Mortality following noncardiac surgery assessed by the Saint Louis University Score (SLUScore) for hypotension: a retrospective observational cohort study.

BACKGROUND: The Saint Louis University Score (SLUScore) was developed to quantify intraoperative blood pressure trajectories and their associated risk for adverse outcomes. This study examines the prevalence and severity of intraoperative hypotension described by the SLUScore and its relationship with 30-day mortality in surgical subtypes. METHODS: This retrospective analysis of perioperative data included surgical cases performed between January 1, 2010, and December 31, 2020. The SLUScore is calculated from cumulative time-periods for which the mean arterial pressure is below a range of hypotensive thresholds. After calculating the SLUScore for each surgical procedure, we quantified the prevalence and severity of intraoperative hypotension for each surgical procedure and the association between intraoperative hypotension and 30-day mortality. We used binary logistic regression to quantify the potential contribution of intraoperative hypotension to mortality. RESULTS: We analysed 490 982 cases (57.7% female; mean age 57 yr); 33.2% of cases had a SLUScore>0, a median SLUScore of 13 (inter-quartile range [IQR] 7-21), with 1.19% average mortality. The SLUScore was associated with mortality in 12/14 surgical groups. The increases in the odds ratio for death within 30 days of surgery per SLUScore increment were: all surgery types 3.5% (95% confidence interval [95% CI] 3.2-3.9); abdominal/transplant surgery 6% (95% CI 1.5-10.7); thoracic surgery1.5% (95% CI 1-3.3); vascular surgery 3.01% (95% CI 1.9-4.05); spine/neurosurgery 1.1% (95% CI 0.1-2.1); orthopaedic surgery 1.4% (95% CI 0.7-2.2); gynaecological surgery 6.3% (95% CI 2.5-10.1); genitourinary surgery 4.84% (95% CI 3.5-6.15); gastrointestinal surgery 5.2% (95% CI 3.9-6.4); gastroendoscopy 5.5% (95% CI 4.4-6.7); general surgery 6.3% (95% CI 5.5-7.1); ear, nose, and throat surgery 1.6% (95% CI 0-3.27); and cardiac electrophysiology (including pacemaker procedures) 6.6% (95% CI 1.1-12.4). CONCLUSIONS: The SLUScore was independently, but variably, associated with 30-day mortality after noncardiac surgery.

Efficacy of Sacubitril-Valsartan on Survival and Cardiac Remodeling in Hypotensive Heart Failure With Reduced Ejection Fraction: A Multicenter Study.

OBJECTIVE: To investigate whether hypotensive patients diagnosed with heart failure and reduced ejection fraction (HFrEF) might benefit from angiotensin receptor-neprilysin inhibitors (ARNis) in real-world practice because patients with baseline systolic blood pressure (SBP) of less than 100 mm Hg have been excluded from landmark trials. PATIENTS AND METHODS: In this multicenter study conducted between January 1, 2013, and December 31, 2021, a total of 7562 symptomatic patients with HFrEF were enrolled and grouped by SBP (hypotension was defined as an SBP of less than 100 mm Hg) and ARNi use as follows: group 1, hypotensive/non-ARNi users (n=484); group 2, hypotensive/ARNi users (n=308); group 3, nonhypotensive/non-ARNi users (n=4560); and group 4, nonhypotensive/ARNi users (n=2210). Inverse probability of treatment weighting was used to balance baseline characteristics for survival analysis. RESULTS: Diverse baseline characteristics and lower rates of medication use were found among non-ARNi users compared with ARNi users. Hypotensive/ARNi users had lower ARNi initiation doses than nonhypotensive/ARNi users. We observed significantly lower mortality, composite heart failure hospitalization, and CV death for hypotensive/ARNi and the other 2 nonhypotensive groups (groups 3 and 4) during a median follow-up of 3.43 years (all P<.05), with a similar effect on reverse remodeling for the hypotensive/ARNi group compared with the hypotensive/non-ARNi group. The event-free survival benefits of ARNi vs renin-angiotensin system inhibitors were consistent with the lower boundary of SBP for clinical benefits found until 88 mm Hg (spline curves) after inverse probability of treatment weighting. CONCLUSION: Patients with HFrEF and hypotension may still benefit from ARNi treatment. Patients with hypotensive HFrEF should not be routinely excluded from ARNi use in a real-world setting.

Low Blood Pressure, Comorbidities, and Ischemic Stroke Mortality in US Veterans.

BACKGROUND AND PURPOSE: Low blood pressure (BP) is associated with higher stroke mortality, although the factors underlying this association have not been fully explored. We investigated prestroke BP and long-term mortality after ischemic stroke in a national sample of US veterans. METHODS: Using a retrospective cohort study design of veterans hospitalized between 2002 and 2007 with a first ischemic stroke and with ≥1 outpatient BP measurements 1 to 18 months before admission, we defined 6 categories each of average prestroke systolic BP (SBP) and diastolic BP, and 7 categories of pulse pressure. Patients were followed-up to 12 years for primary outcomes of all-cause and cardiovascular mortality. We used Cox models to relate prestroke BP indices to mortality and stratified analyses by the presence of preexisting comorbidities (smoking, myocardial infarction, heart failure, atrial fibrillation/flutter, cancer, and dementia), race and ethnicity. RESULTS: Of 29 690 eligible veterans with stroke (mean±SD age 67±12 years, 98% men, 67% White), 2989 (10%) had average prestroke SBP<120 mm Hg. During a follow-up of 4.1±3.3 years, patients with SBP<120 mm Hg experienced 61% all-cause and 27% cardiovascular mortality. In multivariable analyses, patients with the lowest SBP, lowest diastolic BP, and highest pulse pressure had the highest mortality risk: SBP<120 versus 130 to 139 mm Hg (hazard ratio=1.26 [95% CI, 1.19-1.34]); diastolic BP <60 versus 70 to 79 mm Hg (hazard ratio=1.35 [95% CI, 1.23-1.49]); and pulse pressure ≥90 versus 60 to 69 mm Hg (hazard ratio=1.24 [95% CI, 1.15-1.35]). Patients with average SBP<120 mm Hg and at least one comorbidity (smoking, heart disease, cancer, or dementia) had the highest mortality risk (hazard ratio=1.45 [95% CI, 1.37-1.53]). CONCLUSIONS: Compared with normotension, low prestroke BP was associated with mortality after stroke, particularly among patients with at least one comorbidity.

The effect of intra-operative hypotension on acute kidney injury, postoperative mortality and length of stay following emergency hip fracture surgery.

The association between intra-operative hypotension and postoperative acute kidney injury, mortality and length of stay has not been comprehensively evaluated in a large single-centre hip fracture population. We analysed electronic anaesthesia records of 1063 patients undergoing unilateral hip fracture surgery, collected from 2015 to 2018. Acute kidney injury, 3-, 30- and 365-day mortality and length of stay were evaluated to assess the relationship between intra-operative hypotension absolute values (≤ 55, 60, 65, 70 and 75 mmHg) and duration of hypotension. The rate of acute kidney injury was 23.7%, mortality at 3-, 30- and 365 days was 3.7%, 8.0% and 25.3%, respectively, and median (IQR [range]) length of stay 8 (6-12 [0-99]) days. Median (IQR [range]) time ≤ MAP 55, 60, 65, 70 and 75 mmHg was 0 (0-0.5[0-72.1]); 0 (0-4.4 [0-104.9]); 2.2 (0-8.7 [0-144.2]); 6.6 (2.2-19.7 [0-198.8]); 17.5 (6.6-37.1 [0-216.3]) minutes, and percentage of surgery time below these thresholds was 1%, 2.5%, 7.9%, 12% and 21% respectively. There were some univariate associations between hypotension and mortality; however, these were no longer evident in multivariable analysis. Multivariable analysis found no association between hypotension and acute kidney injury. Acute kidney injury was associated with male sex, antihypertensive medications and cardiac/renal comorbidities. Three-day mortality was associated with delay to surgery ? 48 hours, whilst 30-day and 365-day mortality was associated with delay to surgery ≥ 48 hours, impaired cognition and cardiac/renal comorbidities. While the rate of acute kidney injury was similar to other studies, use of vasopressors and fluids to reduce the time spent at hypotensive levels failed to reduce this complication. Intra-operative hypotension at the levels observed in this cohort may not be an important determinant of acute kidney injury, postoperative mortality and length of stay.

Physician-staffed ambulance and increased in-hospital mortality of hypotensive trauma patients following prolonged prehospital stay: A nationwide study.

BACKGROUND: The benefits of physician-staffed emergency medical services (EMS) for trauma patients remain unclear because of the conflicting results on survival. Some studies suggested potential delays in definitive hemostasis due to prolonged prehospital stay when physicians are dispatched to the scene. We examined hypotensive trauma patients who were transported by ambulance, with the hypothesis that physician-staffed ambulances would be associated with increased in-hospital mortality, compared with EMS personnel-staffed ambulances. METHODS: A retrospective cohort study that included hypotensive trauma patients (systolic blood pressure ≤ 90 mm Hg at the scene) transported by ambulance was conducted using the Japan Trauma Data Bank (2004-2019). Physician-staffed ambulances are capable of resuscitative procedures, such as thoracotomy and surgical airway management, while EMS personnel-staffed ambulances could only provide advanced life support. In-hospital mortality and prehospital time until the hospital arrival were compared between patients who were classified based on the type of ambulance. Inverse probability weighting was conducted to adjust baseline characteristics including age, sex, comorbidities, mechanism of injury, vital signs at the scene, injury severity, and ambulance dispatch time. RESULTS: Among 14,652 patients eligible for the study, 738 were transported by a physician-staffed ambulance. In-hospital mortality was higher in the physician-staffed ambulance than in the EMS personnel-staffed ambulance (201/699 [28.8%] vs. 2287/13,090 [17.5%]; odds ratio, 1.90 [1.61-2.26]; adjusted odds ratio, 1.22 [1.14-1.30]; p < 0.01), and the physician-staffed ambulance showed longer prehospital time (50 [36-66] vs. 37 [29-48] min, difference = 12 [11-12] min, p < 0.01). Such potential harm of the physician-staffed ambulance was only observed among patients who arrived at the hospital with persistent hypotension (systolic blood pressure < 90 mm Hg on hospital arrival) in subgroup analyses. CONCLUSION: Physician-staffed ambulances were associated with prolonged prehospital stay and increased in-hospital mortality among hypotensive trauma patients compared with EMS personnel-staffed ambulance. LEVEL OF EVIDENCE: Therapeutic, level IV.

Association of intraoperative hypotension with postoperative morbidity and mortality: systematic review and meta-analysis.

BACKGROUND: Intraoperative hypotension, with varying definitions in literature, may be associated with postoperative complications. The aim of this meta-analysis was to assess the association of intraoperative hypotension with postoperative morbidity and mortality. METHODS: MEDLINE, Embase and Cochrane databases were searched for studies published between January 1990 and August 2018. The primary endpoints were postoperative overall morbidity and mortality. Secondary endpoints were postoperative cardiac outcomes, acute kidney injury, stroke, delirium, surgical outcomes and combined outcomes. Subgroup analyses, sensitivity analyses and a meta-regression were performed to test the robustness of the results and to explore heterogeneity. RESULTS: The search identified 2931 studies, of which 29 were included in the meta-analysis, consisting of 130 862 patients. Intraoperative hypotension was associated with an increased risk of morbidity (odds ratio (OR) 2.08, 95 per cent confidence interval 1.56 to 2.77) and mortality (OR 1.94, 1.32 to 2.84). In the secondary analyses, intraoperative hypotension was associated with cardiac complications (OR 2.44, 1.52 to 3.93) and acute kidney injury (OR 2.69, 1.31 to 5.55). Overall heterogeneity was high, with an I2 value of 88 per cent. When hypotension severity, outcome severity and study population variables were added to the meta-regression, heterogeneity was reduced to 50 per cent. CONCLUSION: Intraoperative hypotension during non-cardiac surgery is associated with postoperative cardiac and renal morbidity, and mortality. A universally accepted standard definition of hypotension would facilitate further research into this topic.

Postoperative Hypotension and Adverse Clinical Outcomes in Patients Without Intraoperative Hypotension, After Noncardiac Surgery.

BACKGROUND: Postoperative hypotension (POH) is associated with major adverse events. However, little is known about the association of blood pressure thresholds and outcomes in postoperative patients without intraoperative hypotension (IOH) on the general-care ward. We evaluated the association of POH with major adverse cardiac or cerebrovascular events (MACCE) in patients without IOH. METHODS: This retrospective analysis included 67,968 noncardiac patient-procedures (2008-2017) for patients discharged to the ward with postoperative mean arterial pressure (MAP) readings, managed for ≥48 hours postsurgery, with no evidence of IOH. The primary outcome was 30-day MACCE evaluated by postoperative MAP thresholds: ≤75, ≤65, and ≤55 mm Hg (POH defined as a single measurement below threshold). Secondary outcomes included all-cause mortality (30-/90-day), 30-day acute myocardial infarction, 30-day acute ischemic stroke, 30-day readmission, 7-day acute kidney injury, and 30-day readmission. Associations between POH and adverse events were also evaluated in a cohort (#2) of 16,034 patient-procedures with IOH (intraoperative MAP ≤65 mm Hg). RESULTS: In patients without IOH, exposure to POH was not associated with MACCE at any investigated MAP threshold (P < .016 was considered significant: ≤75 mm Hg, hazard ratio [HR] 1.18 [98.4% confidence interval {CI} 0.99-1.39], P = .023; ≤65 mm Hg, HR 1.18 [0.99-1.41], P = .028; ≤55 mm Hg, HR 1.23 [0.90-1.71], P = .121); however, associations were observed at all MAP thresholds for secondary outcomes of acute kidney injury and 30-day readmission, for 30-/90-day mortality for MAP ≤65 mm Hg, and 90-day mortality for MAP ≤55 mm Hg, compared to those without POH. No associations were detected between POH and secondary outcomes of acute ischemic stroke or acute myocardial infarction at any MAP threshold. No interaction between POH and IOH was found when we evaluated the association of POH on outcomes in the data set including all patients, regardless of IOH status (P values for interaction terms nonsignificant). When the interaction term was utilized, the association between POH without IOH and MACCE was significant for MAP ≤75 mm Hg (HR 1.20 [1.01-1.41]) and MAP ≤65 mm Hg (HR 1.21 [1.02-1.45]), but not MAP ≤55 mm Hg. Cohort #2 (POH with IOH) showed largely similar results for MACCE: not significant for MAP ≤75 and ≤65 mm Hg, but significant for MAP ≤55 mm Hg (HR 1.53 [1.05-2.22], P = .006). CONCLUSIONS: POH in patients without IOH was not associated with MACCE at any MAP investigated. No interaction was identified between POH and IOH. Large prospective randomized trials are necessary to develop better evidence and inform clinicians the value of postoperative blood pressure management.

Development and Evaluation of a Risk-Adjusted Measure of Intraoperative Hypotension in Patients Having Nonemergent, Noncardiac Surgery.

BACKGROUND: Intraoperative hypotension is common and associated with organ injury and death, although randomized data showing a causal relationship remain sparse. A risk-adjusted measure of intraoperative hypotension may therefore contribute to quality improvement efforts. METHODS: The measure we developed defines hypotension as a mean arterial pressure <65 mm Hg sustained for at least 15 cumulative minutes. Comparisons are based on whether clinicians have more or fewer cases of hypotension than expected over 12 months, given their patient mix. The measure was developed and evaluated with data from 225,389 surgeries in 5 hospitals. We assessed discrimination and calibration of the risk adjustment model, then calculated the distribution of clinician-level measure scores, and finally estimated the signal-to-noise reliability and predictive validity of the measure. RESULTS: The risk adjustment model showed acceptable calibration and discrimination (area under the curve was 0.72 and 0.73 in different validation samples). Clinician-level, risk-adjusted scores varied widely, and 36% of clinicians had significantly more cases of intraoperative hypotension than predicted. Clinician-level score distributions differed across hospitals, indicating substantial hospital-level variation. The mean signal-to-noise reliability estimate was 0.87 among all clinicians and 0.94 among clinicians with >30 cases during the 12-month measurement period. Kidney injury and in-hospital mortality were most common in patients whose anesthesia providers had worse scores. However, a sensitivity analysis in 1 hospital showed that score distributions differed markedly between anesthesiology fellows and attending anesthesiologists or certified registered nurse anesthetists; score distributions also varied as a function of the fraction of cases that were inpatients. CONCLUSIONS: Intraoperative hypotension was common and was associated with acute kidney injury and in-hospital mortality. There were substantial variations in clinician-level scores, and the measure score distribution suggests that there may be opportunity to reduce hypotension which may improve patient safety and outcomes. However, sensitivity analyses suggest that some portion of the variation results from limitations of risk adjustment. Future versions of the measure should risk adjust for important patient and procedural factors including comorbidities and surgical complexity, although this will require more consistent structured data capture in anesthesia information management systems. Including structured data on additional risk factors may improve hypotension risk prediction which is integral to the measure's validity.

What Are the Frequency, Related Mortality, and Factors Associated with Bone Cement Implantation Syndrome in Arthroplasty Surgery?

BACKGROUND: Bone cement implantation syndrome (BCIS) is characterized by hypoxia, hypotension, and the loss of consciousness during cemented arthroplasty; it may result in death. Its incidence has only been explored for hemiarthroplasty and THA after fracture or cancer. To our knowledge, there are no studies that comprehensively explore and compare the incidence of BCIS in other arthroplasty procedures. QUESTIONS/PURPOSES: (1) To report the incidence of BCIS in TKA, unicondylar knee arthroplasty, hip hemiarthroplasty, THA, shoulder arthroplasty, TKA, and revision THA and TKA; (2) to determine whether severe BCIS is associated with an increased risk of death within 30 days of surgery; and (3) to identify factors associated with the development of severe BCIS. METHODS: All patients undergoing cemented arthroplasty for any reason (TKA [11% cemented, 766 of 7293], unicondylar knee arthroplasty [100% cemented, 562 procedures], hip hemiarthroplasty for femur fractures [100% cemented, 969 procedures], THA [8% cemented, 683 of 8447], shoulder arthroplasty [84% cemented, 185 of 219], and revision arthroplasty of the hip and knee [36% cemented, 240 of 660]) between January 2008 and August 2019 were considered for inclusion in the current retrospective observational study. Fixation choice was dependent on surgeon preference (THA and TKA), prosthesis design (shoulder arthroplasty), or bone quality (revision arthroplasty). The following procedures were excluded because of insufficient data: < 1% (1 of 766) of TKAs, 1% (4 of 562) of unicondylar knee arthroplasties, 6% (54 of 969) of hip hemiarthroplasties, 1% (6 of 683) of THAs, 6% (12 of 185) of shoulder arthroplasties, and 14% (34 of 240) of revision procedures. This resulted in a final inclusion of 3294 procedures (765 TKAs [23%], 558 unicondylar knee arthroplasties [17%], 915 hip hemiarthroplasties [28%], 677 THA [21%], 173 shoulder arthroplasties [5%], and 206 revision arthroplasties [6%]), of which 28% (930 of 3294) had an emergent indication for surgery. Of the patients, 68% (2240 of 3294) were females, with a mean age of 75 ± 11 years. All anesthetic records were extracted from our hospital's database, and the severity of BCIS was retrospectively scored (Grade 0 [no BCIS], Grade 1 [O2% < 94% or fall in systolic blood pressure of 20% to 40%], Grade 2 [O2% < 88% or fall in systolic blood pressure of > 40%], and Grade 3 [cardiovascular collapse requiring CPR]). Procedures were dichotomized into no or moderate BCIS (Grades 0 and 1) and severe BCIS (Grades 2 and 3). The adjusted 30-day mortality of patients with severe BCIS was assessed with a multivariate Cox regression analysis. A multivariate logistic regression analysis was performed to identify factors associated with the development of severe BCIS. RESULTS: BCIS occurred in 26% (845 of 3294) of arthoplasty procedures. The incidence was 31% (282 of 915) in hip hemiarthroplasty, 28% (210 of 765) in TKA, 24% (165 of 677) in THA, 23% (47 of 206) in revision arthroplasty, 20% (113 of 558) in unicondylar knee arthroplasty, and 16% (28 of 173) in shoulder arthroplasty. Patients with severe BCIS were more likely (hazard ratio 3.46 [95% confidence interval 2.07 to 5.77]; p < 0.001) to die within 30 days of the index procedure than were patients with less severe or no BCIS. Factors independently associated with the development of severe BCIS were age older than 75 years (odds ratio 1.57 [95% CI 1.09 to 2.27]; p = 0.02), American Society of Anesthesiologists Class III or IV (OR 1.58 [95% CI 1.09 to 2.30]; p = 0.02), and renal impairment (OR 3.32 [95% CI 1.45 to 7.46]; p = 0.004). CONCLUSION: BCIS is common during cemented arthroplasty; severe BCIS is uncommon, but it is associated with an increased risk of death within 30 days of surgery. Medically complex patients undergoing hip hemiarthroplasty may be at particular risk. Patients at high risk for severe BCIS (renal impairment, ASA III/IV, and age older than 75 years) should be identified and preventive measures such as medullary lavage before cementation, femoral venting, and avoidance of excessive pressurization of implants should be taken to reduce the likelihood and consequences of BCIS. Because of the increased risk of periprosthetic fractures in uncemented hip stems, factors associated with the development of BCIS should be weighed against the risk factors for sustaining periprosthetic fractures (poor bone quality, female sex) to balance the risks of fixation method against those of BCIS for each patient. LEVEL OF EVIDENCE: Level III, therapeutic study.

Risk factors and impact of postoperative hypotension after carotid artery stenting in the Vascular Quality Initiative.

OBJECTIVE: Hypotension is a frequent complication of carotid artery stenting (CAS). Although common, its occurrence is unpredictable, and association with adverse events has not been well defined. The aim of this study was to identify predictors of postoperative hypotension after CAS and the association with stroke/transient ischemic attack (TIA), major adverse cardiac events (MACEs), increased length of stay (LOS), and in-hospital mortality. METHODS: This is a retrospective analysis of all CAS procedures, including transfemoral CAS (TF-CAS) and transcarotid artery revascularization (TCAR), performed in the Vascular Quality Initiative between 2003 and 2018. The primary study end point was postoperative hypotension, defined as hypotension treated with continuous infusion of a vasoactive agent for ≥15 minutes. Secondary end points included any postoperative neurologic events (stroke/TIA), MACEs (myocardial infarction, congestive heart failure, and dysrhythmias), prolonged LOS (>1 day), and in-hospital mortality. Patients' demographics predictive of hypotension were determined by multivariable logistic regression, and a risk score was developed for correlation with outcomes. RESULTS: During the time period of study, 24,699 patients underwent CAS; 19,716 (80%) were TF-CAS, 3879 (16%) were TCAR, and 1104 (4%) were not defined. Fifty-six percent were for symptomatic disease, 75% were for a primary atherosclerotic lesion, and 72% were performed under local or regional anesthesia. Postoperative hypotension occurred in 15% of TF-CAS and 14% of TCAR patients (P = .50). Patients with hypotension (vs no hypotension) had higher rates of stroke/TIA (7.3% vs 2.6%; P < .001), MACEs (9.6% vs 2.1%; P < .001), prolonged LOS (65% vs 28%; P < .001), and in-hospital mortality (2.9% vs 0.7%; P < .001). By multivariable analysis, risk factors associated with hypotension included an atherosclerotic (vs restenotic) lesion (odds ratio, 2.2; 95% confidence interval, 2.0-2.4; P < .001), female sex (1.3 [1.2-1.4]; P < .001), positive stress test result (1.3 [1.2-1.4]; P < .001), age 70 to 79 years (1.1 [1.1-1.3]; P < .002), age >80 years (1.2 [1.1-1.4]; P < .001), history of myocardial infarction or angina (1.3 [1.2-1.4]; P < .001), and an urgent (vs elective) procedure (1.1 [1.0-1.2]; P < .01). A history of hypertension was protective (0.9 [0.8-0.9]; P < .02). A normalized risk score for hypotension was created from the multivariable model. Increasing risk scores correlated directly with rates of adverse events, including postoperative stroke/TIA, MACEs, increased LOS, and increased in-hospital mortality. CONCLUSIONS: Hypotension after CAS is associated with adverse neurologic and cardiac events as well as with prolonged LOS and in-hospital mortality. A scoring tool may be valuable in stratifying patients at risk. Interventions aimed at preventing postoperative hypotension may improve outcomes with CAS.

The cumulative duration of bispectral index less than 40 concurrent with hypotension is associated with 90-day postoperative mortality: a retrospective study.

BACKGROUND: The relationship between intraoperative low bispectral index (BIS) values and poor clinical outcomes has been controversial. Intraoperative hypotension is associated with postoperative complication. The purpose of this study was to investigate the influence of intraoperative low BIS values and hypotension on postoperative mortality in patients undergoing major abdominal surgery. METHODS: This retrospective study analyzed 1862 cases of general anesthesia. We collected the cumulative time of BIS values below 20 and 40 as well as electroencephalographic suppression and documented the incidences in which these states were maintained for at least 5 min. Durations of intraoperative mean arterial pressures (MAP) less than 50 mmHg were also recorded. Multivariable logistic regression was used to evaluate the association between suspected risk factors and postoperative mortality. RESULTS: Ninety-day mortality and 180-day mortality were 1.5 and 3.2% respectively. The cumulative time in minutes for BIS values falling below 40 coupled with MAP falling below 50 mmHg was associated with 90-day mortality (odds ratio, 1.26; 95% confidence interval, 1.04-1.53; P = .019). We found no association between BIS related values and 180-day mortality. CONCLUSIONS: The cumulative duration of BIS values less than 40 concurrent with MAP less than 50 mmHg was associated with 90-day postoperative mortality, not 180-day postoperative mortality.

Characteristics and outcomes of rapid response team activations for hypotension in orthopaedic patients.

BACKGROUND: Hypotension following orthopaedic surgery has been associated with increased morbidity and mortality. Rapid response teams (RRT) review patients on hospital wards with hypotension. AIM: To evaluate the epidemiology of hypotensive RRT activations in adult orthopaedic patients to identify contributing factors and areas for future quality improvement. METHODS: Timing of RRT activations, presumed causes of hypotension and associated treatments were assessed. RESULTS: Among 963 RRT activations in 605 patients over 3 years, the first calls of 226 of 605 patients were due to hypotension, and 213 (94.2%) of 226 had sufficient data for analysis. The median age was 79 (interquartile range 66-87) years; 58 (27.2%) were male, and comorbidities were common. Most (68%) surgery was emergent, and 75.1% received intraoperative vasopressors for hypotension. Most activations occurred within 24 h of surgery, and hypovolaemia, infection and arrhythmias were common presumed causes. Fluid boluses occurred in 173 (81.2%), and the time between surgery and RRT activation was 10 (4.0-26.5) h. in cases where fluid boluses were given, compared with 33 (15.5-61.5) h. where they were not (P < 0.001). Blood transfusion (30, 14.1%) and withholding of medications were also common. Hospital mortality was 8.5% (18), and 13.6% (29) were admitted to critical care at some stage. In-hospital death was associated with older age, functional dependence, arrhythmia and presumed infection. CONCLUSIONS: Hypotension-related RRT calls in orthopaedic patients are common. Future interventional studies might focus on perioperative fluid therapy and vaso-active medications, as well as withholding of anti-hypertensive medications preoperatively.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity in adults undergoing non-cardiac surgery.

BACKGROUND: Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in an unselected population remains a controversial issue. A previous version of this review assessing the effectiveness of perioperative beta-blockers in cardiac and non-cardiac surgery was last published in 2018. The previous review has now been split into two reviews according to type of surgery. This is an update, and assesses the evidence in non-cardiac surgery only. OBJECTIVES: To assess the effectiveness of perioperatively administered beta-blockers for the prevention of surgery-related mortality and morbidity in adults undergoing non-cardiac surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Biosis Previews and Conference Proceedings Citation Index-Science on 28 June 2019. We searched clinical trials registers and grey literature, and conducted backward- and forward-citation searching of relevant articles. SELECTION CRITERIA: We included RCTs and quasi-randomized studies comparing beta-blockers with a control (placebo or standard care) administered during the perioperative period to adults undergoing non-cardiac surgery. If studies included surgery with different types of anaesthesia, we included them if 70% participants, or at least 100 participants, received general anaesthesia. We excluded studies in which all participants in the standard care control group were given a pharmacological agent that was not given to participants in the intervention group, studies in which all participants in the control group were given a beta-blocker, and studies in which beta-blockers were given with an additional agent (e.g. magnesium). We excluded studies that did not measure or report review outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 83 RCTs with 14,967 participants; we found no quasi-randomized studies. All participants were undergoing non-cardiac surgery, and types of surgery ranged from low to high risk. Types of beta-blockers were: propranolol, metoprolol, esmolol, landiolol, nadolol, atenolol, labetalol, oxprenolol, and pindolol. In nine studies, beta-blockers were titrated according to heart rate or blood pressure. Duration of administration varied between studies, as did the time at which drugs were administered; in most studies, it was intraoperatively, but in 18 studies it was before surgery, in six postoperatively, one multi-arm study included groups of different timings, and one study did not report timing of drug administration. Overall, we found that more than half of the studies did not sufficiently report methods used for randomization. All studies in which the control was standard care were at high risk of performance bias because of the open-label study design. Only two studies were prospectively registered with clinical trials registers, which limited the assessment of reporting bias. In six studies, participants in the control group were given beta-blockers as rescue therapy during the study period.The evidence for all-cause mortality at 30 days was uncertain; based on the risk of death in the control group of 25 per 1000, the effect with beta-blockers was between two fewer and 13 more per 1000 (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.89 to 1.54; 16 studies, 11,446 participants; low-certainty evidence). Beta-blockers may reduce the incidence of myocardial infarction by 13 fewer incidences per 1000 (RR 0.72, 95% CI 0.60 to 0.87; 12 studies, 10,520 participants; low-certainty evidence). We found no evidence of a difference in cerebrovascular events (RR 1.65, 95% CI 0.97 to 2.81; 6 studies, 9460 participants; low-certainty evidence), or in ventricular arrhythmias (RR 0.72, 95% CI 0.35 to 1.47; 5 studies, 476 participants; very low-certainty evidence). Beta-blockers may reduce atrial fibrillation or flutter by 26 fewer incidences per 1000 (RR 0.41, 95% CI 0.21 to 0.79; 9 studies, 9080 participants; low-certainty evidence). However, beta-blockers may increase bradycardia by 55 more incidences per 1000 (RR 2.49, 95% CI 1.74 to 3.56; 49 studies, 12,239 participants; low-certainty evidence), and hypotension by 44 more per 1000 (RR 1.40, 95% CI 1.29 to 1.51; 49 studies, 12,304 participants; moderate-certainty evidence).We downgraded the certainty of the evidence owing to study limitations; some studies had high risks of bias, and the effects were sometimes altered when we excluded studies with a standard care control group (including only placebo-controlled trials showed an increase in early mortality and cerebrovascular events with beta-blockers). We also downgraded for inconsistency; one large, well-conducted, international study found a reduction in myocardial infarction, and an increase in cerebrovascular events and all-cause mortality, when beta-blockers were used, but other studies showed no evidence of a difference. We could not explain the reason for the inconsistency in the evidence for ventricular arrhythmias, and we also downgraded this outcome for imprecision because we found few studies with few participants. AUTHORS' CONCLUSIONS: The evidence for early all-cause mortality with perioperative beta-blockers was uncertain. We found no evidence of a difference in cerebrovascular events or ventricular arrhythmias, and the certainty of the evidence for these outcomes was low and very low. We found low-certainty evidence that beta-blockers may reduce atrial fibrillation and myocardial infarctions. However, beta-blockers may increase bradycardia (low-certainty evidence) and probably increase hypotension (moderate-certainty evidence). Further evidence from large placebo-controlled trials is likely to increase the certainty of these findings, and we recommend the assessment of impact on quality of life. We found 18 studies awaiting classification; inclusion of these studies in future updates may also increase the certainty of the evidence.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity in adults undergoing cardiac surgery.

BACKGROUND: Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. A previous version of this review assessing the effectiveness of perioperative beta-blockers in cardiac and non-cardiac surgery was last published in 2018. The previous review has now been split into two reviews according to type of surgery. This is an update and assesses the evidence in cardiac surgery only. OBJECTIVES: To assess the effectiveness of perioperatively administered beta-blockers for the prevention of surgery-related mortality and morbidity in adults undergoing cardiac surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Biosis Previews and Conference Proceedings Citation Index-Science on 28 June 2019. We searched clinical trials registers and grey literature, and conducted backward- and forward-citation searching of relevant articles. SELECTION CRITERIA: We included RCTs and quasi-randomized studies comparing beta-blockers with a control (placebo or standard care) administered during the perioperative period to adults undergoing cardiac surgery. We excluded studies in which all participants in the standard care control group were given a pharmacological agent that was not given to participants in the intervention group, studies in which all participants in the control group were given a beta-blocker, and studies in which beta-blockers were given with an additional agent (e.g. magnesium). We excluded studies that did not measure or report review outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 63 studies with 7768 participants; six studies were quasi-randomized and the remaining were RCTs. All participants were undergoing cardiac surgery, and in most studies, at least some of the participants were previously taking beta-blockers. Types of beta-blockers were: propranolol, metoprolol, sotalol, esmolol, landiolol, acebutolol, timolol, carvedilol, nadolol, and atenolol. In twelve studies, beta-blockers were titrated according to heart rate or blood pressure. Duration of administration varied between studies, as did the time at which drugs were administered; in nine studies this was before surgery, in 20 studies during surgery, and in the remaining studies beta-blockers were started postoperatively. Overall, we found that most studies did not report sufficient details for us to adequately assess risk of bias. In particular, few studies reported methods used to randomize participants to groups. In some studies, participants in the control group were given beta-blockers as rescue therapy during the study period, and all studies in which the control was standard care were at high risk of performance bias because of the open-label study design. No studies were prospectively registered with clinical trials registers, which limited the assessment of reporting bias. We judged 68% studies to be at high risk of bias in at least one domain.Study authors reported few deaths (7 per 1000 in both the intervention and control groups), and we found low-certainty evidence that beta-blockers may make little or no difference to all-cause mortality at 30 days (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.47 to 1.90; 29 studies, 4099 participants). For myocardial infarctions, we found no evidence of a difference in events (RR 1.05, 95% CI 0.72 to 1.52; 25 studies, 3946 participants; low-certainty evidence). Few study authors reported cerebrovascular events, and the evidence was uncertain (RR 1.37, 95% CI 0.51 to 3.67; 5 studies, 1471 participants; very low-certainty evidence). Based on a control risk of 54 per 1000, we found low-certainty evidence that beta-blockers may reduce episodes of ventricular arrhythmias by 32 episodes per 1000 (RR 0.40, 95% CI 0.25 to 0.63; 12 studies, 2296 participants). For atrial fibrillation or flutter, there may be 163 fewer incidences with beta-blockers, based on a control risk of 327 incidences per 1000 (RR 0.50, 95% CI 0.42 to 0.59; 40 studies, 5650 participants; low-certainty evidence). However, the evidence for bradycardia and hypotension was less certain. We found that beta-blockers may make little or no difference to bradycardia (RR 1.63, 95% CI 0.92 to 2.91; 12 studies, 1640 participants; low-certainty evidence), or hypotension (RR 1.84, 95% CI 0.89 to 3.80; 10 studies, 1538 participants; low-certainty evidence).We used GRADE to downgrade the certainty of evidence. Owing to studies at high risk of bias in at least one domain, we downgraded each outcome for study limitations. Based on effect size calculations in the previous review, we found an insufficient number of participants in all outcomes (except atrial fibrillation) and, for some outcomes, we noted a wide confidence interval; therefore, we also downgraded outcomes owing to imprecision. The evidence for atrial fibrillation and length of hospital stay had a moderate level of statistical heterogeneity which we could not explain, and we, therefore, downgraded these outcomes for inconsistency. AUTHORS' CONCLUSIONS: We found no evidence of a difference in early all-cause mortality, myocardial infarction, cerebrovascular events, hypotension and bradycardia. However, there may be a reduction in atrial fibrillation and ventricular arrhythmias when beta-blockers are used. A larger sample size is likely to increase the certainty of this evidence. Four studies awaiting classification may alter the conclusions of this review.

Association of intra-operative hypotension with acute kidney injury, myocardial injury and mortality in non-cardiac surgery: A meta-analysis.

BACKGROUND: Intra-operative hypotension might induce poor postoperative outcomes in non-cardiac surgery, and the relationship between the level or duration of Intra-operative hypotension (IOH) and postoperative adverse events is still unclear. In this study, we performed a meta-analysis to determine how IOH could affect acute kidney injury (AKI), myocardial injury and mortality in non-cardiac surgery. METHODS: We searched PubMed (Medline), Embase, Springer, The Cochrane Library, Ovid and Google Scholar, and retrieved the related clinical trials on intra-operative hypotension and prognosis in non-cardiac surgery. RESULTS: Fifteen observational studies were included. The meta-analysis showed that in non-cardiac surgery, intra-operative hypotension (mean arterial pressure [MAP]) <60 mm Hg for more than 1 minute was associated with an increased risk of postoperative acute kidney injury(AKI) [1-5 minutes: odds ratio (OR) = 1.13, 95% CI (1.04, 1.23), I2  = 0, P = .003; 5-10 minutes: OR = 1.18, 95% CI (1.07, 1.31), I2  = 0, P = .001; >10 minutes: OR = 1.35, 95% CI (1.1, 1.67), I2  = 52.6%, P = .004] and myocardial injury [1-5 minutes: OR = 1.16, 95% CI (1.01, 1.33), I2  = 30.6%, P = .04; 5-10 minutes: OR = 1.34, 95% CI (1.01, 1.77), I2  = 70.4%, P = .046; >10 minutes: OR = 1.43, 95% CI (1.18, 1.72), I2  = 39.4%, P < .0001]. Intra-operative hypotension (MAP < 60 mm Hg) for 1-5 minutes was not associated with postoperative 30-day mortality [OR = 1.15, 95% CI (0.95, 1.4), I2  = 0, P = .154], but intra-operative hypotension (MAP < 60 mm Hg) for more than 5 min was associated with an increased risk of postoperative 30-day mortality [OR = 1.11, 95% CI (1.06, 1.17), I2  = 51.9%, P < .0001]. CONCLUSION: Intra-operative hypotension was associated with an increased risk of postoperative AKI, myocardial injury and 30-day mortality in non-cardiac surgery. Intra-operative MAP < 60 mm Hg more than 1 minute should be avoided.

Implementation of a prehospital air medical thawed plasma program: Is it even feasible?

BACKGROUND: The Prehospital Air Medical Plasma (PAMPer) trial demonstrated a 30-day survival benefit among hypotensive trauma patients treated with prehospital plasma during air medical transport. We characterized resources, costs and feasibility of air medical prehospital plasma program implementation. METHODS: We performed a secondary analysis using data derived from the recent PAMPer trial. Intervention patients received thawed plasma (5-day shelf life). Unused plasma units were recycled back to blood bank affiliates, when possible. Distribution method and capability of recycling varied across sites. We determined the status of plasma units deployed, utilized, wasted, and returned. We inventoried thawed plasma use and annualized costs for distribution and recovery. RESULTS: The PAMPer trial screened 7,275 patients and 5,103 plasma units were deployed across 22 air medical bases during a 42-month period. Only 368 (7.2%) units of this total thawed plasma pool were provided to plasma randomized PAMPer patients. Of the total plasma pool, 3,716 (72.8%) units of plasma were returned to the blood bank with the potential for transfusion prior to expiration and 1,019 (20.0%) thawed plasma units were deemed wasted for this analysis. The estimated average annual cost of implementation of a thawed plasma program per air medical base at an average courier distance would be between US $24,343 and US $30,077, depending on the ability to recycle plasma and distance of courier delivery required. CONCLUSION: A prehospital plasma program utilizing thawed plasma is resource intensive. Plasma waste can be minimized depending on trauma center and blood bank specific logistics. Implementation of a thawed plasma program can occur with financial cost. Products with a longer shelf life, such as liquid plasma or freeze-dried plasma, may provide a more cost-effective prehospital product relative to thawed plasma. LEVEL OF EVIDENCE: Therapeutic, level III.

Triple-low Alerts Do Not Reduce Mortality: A Real-time Randomized Trial.

BACKGROUND: Triple-low events (mean arterial pressure less than 75 mmHg, Bispectral Index less than 45, and minimum alveolar fraction less than 0.8) are associated with mortality but may not be causal. This study tested the hypothesis that providing triple-low alerts to clinicians reduces 90-day mortality. METHODS: Adults having noncardiac surgery with volatile anesthesia and Bispectral Index monitoring were electronically screened for triple-low events. Patients having triple-low events were randomized in real time, with clinicians either receiving an alert, "consider hemodynamic support," or not. Patients were blinded to treatment. Helpful responses to triple-low events were defined by administration of a vasopressor within 5 min or a 20% reduction in end-tidal volatile anesthetic concentration within 15 min. RESULTS: Of the qualifying patients, 7,569 of 36,670 (20%) had triple-low events and were randomized. All 7,569 were included in the primary analysis. Ninety-day mortality was 8.3% in the alert group and 7.3% in the nonalert group. The hazard ratio (95% CI) for alert versus nonalert was 1.14 (0.96, 1.35); P = 0.12, crossing a prespecified futility boundary. Clinical responses were helpful in about half the patients in each group, with 51% of alert patients and 47% of nonalert patients receiving vasopressors or having anesthetics lowered after start of triple low (P < 0.001). There was no relationship between the response to triple-low events and adjusted 90-day mortality. CONCLUSIONS: Real-time alerts to triple-low events did not lead to a reduction in 90-day mortality, and there were fewer responses to alerts than expected. However, similar mortality with and without responses suggests that there is no strong relationship between responses to triple-low events and mortality.

Risk factors and inpatient outcomes associated with acute kidney injury at pediatric severe sepsis presentation.

BACKGROUND: Little data exist on acute kidney injury (AKI) risk factors in pediatric sepsis. We identified risk factors and inpatient outcomes associated with AKI at sepsis recognition in children with severe sepsis. METHODS: Retrospective, cross-sectional study with inpatient outcome description of 315 patients > 1 month to < 20 years old with severe sepsis in a pediatric intensive care unit over 3 years. Exposures included demographics, vitals, and laboratory data. The primary outcome was kidney disease: Improving Global Outcomes creatinine-defined AKI within 24 h of sepsis recognition. Factors associated with AKI and AKI severity were identified using multivariable Poisson and multinomial logistic regression, respectively. RESULTS: AKI was present in 42% (133/315) of severe sepsis patients, and 26% (83/315) had severe (stage 2/3) AKI. In multivariable-adjusted analysis, hematologic/immunologic comorbidities, malignancies, chronic kidney disease (CKD), abdominal infection, admission illness severity, and minimum systolic blood pressure (SBP) ≤ 5th percentile for age and sex within 24 h of sepsis recognition were associated with AKI. Factors associated with mild AKI were CKD and abdominal infection, while factors associated with severe AKI were younger age, hematologic/immunologic comorbidities, malignancy, abdominal infection, and minimum SBP ≤ 5th percentile. Patients with AKI had increased hospital mortality (17 vs. 8%, P = 0.02) and length of stay [median 20 (IQR 10-47) vs. 16 days (IQR 7-37), P = 0.03]. CONCLUSIONS: In pediatric severe sepsis, AKI is associated with age, comorbidities, infection characteristics, and hypotension. Future evaluation of risk factors for AKI progression during sepsis is warranted to minimize AKI progression in this high-risk population.

Outcomes following trauma laparotomy for hypotensive trauma patients: A UK military and civilian perspective.

BACKGROUND: The management of trauma patients has changed radically in the last decade, and studies have shown overall improvements in survival. However, reduction in mortality for the many may obscure a lack of progress in some high-risk patients. We sought to examine the outcomes for hypotensive patients requiring laparotomy in UK military and civilian cohorts. METHODS: We undertook a review of two prospectively maintained trauma databases: the UK Joint Theatre Trauma Registry for the military cohort (February 4, 2003, to September 21, 2014) and the trauma registry of the Royal London Hospital major trauma center (January 1, 2012, to January 1, 2017) for civilian patients. Adults undergoing trauma laparotomy within 90 minutes of arrival at the emergency department (ED) were included. RESULTS: Hypotension was present on arrival at the ED in 155 (20.4%) of 761 military patients. Mortality was higher in hypotensive casualties (25.8% vs. 9.7% in normotensive casualties; p < 0.001). Hypotension was present on arrival at the ED in 63 (35.7%) of 176 civilian patients. Mortality was higher in hypotensive patients (47.6% vs. 12.4% in normotensive patients; p < 0.001). In both cohorts of hypotensive patients, neither the average injury severity, the prehospital time, the ED arrival systolic blood pressure, nor mortality rate changed significantly during the study period. CONCLUSIONS: Despite improvements in survival after trauma for patients overall, the mortality for patients undergoing laparotomy who arrive at the ED with hypotension has not changed and appears stubbornly resistant to all efforts. Specific enquiry and research should continue to be directed at this high-risk group of patients. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, level IV.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

BACKGROUND: Randomized controlled trials have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. OBJECTIVES: The objective of this review was to systematically analyse the effects of perioperatively administered beta-blockers for prevention of surgery-related mortality and morbidity in patients undergoing any type of surgery while under general anaesthesia. SEARCH METHODS: We identified trials by searching the following databases from the date of their inception until June 2013: MEDLINE, Embase , the Cochrane Central Register of Controlled Trials (CENTRAL), Biosis Previews, CAB Abstracts, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Derwent Drug File, Science Citation Index Expanded, Life Sciences Collection, Global Health and PASCAL. In addition, we searched online resources to identify grey literature. SELECTION CRITERIA: We included randomized controlled trials if participants were randomly assigned to a beta-blocker group or a control group (standard care or placebo). Surgery (any type) had to be performed with all or at least a significant proportion of participants under general anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from all studies. In cases of disagreement, we reassessed the respective studies to reach consensus. We computed summary estimates in the absence of significant clinical heterogeneity. Risk ratios (RRs) were used for dichotomous outcomes, and mean differences (MDs) were used for continuous outcomes. We performed subgroup analyses for various potential effect modifiers. MAIN RESULTS: We included 88 randomized controlled trials with 19,161 participants. Six studies (7%) met the highest methodological quality criteria (studies with overall low risk of bias: adequate sequence generation, adequate allocation concealment, double/triple-blinded design with a placebo group, intention-to-treat analysis), whereas in the remaining trials, some form of bias was present or could not be definitively excluded (studies with overall unclear or high risk of bias). Outcomes were evaluated separately for cardiac and non-cardiac surgery.CARDIAC SURGERY (53 trials)We found no clear evidence of an effect of beta-blockers on the following outcomes.• All-cause mortality: RR 0.73, 95% CI 0.35 to 1.52, 3783 participants, moderate quality evidence.• Acute myocardial infarction (AMI): RR 1.04, 95% CI 0.71 to 1.51, 3553 participants, moderate quality evidence.• Myocardial ischaemia: RR 0.51, 95% CI 0.25 to 1.05, 166 participants, low quality evidence.• Cerebrovascular events: RR 1.52, 95% CI 0.58 to 4.02, 1400 participants, low quality evidence.• Hypotension: RR 1.54, 95% CI 0.67 to 3.51, 558 participants, low quality evidence.• Bradycardia: RR 1.61, 95% CI 0.97 to 2.66, 660 participants, low quality evidence.• Congestive heart failure: RR 0.22, 95% CI 0.04 to 1.34, 311 participants, low quality evidence.Beta-blockers significantly reduced the occurrence of the following endpoints.• Ventricular arrhythmias: RR 0.37, 95% CI 0.24 to 0.58, number needed to treat for an additional beneficial outcome (NNTB) 29, 2292 participants, moderate quality evidence.• Supraventricular arrhythmias: RR 0.44, 95% CI 0.36 to 0.53, NNTB five, 6420 participants, high quality evidence.• On average, beta-blockers reduced length of hospital stay by 0.54 days (95% CI -0.90 to -0.19, 2450 participants, low quality evidence).NON-CARDIAC SURGERY (35 trials)Beta-blockers significantly increased the occurrence of the following adverse events.• All-cause mortality: RR 1.25, 95% CI 1.00 to 1.57, 11,413 participants, low quality of evidence, number needed to treat for an additional harmful outcome (NNTH) 167.• Hypotension: RR 1.50, 95% CI 1.38 to 1.64, NNTH 16, 10,947 participants, high quality evidence.• Bradycardia: RR 2.23, 95% CI 1.48 to 3.36, NNTH 21, 11,033 participants, moderate quality evidence.We found a potential increase in the occurrence of the following outcomes with the use of beta-blockers.• Cerebrovascular events: RR 1.59, 95% CI 0.93 to 2.71, 9150 participants, low quality evidence.Whereas no clear evidence of an effect was found when all studies were analysed, restricting the meta-analysis to low risk of bias studies revealed a significant increase in cerebrovascular events with the use of beta-blockers: RR 2.09, 95% CI 1.14 to 3.82, NNTH 265, 8648 participants.Beta-blockers significantly reduced the occurrence of the following endpoints.• AMI: RR 0.73, 95% CI 0.61 to 0.87, NNTB 76, 10,958 participants, high quality evidence.• Myocardial ischaemia: RR 0.51, 95% CI 0.34 to 0.77, NNTB nine, 978 participants, moderate quality evidence.• Supraventricular arrhythmias: RR 0.73, 95% CI 0.57 to 0.94, NNTB 112, 8744 participants, high quality evidence.We found no clear evidence of an effect of beta-blockers on the following outcomes.• Ventricular arrhythmias: RR 0.68, 95% CI 0.31 to 1.49, 476 participants, moderate quality evidence.• Congestive heart failure: RR 1.18, 95% CI 0.94 to 1.48, 9173 participants, moderate quality evidence.• Length of hospital stay: mean difference -0.45 days, 95% CI -1.75 to 0.84, 551 participants, low quality evidence. AUTHORS' CONCLUSIONS: According to our findings, perioperative application of beta-blockers still plays a pivotal role in cardiac surgery, as they can substantially reduce the high burden of supraventricular and ventricular arrhythmias in the aftermath of surgery. Their influence on mortality, AMI, stroke, congestive heart failure, hypotension and bradycardia in this setting remains unclear.In non-cardiac surgery, evidence shows an association of beta-blockers with increased all-cause mortality. Data from low risk of bias trials further suggests an increase in stroke rate with the use of beta-blockers. As the quality of evidence is still low to moderate, more evidence is needed before a definitive conclusion can be drawn. The substantial reduction in supraventricular arrhythmias and AMI in this setting seems to be offset by the potential increase in mortality and stroke.