step approach using the generalised linear mixed model framework and the statistical model appropriate for the type of outcome being analysed (logistic and cox regression, respectively), with a random treatment effect term to account for the clustering of patients within studies. The bias will be assessed using the Cochrane risk-of-bias tool for randomised trials V.2 and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. Prespecified subgroup analyses include use of mechanical ventilation, nitrous oxide, preoperative antibiotic prophylaxis, temperature (<35°C), fluid supplementation (<15 mL/kg/hour) and procedure duration (>2.5 hour). ETHICS AND DISSEMINATION: Ethics approval is not required. Investigators will deidentify individual participant data before it is shared. The results will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42018090261.