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.

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.

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.

Year in Review 2021: Noteworthy Literature in Cardiothoracic Anesthesia.

In 2021, progress in clinical science related to Cardiac Anesthesiology continued, but at a slower rate due to the ongoing pandemic and disruptions to clinical research. Most progress was incremental and addressed persistent questions related to our field. To identify articles for this review, we completed a structured review using our previously reported methods (1). Specifically, we used the search terms: "cardiac anesthesiology and outcomes" (n = 177), "cardiothoracic anesthesiology" (n = 34), "cardiac anesthesia," and "clinical outcomes" (n = 42) filtered on clinical trials and the year 2021 in PubMed. We also reviewed clinical trials from the most prominent clinical journals to identify additional studies for a narrative review. We then selected the most noteworthy publications for inclusion in this review and identified key themes.

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.

Anemia at Intensive Care Unit Admission and Hospital Mortality Among Patients at a Referral Hospital in Malawi.

BACKGROUND: Anemia is associated with intensive care unit (ICU) outcomes, but data describing this association in sub-Saharan Africa are scarce. Patients in this region are at risk for anemia due to endemic conditions like malaria and because transfusion services are limited. METHODS: This was a prospective cohort study of ICU patients at Kamuzu Central Hospital (KCH) in Malawi. Exclusion criteria included age <5 years, pregnancy, ICU readmission, or admission for head injury. Cumulative incidence functions and Fine-Gray competing risk models were used to evaluate hemoglobin (Hgb) at ICU admission and hospital mortality. RESULTS: Of 499 patients admitted to ICU, 359 were included. The median age was 28 years (interquartile ranges (IQRs) 20-40) and 37.5% were men. Median Hgb at ICU admission was 9.9 g/dL (IQR 7.5-11.4 g/dL; range 1.8-18.1 g/dL). There were 61 (19%) patients with Hgb < 7.0 g/dL, 59 (19%) with Hgb 7.0-8.9 g/dL, and 195 (62%) with Hgb ≥ 9.0 g/dL. Hospital mortality was 51%, 59%, and 54%, respectively. In adjusted analyses, anemia was associated with hospital mortality but was not statistically significant. CONCLUSIONS: This study provides preliminary evidence that anemia at ICU admission may be an independent predictor of hospital mortality in Malawi. Larger studies are needed to confirm this association.

Two success stories in the management of Guillain-Barré syndrome illustrate the challenges of intensive care unit care in Malawi.

The management of critical illness is especially challenging in low-resource environments, and early recognition and supportive care are essential, regardless of the ability to employ advanced or invasive therapy. In this report, we discuss two patients with Guillain-Barré syndrome who were managed successfully in the intensive care unit of a tertiary hospital in Malawi. Both patients recovered and were discharged home. The management and outcomes of these patients provide case-based lessons for improving intensive care unit medicine in low-resource contexts.

Intensive Care Unit Bed Utilization and Head Injury Burden in a Resource-Poor Setting.

INTRODUCTION: In high-income countries (HICs), the intensive care unit (ICU) bed density is approximately 20-32 beds/100 000 population compared with countries in sub-Saharan Africa, like Malawi, with an ICU bed density of 0.1 beds/100 000 population. We hypothesize that the ICU bed utilization in Malawi will be high. METHODS: This is an observational study at a tertiary care center in Malawi from August 2016 to May 2018. Variables used to evaluate ICU bed utilization include ICU length of stay (LOS), bed occupancy rates (average daily ICU census/number of ICU beds), bed turnover (total number of admissions/number of ICU beds), and turnover intervals (number of ICU bed days/total number of admissions - average ICU LOS). RESULTS: 494 patients were admitted to the ICU during the study period. The average LOS during the study period was 4.8 ± 6.0 days. Traumatic brain injury patients had the most extended LOS (8.7 ± 6.8 days) with a 49.5% ICU mortality. The bed occupancy rate per year was 74.7%. The calculated bed turnover was 56.5 persons treated per bed per year. The average turnover interval, defined as the number of days for a vacant bed to be occupied by the successive patient admission, was 1.63 days. CONCLUSION: Despite the high burden of critical illness, the bed occupancy rates, turn over days, and turnover interval reveal significant underutilization of the available ICU beds. ICU bed underutilization may be attributable to the absence of an admission and discharge protocols. A lack of brain death policy further impedes appropriate ICU utilization.

Associations of day of week and time of day of ICU admission with hospital mortality in Malawi.

This prospective cohort study evaluated the associations of day and time of admission to the Intensive Care Unit (ICU) with hospital mortality at a referral hospital in Malawi, a low-income country in sub-Saharan Africa. Patients admitted to the ICU during the day (08:00-16:00) were compared to those admitted at night (16:01-07:59); patients admitted on weekdays (Monday-Friday) were compared to admissions on weekends/holidays. The primary outcome was hospital mortality. Most patients were admitted during daytime (56%) and on weekdays (72%). There was no difference in mortality between night and day admissions (58% vs. 56%, P = 0.8828; hazard ratio [HR] = 1.09, 95% confidence interval [CI = 0.82-1.44, P = 0.5614) or weekend/holiday versus weekday admissions (56% vs. 57%, P = 0.9011; HR = 0.87, 95% CI = 0.62-1.21, P = 0.4133). No interaction between time and day was found. These results may be affected by high overall hospital mortality.

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.

Prevalence, Etiology, and Outcome of Sepsis among Critically Ill Patients in Malawi.

There are scarce data describing the etiology and clinical sequelae of sepsis in low- and middle-income countries (LMICs). This study describes the prevalence and etiology of sepsis among critically ill patients at a referral hospital in Malawi. We conducted an observational prospective cohort study of adults admitted to the intensive care unit or high-dependency unit (HDU) from January 29, 2018 to March 15, 2018. We stratified the cohort based on the prevalence of sepsis as defined in the following three ways: quick sequential organ failure assessment (qSOFA) score ≥ 2, clinical suspicion of systemic infection, and qSOFA score ≥ 2 plus suspected systemic infection. We measured clinical characteristics and blood and urine cultures for all patients; antimicrobial sensitivities were assessed for positive cultures. During the study period, 103 patients were admitted and 76 patients were analyzed. The cohort comprised 39% male, and the median age was 30 (interquartile range: 23-40) years. Eighteen (24%), 50 (66%), and 12 patients (16%) had sepsis based on the three definitions, respectively. Four blood cultures (5%) were positive, two from patients with sepsis by all three definitions and two from patients with clinically suspected infection only. All blood bacterial isolates were multidrug resistant. Of five patients with urinary tract infection, three had sepsis secondary to multidrug-resistant bacteria. Hospital mortality for patients with sepsis based on the three definitions ranged from 42% to 75% versus 12% to 26% for non-septic patients. In summary, mortality associated with sepsis at this Malawi hospital is high. Bacteremia was infrequently detected, but isolated pathogens were multidrug resistant.

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.