Intraoperative hypotension during liver transplantation and postoperative outcomes: Retrospective cohort study.

STUDY OBJECTIVES: Evaluation of the association between intraoperative hypotension (IOH) and important postoperative outcomes after liver transplant such as incidence and severity of acute kidney injury (AKI), MACE and early allograft dysfunction (EAD). DESIGN: Retrospective, single institution study. SETTINGS: Operating room. PATIENTS: 1576 patients who underwent liver transplant in our institution between January 2005 and February 2022. MEASUREMENTS: IOH was measured as the time, area under the threshold (AUT), or time-weighted average (TWA) of mean arterial pressure (MAP) less than certain thresholds (55,60 and 65 mmHg). Associations between IOH exposures and AKI severity were assessed via proportional odds models. The odds ratio from the proportional odds model estimated the relative odds of having higher stage of AKI for higher exposure to IOH. Associations between exposures and MACE and EAD were assessed through logistic regression models. Potential confounding variables including patient baseline and surgical characteristics were adjusted for all models. MAIN RESULTS: The primary analysis included 1576 surgeries that met the inclusion and exclusion criteria. Of those, 1160 patients (74%) experienced AKI after liver transplant surgery, with 780 (49%), 248(16%), and 132 (8.4%) experiencing mild, moderate, and severe injury, respectively. No significant association between hypotension exposure and postoperative AKI (yes or no) nor severity of AKI was observed. The odds ratios (95% CI) of having more severe AKI were 1.02 (0.997, 1.04) for a 50-mmHg·min increase in AUT of MAP <55 mmHg (P = 0.092); 1.03 (0.98, 1.07) for a 15-min increase in time spent under MAP <55 mmHg (P = 0.27); and 1.24 (0.98, 1.57) for a 1 mmHg increase in TWA of MAP <55 mmHg (P = 0.068). The associations between IOH and the incidence of MACE or EAD were not significant. CONCLUSION: Our results did not show the association between IOH and investigated outcomes.

Comparison of differences in cohort (forwards) and case control (backwards) methodological approaches for validation of the Hypotension Prediction Index.

BACKGROUND: The Hypotension Prediction Index (the index) software is a machine learning algorithm that detects physiological changes that may lead to hypotension. The original validation used a case control (backwards) analysis that has been suggested to be biased. We therefore conducted a cohort (forwards) analysis and compared this to the original validation technique. METHODS: We conducted a retrospective analysis of data from previously reported studies. All data were analysed identically with 2 different methodologies and receiver operating characteristic curves (ROC) constructed. Both backwards and forwards analyses were performed to examine differences in area under the ROC for HPI and other haemodynamic variables to predict a MAP < 65mmHg for at least 1 minute 5, 10 and 15 minutes in advance. RESULTS: Two thousand and twenty-two patients were included in the analysis, yielding 4,152,124 measurements taken at 20 second intervals. The area-under-the-curve for the index predicting hypotension analysed by backward and forward methodologies respectively was 0.957 (95% CI, 0.947-0.964) vs 0.923 (95% CI, 0.912-0.933) 5 minutes in advance, 0.933 (95% CI, 0.924-0.942) vs 0.923 (95% CI, 0.911-0.933) 10 minutes in advance , and 0.929 (95% CI, 0.918-0.938) vs. 0.926 (95% CI, 0.914-0.937) 15 minutes in advance. No other variable had an area-under-the-curve > 0.7 except for MAP. Area-under-the-curve using forward analysis for MAP predicting hypotension 5, 10, and 15 minutes in advance was 0.932 (95% CI, 0.920-0.940), 0.929 (95% CI, 0.918-0.938), and 0.932 (95% CI, 0.921-0.940). The R 2 for the variation in the index due to MAP was 0.77. CONCLUSION: Using an updated methodology, we found the utility of the HPI index to predict future hypotensive events is high, with an area under the receiver-operating-characteristics curve similar to that of the original validation method.

AcumenTM hypotension prediction index guidance for prevention and treatment of hypotension in noncardiac surgery: a prospective, single-arm, multicenter trial.

BACKGROUND: Intraoperative hypotension is common during noncardiac surgery and is associated with postoperative myocardial infarction, acute kidney injury, stroke, and severe infection. The Hypotension Prediction Index software is an algorithm based on arterial waveform analysis that alerts clinicians of the patient's likelihood of experiencing a future hypotensive event, defined as mean arterial pressure < 65 mmHg for at least 1 min. METHODS: Two analyses included (1) a prospective, single-arm trial, with continuous blood pressure measurements from study monitors, compared to a historical comparison cohort. (2) A post hoc analysis of a subset of trial participants versus a propensity score-weighted contemporaneous comparison group, using external data from the Multicenter Perioperative Outcomes Group (MPOG). The trial included 485 subjects in 11 sites; 406 were in the final effectiveness analysis. The post hoc analysis included 457 trial participants and 15,796 comparison patients. Patients were eligible if aged 18 years or older, American Society of Anesthesiologists (ASA) physical status 3 or 4, and scheduled for moderate- to high-risk noncardiac surgery expected to last at least 3 h. MEASUREMENTS: minutes of mean arterial pressure (MAP) below 65 mmHg and area under MAP < 65 mmHg. RESULTS: Analysis 1: Trial subjects (n = 406) experienced a mean of 9 ± 13 min of MAP below 65 mmHg, compared with the MPOG historical control mean of 25 ± 41 min, a 65% reduction (p < 0.001). Subjects with at least one episode of hypotension (n = 293) had a mean of 12 ± 14 min of MAP below 65 mmHg compared with the MPOG historical control mean of 28 ± 43 min, a 58% reduction (p< 0.001). Analysis 2: In the post hoc inverse probability treatment weighting model, patients in the trial demonstrated a 35% reduction in minutes of hypotension compared to a contemporaneous comparison group [exponentiated coefficient: - 0.35 (95%CI - 0.43, - 0.27); p < 0.001]. CONCLUSIONS: The use of prediction software for blood pressure management was associated with a clinically meaningful reduction in the duration of intraoperative hypotension. Further studies must investigate whether predictive algorithms to prevent hypotension can reduce adverse outcomes. TRIAL REGISTRATION: Clinical trial number: NCT03805217. Registry URL: https://clinicaltrials.gov/ct2/show/NCT03805217 . Principal investigator: Xiaodong Bao, MD, PhD. Date of registration: January 15, 2019.

Association of Intravenous Neostigmine and Anticholinergics or Sugammadex with Postoperative Delirium: A Retrospective Cohort Study.

BACKGROUND: Administration of cholinesterase inhibitors in combination with anticholinergic drugs for reversal of neuromuscular blocks may precipitate delirium through impairment of central cholinergic transmission, which could be avoided by using sugammadex. Therefore, we tested the primary hypothesis that postoperative delirium is less common when neuromuscular block is reversed with sugammadex than with neostigmine combined with glycopyrrolate or atropine. METHODS: We conducted a single-center retrospective cohort study, analyzing all adult patients having general anesthesia for noncardiac surgery who received neostigmine or sugammadex from January 2016 to March 2022. Inverse propensity score weighting and propensity score calibration were used to adjust for appropriate confounders. Our primary outcome was presence of delirium within the first 4 days after surgery, defined as at least 1 positive brief Confusion Assessment Method (bCAM) screening. The secondary outcome was the presence of early delirium within 24 hours of surgery. RESULTS: Among 49,468 cases in our analysis, 6881 received sugammadex and 42,587 received neostigmine. After propensity weighting, the incidence of delirium was 1.09% in the sugammadex group and 0.82% in the neostigmine group. The odds of postoperative delirium did not differ between the sugammadex and neostigmine groups, with an estimated odds ratio (95% confidence interval) of 1.33 (0.91-1.95), P = .147. A sensitivity analysis restricted to only include cases with at least 6 bCAM measurements over postoperative day (POD) 1 to 4 had consistent results, as sugammadex compared with neostigmine was associated with an estimated odds ratio for postoperative delirium of 1.20 (0.82-1.77), P = .346. Sugammadex was significantly associated with an increased incidence of early postoperative delirium, with an estimated odds ratio of 1.71 (1.07-2.72), P = .025. Further analysis showed no treatment-by-age interaction for either postoperative delirium (P = .637) or postoperative early delirium (P = .904). CONCLUSIONS: Compared to neostigmine, use of sugammadex for reversal of neuromuscular block was not associated with an increased risk of postoperative delirium in this retrospective single-center study. Though sugammadex was associated with a statistically significant increased risk of postoperative early delirium, the difference was small and not clinically relevant, and may reflect the presence of unknown confounders.

Development and validation of delirium prediction models for noncardiac surgery patients.

STUDY OBJECTIVE: Postoperative delirium is associated with morbidity and mortality, and its incidence varies widely. Using known predisposing and precipitating factors, we sought to develop postoperative delirium prediction models for noncardiac surgical patients. DESIGN: Retrospective prediction model study. SETTING: Major quaternary medical center. PATIENTS: Our January 2016 to June 2020 training dataset included 51,677 patients of whom 2795 patients had delirium. Our July 2020 to January 2022 validation dataset included 14,438 patients of whom 912 patients had delirium. INTERVENTIONS: None. MEASUREMENTS: We trained and validated two static prediction models and one dynamic delirium prediction model. For the static models, we used random survival forests and traditional Cox proportional hazard models to predict postoperative delirium from preoperative variables, or from a combination of preoperative and intraoperative variables. We also used landmark modeling to dynamically predict postoperative delirium using preoperative, intraoperative, and postoperative variables before onset of delirium. MAIN RESULTS: In the validation analyses, the static random forest model had a c-statistic of 0.81 (95% CI: 0.79, 0.82) and a Brier score of 0.04 with preoperative variables only, and a c-statistic of 0.86 (95% CI: 0.84, 0.87) and a Brier score of 0.04 when preoperative and intraoperative variables were combined. The corresponding Cox models had similar discrimination metrics with slightly better calibration. The dynamic model - using all available data, i.e., preoperative, intraoperative and postoperative data - had an overall c-index of 0.84 (95% CI: 0.83, 0.85). CONCLUSIONS: Using preoperative and intraoperative variables, simple static models performed as well as a dynamic delirium prediction model that also included postoperative variables. Baseline predisposing factors thus appear to contribute far more to delirium after noncardiac surgery than intraoperative or postoperative variables. Improved postoperative data capture may help improve delirium prediction and should be evaluated in future studies.

Processing speed test and 30-day readmission in elderly non-cardiac surgery patients- A retrospective study.

Background and Aims: Preoperative cognitive function screening can help identify high-risk patients, but resource-intensive testing limits its widespread use. A novel self-administered tablet computer-based Processing Speed Test (PST) was used to assess cognitive "executive" function in non-cardiac surgery patients, but the relationship between preoperative test scores and postoperative outcomes is unclear. The primary outcome was a composite of 30-day readmission/death. The secondary outcome was a collapsed composite of discharge to a long-term care facility/death. Exploratory outcomes were 1) time to discharge alive, 2) 1-year mortality and 3) a collapsed composite of postoperative complications. Methods: This retrospective study, after approval, was conducted in elective non-cardiac surgery patients ≥65 years old. We assessed the relationship between processing speed test scores and primary/secondary outcomes using multivariable logistic regression, adjusting for potential confounding variables. Results: Overall 1568 patients completed the PST, and the mean ± standard deviation test score was 33 ± 10. The higher PST score is associated with better executive function. A 10-unit increase in the test score was associated with an estimated 19% lower 30-day readmission/death odds, with an odds ratio (OR) and 95% confidence interval (CI) of 0.81 (0.68, 0.96) (P = 0.015). Similarly, 10-unit increase in test score was associated with an estimated 26% lower odds of long-term care need/death, with OR (95% CI) of 0.74 (0.61, 0.91) (P = 0.004). We also found statistically significant associations between the test scores and time to discharge alive and to 1-year mortality, however, not with a composite of postoperative complications. Conclusion: Elderly non-cardiac surgery patients with better PST scores were less likely to be readmitted, need long-term care after discharge or die within 30 days. Preoperative assessment of cognitive function using a simple self-administered test is feasible and may guide perioperative care.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

Patient-centered results from a multicenter study of continuous peripheral nerve blocks and postamputation phantom and residual limb pain: secondary outcomes from a randomized, clinical trial.

INTRODUCTION: We previously reported that a 6-day continuous peripheral nerve block reduces established postamputation phantom pain. To provide patients and providers with the information to best inform treatment decisions, here we reanalyze the data and present the results in a more patient-centered format. We also provide information on patient-defined clinically relevant benefits to facilitate evaluation of available studies and guide future trial design. METHODS: The original trial enrolled participants with a limb amputation and phantom pain who were randomized to receive a 6-day continuous peripheral nerve block(s) of either ropivacaine (n=71) or saline (n=73) in a double-masked fashion. Here we calculate the percentage of each treatment group that experienced a clinically relevant improvement as defined by previous studies as well as present what the participants of our study defined as small, medium, and large analgesic improvements using the 7-point ordinal Patient Global Impression of Change scale. RESULTS: Among patients who were given a 6-day ropivacaine infusion, 57% experienced at least a 2-point improvement on the 11-point numeric rating scale in their average and worst phantom pain 4 weeks postbaseline as compared with 26% (p<0.001) for average and 25% (p<0.001) for worst pain in patients given a placebo infusion. At 4 weeks, the percentage of participants rating their pain as improved was 53% for the active vs 30% for the placebo groups (95% CI 1.7 (1.1, 2.7), p=0.008). For all patients combined, the median (IQR) phantom pain Numeric Rating Scale improvements at 4 weeks considered small, medium, and large were 2 (0-2), 3 (2-5), and 5 (3-7), respectively. The median improvements in the Brief Pain Inventory interference subscale (0-70) associated with small, medium, and large analgesic changes were 8 (1-18), 22 (14-31), and 39 (26-47). CONCLUSIONS: Among patients with postamputation phantom pain, a continuous peripheral nerve block more than doubles the chance of a clinically relevant improvement in pain intensity. Amputees with phantom and/or residual limb pain rate analgesic improvements as clinically relevant similarly to other chronic pain etiologies, although their smallest relevant improvement in the Brief Pain Inventory was significantly larger than previously published values. TRIAL REGISTRATION NUMBER: NCT01824082.

Relative contributions of anaemia and hypotension to myocardial infarction and renal injury: Post hoc analysis of the POISE-2 trial.

BACKGROUND: Hypotension and postoperative anaemia are associated with myocardial and renal injury after noncardiac surgery, but the interaction between them remains unknown. OBJECTIVES: To test the hypothesis that a double-hit of postoperative anaemia and hypotension synergistically worsens a 30-day composite of myocardial infarction (MI) and mortality and acute kidney injury (AKI). Characterising the interaction when hypotension and anaemia occur at same time on myocardial infarction and acute kidney injury. DESIGN: Post hoc analysis of the POISE-2 trial. SETTING: Patients were enrolled between July 2010 and December 2013 at 135 hospitals in 23 countries. PATIENTS: Adults at least 45 years old with known or suspected cardiovascular disease. We excluded patients without available postoperative haemoglobin measurements or hypotension duration records. Exposures were the lowest haemoglobin concentration and the average daily duration of SBP less than 90 mmHg within the first four postoperative days. MAIN OUTCOME MEASURES: The primary outcome was a collapsed composite of nonfatal MI and all-cause mortality during the initial 30 postoperative days; our secondary outcome was AKI. RESULTS: We included 7940 patients. The mean ±â€ŠSD lowest postoperative haemoglobin was 10 ±â€Š2 g dl -1 , and 24% of the patients had SBP less than 90 mmHg with daily duration ranging from 0 to 15 h. Four hundred and nine (5.2%) patients had an infarction or died within 30 postoperative days, and 417 (6.4%) patients developed AKI. Lowest haemoglobin concentrations less than 11 g dl -1 , and duration of SBP less than 90 mmHg was associated with greater hazard of composite outcome of nonfatal MI and all-cause mortality, as well as with AKI. However, we did not find significant multiplicative interactions between haemoglobin splines and hypotension duration on the primary composite or on AKI. CONCLUSION: Postoperative anaemia and hypotension were meaningfully associated with both our primary composite and AKI. However, lack of significant interaction suggests that the effects of hypotension and anaemia are additive rather than multiplicative. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01082874.

Odevixibat: A Review of a Bioactive Compound for the Treatment of Pruritus Approved by the FDA.

Odevixibat is synthesized through chemical modification of Benzothiazepine's structure. It is a tiny chemical that inhibits the ileal bile acid transporter and is used to treat a variety of cholestatic illnesses, including progressive familial intrahepatic cholestasis (PFIC). For cholestatic pruritus and liver disease development, bile acid transporter inhibition is a unique treatment strategy. Odevixibat reduces enteric bile acid reuptake. Oral odevixibat was also studied in children with cholestatic liver disease. Odevixibat received its first approval in the European Union (EU) in July 2021 for the treatment of PFIC in patients aged 6 months, followed by approval in the USA in August 2021 for the treatment of pruritus in PFIC patients aged 3 months. Bile acids in the distal ileum can be reabsorbed by the ileal sodium/bile acid cotransporter, a transport glycoprotein. Odevixibat is a sodium/bile acid co-transporter reversible inhibitor. An average 3 mg once-daily dose of odevixibat for a week resulted in a 56% reduction in the area under the curve of bile acid. A daily dose of 1.5 mg resulted in a 43% decrease in the area under the curve for bile acid. Odevixibat is also being evaluated in many countries for the treatment of other cholestatic illnesses, including Alagille syndrome and biliary atresia. This article reviews the updated information on odevixibat with respect to its clinical pharmacology, mechanism of action, pharmacokinetics, pharmacodynamics, metabolism, drug-drug interactions, pre-clinical studies, and clinical trials.

Goal-directed haemodynamic therapy: an imprecise umbrella term to avoid.

'Goal-directed haemodynamic therapy' describes various haemodynamic treatment strategies that have in common that interventions are titrated to achieve predefined haemodynamic targets. However, the treatment strategies differ substantially regarding the underlying haemodynamic target variables and target values, and thus presumably have different effects on outcome. It is an over-simplifying approach to lump complex and substantially differing haemodynamic treatment strategies together under the term 'goal-directed haemodynamic therapy', an imprecise umbrella term that we should thus stop using.

Association of systolic, diastolic, mean, and pulse pressure with morbidity and mortality in septic ICU patients: a nationwide observational study.

BACKGROUND: Intensivists target different blood pressure component values to manage intensive care unit (ICU) patients with sepsis. We aimed to evaluate the relationship between individual blood pressure components and organ dysfunction in critically ill septic patients. METHODS: In this retrospective observational study, we evaluated 77,328 septic patients in 364 ICUs in the eICU Research Institute database. Primary exposure was the lowest cumulative value of each component; mean, systolic, diastolic, and pulse pressure, sustained for at least 120 min during ICU stay. Primary outcome was ICU mortality and secondary outcomes were composite outcomes of acute kidney injury or death and myocardial injury or death during ICU stay. Multivariable logistic regression spline and threshold regression adjusting for potential confounders were conducted to evaluate associations between exposures and outcomes. Sensitivity analysis was conducted in 4211 patients with septic shock. RESULTS: Lower values of all blood pressures components were associated with a higher risk of ICU mortality. Estimated change-points for the risk of ICU mortality were 69 mmHg for mean, 100 mmHg for systolic, 60 mmHg for diastolic, and 57 mmHg for pulse pressure. The strength of association between blood pressure components and ICU mortality as determined by slopes of threshold regression were mean (- 0.13), systolic (- 0.11), diastolic (- 0.09), and pulse pressure (- 0.05). Equivalent non-linear associations between blood pressure components and ICU mortality were confirmed in septic shock patients. We observed a similar relationship between blood pressure components and secondary outcomes. CONCLUSION: Blood pressure component association with ICU mortality is the strongest for mean followed by systolic, diastolic, and weakest for pulse pressure. Critical care teams should continue to follow MAP-based resuscitation, though exploratory analysis focusing on blood pressure components in different sepsis phenotypes in critically ill ICU patients is needed.

Regional analgesia and surgical site infections after colorectal surgery: a retrospective cohort analysis

Abstract Background The effect of regional analgesia on perioperative infectious complications remains unknown. We therefore tested the hypothesis that a composite of serious infections after colorectal surgery is less common in patients with regional analgesia than in those given Intravenous Patient-Controlled Analgesia (IV-PCA) with opiates. Methods Patients undergoing elective colorectal surgery lasting one hour or more under general anesthesia at the Cleveland Clinic Main Campus between 2009 and 2015 were included in this retrospective analysis. Exposures were defined as regional postoperative analgesia with epidurals or Transversus Abdominis Plane blocks (TAP); or IV-PCA with opiates only. The outcome was defined as a composite of in-hospital serious infections, including intraabdominal abscess, pelvic abscess, deep or organ-space Surgical Site Infection (SSI), clostridium difficile, pneumonia, or sepsis. Logistic regression model adjusted for the imbalanced potential confounding factors among the subset of matched surgeries was used to report the odds ratios along with 95% confidence limits. The significance criterion was p < 0.05. Results A total of 7811 patients met inclusion and exclusion criteria of which we successfully matched 681 regional anesthesia patients to 2862 IV-PCA only patients based on propensity scores derived from potential confounding factors. There were 82 (12%) in-hospital postoperative serious infections in the regional analgesia group vs. 285 (10%) in IV-PCA patients. Regional analgesia was not significantly associated with serious infection (odds ratio: 1.14; 95% Confidence Interval 0.87‒1.49; p-value = 0.339) after adjusting for surgical duration and volume of intraoperative crystalloids. Conclusion Regional analgesia should not be selected as postoperative analgesic technique to reduce infections.

Endotypes of intraoperative hypotension during major abdominal surgery: a retrospective machine learning analysis of an observational cohort study.

BACKGROUND: Intraoperative hypotension is associated with myocardial injury, acute kidney injury, and death. In routine practice, specific causes of intraoperative hypotension are often unclear. A more detailed understanding of underlying haemodynamic alterations of intraoperative hypotension may identify specific treatments. We thus aimed to use machine learning - specifically, hierarchical clustering - to identify underlying haemodynamic alterations causing intraoperative hypotension in major abdominal surgery patients. Specifically, we tested the hypothesis that there are distinct endotypes of intraoperative hypotension, which may help refine therapeutic interventions. METHODS: We conducted a secondary analysis of intraoperative haemodynamic measurements from a prospective observational study in 100 patients who had major abdominal surgery under general anaesthesia. We used stroke volume index, heart rate, cardiac index, systemic vascular resistance index, and pulse pressure variation measurements. Intraoperative hypotension was defined as any mean arterial pressure ≤65 mm Hg or a mean arterial pressure between 66 and 75 mm Hg requiring a norepinephrine infusion rate exceeding 0.1 µg kg-1 min-1. To identify endotypes of intraoperative hypotension, we used hierarchical clustering (Ward's method). RESULTS: A total of 615 episodes of intraoperative hypotension occurred in 82 patients (46 [56%] female; median age: 64 [57, 73] yr) who had surgery of a median duration of 270 (195, 335) min. Hierarchical clustering revealed six distinct intraoperative hypotension endotypes. Based on their clinical characteristics, we labelled these endotypes as (1) myocardial depression, (2) bradycardia, (3) vasodilation with cardiac index increase, (4) vasodilation without cardiac index increase, (5) hypovolaemia, and (6) mixed type. CONCLUSION: Hierarchical clustering identified six endotypes of intraoperative hypotension. If validated, considering these intraoperative hypotension endotypes may enable causal treatment of intraoperative hypotension.

Extended-age Out-of-sample Validation of Risk Stratification Index 3.0 Models Using Commercial All-payer Claims.

BACKGROUND: The authors previously reported a broad suite of individualized Risk Stratification Index 3.0 (Health Data Analytics Institute, Inc., USA) models for various meaningful outcomes in patients admitted to a hospital for medical or surgical reasons. The models used International Classification of Diseases, Tenth Revision, trajectories and were restricted to information available at hospital admission, including coding history in the previous year. The models were developed and validated in Medicare patients, mostly age 65 yr or older. The authors sought to determine how well their models predict utilization outcomes and adverse events in younger and healthier populations. METHODS: The authors' analysis was based on All Payer Claims for surgical and medical hospital admissions from Utah and Oregon. Endpoints included unplanned hospital admissions, in-hospital mortality, acute kidney injury, sepsis, pneumonia, respiratory failure, and a composite of major cardiac complications. They prospectively applied previously developed Risk Stratification Index 3.0 models to the younger and healthier 2017 Utah and Oregon state populations and compared the results to their previous out-of-sample Medicare validation analysis. RESULTS: In the Utah dataset, there were 55,109 All Payer Claims admissions across 40,710 patients. In the Oregon dataset, there were 21,213 admissions from 16,951 patients. Model performance on the two state datasets was similar or better than in Medicare patients, with an average area under the curve of 0.83 (0.71 to 0.91). Model calibration was reasonable with an R2 of 0.93 (0.84 to 0.97) for Utah and 0.85 (0.71 to 0.91) for Oregon. The mean sensitivity for the highest 5% risk population was 28% (17 to 44) for Utah and 37% (20 to 56) for Oregon. CONCLUSIONS: Predictive analytical modeling based on administrative claims history provides individualized risk profiles at hospital admission that may help guide patient management. Similar predictive performance in Medicare and in younger and healthier populations indicates that Risk Stratification Index 3.0 models are valid across a broad range of adult hospital admissions.

Regional analgesia and surgical site infections after colorectal surgery: a retrospective cohort analysis.

BACKGROUND: The effect of regional analgesia on perioperative infectious complications remains unknown. We therefore tested the hypothesis that a composite of serious infections after colorectal surgery is less common in patients with regional analgesia than in those given Intravenous Patient-Controlled Analgesia (IV-PCA) with opiates. METHODS: Patients undergoing elective colorectal surgery lasting one hour or more under general anesthesia at the Cleveland Clinic Main Campus between 2009 and 2015 were included in this retrospective analysis. Exposures were defined as regional postoperative analgesia with epidurals or Transversus Abdominis Plane blocks (TAP); or IV-PCA with opiates only. The outcome was defined as a composite of in-hospital serious infections, including intraabdominal abscess, pelvic abscess, deep or organ-space Surgical Site Infection (SSI), clostridium difficile, pneumonia, or sepsis. Logistic regression model adjusted for the imbalanced potential confounding factors among the subset of matched surgeries was used to report the odds ratios along with 95% confidence limits. The significance criterion was p < 0.05. RESULTS: A total of 7811 patients met inclusion and exclusion criteria of which we successfully matched 681 regional anesthesia patients to 2862 IV-PCA only patients based on propensity scores derived from potential confounding factors. There were 82 (12%) in-hospital postoperative serious infections in the regional analgesia group vs. 285 (10%) in IV-PCA patients. Regional analgesia was not significantly associated with serious infection (odds ratio: 1.14; 95% Confidence Interval 0.87‒1.49; p-value = 0.339) after adjusting for surgical duration and volume of intraoperative crystalloids. CONCLUSION: Regional analgesia should not be selected as postoperative analgesic technique to reduce infections.

Artificial Intelligence for Perioperative Medicine: Perioperative Intelligence.

The anesthesiologist's role has expanded beyond the operating room, and anesthesiologist-led care teams can deliver coordinated care that spans the entire surgical experience, from preoperative optimization to long-term recovery of surgical patients. This expanded role can help reduce postoperative morbidity and mortality, which are regrettably common, unlike rare intraoperative mortality. Postoperative mortality, if considered a disease category, will be the third leading cause of death just after heart disease and cancer. Rapid advances in technologies like artificial intelligence provide an opportunity to build safe perioperative practices. Artificial intelligence helps by analyzing complex data across disparate systems and producing actionable information. Using artificial intelligence technologies, we can critically examine every aspect of perioperative medicine and devise innovative value-based solutions that can potentially improve patient safety and care delivery, while optimizing cost of care. In this narrative review, we discuss specific applications of artificial intelligence that may help advance all aspects of perioperative medicine, including clinical care, education, quality improvement, and research. We also discuss potential limitations of technology and provide our recommendations for successful adoption.

Risk Stratification Index 3.0, a Broad Set of Models for Predicting Adverse Events during and after Hospital Admission.

BACKGROUND: Risk stratification helps guide appropriate clinical care. Our goal was to develop and validate a broad suite of predictive tools based on International Classification of Diseases, Tenth Revision, diagnostic and procedural codes for predicting adverse events and care utilization outcomes for hospitalized patients. METHODS: Endpoints included unplanned hospital admissions, discharge status, excess length of stay, in-hospital and 90-day mortality, acute kidney injury, sepsis, pneumonia, respiratory failure, and a composite of major cardiac complications. Patient demographic and coding history in the year before admission provided features used to predict utilization and adverse events through 90 days after admission. Models were trained and refined on 2017 to 2018 Medicare admissions data using an 80 to 20 learn to test split sample. Models were then prospectively tested on 2019 out-of-sample Medicare admissions. Predictions based on logistic regression were compared with those from five commonly used machine learning methods using a limited dataset. RESULTS: The 2017 to 2018 development set included 9,085,968 patients who had 18,899,224 inpatient admissions, and there were 5,336,265 patients who had 9,205,835 inpatient admissions in the 2019 validation dataset. Model performance on the validation set had an average area under the curve of 0.76 (range, 0.70 to 0.82). Model calibration was strong with an average R 2 for the 99% of patients at lowest risk of 1.00. Excess length of stay had a root-mean-square error of 0.19 and R 2 of 0.99. The mean sensitivity for the highest 5% risk population was 19.2% (range, 11.6 to 30.1); for positive predictive value, it was 37.2% (14.6 to 87.7); and for lift (enrichment ratio), it was 3.8 (2.3 to 6.1). Predictive accuracies from regression and machine learning techniques were generally similar. CONCLUSIONS: Predictive analytical modeling based on administrative claims history can provide individualized risk profiles at hospital admission that may help guide patient management. Similar results from six different modeling approaches suggest that we have identified both the value and ceiling for predictive information derived from medical claims history.

Effect of a Rapid Response Team on the Incidence of In-Hospital Mortality.

BACKGROUND: Approximately half of the life-limiting events, such as cardiopulmonary arrests or cardiac arrhythmias occurring in hospitals, are considered preventable. These critical events are usually preceded by clinical deterioration. Rapid response teams (RRTs) were introduced to intervene early in the course of clinical deterioration and possibly prevent progression to an event. An RRT was introduced at the Cleveland Clinic in 2009 and transitioned to an anesthesiologist-led system in 2012. We evaluated the association between in-hospital mortality and: (1) the introduction of the RRT in 2009 (primary analysis), and (2) introduction of the anesthesiologist-led system in 2012 and other policy changes in 2014 (secondary analyses). METHODS: We conducted a single-center, retrospective analysis using the medical records of overnight hospitalizations from March 1, 2005, to December 31, 2018, at the Cleveland Clinic. We assessed the association between the introduction of the RRT in 2009 and in-hospital mortality using segmented regression in a generalized estimating equation model to account for within-subject correlation across repeated visits. Baseline potential confounders (demographic factors and surgery type) were controlled for using inverse probability of treatment weighting on the propensity score. We assessed whether in-hospital mortality changed at the start of the intervention and whether the temporal trend (slope) differed from before to after initiation. Analogous models were used for the secondary outcomes. RESULTS: Of 628,533 hospitalizations in our data set, 177,755 occurred before and 450,778 after introduction of our RRT program. Introduction of the RRT was associated with a slight initial increase in in-hospital mortality (odds ratio [95% confidence interval {CI}], 1.17 [1.09-1.25]; P < .001). However, while the pre-RRT slope in in-hospital mortality over time was flat (odds ratio [95% CI] per year, 1.01 [0.98-1.04]; P = .60), the post-RRT slope decreased over time, with an odds ratio per additional year of 0.961 (0.955-0.968). This represented a significant improvement (P < .001) from the pre-RRT slope. CONCLUSIONS: We found a gradual decrease in mortality over a 9-year period after introduction of an RRT program. Although mechanisms underlying this decrease are unclear, possibilities include optimization of RRT implementation, anesthesiology department leadership of the RRT program, and overall improvements in health care delivery over the study period. Our findings suggest that improvements in outcome after RRT introduction may take years to manifest. Further work is needed to better understand the effects of RRT implementation on in-hospital mortality.

New-Onset Atrial Fibrillation in Patients Undergoing Liver Transplantation: Retrospective Analysis of Risk Factors and Outcomes.

OBJECTIVE: The authors aimed to identify predictors of new-onset postoperative atrial fibrillation (POAF) during the initial 90 days following liver transplantation, and to assess the association between POAF in-hospital and 1-year mortality. DESIGN: A retrospective cohort study. SETTING: At a university hospital between 2005 and 2017. PATIENTS: Adults without a history of preoperative atrial fibrillation who underwent orthotopicliver transplantation. MEASUREMENT AND MAIN RESULTS: The authors assessed the univariate association between new-onset of POAF in the postoperative period and each potential factor through a logistic regression model. Moreover, they explored predictors for POAF through stepwise selection. Finally, the authors assessed the relationship between POAF and in-hospital and 1-year mortality using logistic regression models, and whether the duration of atrial fibrillation was associated with in-hospital and 1-year mortality. Among 857 patients, 89 (10.4%) developed POAF. Using only preoperative variables, pulmonary hypertension, age, Model for End-Stage Liver Disease (MELD) score, and White race were identified as the most important predictors. Model discrimination was 0.75 (95% CI: 0.69-0.80), and incorporating intraoperative variables was 0.77 (95% CI: 0.72-0.82). In-hospital mortality was observed in 7.2% (6/83) of patients with new-onset of POAF, and in 2.8% (22/768) without, with confounder-adjusted odds ratio (OR) 1.00 (97.5% CI: 0.29,3.45; p = 0.996). One-year mortality was 22.4% (20/89) in patients who developed POAF and 8.3% (64/768) in patients who did not, confounder-adjusted OR 2.64 (97.5% CI: 1.35-5.16; p = 0.001). The duration of POAF did not affect long-term postoperative mortality. CONCLUSION: Preoperative, mostly unmodifiable comorbidities are important risk factors for new-onset POAF after liver transplantation. The POAF was not associated with in-hospital mortality, but with increased 1-year mortality. Once developed, the duration of POAF did not affect long-term mortality after a liver transplant.