Meeting Report: First Cardiovascular Outcomes Research in Perioperative Medicine Conference.

The first Cardiovascular Outcomes Research in Perioperative Medicine (COR-PM) conference took place on May 13, 2022, in Palm Springs, CA, and online. Here, we: (1) summarize the background, objective, and aims of the COR-PM meeting; (2) describe the conduct of the meeting; and (3) outline future directions for scientific meetings aimed at fostering high-quality clinical research in the broader perioperative medicine community.

Tracheostomy Practices for Mechanically Ventilated Patients in Malawi.

BACKGROUND: Tracheostomy is used for patients who require prolonged mechanical ventilation. Extensive research has described the provision and optimal timing of tracheostomy, but very little describes tracheostomy utilization in low- and middle-income countries, particularly in sub-Saharan Africa. METHODS: This prospective cohort study describes patients admitted to the intensive care unit (ICU) of a tertiary hospital in Malawi who received tracheostomy versus those who did not, with a primary outcome of hospital mortality. We performed subgroup analysis of patients with severe head injuries. RESULTS: The analysis included 451 patients admitted to the study ICU between September 2016 and July 2018. Overall hospital mortality was 40% for patients who received tracheostomy and 63% for patients who did not. Logistic regression modeling revealed an odds ratio (OR) of 0.34 (95% CI 0.18-0.64) for hospital mortality among patients who received tracheostomy versus those who did not (p < 0.001). Standardized mortality ratio weighting revealed an odds ratio of 0.81 (95% CI 0.65-0.99, p < 0.001) for hospital death among patients who received tracheostomy versus those who did not. In the subgroup excluding severe head injury, both ICU (50%) and hospital mortality (75%) were higher overall, but hospital mortality was not more common for patients with tracheostomy versus without (OR 1.28, 95% CI 0.94-1.74, p = 0.104). CONCLUSIONS: Tracheostomy is not associated with hospital mortality in a Malawi ICU cohort, but these results are affected by the presence of head injury. Research may focus on home tracheostomy care given the lack of hospital discharge options for patients in austere settings.

Outcomes Following Intensive Care Unit Admission in a Pediatric Cohort in Malawi.

INTRODUCTION: The burden of critical illness in low- and middle-income countries (LMICs) is high; however, there is a paucity of data describing pediatric critical care outcomes in this setting. METHODS: We performed a prospective observational study of the pediatric (≤18 years) intensive care population in Malawi, from August 2016 to May 2018. Data collected include patient demographics and clinical data, admission criteria and outcome. A multivariate Poisson regression was performed to determine risk factors for mortality. RESULTS: Over the study period, 499 patients were admitted to the intensive care unit (ICU) and 105 (21.0%) were children. The average age was 10.6 ± 5.4 years. Primary indications for ICU admission were sepsis (n = 30, 30.3%) and traumatic brain injury (TBI, n = 23, 23.2%). Of those who died, sepsis (n = 18, 32.7%), acute respiratory failure (n = 11, 20.0%) and TBI (n = 11, 20.0%) were the primary admission diagnoses. Overall, ICU mortality was 54.3% (n = 57). Multivariate regression for increased ICU mortality revealed: age ≤5 years [risk ratio (RR) 1.96, 95% CI 1.10-2.26, p < 0.001], hemoglobin < 10 g/dl (RR 1.58, 95% CI 1.08-2.01, p = 0.01) and shock requiring epinephrine support (RR 2.76, 95% CI 1.80-4.23, p < 0.001). CONCLUSIONS: Pediatric ICU mortality is high. Predictors of mortality were age ≤5 years, anemia at ICU admission and the need for epinephrine support. Training of pediatric intensive care specialists and increased blood product availability may attenuate the high mortality for critically ill children in Malawi.

ICU Risk Stratification Models Feasible for Use in Sub-Saharan Africa Show Poor Discrimination in Malawi: A Prospective Cohort Study.

BACKGROUND: Critical illness disproportionately affects people in low-income countries (LICs). Efforts to improve critical care in LICs must account for differences in demographics and infrastructure compared to high-income settings. Part of this effort includes the development and validation of intensive care unit (ICU) risk stratification models feasible for use in LICs. The purpose of this study was to validate and compare the performance of ICU mortality models developed for use in sub-Saharan Africa. MATERIALS AND METHODS: This was a prospective, observational cohort study of ICU patients in a referral hospital in Malawi. Models were selected for comparison based on a Medline search for studies which developed ICU mortality models based on cohorts in sub-Saharan Africa. Model discrimination was evaluated using the area under the curve with 95% confidence intervals (CI). RESULTS: During the study, 499 patients were admitted to the study ICU, and after exclusions, there were 319 patients. The cohort was 62% female, with the mean age 31 years (IQR: 23-41), and 74% had surgery preceding ICU admission. Discrimination for hospital mortality ranged from 0.54 (95% CI 0.48, 0.60) for the Universal Vital Assessment (UVA) to 0.72 (95% CI 0.66, 0.78) for the Malawi Intensive care Mortality Evaluation (MIME). After tenfold cross-validation, these results were unchanged. CONCLUSIONS: The MIME outperformed other models in this prospective study. Most ICU models developed for LICs had poor to modest discrimination for hospital mortality. Future research may contribute to a better risk stratification model for LICs by refining and enhancing the MIME.

Intraoperative Mortality in Malawi.

BACKGROUND: Surgical care is essential to improving population health, but metrics to monitor and evaluate the continuum of surgical care delivery have rarely been applied in low-resource settings, and improved efforts at benchmarking progress are needed. The objective of this study was to measure the intraoperative mortality at a Central Referral Hospital in Malawi, evaluate whether there have been changes in intraoperative mortality between 2 time periods, and assess factors associated with intraoperative mortality. METHODS: This was a retrospective cohort study of patients undergoing surgery at Kamuzu Central Hospital in Lilongwe, Malawi. Data describing daily consecutive operative cases were collected prospectively during 2 time periods: 2004-2006 (early cohort) and 2015-2016 (late cohort). The primary outcome was intraoperative mortality. Inverse probability of treatment weighting was used to analyze the association of intraoperative mortality with time using logistic regression models. Multivariable logistic models were performed to evaluate factors associated with intraoperative mortality. RESULTS: There were 21,090 surgeries performed during the 2 time periods, with 15,846 (75%) and 5244 (25%) completed from 2004 to 2006 and 2015 to 2016, respectively. Intraoperative mortality in the early cohort was 57 deaths per 100,000 surgeries (95% confidence interval [CI], 26-108) and in the late cohort was 133 per 100,000 surgeries (95% CI, 56-286), with 76 per 100,000 surgeries (95% CI, 44-124) overall. After applying inverse probability of treatment weighting, there was no evidence of an association between time periods and intraoperative mortality (odds ratio [OR], 1.6; 95% CI, 0.9-2.8; P = .08). Factors associated with intraoperative mortality, adjusting for demographics, included American Society of Anesthesiology physical status III or IV versus I or II (OR, 4.4; 95% CI, 1.5-12.5; P = .006) and emergency versus elective surgery (OR, 7.7; 95% CI, 2.5-23.6; P < .001). CONCLUSIONS: Intraoperative mortality in the study hospital in Malawi is high and has not improved over time. These data demonstrate an urgent need to improve the safety and quality of perioperative care in developing countries and integrate perioperative care into global health efforts.

Emergency-to-Elective Surgery Ratio: A Global Indicator of Access to Surgical Care.

BACKGROUND: Surgical care is essential to health systems but remains a challenge for low- and middle-income countries (LMICs). Current metrics to assess access and delivery of surgical care focus on the structural components of surgery and are not readily applicable to all settings. This study assesses a new metric for surgical care access and delivery, the ratio of emergent surgery to elective surgery (Ee ratio), which represents the number of emergency surgeries performed for every 100 elective surgeries. METHODS: A systematic search of PubMed and Medline was conducted for studies describing surgical volume and acuity published between 2006 and 2016. The relationship between Ee ratio and three national indicators (gross domestic product, per capital healthcare spending, and physician density) was analyzed using weighted Pearson correlation coefficients (r w) and linear regression models. RESULTS: A total of 29 studies with 33 datasets were included for analyses. The median Ee ratio was 14.6 (IQR 5.5-62.6), with a range from 1.6 to 557.4. For countries in sub-Saharan Africa the median value was 62.6 (IQR 17.8-111.0), compared to 9.4 (IQR 3.4-13.4) for the United States and 5.5 (IQR 4.4-10.1) for European countries. In multivariable linear regression, the per capita healthcare spending was inversely associated with the Ee ratio, with a 63-point decrease in the Ee ratio for each 1 point increase in the log of the per capita healthcare spending (regression coefficient ß = -63.2; 95% CI -119.6 to -6.9; P = 0.036). CONCLUSIONS: The Ee ratio appears to be a simple and valid indicator of access to available surgical care. Global health efforts may focus on investment in low-resource settings to improve access to available surgical care.

High Elective Surgery Cancellation Rate in Malawi Primarily Due to Infrastructural Limitations.

BACKGROUND: The provision of safe and timely surgical care is essential to global health care. Low- and middle-income countries have a disproportionate share of the global surgical disease burden and struggle to provide care with the given resources. Surgery cancellation worldwide occurs for many reasons, which are likely to differ between high-income and low-income settings. We sought to evaluate the proportion of elective surgery that is cancelled and the associated reasons for cancellation at a tertiary hospital in Malawi. METHODS: This was a retrospective review of a database maintained by the Department of Anesthesiology at Kamuzu Central Hospital in Lilongwe, Malawi. Data were available from August 2011 to January 2015 and included weekday records for the number of scheduled surgeries, the number of cancelled surgeries, and the reasons for cancellation. Descriptive statistics were performed. RESULTS: Of 10,730 scheduled surgeries, 4740 (44.2%) were cancelled. The most common reason for cancellation was infrastructural limitations (84.8%), including equipment shortages (50.9%) and time constraints (33.3%). Provider limitations accounted for 16.5% of cancellations, most often due to shortages of anaesthesia providers. Preoperative medical conditions contributed to 26.3% of cancellations. CONCLUSION: This study demonstrates a high case cancellation rate at a tertiary hospital in Malawi, attributable primarily to infrastructural limitations. These data provide evidence that investments in medical infrastructure and prevention of workforce brain drain are critical to surgical services in this region.

Viral load monitoring and antiretroviral treatment outcomes in a pediatric HIV cohort in Ghana.

BACKGROUND: HIV-infected children in sub-Saharan Africa may be at a high risk of staying on a failing first-line regimen and developing drug-resistance HIV variants due to lack of routine viral load monitoring. We investigated whether cumulative viral load, measured as viremia copy-years (VCY) could predict morbidity in a setting where viral load is not routinely monitored. METHODS: This was a single-center prospective observational longitudinal study of HIV-infected children initiating antiretroviral therapy (ART) at the Pediatric HIV/AIDS Care program at Korle-Bu Teaching Hospital in Accra, Ghana. The main outcome was morbidity measured as frequency of hospitalizations, opportunistic infections, and outpatient sick visits. The main explanatory variable was viral load measured as VCY. RESULTS: The study included 140 children who initiated ART between September 2009 and May 2013 and had at least 2 viral load measurements. There were 184 hospitalizations, with pneumonia being the most common cause (22.8 %). A total of 102 opportunistic infections was documented, with tuberculosis being the most common opportunistic infection (68 %). A total of 823 outpatient sick visits was documented, with upper respiratory infections (14.2 %) being the most common cause. Forty-four percent of our study participants had >4 log10 VCY. Children in this sub-cohort had a higher frequency of sick visits compared with those with <4 log10 VCY (p = 0.03). Only 6.5 % of children with >4 log10 VCY had been identified as treatment failure using WHO clinical and immunological treatment failure criteria. CONCLUSIONS: High level of cumulative viral load may translate to virological failure and subsequent increased all-cause morbidity. Our finding of potential utility of VCY in pediatrics warrants further investigations. VCY may be a good alternate to routine viral load measurement as its determination may be less frequent and could be personalized to save cost.

Critical Care in a Tertiary Hospital in Malawi.

BACKGROUND: The provision of critical care services is essential to healthcare systems and increasingly a global health focus, but many hospitals in sub-Saharan Africa are unable to meet this need. Intensive care unit (ICU) mortality in this region is high, but studies describing the provision of critical care services are scarce. METHODS: This was a retrospective cohort study of all patients admitted to the ICU at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi, between September 1, 2013, and October 17, 2014. We summarized demographics, clinical characteristics, and outcomes, and analyzed factors associated with mortality. RESULTS: Of 390 patients admitted to ICU during the study, 44.9 % of patients were male, and the median age was 22 years (IQR 6-35) years. Although most patients (73.1 %) were admitted with surgical diagnoses, the highest mortality was among patients admitted with sepsis (59.3 %), or obstetric (44.7 %) or medical (40.0 %) diagnoses. Overall ICU mortality was high (23.6 %). CONCLUSIONS: There is a shortage of data describing critical care in low-resource settings, particularly in sub-Saharan Africa. Surgical disease comprises the majority of ICU utilization in this study site, but medical and obstetric illness carried higher ICU mortality. These data may guide strategies for improving critical care in the region.

Prophylactic Ondansetron for the Prevention of Intrathecal Fentanyl- or Sufentanil-Mediated Pruritus: A Meta-Analysis of Randomized Trials.

BACKGROUND: Pruritus is a common side effect of intrathecal fentanyl or sufentanil that decreases patient satisfaction and may delay hospital discharge. There are conflicting reports about the efficacy of prophylactic ondansetron in reducing the incidence of pruritus. This meta-analysis aimed to assess the effect of prophylactic ondansetron on the incidence of intrathecal fentanyl- or sufentanil-mediated pruritus and the need for rescue treatment. METHODS: A systematic search on PubMed, Medline, and the Cochrane Central Register of Controlled Trials from January 1, 1994, to January 1, 2014, was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Randomized controlled trials evaluating the efficacy of prophylactic ondansetron on pruritus associated with intrathecal fentanyl or sufentanil were included. The primary outcome was the incidence of pruritus, and the secondary outcome was patients' need for rescue therapy. Sensitivity analyses were conducted to assess the outcomes in obstetric and nonobstetric patients and in patients who received ondansetron before or after intrathecal opioid injection. Analyses used random-effect models. RESULTS: Six randomized controlled trials involving 555 patients were included. In the overall analysis, prophylactic ondansetron did not significantly decrease the incidence of pruritus, but there was a trend toward reduced rescue medication use (risk ratio [RR], 0.57; 95% confidence interval [CI], 0.35-0.91; I = 0%; P = 0.02). Exploratory subgroups, including nonobstetric surgery patients and patients who received ondansetron before spinal opioid administration, also suggest a trend toward less rescue medication use (RR, 0.47; 95% CI, 0.26-0.85; P = 0.01; and RR, 0.62; 95% CI, 0.38-1.00; P = 0.05). CONCLUSIONS: IV 8 mg prophylactic ondansetron does not decrease the incidence of fentanyl- or sufentanil-mediated pruritus but may decrease the need for pruritus rescue medication, particularly in specific subgroups. Randomized trials are needed to confirm these results.

The role of stepdown beds in hospital care.

Stepdown beds provide an intermediate level of care for patients with requirements somewhere between that of the general ward and the intensive care unit. Models of care include incorporation of stepdown beds into intensive care units, stand-alone units, or incorporation of beds into standard wards. Stepdown beds may be used to provide a higher level of care for patients deteriorating on a ward ("step-up"), a lower level of care for patients transitioning out of intensive care ("stepdown") or a lateral transfer of care from a recovery room for postoperative patients. These units are one possible strategy to improve critical care cost-effectiveness and patient flow without compromising quality, but these potential benefits remain primarily theoretical as few patient-level studies provide concrete evidence. This narrative review provides a general overview of the theory of stepdown beds in the care of hospitalized patients and a summary of what is known about their impact on patient flow and outcomes and highlights areas for future research.

Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana.

BACKGROUND: Antiretroviral therapy (ART) scale-up in resource-limited countries, with limited capacity for CD4 and HIV viral load monitoring, presents a unique challenge. We determined the effectiveness of first-line ART in a real world pediatric HIV clinic and explored associations between readily obtainable patient data and the trajectories of change in CD4 count and HIV viral load. METHODS: We performed a longitudinal study of a cohort of HIV-infected children initiating ART at the Korle-Bu Teaching Hospital Pediatric HIV clinic in Accra, Ghana, aged 0-13 years from 2009-2012. CD4 and viral load testing were done every 4 to 6 months and genotypic resistance testing was performed for children failing therapy. A mixed linear modeling approach, combining fixed and random subject effects, was employed for data analysis. RESULTS: Ninety HIV-infected children aged 0 to 13 years initiating ART were enrolled. The effectiveness of first-line regimen among study participants was 83.3%, based on WHO criteria for virologic failure. Fifteen of the 90 (16.7%) children met the criteria for virologic treatment failure after at least 24 weeks on ART. Sixty-seven percent virologic failures harbored viruses with ≥ 1 drug resistant mutations (DRMs); M184V/K103N was the predominant resistance pathway. Age at initiation of therapy, child's gender, having a parent as a primary care giver, severity of illness, and type of regimen were associated with treatment outcomes. CONCLUSIONS: First-line ART regimens were effective and well tolerated. We identified predictors of the trajectories of change in CD4 and viral load to inform targeted laboratory monitoring of ART among HIV-infected children in resource-limited countries.

Enhancing circadian rhythms-the circadian MEGA bundle as novel approach to treat critical illness.

Circadian rhythms are essential to physiological homeostasis, but often disrupted in the intensive care unit (ICU) due to the absence of natural zeitgebers and exposure to treatments which affect circadian regulators. This is increasingly recognized as a contributor to morbidity and mortality across a variety of medical conditions including critical illness. Maintenance of circadian rhythms is particularly relevant to critically ill patients, who are restricted not only to the ICU environment but often bed bound. Circadian rhythms have been evaluated in several ICU studies, but effective therapies to maintain, restore, or amplify circadian rhythms have not been fully established yet. Circadian entrainment and circadian amplitude enhancement are integral to patients' overall health and well-being, and likely even more important during response to and recovery from critical illness. In fact, studies have shown that enhancing the amplitude of circadian cycles has significant beneficial effects on health and wellbeing. In this review, we discuss up-to-date literature on novel circadian mechanism that could not only restore but enhance circadian rhythms in critical illness by using a MEGA bundle consisting of intense light therapy each morning, cyclic nutrition support, timed physical therapy, nighttime melatonin administration, morning administration of circadian rhythm amplitude enhancers, cyclic temperature control and a nocturnal sleep hygiene bundle.

Hyperoxemia During Cardiac Surgery Is Associated With Postoperative Pulmonary Complications.

The use of hyperoxemia during cardiac surgery remains controversial. We hypothesized that intraoperative hyperoxemia during cardiac surgery is associated with an increased risk of postoperative pulmonary complications. DESIGN: Retrospective cohort study. SETTING: We analyzed intraoperative data from five hospitals within the Multicenter Perioperative Outcomes Group between January 1, 2014, and December 31, 2019. We assessed intraoperative oxygenation of adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Hyperoxemia pre and post CPB was quantified as the area under the curve (AUC) of Fio2 above 0.21 in minutes when the corresponding peripheral oxygen saturation was greater than 92% measured by pulse oximetry. We quantified hyperoxemia during CPB as the AUC of Pao2 greater than 200 mm Hg measured by arterial blood gas. We analyzed the association of hyperoxemia during all phases of cardiac surgery with the frequency of postoperative pulmonary complications within 30 days, including acute respiratory insufficiency or failure, acute respiratory distress syndrome, need for reintubation, and pneumonia. PATIENTS: Twenty-one thousand six hundred thirty-two cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During 21,632 distinct cardiac surgery cases, 96.4% of patients spent at least 1 minute in hyperoxemia (99.1% pre-CPB, 98.5% intra-CPB, and 96.4% post-CPB). Increasing exposure to hyperoxemia was associated with an increased risk of postoperative pulmonary complications throughout three distinct surgical periods. During CPB, increasing exposure to hyperoxemia was associated with an increased odds of developing postoperative pulmonary complications (p < 0.001) in a linear manner. Hyperoxemia before CPB (p < 0.001) and after CPB (p = 0.02) were associated with increased odds of developing postoperative pulmonary complications in a U-shaped relationship. CONCLUSIONS: Hyperoxemia occurs almost universally during cardiac surgery. Exposure to hyperoxemia assessed continuously as an AUC during the intraoperative period, but particularly during CPB, was associated with an increased incidence of postoperative pulmonary complications.

International comparisons of intensive care: informing outcomes and improving standards.

PURPOSE OF REVIEW: Interest in international comparisons of critical illness is growing, but the utility of these studies is questionable. This review examines the challenges of international comparisons and highlights areas in which international data provide information relevant to clinical practice and resource allocation. RECENT FINDINGS: International comparisons of ICU resources demonstrate that definitions of critical illness and ICU beds vary due to differences in ability to provide organ support and variable staffing. Despite these limitations, recent international data provide key information to understand the pros and cons of different availability of ICU beds on patient flow and outcomes, and also highlight the need to ensure long-term follow-up due to heterogeneity in discharge practices for critically ill patients. With increasing emphasis on curbing costs of healthcare, systems that deliver lower cost care provide data on alternative options, such as regionalization, flexible allocation of beds, and bed rationing. SUMMARY: Differences in provision of critical care can be leveraged to inform decisions on allocation of ICU beds, improve interpretation of clinical outcomes, and assess ways to decrease costs of care. International definitions of key components of critical care are needed to facilitate research and ensure rigorous comparisons.

Time-of-day dependent effects of midazolam administration on myocardial injury in non-cardiac surgery.

Background: Animal studies have shown that midazolam can increase vulnerability to cardiac ischemia, potentially via circadian-mediated mechanisms. We hypothesized that perioperative midazolam administration is associated with an increased incidence of myocardial injury in patients undergoing non-cardiac surgery (MINS) and that circadian biology may underlie this relationship. Methods: We analyzed intraoperative data from the Multicenter Perioperative Outcomes Group for the occurrence of MINS across 50 institutions from 2014 to 2019. The primary outcome was the occurrence of MINS. MINS was defined as having at least one troponin-I lab value ≥0.03 ng/ml from anesthesia start to 72 h after anesthesia end. To account for bias, propensity scores and inverse probability of treatment weighting were applied. Results: A total of 1,773,118 cases were available for analysis. Of these subjects, 951,345 (53.7%) received midazolam perioperatively, and 16,404 (0.93%) met criteria for perioperative MINS. There was no association between perioperative midazolam administration and risk of MINS in the study population as a whole (odds ratio (OR) 0.98, confidence interval (CI) [0.94, 1.01]). However, we found a strong association between midazolam administration and risk of MINS when surgery occurred overnight (OR 3.52, CI [3.10, 4.00]) or when surgery occurred in ASA 1 or 2 patients (OR 1.25, CI [1.13, 1.39]). Conclusion: Perioperative midazolam administration may not pose a significant risk for MINS occurrence. However, midazolam administration at night and in healthier patients could increase MINS, which warrants further clinical investigation with an emphasis on circadian biology.