The BJA Editorial Fellowship 2024: a barometer for the state of academic anaesthesiology, perioperative, pain, and critical care medicine.

Throughout its 100-yr history, a key ambition of the British Journal of Anaesthesia has been to foster our academic community by addressing the needs of individuals in the early stages of their independent clinical and research careers. Longitudinal mentoring and peer networking are critical for establishing a community of like-minded peers and mentor-advisors required to navigate the challenges of academic medicine. In 2019, the Journal launched an Editorial Fellowship scheme, aimed at comprehensively demystifying the process of peer review, editing, and publishing through guided mentorship and experiential learning.

The Association of Pregnancy With Outcomes Among Critically Ill Reproductive-Aged Women: A Propensity Score-Matched Retrospective Cohort Analysis.

BACKGROUND: The maternal mortality rate in the United States is unacceptably high. However, the relative contribution of pregnancy to these outcomes is unknown. Studies comparing outcomes among pregnant vs nonpregnant critically ill patients show mixed results and are limited by small sample sizes. RESEARCH QUESTION: What is the association of pregnancy with critical illness outcomes? STUDY DESIGN AND METHODS: We performed a retrospective cohort study of women 18 to 55 years of age who received invasive mechanical ventilation (MV) on hospital day 0 or 1 or who demonstrated sepsis on admission (infection with organ failure) discharged from Premier Healthcare Database hospitals from 2008 through 2021. The exposure was pregnancy. The primary outcome was in-hospital mortality. We created propensity scores for pregnancy (using patient and hospital characteristics) and performed 1:1 propensity score matching without replacement within age strata (to ensure exact age matching). We performed multilevel multivariable mixed-effects logistic regression for propensity-matched pairs with pair as a random effect. RESULTS: Three thousand ninety-three pairs were included in the matched MV cohort, and 13,002 pairs were included in the sepsis cohort. The characteristics of both cohorts were well balanced (all standard mean differences, < 0.1). Among matched pairs, unadjusted mortality was 8.0% vs 13.8% for MV and 1.4% vs 2.3% for sepsis among pregnant and nonpregnant patients, respectively. In adjusted regression, pregnancy was associated with lower odds of in-hospital mortality (MV: OR, 0.50; 95% CI, 0.41-0.60; P < .001; sepsis: OR, 0.52; 95% CI, 0.40-0.67; P < .001). INTERPRETATION: In this large US cohort, critically ill pregnant women receiving MV or with sepsis showed better survival than propensity score-matched nonpregnant women. These findings must be interpreted in the context of likely residual confounding.

Characterizing proximity and transfers of deceased organ donors to donor care units in the United States.

Some United States organ procurement organizations transfer deceased organ donors to donor care units (DCUs) for recovery procedures. We used Organ Procurement and Transplantation Network data, from April 2017 to June 2021, to describe the proximity of adult deceased donors after brain death to DCUs and understand the impact of donor service area (DSA) boundaries on transfer efficiency. Among 19 109 donors (56.1% of the cohort) in 25 DSAs with DCUs, a majority (14 593 [76.4%]) were in hospitals within a 2-hour drive. In areas with DCUs detectable in the study data set, a minority of donors (3582 of 11 532 [31.1%]) were transferred to a DCU; transfer rates varied between DSAs (median, 27.7%, range, 4.0%-96.5%). Median hospital-to-DCU driving times were not meaningfully shorter among transferred donors (50 vs 51 minutes for not transferred, P < .001). When DSA boundaries were ignored, 3241 cohort donors (9.5%) without current DCU access were managed in hospitals within 2 hours of a DCU and thus potentially eligible for transfer. In summary, approximately half of United States deceased donors after brain death are managed in hospitals in DSAs with a DCU. Transfer of donors between DSAs may increase DCU utilization and improve system efficiency.

Long-term Outcomes with Spinal versus General Anesthesia for Hip Fracture Surgery: A Randomized Trial.

BACKGROUND: The effects of spinal versus general anesthesia on long-term outcomes have not been well studied. This study tested the hypothesis that spinal anesthesia is associated with better long-term survival and functional recovery than general anesthesia. METHODS: A prespecified analysis was conducted of long-term outcomes of a completed randomized superiority trial that compared spinal anesthesia versus general anesthesia for hip fracture repair. Participants included previously ambulatory patients 50 yr of age or older at 46 U.S. and Canadian hospitals. Patients were randomized 1:1 to spinal or general anesthesia, stratified by sex, fracture type, and study site. Outcome assessors and investigators involved in the data analysis were masked to the treatment arm. Outcomes included survival at up to 365 days after randomization (primary); recovery of ambulation among 365-day survivors; and composite endpoints for death or new inability to ambulate and death or new nursing home residence at 365 days. Patients were included in the analysis as randomized. RESULTS: A total of 1,600 patients were enrolled between February 12, 2016, and February 18, 2021; 795 were assigned to spinal anesthesia, and 805 were assigned to general anesthesia. Among 1,599 patients who underwent surgery, vital status information at or beyond the final study interview (conducted at approximately 365 days after randomization) was available for 1,427 (89.2%). Survival did not differ by treatment arm; at 365 days after randomization, there were 98 deaths in patients assigned to spinal anesthesia versus 92 deaths in patients assigned to general anesthesia (hazard ratio, 1.08; 95% CI, 0.81 to 1.44, P = 0.59). Recovery of ambulation among patients who survived a year did not differ by type of anesthesia (adjusted odds ratio for spinal vs. general, 0.87; 95% CI, 0.67 to 1.14; P = 0.31). Other outcomes did not differ by treatment arm. CONCLUSIONS: Long-term outcomes were similar with spinal versus general anesthesia.

Practice Patterns and Outcomes of Potassium Repletion Thresholds during Critical Illness.

Rationale: Potassium repletion is common in critically ill patients. However, practice patterns and outcomes related to different intensive care unit (ICU) potassium repletion strategies are unclear. Objectives: 1) Describe potassium repletion practices in critically ill adults; 2) compare the effectiveness of potassium repletion strategies; and 3) compare effectiveness and safety of specific potassium repletion thresholds on patient outcomes. Methods: This was a retrospective analysis of the PINC AI Healthcare Database (2016-2022), including all critically ill adults admitted to an ICU on Hospital Day 1 and with a serum potassium concentration measured on Hospital Day 2. We determined the frequency of potassium repletion (any formulation) at each measured serum potassium concentration in each ICU, then classified ICUs as having threshold-based (a large increase in potassium repletion rates at a specific serum potassium concentration) or probabilistic (linear relationship between serum concentration and the repletion probability) patterns of repletion. Between patients in threshold-based and probabilistic repletion ICUs, we compared outcomes (primary outcome: potassium repletion frequency). We reported unadjusted percentages per exposure group and the adjusted odds ratios (from hierarchical regression models) for each outcome. Among patients in threshold-based ICUs with the most common repletion thresholds (3.5 mEq/L and 4.0 mEq/L), we conducted regression discontinuity analyses to examine the effectiveness of potassium repletion at each potassium threshold. Results: We included 190,490 patients in 88 ICUs; 35.0% received at least one dose of potassium on the same calendar day. Rates of potassium repletion were similar between 22 threshold-based strategy ICUs (33.5%) and 22 probabilistic strategy ICUs (36.4%). There was no difference in the adjusted risk of potassium repletion between patients admitted to threshold-based strategy ICUs versus probabilistic strategy ICUs (adjusted odds ratio, 1.09; 95% confidence interval [CI], 0.76-1.57). In regression discontinuity analysis, crossing the 3.5 mEq/L threshold from high to low potassium levels resulted in a 39.1% (95% CI, 23.7-42.4) absolute increase in potassium repletion but no change in other outcomes. Similarly, crossing the 4.0 mEq/L threshold resulted in a 36.4% (95% CI, 22.4-42.2) absolute increase in potassium repletion but no change in other outcomes. Conclusions: Potassium repletion is common in critically ill patients and occurs over a narrow range of "normal" potassium levels (3.5-4.0 mEq/L); use of a threshold-based repletion strategy to guide potassium repletion in ICU patients is not associated with clinically meaningful differences in outcomes.

Deceased Organ Donor Management and Organ Distribution From Organ Procurement Organization-Based Recovery Facilities Versus Acute-Care Hospitals.

Introduction: Organ recovery facilities address the logistical challenges of hospital-based deceased organ donor management. While more organs are transplanted from donors in facilities, differences in donor management and donation processes are not fully characterized. Research Question: Does deceased donor management and organ transport distance differ between organ procurement organization (OPO)-based recovery facilities versus hospitals? Design: Retrospective analysis of Organ Procurement and Transplant Network data, including adults after brain death in 10 procurement regions (April 2017-June 2021). The primary outcomes were ischemic times of transplanted hearts, kidneys, livers, and lungs. Secondary outcomes included transport distances (between the facility or hospital and the transplant program) for each transplanted organ. Results: Among 5010 deceased donors, 51.7% underwent recovery in an OPO-based recovery facility. After adjustment for recipient and system factors, mean differences in ischemic times of any transplanted organ were not significantly different between donors in facilities and hospitals. Transplanted hearts recovered from donors in facilities were transported further than hearts from hospital donors (median 255 mi [IQR 27, 475] versus 174 [IQR 42, 365], P = .002); transport distances for livers and kidneys were significantly shorter (P < .001 for both). Conclusion: Organ recovery procedures performed in OPO-based recovery facilities were not associated with differences in ischemic times in transplanted organs from organs recovered in hospitals, but differences in organ transport distances exist. Further work is needed to determine whether other observed differences in donor management and organ distribution meaningfully impact donation and transplantation outcomes.

Academic anaesthesiology: a global perspective on training, support, and future development of early career researchers.

As anaesthesiologists face increasing clinical demands and a limited and competitive funding environment for academic work, the sustainability of academic anaesthesiologists has never been more tenuous. Yet, the speciality needs academic anaesthesiologists in many roles, extending beyond routine clinical duties. Anaesthesiologist educators, researchers, and administrators are required not only to train future generations but also to lead innovation and expansion of anaesthesiology and related specialities, all to improve patient care. This group of early career researchers with geographically distinct training and practice backgrounds aim to highlight the diversity in clinical and academic training and career development pathways for anaesthesiologists globally. Although multiple routes to success exist, one common thread is the need for consistent support of strong mentors and sponsors. Moreover, to address inequitable opportunities, we emphasise the need for diversity and inclusivity through global collaboration and exchange that aims to improve access to research training and participation. We are optimistic that by focusing on these fundamental principles, we can help build a more resilient and sustainable future for academic anaesthesiologists around the world.

Organ Transplantation Outcomes of Deceased Organ Donors in Organ Procurement Organization-Based Recovery Facilities Versus Acute-Care Hospitals.

INTRODUCTION: Recovery of donated organs at organ procurement organization (OPO)-based recovery facilities has been proposed to improve organ donation outcomes, but few data exist to characterize differences between facilities and acute-care hospitals. RESEARCH QUESTION: To compare donation outcomes between organ donors that underwent recovery procedures in OPO-based recovery facilities and hospitals. DESIGN: Retrospective study of Organ Procurement and Transplantation Network data. From a population-based sample of deceased donors after brain death April 2017 to June 2021, donation outcomes were examined in 10 OPO regions with organ recovery facilities. Primary exposure was organ recovery procedure in an OPO-based organ recovery. Primary outcome was the number of organs transplanted per donor. Multivariable regression models were used to adjust for donor characteristics and managing OPO. RESULTS: Among 5010 cohort donors, 2590 (51.7%) underwent recovery procedures in an OPO-based facility. Donors in facilities differed from those in hospitals, including recovery year, mechanisms of death, and some comorbid diseases. Donors in OPO-based facilities had higher total numbers of organs transplanted per donor (mean 3.5 [SD1.8] vs 3.3 [SD1.8]; adjusted mean difference 0.27, 95% confidence interval 0.18-0.36). Organ recovery at an OPO-based facility was also associated with more lungs, livers, and pancreases transplanted. CONCLUSION: Organ recovery procedures at OPO-based facilities were associated with more organs transplanted per donor than in hospitals. Increasing access to OPO-based organ recovery facilities may improve rates of organ transplantation from deceased organ donors, although further data are needed on other important donor management quality metrics.

The snapshot audit methodology: design, implementation and analysis of prospective observational cohort studies in surgery.

PURPOSE: For some surgical conditionns and scientific questions, the "real world" effectiveness of surgical patient care may be better explored using a multi-institutional time-bound observational cohort assessment approach (termed a "snapshot audit") than by retrospective review of administrative datasets or by prospective randomized control trials. We discuss when this might be the case, and present the key features of developing, deploying, and assessing snapshot audit outcomes data. METHODS: A narrative review of snapshot audit methodology was generated using the Scale for the Assessment of Narrative Review Articles (SANRA) guideline. Manuscripts were selected from domains including: audit design and deployment, statistical analysis, surgical therapy and technique, surgical outcomes, diagnostic testing, critical care management, concomitant non-surgical disease, implementation science, and guideline compliance. RESULTS: Snapshot audits all conform to a similar structure: being time-bound, non-interventional, and multi-institutional. A successful diverse steering committee will leverage expertise that includes clinical care and data science, coupled with librarian services. Pre-published protocols (with specified aims and analyses) greatly helps site recruitment. Mentored trainee involvement at collaborating sites should be encouraged through manuscript contributorship. Current funding principally flows from medical professional organizations. CONCLUSION: The snapshot audit approach to assessing current care provides insights into care delivery, outcomes, and guideline compliance while generating testable hypotheses.

Inhaled Nitric Oxide vs Epoprostenol During Acute Respiratory Failure: An Observational Target Trial Emulation.

BACKGROUND: The inhaled vasodilators nitric oxide and epoprostenol may be initiated to improve oxygenation in mechanically ventilated patients with severe acute respiratory failure (ARF); however, practice patterns and head-to-head comparisons of effectiveness are unclear. RESEARCH QUESTION: What are the practice patterns and comparative effectiveness for inhaled nitric oxide and epoprostenol in severe ARF? STUDY DESIGN AND METHODS: Using a large US database (Premier Healthcare Database), we identified adult patients with ARF or ARDS who were mechanically ventilated and started on inhaled nitric oxide, epoprostenol, or both. Leveraging large hospital variation in the choice of initial inhaled vasodilator, we compared the effectiveness of inhaled nitric oxide with that of epoprostenol by limiting analysis to patients admitted to hospitals that exclusively used either inhaled nitric oxide or epoprostenol. The primary outcome of successful extubation was modeled using multivariate Fine-Grey competing risk (death or hospice discharge) time-to-event models. RESULTS: Among 11,200 patients (303 hospitals), 6,366 patients (56.8%) received inhaled nitric oxide first, 4,720 patients (42.1%) received inhaled epoprostenol first, and 114 patients (1.0%) received both therapies on the same day. One hundred four hospitals (34.3%; 1,666 patients) exclusively used nitric oxide and 118 hospitals (38.9%; 1,812 patients) exclusively used epoprostenol. No differences were found in the likelihood of successful extubation between patients admitted to nitric oxide-only hospitals vs those admitted to epoprostenol-only hospitals (subdistribution hazard ratio, 0.97; 95% CI, 0.80-1.18). Also no differences were found in total hospital costs or death. Results were robust to multiple sensitivity analyses. INTERPRETATION: Large variation exists in the use of initial inhaled vasodilator for respiratory failure across US hospitals. Comparative effectiveness analyses identified no differences in outcomes based on inhaled vasodilator type.

Trials with 'non-significant' results are not insignificant trials: a common significance threshold distorts reporting and interpretation of trial results.

We discuss a newly published study examining how phrases are used in clinical trials to describe results when the estimated P-value is close to (slightly above or slightly below) 0.05, which has been arbitrarily designated by convention as the boundary for 'statistical significance'. Terms such as 'marginally significant', 'trending towards significant', and 'nominally significant' are well represented in biomedical literature, but are not actually scientifically meaningful. Acknowledging that 'statistical significance' remains a major determinant of publication, we propose that scientific journals de-emphasise the use of P-values for null hypothesis significance testing, a purpose for which they were never intended, and avoid the use of these ambiguous and confusing terms in scientific articles. Instead, investigators could simply report their findings: effect sizes, P-values, and confidence intervals (or their Bayesian equivalents), and leave it to the discerning reader to infer the clinical applicability and importance. Our goal should be to move away from describing studies (or trials) as positive or negative based on an arbitrary P-value threshold, and rather to judge whether the scientific evidence provided is informative or uninformative.

Silver linings: will the COVID-19 pandemic instigate long overdue mental health support services for healthcare workers?

A study in this month's journal adds to the growing body of evidence regarding the potential mental health impacts on frontline healthcare staff working during the COVID-19 pandemic. As clinical academics representing critical care, nursing, and medicine, and a psychologist guiding support for frontline health and social workers, we offer our perspectives on this study. We discuss the balance between pragmatic and rigorous data collection on this topic and offer perspectives on the observed differential impact on nurses. Finally, we suggest that the pandemic might have a positive effect by instigating more robust mental health support services for National Health Service workers.

Attention to Immortal Time Bias in Critical Care Research.

Observational studies in critical care medicine offer a popular and practical approach to questions of treatment effectiveness. Although observational research is widely understood to be susceptible to design and interpretation challenges, one well-described source of bias-immortal time bias (ITB)-is frequently present yet often overlooked. ITB may be introduced by study design oversights or mishandled during data analysis. When present, ITB can create inappropriate estimates of the benefit or harm of an exposure or intervention. Studies examining treatments in critically ill patients may be particularly susceptible to ITB, with consequences for clinical adoption and design and initiation of randomized trials. In this Critical Care Perspective, we illustrate the persistent problem of ITB in observational research using recent studies of hydrocortisone, ascorbic acid, and thiamine therapy in patients with sepsis and septic shock. Of the eight studies examined, none contained enough design or reporting elements to rule out the presence of ITB. To mitigate the influence of ITB in future observational studies, we present a novel checklist to help readers assess the features of study design, analysis, and reporting that introduce ITB or obscure its presence. We recommend that commonly used tools designed to evaluate observational research studies should include an ITB assessment.

Use of Vasoactive Medications after Cardiac Surgery in the United States.

Rationale: Patients undergoing cardiac surgery often require vasopressor or inotropic ("vasoactive") medications, but patterns of postoperative use are not well described.Objectives: This study aimed to describe vasoactive medication administration throughout hospitalization for cardiac surgery, to identify patient- and hospital-level factors associated with postoperative use, and to quantify variation in treatment patterns among hospitals.Methods: Retrospective study using the Premier Healthcare Database. The cohort included adult patients who underwent coronary artery bypass grafting or open valve repair or replacement (or in combination) from January 1, 2016, to June 30, 2018. Primary outcome was receipt of vasoactive medication(s) on the first postoperative day (POD1). We identified patient- and hospital-level factors associated with receipt of vasoactive medications using multilevel mixed-effects logistic regression modeling. We calculated adjusted median odds ratios to determine the extent to which receipt of vasoactive medications on POD1 was determined by each hospital, then calculated quotients of Akaike Information Criteria to compare the relative contributions of patient and hospital characteristics and individual hospitals with observed variation.Results: Among 104,963 adults in 294 hospitals, 95,992 (92.2%) received vasoactive medication(s) during hospitalization; 30,851 (29.7%) received treatment on POD1, most commonly norepinephrine (n = 11,427, 37.0%). A median of 29.0% (range, 0.0-94.4%) of patients in each hospital received vasoactive drug(s) on POD1. After adjustment, hospital of admission was associated with twofold increased odds of receipt of any vasoactive medication on POD1 (adjusted median odds ratio, 2.07; 95% confidence interval, 1.93-2.21). Admitting hospital contributed more to observed variation in POD1 vasoactive medication use than patient or hospital characteristics (quotients of Akaike Information Criteria 0.58, 0.44, and <0.001, respectively).Conclusions: Nearly all cardiac surgical patients receive vasoactive medications during hospitalization; however, only one-third receive treatment on POD1, with significant variability by institution. Further research is needed to understand the causes of variability across hospitals and whether these differences are associated with outcomes.

Use of Hydrocortisone, Ascorbic Acid, and Thiamine in Adults with Septic Shock.

Rationale: In December 2016, a single-center study describing significant improvements in mortality among a small group of patients with severe sepsis and septic shock treated with hydrocortisone, high-dose ascorbic acid, and thiamine (HAT therapy) was published online.Objectives: This study aims to describe the administration of HAT therapy among U.S. adults with septic shock before and after study publication and to compare outcomes between patients who received and did not receive HAT therapy.Methods: We performed a retrospective cohort study of 379 acute care hospitals in the Premier Healthcare Database including patients discharged from October 1, 2015, to September 30, 2018. Exposure was quarter year of hospital discharge; postpublication was defined as January 2017 onward (July 2017 for effectiveness analyses). The primary outcome was receipt of HAT at least once during hospitalization. We conducted unadjusted segmented regression analyses to examine temporal trends in HAT administration. In patients with early septic shock, we compared the association of early HAT therapy (within 2 d of hospitalization) with hospital mortality using multivariable modeling and propensity score matching.Measurements and Main Results: Among 338,597 patients, 3,574 (1.1%) received HAT therapy, 98.7% in the postpublication period. HAT administration increased from 0.03% of patients (95% confidence interval [CI], 0.02-0.04) before publication to 2.65% (95% CI, 2.46-2.83) in the last quarter, with a significant step up in use after December 2016 (P < 0.001). Receipt of early HAT was associated with higher hospital mortality (28.2% vs. 19.7%; P < 0.001; adjusted odds ratio, 1.17 [95% CI, 1.02-1.33]; primary propensity-matched model adjusted odds ratio, 1.19 [95% CI, 1.02-1.40]).Conclusions: Publication of a single-center retrospective study was associated with significantly increased administration of HAT. Among patients with early septic shock, receipt of HAT was not associated with mortality benefit.