The Association between Preoperative Blood Pressures and Postoperative Adverse Events.

BACKGROUND: The relationship between postoperative adverse events and blood pressures in the preoperative period remains poorly understood. This study tested the hypothesis that day-of-surgery preoperative blood pressures are associated with postoperative adverse events. METHODS: We conducted a retrospective, observational study of adult patients having elective procedures requiring an inpatient stay between November 2017 and July 2021 at Vanderbilt University Medical Center to examine the independent associations between preoperative systolic and diastolic blood pressures (SBP, DBP) recorded immediately before anesthesia care and number of postoperative adverse events - myocardial injury, stroke, acute kidney injury (AKI), and mortality, while adjusting for potential confounders. We used multivariable ordinal logistic regression to model the relationship. RESULTS: The analysis included 57,389 cases. The overall incidence of myocardial injury, stroke, AKI, and mortality within 30 days of surgery was 3.4% (1,967 events), 0.4% (223), 10.2% (5,871), and 2.1% (1,223), respectively. The independent associations between both SBP and DBP measurements and number of postoperative adverse events were found to be U-shaped, with greater risk both above and below SBP 143 mmHg and DBP 86 mmHg - the troughs of the curves. The associations were strongest at SBP 173 mmHg (adjusted odds ratio [aOR] 1.212 versus 143 mmHg; 95% CI, 1.021 to 1.439; p = 0.028), SBP 93 mmHg (aOR 1.339 versus 143 mmHg; 95% CI, 1.211 to 1.479; p < 0.001), DBP 106 mmHg (aOR 1.294 versus 86 mmHg; 95% CI, 1.003 to 1.17671; p = 0.048), and DBP 46 mmHg (aOR 1.399 versus 86 mmHg; 95% CI, 1.244 to 1.558; p < 0.001). CONCLUSIONS: Preoperative blood pressures both below and above a specific threshold were independently associated with a higher number of postoperative adverse events, but the data do not support specific strategies for managing patients with low or high blood pressure on the day of surgery.

Neuraxial clonidine is not associated with lower post-cesarean opioid consumption or pain scores in parturients on chronic buprenorphine therapy: a retrospective cohort study.

PURPOSE: Adequate post-cesarean delivery analgesia can be difficult to achieve for women diagnosed with opioid use disorder receiving buprenorphine. We sought to determine if neuraxial clonidine administration is associated with decreased opioid consumption and pain scores following cesarean delivery in women receiving chronic buprenorphine therapy. METHODS: This was a retrospective cohort study at a tertiary care teaching hospital of women undergoing cesarean delivery with or without neuraxial clonidine administration while receiving chronic buprenorphine. The primary outcome was opioid consumption (in morphine milligram equivalents) 0-6 h following cesarean delivery. Secondary outcomes included opioid consumption 0-24 h post-cesarean, median postoperative pain scores 0-24 h, and rates of intraoperative anesthetic supplementation. Multivariable analysis evaluating the adjusted effects of neuraxial clonidine on outcomes was conducted using linear regression, proportional odds model, and logistic regression separately. RESULTS: 196 women met inclusion criteria, of which 145 (74%) received neuraxial clonidine while 51 (26%) did not. In univariate analysis, there was no significant difference in opioid consumption 0-6 h post-cesarean delivery between the clonidine (8 [IQR 0, 15]) and control (1 [IQR 0, 8]) groups (P = 0.14). After adjusting for potential confounders, there remained no significant association with neuraxial clonidine administration 0-6 h (Difference in means 2.77, 95% CI [- 0.89 to 6.44], P = 0.14) or 0-24 h (Difference in means 8.56, 95% CI [- 16.99 to 34.11], P = 0.51). CONCLUSION: In parturients receiving chronic buprenorphine therapy at the time of cesarean delivery, neuraxial clonidine administration was not associated with decreased postoperative opioid consumption, median pain scores, or the need for intraoperative supplementation.

Improving Neuromuscular Monitoring Through Education-Based Interventions and Studying Its Association With Adverse Postoperative Outcomes: A Retrospective Observational Study.

BACKGROUND: We assessed the association between education-based interventions, the frequency of train-of-four (TOF) monitoring, and postoperative outcomes. METHODS: We studied adults undergoing noncardiac surgery from February 1, 2020 through October 31, 2021. Our education-based interventions consisted of 3 phases. An interrupted time-series analysis, adjusting for patient- and procedure-related characteristics and secular trends over time, was used to assess the associations between education-based interventions and the frequency of TOF monitoring, postoperative pulmonary complications (PPCs), 90-day mortality, and sugammadex dosage. For each outcome and intervention phase, we tested whether the intervention at that phase was associated with an immediate change in the outcome or its trend (weekly rate of change) over time. In a sensitivity analysis, the association between education-based interventions and postoperative outcomes was adjusted for TOF monitoring. RESULTS: Of 19,422 cases, 11,636 (59.9%) had documented TOF monitoring. Monitoring frequency increased from 44.2% in the first week of preintervention stage to 83.4% in the final week of the postintervention phase. During the preintervention phase, the odds of TOF monitoring trended upward by 0.5% per week (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.007). Phase 1 saw an immediate 54% increase (OR, 1.54; 95% CI, 1.33-1.79) in the odds, and the trend OR increased by 3% (OR, 1.03; 95% CI, 1.01-1.05) to 1.035, or 3.5% per week (joint Wald test, P < .001). Phase 2 was associated with a further immediate 29% increase (OR, 1.29; 95% CI, 1.02-1.64) but no significant association with trend (OR, 0.96; 95% CI, 0.93-1.01) of TOF monitoring (joint test, P = .04). Phase 3 and postintervention phase were not significantly associated with the frequency of TOF monitoring (joint test, P = .16 and P = .61). The study phases were not significantly associated with PPCs or sugammadex administration. The trend OR for 90-day mortality was larger by 24% (OR, 1.24; 95% CI, 1.06-1.45; joint test, P = .03) in phase 2 versus phase 1, from a weekly decrease of 8% to a weekly increase of 14%. However, this trend reversed again at the transition from phase 3 to the postintervention phase (OR, 0.82; 95% CI, 0.68-0.99; joint test, P = .05), from a 14% weekly increase to a 6.2% weekly decrease in the odds of 90-day mortality. In sensitivity analyses, adjusting for TOF monitoring, we found similar associations between study initiatives and postoperative outcomes. TOF monitoring was associated with lower odds of PPCs (OR, 0.69; 95% CI, 0.55-0.86) and 90-day mortality (OR, 0.79; 95% CI, 0.63-0.98), but not sugammadex dosing (mean difference, -0.02; 95% CI, -0.04 to 0.01). CONCLUSIONS: Our education-based interventions were associated with both TOF utilization and 90-day mortality but were not associated with either the odds of PPCs or sugammadex dosing. TOF monitoring was associated with reduced odds of PPCs and 90-day mortality.

Red Blood Cell Transfusion and Pulmonary Complications: The Society of Thoracic Surgeons Adult Cardiac Surgery Database Analysis.

BACKGROUND: Intraoperative packed red blood cell (PRBC) transfusion during cardiac surgery is associated with increased postoperative morbidity and mortality; however, data on the association between PRBC transfusion and postoperative pulmonary complications (PPCs) are somewhat conflicting. Using The Society of Thoracic Surgeons Adult Cardiac Surgery Database, we sought to determine whether intraoperative PRBC transfusion was associated with PPCs as well as with longer intensive care unit (ICU) stay after isolated coronary artery bypass grafting (CABG) surgery. METHODS: A registry-based cohort study was performed on 751,893 patients with isolated CABG between January 1, 2015, to December 31, 2019. Using propensity score-weighted regression analysis, we analyzed the effect of intraoperative PRBC on the incidence of PPCs (hospital-acquired pneumonia [HAP], mechanical ventilation for >24 hours, or reintubation), ICU length of stay, and ICU readmission. RESULTS: Transfusion of 1, 2, 3, and ≥4 units of PRBCs was associated with increased odds for HAP (odds ratios [ORs], 1.24 [95% CI, 1.21-1.26], 1.28 [95% CI, 1.26-1.32], 1.36 [95% CI, 1.33-1.39], 1.31 [95% CI, 1.28-1.34]), reintubation (ORs, 1.23 [95% CI, 1.21-1.25], 1.38 [95% CI, 1.35-1.40], 1.57 [95% CI, 1.55-1.60], 1.70 [95% CI, 1.67-1.73]), prolonged ventilation (ORs, 1.34 [95% CI, 1.33-1.36], 1.56 [95% CI, 1.53-1.58], 1.97 [95% CI, 1.94-2.00], 2.27 [95% CI, 2.24-2.30]), initial ICU length of stay (mean difference in hours, 6.79 [95% CI, 6.00-7.58], 9.55 [95% CI, 8.71-10.38], 17.26 [95% CI, 16.38-18.15], 22.14 [95% CI, 21.22-23.06]), readmission to ICU (ORs, 1.14 [95% CI, 1.12-1.64], 1.15 [95% CI, 1.12-1.17], 1.15 [95% CI, 1.13-1.18], 1.32 [95% CI, 1.29-1.35]), and additional ICU length of stay (mean difference in hours, 0.55 [95% CI, 0.18-0.92], 0.38 [95% CI, 0.00-0.77], 1.02 [95% CI, 0.61-1.43], 1.83 [95% CI, 1.40-2.26]), respectively. CONCLUSIONS: Intraoperative PRBC transfusion was associated with increased incidence of PPCs, prolonged ICU stay, and ICU readmissions after isolated CABG surgery.

The Association of Nonmodifiable Patient Factors on Antipsychotic Medication use in the Intensive Care Unit.

PURPOSE: We investigated the association of age, sex, race, and insurance status on antipsychotic medication use among intensive care unit (ICU) patients. MATERIALS AND METHODS: Retrospective study of adults admitted to ICUs at a tertiary academic center. Patient characteristics, hospital course, and medication (olanzapine, quetiapine, and haloperidol) data were collected. Logistic regression models evaluated the independent association of age, sex, race, and insurance status on the use of each antipsychotic, adjusting for prespecified covariates. RESULTS: Of 27,137 encounters identified, 6191 (22.8%) received antipsychotics. Age was significantly associated with the odds of receiving olanzapine (P < .001), quetiapine (P = .001), and haloperidol (P = .0046). Male sex and public insurance status were associated with increased odds of receiving antipsychotics olanzapine, quetiapine, and haloperidol (Male vs Female: OR 1.13, 95% CI [1.04, 1.24], P = .0005; OR 1.22, 95% CI [1.10, 1.34], P = .0001; OR 1.28, 95% CI [1.17, 1.40], P < .0001, respectively; public insurance vs private insurance: OR 1.32, 95% CI [1.20, 1.46], P < .0001; OR 1.21, 95% CI [1.09, 1.34], P = .0004; OR 1.15, 95% CI [1.04, 1.27], P = .0058, respectively). Black race was also associated with a decreased odds of receiving all antipsychotics (olanzapine (P = .0177), quetiapine (P = .004), haloperidol (P = .0041)). CONCLUSIONS: Age, sex, race, and insurance status were associated with the use of all antipsychotic medications investigated, highlighting the importance of investigating the potential impact of these prescribing decisions on patient outcomes across diverse populations. Recognizing how nonmodifiable patient factors have the potential to influence prescribing practices may be considered an important factor toward optimizing medication regimens.

Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial.

Importance: Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial. Objective: To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction. Design, Setting, and Participants: The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022. Interventions: Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam. Main Outcomes and Measures: The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days. Results: There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]). Conclusions and Relevance: Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction. Trial Registration: ClinicalTrials.gov Identifier: NCT05094154.

Protocol and statistical analysis plan for the Mode of Ventilation During Critical IllnEss (MODE) trial.

Introduction: For every critically ill adult receiving invasive mechanical ventilation, clinicians must select a mode of ventilation. The mode of ventilation determines whether the ventilator directly controls the tidal volume or the inspiratory pressure. Newer hybrid modes allow clinicians to set a target tidal volume, for which the ventilator controls and adjusts the inspiratory pressure. A strategy of low tidal volumes and low plateau pressure improves outcomes, but the optimal mode to achieve these targets is not known. Methods and analysis: The Mode of Ventilation During Critical Illness (MODE) trial is a cluster-randomized, multiple-crossover pilot trial being conducted in the medical intensive care unit (ICU) at an academic center. The MODE trial compares the use of volume control, pressure control, and adaptive pressure control. The study ICU is assigned to a single ventilator mode (volume control versus pressure control versus adaptive pressure control) for continuous mandatory ventilation during each 1-month study block. The assigned mode switches every month in a randomly generated sequence. The primary outcome is ventilator-free days (VFDs) to study day 28, defined as the number of days alive and free of invasive mechanical ventilation from the final receipt of mechanical ventilation to 28 days after enrollment. Enrollment began November 1, 2022 and will end on July 31, 2023. Ethics and dissemination: The trial was approved by the Vanderbilt University Medical Center institutional review board (IRB# 220446). Results of this study will be submitted to a peer-reviewed journal and presented at scientific conferences. Trial registration number: The trial was registered with clinicaltrials.gov on October 3, 2022, prior to initiation of patient enrollment on November 1, 2022 (ClinicalTrials.gov identifier: NCT05563779).

PeRiOperative Glucose PRAgMatic (PROGRAM) trial protocol and statistical analysis plan for comparing automated intraoperative reminders to standardise insulin administration in surgical patients at high risk of hyperglycaemia.

INTRODUCTION: Studies finding perioperative hyperglycaemia is associated with adverse patient outcomes in surgical procedures spurred the development of blood glucose guidelines at many institutions. In this trial, we will assess the implementation of a clinical decision support tool that is integrated into the intraoperative portion of our electronic health record and provides real-time best practice recommendations for intraoperative insulin dosing in surgical patients at high risk for hyperglycaemia. METHODS AND DESIGN: We will assess this intervention using a sequential and repeated cross-over design at the institutional level with periods of time for wash-out, control and study intervention. The unit of analysis will be the surgical case. The primary outcome will be the frequency of hyperglycaemia (>180 mg/dL (10 mmol/L)) at first postoperative anaesthesia care unit measurement. There are several prespecified secondary analyses focused on perioperative glycaemic control. DISCUSSION: This protocol and statistical analysis plan describes the methodology, primary and secondary analyses. The PeRiOperative Glucose PRAgMatic (PROGRAM) trial was approved by the Vanderbilt University Institutional Review Board (IRB), Vanderbilt University Medical Center, Nashville, Tennessee, USA (IRB, 220991). The study results will be disseminated via publication in a peer-reviewed journal and presented at national scientific conferences. The results of PROGRAM trial will inform best practice for perioperative standardised insulin administration in surgical patients at high risk of hyperglycaemia. TRIAL REGISTRATION NUMBER: NCT05426096.

Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design.

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple clinical trials have investigated initial diuretic strategies for a designated period of time, there is a paucity of evidence to guide diuretic titration strategies continued until decongestion is achieved. The use of urine chemistries (urine sodium and creatinine) in a natriuretic response prediction equation accurately estimates natriuresis in response to diuretic dosing, but a randomized clinical trial is needed to compare a urine chemistry-guided diuresis strategy with a strategy of usual care. The urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE) trial is designed to test the hypothesis that protocolized diuretic therapy guided by spot urine chemistry through completion of intravenous diuresis will be superior to usual care and improve outcomes over the 14 days following randomization. ESCALATE will randomize and obtain complete data on 450 patients with acute heart failure to a diuretic strategy guided by urine chemistry or a usual care strategy. Key inclusion criteria include an objective measure of hypervolemia with at least 10 pounds of estimated excess volume, and key exclusion criteria include significant valvular stenosis, hypotension, and a chronic need for dialysis. Our primary outcome is days of benefit over the 14 days after randomization. Days of benefit combines patient symptoms captured by global clinical status with clinical state quantifying the need for hospitalization and intravenous diuresis. CLINICAL TRIAL REGISTRATION: NCT04481919.

Preemptive Pharmacogenetic-Guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery: The Preemptive Pharmacogenetic-Guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery Pilot Trial.

OBJECTIVES: To test the hypothesis that implementation of a cytochrome P-450 2D6 (CYP2D6) genotype-guided perioperative metoprolol administration will reduce the risk of postoperative atrial fibrillation (AF), the authors conducted the Preemptive Pharmacogenetic-Guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery pilot study. DESIGN: Clinical pilot trial. SETTING: Single academic center. PARTICIPANTS: Seventy-three cardiac surgery patients. MEASUREMENTS AND MAIN RESULTS: Patients were classified as normal, intermediate, poor, or ultrarapid metabolizers after testing for their CYP2D6 genotype. A clinical decision support tool in the electronic health record advised providers on CYP2D6 genotype-guided metoprolol dosing. Using historical data, the Bayesian method was used to compare the incidence of postoperative AF in patients with altered metabolizer status to the reference incidence. A logistic regression analysis was performed to study the association between the metabolizer status and postoperative AF while controlling for the Multicenter Study of Perioperative Ischemia AF Risk Index. Of the 73 patients, 30% (n = 22) developed postoperative AF; 89% (n = 65) were normal metabolizers; 11% (n = 8) were poor/intermediate metabolizers; and there were no ultrarapid metabolizer patients identified. The estimated rate of postoperative AF in patients with altered metabolizer status was 30% (95% CI 8%-60%), compared with the historical reference incidence (27%). In the risk-adjusted analysis, there was insufficient evidence to conclude that modifying metoprolol dosing based on poor/intermediate metabolizer status was associated significantly with the odds of postoperative AF (odds ratio 0.82, 95% CI 0.15-4.55, p = 0.82). CONCLUSIONS: A CYP2D6 genotype-guided metoprolol management was not associated with a reduction of postoperative AF after cardiac surgery.

Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor-Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials.

Importance: Preclinical models suggest dysregulation of the renin-angiotensin system (RAS) caused by SARS-CoV-2 infection may increase the relative activity of angiotensin II compared with angiotensin (1-7) and may be an important contributor to COVID-19 pathophysiology. Objective: To evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor-biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II. Design, Setting, and Participants: Two randomized clinical trials including adults hospitalized with acute COVID-19 and new-onset hypoxemia were conducted at 35 sites in the US between July 22, 2021, and April 20, 2022; last follow-up visit: July 26, 2022. Interventions: A 0.5-mg/kg intravenous infusion of TXA-127 once daily for 5 days or placebo. A 12-mg/h continuous intravenous infusion of TRV-027 for 5 days or placebo. Main Outcomes and Measures: The primary outcome was oxygen-free days, an ordinal outcome that classifies a patient's status at day 28 based on mortality and duration of supplemental oxygen use; an adjusted odds ratio (OR) greater than 1.0 indicated superiority of the RAS agent vs placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included allergic reaction, new kidney replacement therapy, and hypotension. Results: Both trials met prespecified early stopping criteria for a low probability of efficacy. Of 343 patients in the TXA-127 trial (226 [65.9%] aged 31-64 years, 200 [58.3%] men, 225 [65.6%] White, and 274 [79.9%] not Hispanic), 170 received TXA-127 and 173 received placebo. Of 290 patients in the TRV-027 trial (199 [68.6%] aged 31-64 years, 168 [57.9%] men, 195 [67.2%] White, and 225 [77.6%] not Hispanic), 145 received TRV-027 and 145 received placebo. Compared with placebo, both TXA-127 (unadjusted mean difference, -2.3 [95% CrI, -4.8 to 0.2]; adjusted OR, 0.88 [95% CrI, 0.59 to 1.30]) and TRV-027 (unadjusted mean difference, -2.4 [95% CrI, -5.1 to 0.3]; adjusted OR, 0.74 [95% CrI, 0.48 to 1.13]) resulted in no difference in oxygen-free days. In the TXA-127 trial, 28-day all-cause mortality occurred in 22 of 163 patients (13.5%) in the TXA-127 group vs 22 of 166 patients (13.3%) in the placebo group (adjusted OR, 0.83 [95% CrI, 0.41 to 1.66]). In the TRV-027 trial, 28-day all-cause mortality occurred in 29 of 141 patients (20.6%) in the TRV-027 group vs 18 of 140 patients (12.9%) in the placebo group (adjusted OR, 1.52 [95% CrI, 0.75 to 3.08]). The frequency of the safety outcomes was similar with either TXA-127 or TRV-027 vs placebo. Conclusions and Relevance: In adults with severe COVID-19, RAS modulation (TXA-127 or TRV-027) did not improve oxygen-free days vs placebo. These results do not support the hypotheses that pharmacological interventions that selectively block the angiotensin II type 1 receptor or increase angiotensin (1-7) improve outcomes for patients with severe COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04924660.

Peripheral Intravenous Waveform Analysis Responsiveness to Subclinical Hemorrhage in a Rat Model.

BACKGROUND: Early detection and quantification of perioperative hemorrhage remains challenging. Peripheral intravenous waveform analysis (PIVA) is a novel method that uses a standard intravenous catheter to detect interval hemorrhage. We hypothesize that subclinical blood loss of 2% of the estimated blood volume (EBV) in a rat model of hemorrhage is associated with significant changes in PIVA. Secondarily, we will compare PIVA association with volume loss to other static, invasive, and dynamic markers. METHODS: Eleven male Sprague Dawley rats were anesthetized and mechanically ventilated. A total of 20% of the EBV was removed over ten 5 minute-intervals. The peripheral intravenous pressure waveform was continuously transduced via a 22-G angiocatheter in the saphenous vein and analyzed using MATLAB. Mean arterial pressure (MAP) and central venous pressure (CVP) were continuously monitored. Cardiac output (CO), right ventricular diameter (RVd), and left ventricular end-diastolic area (LVEDA) were evaluated via transthoracic echocardiogram using the short axis left ventricular view. Dynamic markers such as pulse pressure variation (PPV) were calculated from the arterial waveform. The primary outcome was change in the first fundamental frequency (F1) of the venous waveform, which was assessed using analysis of variance (ANOVA). Mean F1 at each blood loss interval was compared to the mean at the subsequent interval. Additionally, the strength of the association between blood loss and F1 and each other marker was quantified using the marginal R2 in a linear mixed-effects model. RESULTS: PIVA derived mean F1 decreased significantly after hemorrhage of only 2% of the EBV, from 0.17 to 0.11 mm Hg, P = .001, 95% confidence interval (CI) of difference in means 0.02 to 0.10, and decreased significantly from the prior hemorrhage interval at 4%, 6%, 8%, 10%, and 12%. Log F1 demonstrated a marginal R2 value of 0.57 (95% CI 0.40-0.73), followed by PPV 0.41 (0.28-0.56) and CO 0.39 (0.26-0.58). MAP, LVEDA, and systolic pressure variation displayed R2 values of 0.31, and the remaining predictors had R2 values ≤0.2. The difference in log F1 R2 was not significant when compared to PPV 0.16 (95% CI -0.07 to 0.38), CO 0.18 (-0.06 to 0.04), or MAP 0.25 (-0.01 to 0.49) but was significant for the remaining markers. CONCLUSIONS: The mean F1 amplitude of PIVA was significantly associated with subclinical blood loss and most strongly associated with blood volume among the markers considered. This study demonstrates feasibility of a minimally invasive, low-cost method for monitoring perioperative blood loss.

Automated Emails to Improve Evening Staffing for Anesthesiologists.

Scheduling flexibility and predictability to the end of a clinical workday are strategies aimed at addressing physician burnout. A voluntary relief shift was created to increase the pool of anesthesiologists providing end of the day relief. We hypothesized that an automated email reminder would improve the number of evening relief shifts filled and increase the number of anesthesiologists participating in the program. An automated email reminder was implemented, which selectively emailed anesthesiologists without a clinical assignment one day in advance when the voluntary relief shifts were not filled, and anticipated case volume past 4:00 PM was expected to exceed the capacity of the on-call team. After implementation of the automated email reminder, the median number of providers who worked the relief shift on a typical day was 2.6, compared to 1.75 prior to the intervention. After the initial increase in the number of volunteers post-intervention, the trend in the weekly average number of volunteers tended to decrease but remained higher than before the intervention. A total of 22 unique anesthesiologists chose to participate in this program after the intervention. An automated email reminder increased the number of anesthesiologists volunteering for a relief shift. Leveraging automation to match staffing needs with case volume allows for recruitment of additional personnel on the days when volunteers are most needed. Increasing the pool of anesthesiologists available to provide relief is one strategy to improve end of the day predictability and work-life balance.

Evaluating automated electronic case report form data entry from electronic health records.

Background: Many clinical trials leverage real-world data. Typically, these data are manually abstracted from electronic health records (EHRs) and entered into electronic case report forms (CRFs), a time and labor-intensive process that is also error-prone and may miss information. Automated transfer of data from EHRs to eCRFs has the potential to reduce data abstraction and entry burden as well as improve data quality and safety. Methods: We conducted a test of automated EHR-to-CRF data transfer for 40 participants in a clinical trial of hospitalized COVID-19 patients. We determined which coordinator-entered data could be automated from the EHR (coverage), and the frequency with which the values from the automated EHR feed and values entered by study personnel for the actual study matched exactly (concordance). Results: The automated EHR feed populated 10,081/11,952 (84%) coordinator-completed values. For fields where both the automation and study personnel provided data, the values matched exactly 89% of the time. Highest concordance was for daily lab results (94%), which also required the most personnel resources (30 minutes per participant). In a detailed analysis of 196 instances where personnel and automation entered values differed, both a study coordinator and a data analyst agreed that 152 (78%) instances were a result of data entry error. Conclusions: An automated EHR feed has the potential to significantly decrease study personnel effort while improving the accuracy of CRF data.

High Isoniazid Exposures When Administered with Rifapentine Once Weekly for Latent Tuberculosis in Individuals with Human Immunodeficiency Virus.

Isoniazid pharmacokinetics are not yet well-described during once weekly, high-dose administrations with rifapentine (3HP) for latent tuberculosis infection (LTBI). Fewer data describe 3HP with dolutegravir-based antiretroviral therapy for the treatment of human immunodeficiency virus (HIV). The only prior report of 3HP with dolutegravir reported elevated isoniazid exposures. We measured the plasma isoniazid levels in 30 adults receiving 3HP and dolutegravir for the treatment of LTBI and HIV. The patients were genotyped to determine NAT2 acetylator status, and a population PK model was estimated by nonlinear mixed-effects modeling. The results were compared to previously reported data describing 3HP with dolutegravir, 3HP alone, and isoniazid with neither dolutegravir nor rifapentine. The isoniazid concentrations were adequately described by a one compartment model with a transit compartment absorption process. The isoniazid clearance for slow (8.33 L/h) and intermediate (12 L/h) acetylators were similar to previously reported values. Rapid acetylators (N = 4) had clearance similar to those of intermediate acetylators and much slower than typically reported, but the small sample size was limiting. The absorption rate was lower than usual, likely due to the coadministration with food, and it was faster among individuals with a low body weight. Low-body weight participants were also observed to have greater oral bioavailability. The isoniazid exposures were consistent with, or greater than, the previously reported "elevated" concentrations among individuals receiving 3HP and dolutegravir. The concentrations were substantially greater than those presented in previous reports among individuals receiving 3HP or isoniazid without rifapentine or dolutegravir. We discuss the implications of these findings and the possibility of a drug-drug interaction that is mediated by cellular transport. (This study has been registered at ClinicalTrials.gov under identifier NCT03435146 and has South African National Clinical Trial Registration no. DOH-27-1217-5770.).

Association of Intraoperative Red Blood Cell Transfusions With Venous Thromboembolism and Adverse Outcomes After Cardiac Surgery.

OBJECTIVE: We determined whether intraoperative packed red blood cell (PRBC) transfusion was associated with a higher incidence of hospital-acquired venous thromboembolic (HA-VTE) complications and adverse outcomes after isolated coronary artery bypass grafting (CABG) surgery. BACKGROUND: Intraoperative PRBC has been associated with increased risk for postoperative deep venous thrombosis after cardiac surgery, but validation of these findings in a large, multi-institutional, national cohort of cardiac surgery patients has been lacking. METHODS: A registry-based cohort study of 751,893 patients with isolated CABG between January 1, 2015, to December 31, 2019. Using propensity score-weighted regression analysis, we analyzed the effect of intraoperative PRBC on the incidence of HA-VTE and adverse outcomes. RESULTS: Administration of 1, 2, 3, and ≥4 units of PRBC transfusion was associated with increased odds for HA-VTE [odds ratios (ORs): 1.27 (1.22-1.32), 1.21 (1.16-1.26), 1.93 (1.85-2.00), 1.82 (1.75-1.89)], deep venous thrombosis [ORs: 1.39 (1.33-1.46), 1.38 (1.32-1.44), 2.18 (2.09-2.28), 1.82 (1.74-1.91], operative mortality [ORs: 1.11 (1.08-1.14), 1.16 (1.13-1.19), 1.29 (1.26-1.32), 1.47 (1.43-1.50)], readmission within 30 days [ORs: 1.05 (1.04-1.06), 1.16 (1.13-1.19), 1.29 (1.26-1.32), 1.47 (1.43-1.50)], and a prolonged postoperative length of stay [mean difference in days, 0.23 (0.19-0.27), 0.34 (0.30-0.39), 0.69 (0.64-0.74), 0.77 (0.72-0.820]. The odds of pulmonary venous thromboembolism were lower for patients transfused with 1 or 2 units [ORs: 0.98 (0.91-1.06), 0.75 (0.68-0.81)] of PRBC but remained significantly elevated for those receiving 3 and ≥4 units [ORs: 1.19 (1.09-1.29), 1.35 (1.25-1.48)]. CONCLUSIONS: Intraoperative PRBC transfusion was associated with HA-VTE and adverse outcomes after isolated CABG surgery.

Understanding Patient and Clinician Reported Nonroutine Events in Ambulatory Surgery.

OBJECTIVE: Nonroutine events (NREs, i.e., deviations from optimal care) can identify care process deficiencies and safety risks. Nonroutine events reported by clinicians have been shown to identify systems failures, but this methodology fails to capture the patient perspective. The objective of this prospective observational study is to understand the incidence and nature of patient- and clinician-reported NREs in ambulatory surgery. METHODS: We interviewed patients about NREs that occurred during their perioperative care using a structured interview tool before discharge and in a 7-day follow-up call. Concurrently, we interviewed the clinicians caring for these patients immediately postoperatively to collect NREs. We trained 2 experienced clinicians and 2 patients to assess and code each reported NRE for type, theme, severity, and likelihood of reoccurrence (i.e., likelihood that the same event would occur for another patient). RESULTS: One hundred one of 145 ambulatory surgery cases (70%) contained at least one NRE. Overall, 214 NREs were reported-88 by patients and 126 by clinicians. Cases containing clinician-reported NREs were associated with increased patient body mass index ( P = 0.023) and lower postcase patient ratings of being treated with respect ( P = 0.032). Cases containing patient-reported NREs were associated with longer case duration ( P = 0.040), higher postcase clinician frustration ratings ( P < 0.001), higher ratings of patient stress ( P = 0.019), and lower patient ratings of their quality of life ( P = 0.010), of the quality of clinician teamwork ( P = 0.010), being treated with respect ( P = 0.003), and being listened to carefully ( P = 0.012). Trained patient raters evaluated NRE severity significantly higher than did clinician raters ( P < 0.001), while clinicians rated recurrence likelihood significantly higher than patients for both clinician ( P = 0.032) and patient-reported NREs ( P = 0.001). CONCLUSIONS: Both patients and clinicians readily report events during clinical care that they believe deviate from optimal care expectations. These 2 primary stakeholders in safe, high-quality surgical care have different experiences and perspectives regarding NREs. The combination of patient- and clinician-reported NREs seems to be a promising patient-centered method of identifying healthcare system deficiencies and opportunities for improvement.