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.

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.

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.

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.

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.

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.

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.

Chest pain in patients recovering from noncardiac surgery: A retrospective analysis.

STUDY OBJECTIVE: Chest pain is relatively common postoperatively. Myocardial infarction (MI) is one cause of chest pain after surgery, but chest pain also results from less severe conditions. Because of its potential severity, chest pain usually prompts the activation of Rapid Response Systems (RRS). While chest pain is a cardinal symptom of myocardial ischemia in the non-surgical setting, the significance and relevance of chest pain after noncardiac surgery remains unclear. DESIGN: We conducted a retrospective analysis of noncardiac surgical inpatients for whom postoperative chest pain triggered our multidisciplinary RRS. SETTING: Surgical wards at Cleveland Clinic, Cleveland, OH. PATIENTS: Postsurgical patients after noncardiac surgery in whom the RSS system was activated for chest pain. INTERVENTIONS: RRS specified interventions like ECG readings, troponin measurements, transfer to ICU. MEASUREMENTS: Our primary outcome was MI. Secondary outcomes included the proportion of patients who had an ECG performed, troponin measurements, echocardiography, cardiac catheterization, and were admitted to the Intensive Care Unit (ICU). MAIN RESULTS: 5850 surgical patients experienced postoperative chest pain and triggered an RRS activation between 2009 and 2019. A total of 3110 patients had troponin T measured within 6 h after RRS activation, and 538 of them (17%) had elevated troponin, meeting the Fourth Universal Definition criteria for MI. Additionally, 2 patients had ST-segment elevation infarction (STEMI) without troponin measurement. Among the 540 patients with MI, only 19 (3.5%) were diagnosed with a STEMI by ECG, 388 (72%) had echocardiography, 43 patients (8%) had cardiac catheterization, 8 patients (1.5%) required emergent cardiac surgery, and 424 (79%) were admitted to an ICU. CONCLUSION: Chest pain is a serious clinical sign, often indicating a postoperative myocardial infarction, and therefore should be taken seriously. Troponin screening should be routinely considered in postsurgical patients who report chest pain.

Sugammadex Versus Neostigmine for Reversal of Residual Neuromuscular Blocks After Surgery: A Retrospective Cohort Analysis of Postoperative Side Effects.

BACKGROUND: Sugammadex and neostigmine given to reverse residual neuromuscular blockade can cause side effects including bradycardia, anaphylaxis, bronchospasm, and even cardiac arrest. We tested the hypothesis that sugammadex is noninferior to neostigmine on a composite of clinically meaningful side effects, or vice versa. METHODS: We analyzed medical records of patients who had general, cardiothoracic, or pediatric surgery and were given neostigmine or sugammadex from June 2016 to December 2019. Our primary outcome was a collapsed composite of bradycardia, anaphylaxis, bronchospasm, and cardiac arrest occurring between administration of the reversal agent and departure from the operation room. We a priori restricted our analysis to side effects requiring pharmacologic treatment that were therefore presumably clinically meaningful. Sugammadex would be considered noninferior to neostigmine (or vice versa) if the odds ratio for composite of side effects did not exceed 1.2. RESULTS: Among 89,753 surgeries in 70,690 patients, 16,480 (18%) were given sugammadex and 73,273 (82%) were given neostigmine. The incidence of composite outcome was 3.4% in patients given sugammadex and 3.0% in patients given neostigmine. The most common individual side effect was bradycardia (2.4% in the sugammadex group versus 2.2% neostigmine). Noninferiority was not found, with an estimated odds ratio of 1.21 (sugammadex versus neostigmine; 95% confidence interval [CI], 1.09-1.34; noninferiority P = .57), and neostigmine was superior to sugammadex with an estimated odds ratio of 0.83 (0.74-0.92), 1-side superiority P < .001. CONCLUSIONS: The composite incidence was less with neostigmine than with sugammadex, but only by 0.4% (a negligible clinical effect). Since 250 patients would need to be given neostigmine rather than sugammadex to avoid 1 episode of a minor complication such as bradycardia or bronchospasm, we conclude that sugammadex and neostigmine are comparably safe.

Transversus abdominis plane block with liposomal bupivacaine versus continuous epidural analgesia for major abdominal surgery: The EXPLANE randomized trial.

OBJECTIVE: Compare transversus abdominis plane (TAP) blocks with liposomal bupivacaine were to epidural analgesia for pain at rest and opioid consumption in patients recovering from abdominal surgery. BACKGROUND: ERAS pathways suggest TAP blocks in preference to epidural analgesia for abdominal surgery. However, the relative efficacies of TAP blocks and epidural analgesia remains unknown. METHODS: Patients having major abdominal surgery were enrolled at six sites and randomly assigned 1:1 to thoracic epidural analgesia or bilateral/4-quadrant TAP blocks with liposomal bupivacaine. Intravenous opioids were used as needed. Non-inferiority margins were a priori set at 1 point on an 11-point pain numeric rating scale for pain at rest and at a 25% increase in postoperative opioid consumption. RESULTS: Enrollment was stopped per protocol at 3rd interim analysis after crossing an a priori futility boundary. 498 patients were analyzed (255 had TAP blocks and 243 had epidurals). Pain scores at rest in patients assigned to TAP blocks were significantly non-inferior to those given epidurals, with an estimated difference of 0.09 points (CI: -0.12, 0.30; noninferiority P < 0.001). Opioid consumption during the initial 3 postoperative days in TAP patients was not non-inferior to epidurals, with an estimated ratio of geometric means of 1.37 (CI: 1.05, 1.79; non-inferiority P = 0.754). However, the absolute difference was only 21 mg morphine equivalents over the 3 days. Patients with epidurals were more likely to experience mean arterial pressures <65 mmHg than those given TAP blocks: 48% versus 31%, P = 0.006. CONCLUSION: Pain scores at rest during the initial three days after major abdominal surgery were similar. Patients assigned to TAP blocks required more opioid then epidural patients but had less hypotension. Clinicians should reconsider epidural analgesia in patients at risk from hypotension. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02996227.

The Relation Between Mean Arterial Pressure and Cardiac Index in Major Abdominal Surgery Patients: A Prospective Observational Cohort Study.

BACKGROUND: Cardiac output is an important hemodynamic variable and determines oxygen delivery. In contrast to blood pressure, cardiac output is rarely measured even in high-risk surgical patients, suggesting that clinicians consider blood pressure to be a reasonable indicator of systemic blood flow. However, the relationship depends on constant vascular tone and volume, both of which routinely vary during anesthesia and surgery. We therefore tested the hypothesis that there is no clinically meaningful correlation between mean arterial pressure and cardiac index in major abdominal surgery patients. METHODS: In this prospective observational study, we assessed the relationship between mean arterial pressure and cardiac index in 100 patients having major abdominal surgery under general anesthesia. RESULTS: The pooled within-patient correlation coefficient calculated using meta-analysis methods was r = 0.34 (95% confidence interval, 0.28-0.40). Linear regression using a linear mixed effects model of cardiac index on mean arterial pressure revealed that cardiac index increases by 0.014 L·min-1·m-2 for each 1 mm Hg increase in mean arterial pressure. The 95% Wald confidence interval of this slope was 0.011 to 0.018 L·min-1·m-2·mm Hg-1 and thus within predefined equivalence margins of -0.03 and 0.03 L·min-1·m-2·mm Hg-1, thereby demonstrating lack of clinically meaningful association between mean arterial pressure and cardiac index. CONCLUSIONS: There is no clinically meaningful correlation between mean arterial pressure and cardiac index in patients having major abdominal surgery. Intraoperative blood pressure is thus a poor surrogate for cardiac index.

Preoperative Vitamin D Deficiency Is Associated With Postoperative Delirium in Critically Ill Patients.

INTRODUCTION: Postoperative delirium is common, with a reported incidence of 11% to 80% in critically ill patients. Delirium is an independent prognostic factor for poor hospital outcomes. Low vitamin D concentrations are associated with a decline in cognitive function. We therefore tested the hypothesis that low preoperative serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with postoperative delirium in critically ill patients. METHOD: We conducted a retrospective analysis of adults in a surgical intensive care unit for at least 48 hours immediately after non-cardiac and non-neurosurgical operations at Cleveland Clinic between 2013 and 2018. Delirium was assessed by trained nurses using CAM-ICU twice daily for the initial 5 postoperative days. Any positive value was considered evidence of delirium. We assessed the association between 25(OH)D concentrations within a year before surgery and the incidence of postoperative delirium using logistic regression, adjusted for potential confounders. A linear spline term with a knot at 30 ng/ml, the threshold for normal 25(OH)D concentration, was added to accommodate a nonlinear relationship between 25(OH)D concentrations and delirium. RESULTS: We included 632 patients, who had a mean (SD) 25(OH)D concentration of 25 (15) ng/ml; 55% (346/632) experienced delirium. We observed an adjusted odds ratio of 1.4 (95% CI: [1.1, 1.8], P = 0.01) for delirium per 10 ng/ml decrease in 25(OH)D concentrations when patients' 25(OH)D concentrations were less than 30 ng/ml. In patients whose 25(OH)D concentrations were at least 30 ng/ml, the adjusted odds ratio was 0.9 (95% CI: [0.7, 1.1], P = 0.36). CONCLUSION: Preoperative 25(OH)D concentrations are associated with postoperative delirium in patients whose concentrations are below the normal threshold, but not at concentrations ≥30 ng/ml. A trial will be needed to determine whether the relationship is causal, and whether vitamin D supplementation before surgery might reduce the incidence of delirium.

Pain and Opioid Consumption and Mobilization after Surgery: Post Hoc Analysis of Two Randomized Trials.

BACKGROUND: Early mobilization is incorporated into many enhanced recovery pathways. Inadequate analgesia or excessive opioids may restrict postoperative mobilization. The authors tested the hypotheses that in adults recovering from abdominal surgery, postoperative pain and opioid consumption are inversely related to postoperative mobilization, and that postoperative mobilization is associated with fewer potentially related complications. METHODS: The authors conducted a subanalysis of two trials that enrolled adults recovering from abdominal surgery. Posture and movement were continuously monitored for 48 postoperative hours using noninvasive untethered monitors. Mobilization was defined as the fraction of monitored time spent sitting or standing. RESULTS: A total of 673 patients spent a median [interquartile range] of 7% [3 to 13%] of monitored time sitting or standing. Mobilization time was 1.9 [1.0 to 3.6] h/day for patients with average pain scores 3 or lower, but only 1.2 [0.5 to 2.6] h/day in those with average scores 6 or greater. Each unit increase in average pain score was associated with a decrease in mobilization time of 0.12 (97.5% CI, 0.02 to 0.24; P = 0.009) h/day. In contrast, there was no association between postoperative opioid consumption and mobilization time. The incidence of the composite of postoperative complications was 6.0% (10 of 168) in the lower mobilization quartile, 4.2% (7 of 168) in the second quartile, and 0% among 337 patients in the highest two quartiles (P = 0.009). CONCLUSIONS: Patients recovering from abdominal surgery spent only 7% of their time mobilized, which is considerably less than recommended. Lower pain scores are associated with increased mobility, independently of opioid consumption. Complications were more common in patients who mobilized poorly.

Diurnal blood pressure variation in adults after abdominal surgery-An observational cohort study.

OBJECTIVE: To describe the prevalence of various circadian blood pressure patterns in adults recovering from abdominal surgery, and to evaluate the association between loss of normal circadian variation in blood pressure and hypotension during the initial 2 postoperative days. DESIGN: A post-hoc analysis of data obtained from two randomized trials. SETTING: Operating rooms of the Cleveland Clinic. PATIENTS: Adults having abdominal surgery from 2015 to 2019 with at least one overnight stay. Participants were continuously monitored by wearable vital signs monitors starting in the post-anesthesia care unit and for the first 48 postoperative hours. INTERVENTIONS: None. The exposure of interest was the degree of nocturnal decrease in blood pressure - normal nocturnal decrease in blood pressure ("normal dipping", more than 10% decrease compared to day-time), no nocturnal decrease ("non-dipping", less than 10% nocturnal decrease), or nocturnal increase in blood pressure ("rising"). MEASUREMENTS: Postoperative hypotension, defined by the time weighted average (TWA) area under a mean arterial pressure (MAP) threshold of 70 mmHg. RESULTS: In total, 590 patients were eligible for analysis (mean(SD) age 50(15) years, 56% females, median [IQR] surgery duration 4.0 [2.7, 5.8] hours). Median TWA area under a MAP threshold of 70 mmHg was 0.96 (95%CI 0.59, 1.33) mmHg*minute per monitoring hour lower in patients with either no nocturnal blood pressure decrease (N = 317, 54%), or an increase in nocturnal blood pressure (N = 211, 36%), than in the reference group of patients with normal nocturnal decrease (N = 62, 11%), P < 0.001 for both. CONCLUSIONS: Abnormal diurnal blood pressure patterns are common in adults during the initial 2 days after abdominal surgery. Lack of normal night-time decrease in blood pressure is associated with less postoperative hypotension. Future studies should evaluate whether abnormal postoperative diurnal blood pressure patterns are associated with worse outcomes.