The Association of Guideline-Directed Prophylaxis With Postoperative Nausea and Vomiting in Adult Patients: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Consensus guidelines for postoperative nausea and vomiting (PONV) prophylaxis recommend a risk-based approach in which the number of antiemetics administered is based on a preoperative estimate of PONV risk. These guidelines have been adapted by the Multicenter Perioperative Outcomes Group (MPOG) to serve as measures of clinician and hospital compliance with guideline-recommended care. However, the impact of this approach on clinical outcomes is not known. METHODS: We performed a single-center, retrospective study of adult patients undergoing general anesthesia from 2018 to 2021. Risk factors for PONV were defined using MPOG definitions: female sex, history of PONV or motion sickness, nonsmoker, inhaled anesthesia >60 minutes, high-risk procedure (cholecystectomy, laparoscopic, gynecologic), and age <50 years. Adequate prophylaxis was defined using the MPOG PONV-05 metric: at least 2 agents for patients with 1 to 2 risk factors and at least 3 agents for patients with 3+ risk factors. PONV was defined as documented PONV or receipt of rescue antiemetics. To estimate the association between adequate prophylaxis and PONV, we used Bayesian binomial models with overlap propensity score weighting. RESULTS: We included 76,703 cases (43% receiving adequate prophylaxis) with PONV occurring in 19%. In unadjusted and unweighted comparison, adequate prophylaxis was associated with increased incidence of PONV: median odds ratio 1.21 (95% credible interval [1.16-1.25]). However, after propensity score weighting and multivariable adjustment, adequate prophylaxis was associated with reduced relative and absolute risk for PONV: weighted marginal median odds ratio 0.90 [0.84-0.98] and absolute risk reduction (ARR) 1.6% [0.6%-2.6%]. There was evidence for a differential effect of adequate prophylaxis across the guideline-defined risk spectrum, with benefit seen in patients with 1 to 5 risk factors (conditional probabilities of benefit >0.81), but not in those at high predicted risk. Patient-specific, covariate-adjusted ARR was heterogeneous, with a median patient-specific conditional probability of benefit of 0.84 (95% credible interval, 0.73-0.90). CONCLUSIONS: Guideline-directed PONV prophylaxis is associated with a modest reduction in PONV, although this effect is small and heterogeneous on the absolute scale. We found evidence for a differential association between adequate prophylaxis and PONV across the guideline-defined risk spectrum, with diminution in patients at very high predicted preoperative risk. While patient-specific benefit was heterogenous, most patients had reasonably high predicted probabilities of absolute benefit from a guideline-directed strategy. Further assessment of these associations in a multicenter setting, with more robust investigation of risk prediction methods will allow for better understanding of the optimal approach to PONV prophylaxis.

Propensity score methods in observational research: brief review and guide for authors.

Causal inference in observational research requires a careful approach to adjustment for confounding. One such approach is the use of propensity score analyses. In this editorial, we focus on the role of propensity score-based methods in estimating causal effects from non-randomised observational data. We highlight the details, assumptions, and limitations of these methods and provide authors with guidelines for the conduct and reporting of propensity score analyses.

The Association of Guideline-Directed Prophylaxis with Postoperative Nausea and Vomiting in Pediatric Patients: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Guidelines for postoperative nausea and vomiting (PONV) prophylaxis in pediatric patients recommend escalation of the number of antiemetics based on a preoperative estimate of PONV risk. These recommendations have been translated into performance metrics, most notably by the Multicenter Perioperative Outcomes Group (MPOG), used at over 25 children's hospitals. The impact of this approach on clinical outcomes is not known. METHODS: We performed a single-center, retrospective study of pediatric general anesthetic cases from 2018 to 2021. PONV risk factors were defined using MPOG definitions: age ≥3 years, volatile use ≥30 minutes, PONV history, long-acting opioids, female ≥12 years, and high-risk procedure. Adequate prophylaxis was defined using the MPOG PONV-04 metric: 1 agent for 1 risk factor, 2 agents for 2 risk factors, and 3 agents for 3+ risk factors. PONV was defined as documented postoperative nausea/emesis or administration of a rescue antiemetic. Given the nonrandomized allocation of adequate prophylaxis, we used Bayesian binomial models with propensity score weighting. RESULTS: A total of 14,747 cases were included, with PONV in 11% (9% adequate prophylaxis versus 12% inadequate). Overall, there was evidence for reduced incidence of PONV with adequate prophylaxis: weighted median odds ratio 0.82 (95% credible interval, 0.66-1.02; probability of benefit, 0.97) and weighted marginal absolute risk reduction 1.3% (-0.1% to 3.1%). In unweighted estimates, there was an interaction between sum of risk factors and the association of adequate prophylaxis with PONV, with reduced incidence in patients with 1 to 2 risk factors (probability of benefit 0.96 and 0.95) but increased incidence in patients with 3+ risk factors receiving adequate prophylaxis (probability of benefit 0, 0.01, and 0.03 for 3, 4, and 5 risk factors). This was attenuated by weighting, with persistent benefit in 1 to 2 risk factors (probability of benefit 0.90 and 0.94) but equalization of risk in 3+ risk factors. CONCLUSIONS: Guideline-directed PONV prophylaxis is inconsistently associated with incidence of PONV across the guideline-defined risk spectrum. This phenomenon, and its attenuation with weighting, is consistent with 2 points: dichotomous risk-factor summation ignores differential effects of individual components, and prognostic information might exist beyond these risk factors. PONV risk at a given sum of risk factors is not homogeneous, but rather is determined by the unique composition of risk factors and other prognostic attributes. These differences appear to have been identified by clinicians, prompting use of more antiemetics. Even after accounting for these differences, however, addition of a third agent did not further reduce risk.

Analgesic Effects of a Novel Combination of Regional Anesthesia After Pediatric Cardiac Surgery: A Retrospective Cohort Study.

OBJECTIVE: The objective of this study was to determine whether the use of regional anesthesia in children undergoing congenital heart surgery was associated with differences in outcomes when compared to surgeon-delivered local anesthetic wound infiltration. DESIGN: A retrospective cohort study. SETTING: At a single pediatric tertiary care center. PARTICIPANTS: Pediatric patients who underwent primary repair of septal defects between January 1, 2018, and March 31, 2022. INTERVENTIONS: The patients were grouped by whether they received surgeon-delivered local anesthetic wound infiltration or bilateral pectointercostal fascial blocks (PIFBs) and a unilateral rectus sheath block (RSB) on the side ipsilateral to the chest tube. MEASUREMENTS AND MAIN RESULTS: Using overlap propensity score-weighted models, the authors examined postoperative opioid requirements (morphine milliequivalents per kilogram), pain scores, length of stay, and time under general anesthesia (GA). Eighty-nine patients were eligible for inclusion and underwent analysis. In the first 12 hours postoperatively, the block group used fewer morphine equivalents per kilogram versus the infiltration group, 0.27 ± 0.2 v 0.64 ± 0.42, with a weighted estimated decrease of 0.39 morphine equivalents per kilogram (95% CI -0.52 to -0.25; p < 0.001), and had lower pain scores, 3.2 v 1.6, with a weighted estimated decrease of 1.7 (95% CI -2.3 to -1.1; p < 0.001). The length of stay and time under GA also were shorter in the block group with weighted estimated decreases of 22 hours (95% CI -33 to -11; p = 0.001) and 18 minutes (95% CI -34 to -2; p = 0.03), respectively. CONCLUSIONS: Bilateral PIFBs and a unilateral RSB on the side ipsilateral to the chest tube is a novel analgesic technique for sternotomy in pediatric patients. In this retrospective study, these interventions were associated with decreases in postoperative opioid use, pain scores, and hospital length of stay without prolonging time under GA.

Short-term mortality of patients ≥80 years old admitted to European intensive care units: an international observational study.

BACKGROUND: Limited evidence suggests variation in mortality of older critically ill adults across Europe. We aimed to investigate regional differences in mortality among very old ICU patients. METHODS: Multilevel analysis of two international prospective cohort studies. We included patients ≥80 yr old from 322 ICUs located in 16 European countries. The primary outcome was mortality within 30 days from admission to the ICU. Results are presented as n (%) with 95% confidence intervals and odds ratios (ORs). RESULTS: Of 8457 patients, 2944 (36.9% [35.9-38.0%]) died within 30 days. Crude mortality rates varied widely between participating countries (from 10.1% [6.4-15.6%] to 45.1% [41.1-49.2%] in the ICU and from 21.3% [16.3-28.9%] to 55.3% [51.1-59.5%] within 30 days). After adjustment for confounding variables, the variation in 30-day mortality between countries was substantially smaller than between ICUs (median OR 1.14 vs 1.58). Healthcare expenditure per capita (OR=0.84 per $1000 [0.75-0.94]) and social health insurance framework (OR=1.43 [1.01-2.01]) were associated with ICU mortality, but the direction and magnitude of these relationships was uncertain in 30-day follow-up. Volume of admissions was associated with lower mortality both in the ICU (OR=0.81 per 1000 annual ICU admissions [0.71-0.94]) and in 30-day follow-up (OR=0.86 [0.76-0.97]). CONCLUSION: The apparent variation in short-term mortality rates of older adults hospitalised in ICUs across Europe can be largely attributed to differences in the clinical profile of patients admitted. The volume-outcome relationship identified in this population requires further investigation.

Identification of Trajectory-Based Acute Kidney Injury Phenotypes Among Cardiac Surgery Patients.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication of cardiac surgical procedures for which unrecognized heterogeneity may underpin poor success in identifying effective therapies. We aimed to identify phenotypically similar groups of patients as defined by their postoperative creatinine trajectories. METHODS: This was a retrospective, single-center cohort study in an academic tertiary care center including patients undergoing coronary artery bypass graft procedures. AKI phenotypes were evaluated through latent class mixed modeling of serum creatinine patterns (trajectories). To identify trajectory phenotypes, modeling was performed using postoperative creatinine values from 50% of patients (development cohort) and for comparison similarly conducted for the remaining sample (validation cohort). Subsequent assessments included comparisons of classes between development and validation cohorts for consistency and stability, and among classes for patient and procedural characteristics, complications, and long-term survival. RESULTS: We identified 12 AKI trajectories in both the development (n = 2647) and validation cohorts (n = 2647). Discrimination among classes was good (mean posterior class membership probability, 66%-88%), with differences in rate, timing, and degree of serum creatinine rise/fall, and recovery. In matched class comparisons between cohorts, many other phenotypic similarities were present. Notably, 4 high-risk phenotypes had greater long-term risk for death relative to lower risk classes. CONCLUSIONS: Latent class mixed modeling identified 12 reproducible AKI classes (serum creatinine trajectory phenotypes), including 4 with higher risk of poor outcome, in patients following coronary artery bypass graft procedures. Such hidden structure offers a novel approach to grouping patients for renoprotection investigations in addition to reanalysis of previously conducted trials.

Renal-Resistive Index for Prediction of Acute Kidney Injury in the Setting of Aortic Insufficiency.

Acute kidney injury (AKI) is a common postoperative complication after cardiac surgery with cardiopulmonary bypass (CPB), and leads to significant morbidity, mortality, and cost. Although early recognition and management of AKI may reduce the burden of renal disease, reliance on serum creatinine accumulation to confidently diagnose it leads to a significant and important delay (up to 48 hours). Hence, a search for earlier AKI biomarkers is warranted. The renal-resistive index (RRI) is a promising early AKI biomarker that reflects intrarenal arterial pulsatility as reflected by the peak systolic and end-diastolic blood velocities divided by the peak systolic velocity. During cardiac surgery, post-CPB elevation of RRI is correlated with renal injury. The RRI is influenced by intrarenal and extrarenal factors, as well as different hemodynamic states. Understanding its limitations may increase its usefulness as an early AKI biomarker. For example, tachycardia or aortic stenosis typically results in a lower RRI, whereas bradycardia or increased systemic pulse pressure (as seen with aortic insufficiency) are associated with a higher RRI, unrelated to any intrarenal effects. In this E-Challenge, the authors present two cases in which the RRI was used to evaluate a patient's risk of developing AKI.

Intraoperative renal resistive index threshold as an acute kidney injury biomarker.

STUDY OBJECTIVE: The lag in creatinine-mediated diagnosis of cardiac surgery-associated acute kidney injury (AKI) may be impeding the development of renoprotection therapies. Postoperative renal resistive index (RRI) measured by transabdominal Doppler ultrasound is a promising early AKI biomarker. RRI measured intraoperatively by transesophageal echocardiography (TEE) is available even earlier but is less evaluated. Therefore, we conducted an assessment of intraoperative RRI as an AKI biomarker using previously reported post-renal insult thresholds. DESIGN: Retrospective convenience sample. SETTING: Intraoperative. PATIENTS: 180 adult cardiac surgical patients between July 2013 and July 2014. INTERVENTION: None. MEASUREMENTS: Pre- and post-cardiopulmonary bypass (CPB) RRI thresholds, measured using intraoperative TEE, exceeding 0.74 or 0.79 were used to evaluate for an association with KDIGO AKI risk using the Chi-square test. Other consensus AKI criteria (AKIN, RIFLE) were similarly evaluated. Additional t-test analyses examined the relationship of pre- and pre-to-post (delta) CPB RRI with AKI. MAIN RESULTS: Post-CPB RRI for 99 patients included 36 and 23 with values exceeding 0.74 and 0.79, respectively. Analyses confirmed associations of both RRI thresholds with all consensus AKI definitions (0.74; KDIGO: p = 0.05, AKIN: p = 0.03, RIFLE: p = 0.03, 0.79; KDIGO: p = 0.002, AKIN: p = 0.001, RIFLE: p = 0.004). In contrast, pre-CPB and pre-to post-CPB RRI were not associated with AKI. CONCLUSIONS: RRI obtained intraoperatively in cardiac surgery patients, assessed using previously reported thresholds, is highly associated with AKI and warrants further evaluation as a promising "earliest" AKI biomarker. These significant findings suggest that RRI assessment should be included in the standard intraoperative TEE exam.

Intraoperative Renal Resistive Index as an Acute Kidney Injury Biomarker: Development and Validation of an Automated Analysis Algorithm.

OBJECTIVE: Intraoperative Doppler-determined renal resistive index (RRI) is a promising early acute kidney injury (AKI) biomarker. As RRI continues to be studied, its clinical usefulness and robustness in research settings will be linked to the ease, efficiency, and precision with which it can be interpreted. Therefore, the authors assessed the usefulness of computer vision technology as an approach to developing an automated RRI-estimating algorithm with equivalent reliability and reproducibility to human experts. DESIGN: Retrospective. SETTING: Single-center, university hospital. PARTICIPANTS: Adult cardiac surgery patients from 7/1/2013 to 7/10/2014 with intraoperative transesophageal echocardiography-determined renal blood flow measurements. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Renal Doppler waveforms were obtained retrospectively and assessed by blinded human expert raters. Images (430) were divided evenly into development and validation cohorts. An algorithm for automated RRI analysis was built using computer vision techniques and tuned for alignment with experts using bootstrap resampling in the development cohort. This algorithm then was applied to the validation cohort for an unbiased assessment of agreement with human experts. Waveform analysis time per image averaged 0.144 seconds. Agreement was excellent by intraclass correlation coefficient (0.939; 95% confidence interval [CI] 0.921 to 0.953) and in Bland-Altman analysis (mean difference [human-algorithm] -0.0015; 95% CI -0.0054 to 0.0024), without evidence of systematic bias. CONCLUSION: The authors confirmed the value of computer vision technology to develop an algorithm for RRI estimation from automatically processed intraoperative renal Doppler waveforms. This simple-to-use and efficient tool further adds to the clinical and research value of RRI, already the "earliest" among several early AKI biomarkers being assessed.

The Association of Aortic Valve Pathology With Renal Resistive Index as a Kidney Injury Biomarker.

BACKGROUND: Acute kidney injury (AKI) is a common serious complication after cardiac surgery. Doppler-determined renal resistive index (RRI) is a promising early AKI biomarker in this population. However, the relationship between aortic valve pathology (insufficiency and/or stenosis) and RRI is unknown. This study aimed to investigate RRI variability related to aortic valve pathology. METHODS: In a retrospective review of cardiac surgery patients, RRI and aortic valve pathology were assessed prior to cardiopulmonary bypass using transesophageal echocardiography. Aortic valve status was categorized into four subgroups: normal (insufficiency and stenosis, none/trace/mild), insufficiency (insufficiency, moderate/severe; stenosis, none/trace/mild), combined insufficiency/stenosis (insufficiency and stenosis, moderate/severe), or stenosis (insufficiency, none/trace/mild; stenosis, moderate/severe). RRI and time-matched hemodynamic and Doppler measurements were compared among subgroups. RESULTS: Of 175 patients, 60 had aortic valve pathology (16 insufficiency, 18 insufficiency/stenosis, 26 stenosis). Compared with the normal subgroup, patients with aortic insufficiency had lower diastolic blood pressure and trough renal Doppler velocities, and higher RRI (0.77 versus 0.69; p < 0.001); patients with combined insufficiency/stenosis also had higher RRI (0.72 versus 0.69, p = 0.042). CONCLUSIONS: Patients with aortic insufficiency and combined insufficiency/stenosis had higher median RRI values compared with normal patients. For these individuals, diastolic flow differences related to aortic insufficiency may explain why their presurgery RRI values often exceeded postoperative thresholds typically associated with AKI. Strategies to account for the potentially confounding effects of aortic insufficiency on renal flow patterns, independent of renal injury, may add to the value of RRI as an early AKI biomarker.

mStroke: "Mobile Stroke"-Improving Acute Stroke Care with Smartphone Technology.

OBJECTIVE: This study aimed to evaluate the effect of method and time of system activation on clinical metrics in cases utilizing the Stop Stroke (Pulsara, Inc.) mobile acute stroke care coordination application. METHODS: A retrospective cohort analysis of stroke codes at 12 medical centers using Stop Stroke from March 2013 to May 2016 was performed. Comparison of metrics (door-to-needle time [DTN] and door-to-CT time [DTC], and rate of DTN ≤ 60 minutes [goal DTN]) was performed between subgroups based on method (emergency medical service [EMS] versus emergency department [ED]) and time of activation. Effects were adjusted for confounders (age, sex, National Institutes of Health Stroke Scale [NIHSS] score) using multiple linear and logistic regression. RESULTS: The final dataset included 2589 cases. Cases activated by EMS were more severe (median NIHSS score 8 versus 4, P < .0001) and more likely to receive recombinant tissue plasminogen activator (20% versus 12%, P < .0001) than those with ED activation. After adjustment, cases with EMS activation had shorter DTC (6.1 minutes shorter, 95% CI [-10.3, -2]) and DTN (12.8 minutes shorter, 95% CI [-21, -4.6]) and were more likely to meet goal DTN (OR 1.83, 95% CI [1.1, 3]). Cases between 1200 and 1800 had longer DTC (7.7 minutes longer, 95% CI [2.4, 13]) and DTN (21.1 minutes longer, 95% CI [9.3, 33]), and reduced rate of goal DTN (OR .3, 95% CI [.15, .61]) compared to those between 0000 and 0600. CONCLUSIONS: Incorporating real-time prehospital data obtained via smartphone technology provides unique insight into acute stroke codes. Activation of mobile electronic stroke coordination in the field appears to promote a more expedited and successful care process.

Validation of the Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition Recommendations for Caloric Provision to Critically Ill Obese Patients: A Pilot Study.

BACKGROUND: The Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN) recommend that obese, critically ill patients receive 11-14 kcal/kg/d using actual body weight (ABW) or 22-25 kcal/kg/d using ideal body weight (IBW), because feeding these patients 50%-70% maintenance needs while administering high protein may improve outcomes. It is unknown whether these equations achieve this target when validated against indirect calorimetry, perform equally across all degrees of obesity, or compare well with other equations. METHODS: Measured resting energy expenditure (MREE) was determined in obese (body mass index [BMI] ≥30 kg/m(2)), critically ill patients. Resting energy expenditure was predicted (PREE) using several equations: 12.5 kcal/kg ABW (ASPEN-Actual BW), 23.5 kcal/kg IBW (ASPEN-Ideal BW), Harris-Benedict (adjusted-weight and 1.5 stress-factor), and Ireton-Jones for obesity. Correlation of PREE to 65% MREE, predictive accuracy, precision, bias, and large error incidence were calculated. RESULTS: All equations were significantly correlated with 65% MREE but had poor predictive accuracy, had excessive large error incidence, were imprecise, and were biased in the entire cohort (N = 31). In the obesity cohort (n = 20, BMI 30-50 kg/m(2)), ASPEN-Actual BW had acceptable predictive accuracy and large error incidence, was unbiased, and was nearly precise. In super obesity (n = 11, BMI >50 kg/m(2)), ASPEN-Ideal BW had acceptable predictive accuracy and large error incidence and was precise and unbiased. CONCLUSIONS: SCCM/ASPEN-recommended body weight equations are reasonable predictors of 65% MREE depending on the equation and degree of obesity. Assuming that feeding 65% MREE is appropriate, this study suggests that patients with a BMI 30-50 kg/m(2) should receive 11-14 kcal/kg/d using ABW and those with a BMI >50 kg/m(2) should receive 22-25 kcal/kg/d using IBW.

Choline inadequacy impairs trophoblast function and vascularization in cultured human placental trophoblasts.

Maternal choline intake during gestation may influence placental function and fetal health outcomes. Specifically, we previously showed that supplemental choline reduced placental and maternal circulating concentrations of the anti-angiogenic factor, fms-like tyrosine kinase-1 (sFLT1), in pregnant women as well as sFLT1 production in cultured human trophoblasts. The current study aimed to quantify the effect of choline on a wider array of biomarkers related to trophoblast function and to elucidate possible mechanisms. Immortalized HTR-8/SVneo trophoblasts were cultured in different choline concentrations (8, 13, and 28 µM [control]) for 96-h and markers of angiogenesis, inflammation, apoptosis, and blood vessel formation were examined. Choline insufficiency altered the angiogenic profile, impaired in vitro angiogenesis, increased inflammation, induced apoptosis, increased oxidative stress, and yielded greater levels of protein kinase C (PKC) isoforms δ and ϵ possibly through increases in the PKC activators 1-stearoyl-2-arachidonoyl-sn-glycerol and 1-stearoyl-2-docosahexaenoyl-sn-glycerol. Notably, the addition of a PKC inhibitor normalized angiogenesis and apoptosis, and partially rescued the aberrant gene expression profile. Together these results suggest that choline inadequacy may contribute to placental dysfunction and the development of disorders related to placental insufficiency by activating PKC.