Pressure injury treatment by intermittent electrical stimulation (PROTECT-2): protocol for a multicenter randomized clinical trial.

BACKGROUND: Pressure ulcers account for a substantial fraction of hospital-acquired pathology, with consequent morbidity and economic cost. Treatments are largely focused on preventing further injury, whereas interventions that facilitate healing remain limited. Intermittent electrical stimulation (IES) increases local blood flow and redistributes pressure from muscle-bone interfaces, thus potentially reducing ulcer progression and facilitating healing. METHODS: The Pressure Injury Treatment by Intermittent Electrical Stimulation (PROTECT-2) trial will be a parallel-arm multicenter randomized trial to test the hypothesis that IES combined with routine care reduces sacral and ischial pressure injury over time compared to routine care alone. We plan to enroll 548 patients across various centers. Hospitalized patients with stage 1 or stage 2 sacral or ischial pressure injuries will be randomized to IES and routine care or routine care alone. Wound stage will be followed until death, discharge, or the development of an exclusion criteria for up to 3 months. The primary endpoint will be pressure injury score measured over time. DISCUSSION: Sacral and ischial pressure injuries present a burden to hospitalized patients with both clinical and economic consequences. The PROTECT-2 trial will evaluate whether IES is an effective intervention and thus reduces progression of stage 1 and stage 2 sacral and ischial pressure injuries. TRIAL REGISTRATION: ClinicalTrials.gov NCT05085288 Registered October 20, 2021.

The effect of goal-directed crystalloid versus colloid administration on postoperative spirometry parameters: a substudy of a randomized controlled clinical trial.

BACKGROUND: Pulmonary function is impaired after major abdominal surgery and might be less impaired by restrictive fluid administration. Under the assumption of a fluid-sparing effect of colloids, we tested the hypothesis that an intraoperative colloid-based goal-directed fluid management strategy impairs postoperative pulmonary function parameters less compared to goal-directed crystalloid administration. METHODS: We performed a preplanned, single-center substudy within a recently published trial evaluating the effect of goal-directed crystalloids versus colloids on a composite of major complications. Sixty patients undergoing major open abdominal surgery were randomized to Doppler-guided intraoperative fluid replacement therapy with lactated Ringer's solution (n = 31) or unbalanced 6% hydroxyethyl starch 130/0.4 (n = 29). A blinded investigator performed bedside spirometry (Spirobank-G, Medical International Research, Rome, Italy) preoperatively as well as 6, 24, and 48 h postoperatively. RESULTS: Median total intraoperative fluid requirements were significantly higher during crystalloid administration compared to patients receiving colloids (4567 ml vs. 3044 ml, p = 0.01). Six hours after surgery, pulmonary function parameters did not differ significantly between the crystalloid - and the colloid group: forced vital capacity (FVC): 1.6 l (1.2-2 l) vs. 1.9 l (1.5-2.4 l), p = 0.15; forced expiratory volume in 1 second (FEV1): 1.1 l (0.9-1.6 l) vs. 1.4 l (1.2-1.7 l), p = 0.18; and peak expiratory flow (PEF): 2 l.sec-1 (1.5 - 3.6 l.sec -1) vs. 2.3 l.sec -1 (1.8 - 3.4 l.sec -1), p = 0.23. Moreover, postoperative longitudinal time × group interactions of FVC, FEV1, and PEF between 6 and 48 postoperative hours did not differ significantly. CONCLUSION: Postoperative pulmonary function parameters were similarly impaired in patients receiving goal-directed crystalloid administration as compared to goal-directed colloid administration during open abdominal surgery. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT00517127 , registered on August 16, 2007) and EudraCT (2005-004602-86).

Association between preoperative anemia optimization and major complications after non-cardiac surgery: a retrospective analysis.

BACKGROUND: Anemia is common in the preoperative setting and associated with increased postoperative complications and mortality. However, it is unclear if preoperative anemia optimization reduces postoperative complications. We aimed to assess the association between preoperative anemia optimization and a composite endpoint of major cardiovascular, renal, and pulmonary complications and all-cause mortality within 30 days after noncardiac surgery in adult patients. METHODS: In this retrospective analysis preoperative anemia was defined as hemoglobin concentration below 12.0 g.dl-1 in women and 13.0 g.dl-1 in men within 6 months before surgery. A propensity score-based generalized estimating equation analysis was used to determine the association between preoperative anemia optimization and the primary outcome. Moreover, mediation analysis was conducted to investigate whether intraoperative red blood cell transfusion or duration of intraoperative hypotension were mediators of the relation between anemia optimization and the primary outcome. RESULTS: Fifty-seven hundred anemia optimized, and 8721 non-optimized patients met study criteria. The proportion of patients having any component of the composite of major complications and all-cause mortality was 21.5% in the anemia-optimized versus 18.0% in the non-optimized, with confounder-adjusted odds ratio estimate of 0.99 (95% CI 0.86‒1.15) for anemia optimization versus non-optimization, p = 0.90. Intraoperative red blood cell transfusion had a minor mediation effect on the relationship between preoperative anemia optimization and the primary outcome, whereas duration of intraoperative hypotension was not found to be a mediator. CONCLUSION: Preoperative anemia optimization did not appear to be associated with a composite outcome of major in-hospital postoperative cardiovascular, renal, and pulmonary complications and all-cause in-hospital mortality.

Benefits and harms of perioperative high fraction inspired oxygen for surgical site infection prevention: a protocol for a systematic review and meta-analysis of individual patient data of randomised controlled trials.

INTRODUCTION: The use of high fraction of inspired oxygen (FiO2) intraoperatively for the prevention of surgical site infection (SSI) remains controversial. Promising results of early randomised controlled trials (RCT) have been replicated with varying success and subsequent meta-analysis are equivocal. Recent advancements in perioperative care, including the increased use of laparoscopic surgery and pneumoperitoneum and shifts in fluid and temperature management, can affect peripheral oxygen delivery and may explain the inconsistency in reproducibility. However, the published data provides insufficient detail on the participant level to test these hypotheses. The purpose of this individual participant data meta-analysis is to assess the described benefits and harms of intraoperative high FiO2compared with regular (0.21-0.40) FiO2 and its potential effect modifiers. METHODS AND ANALYSIS: Two reviewers will search medical databases and online trial registries, including MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and WHO regional databases, for randomised and quasi-RCT comparing the effect of intraoperative high FiO2 (0.60-1.00) to regular FiO2 (0.21-0.40) on SSI within 90 days after surgery in adult patients. Secondary outcome will be all-cause mortality within the longest available follow-up. Investigators of the identified trials will be invited to collaborate. Data will be analysed with the one-step approach using the generalised linear mixed model framework and the statistical model appropriate for the type of outcome being analysed (logistic and cox regression, respectively), with a random treatment effect term to account for the clustering of patients within studies. The bias will be assessed using the Cochrane risk-of-bias tool for randomised trials V.2 and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. Prespecified subgroup analyses include use of mechanical ventilation, nitrous oxide, preoperative antibiotic prophylaxis, temperature (<35°C), fluid supplementation (<15 mL/kg/hour) and procedure duration (>2.5 hour). ETHICS AND DISSEMINATION: Ethics approval is not required. Investigators will deidentify individual participant data before it is shared. The results will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42018090261.

PerIoperative iNflammatory reSponse assessment In hiGH-risk patienTs undergoing non-cardiac surgery (INSIGHT): study protocol of a prospective non-interventional observational study.

INTRODUCTION: Increased inflammatory processes after non-cardiac surgery are very common. The association between postoperative inflammation and the occurrence of cardiovascular complications after non-cardiac surgery are still not entirely clear. Therefore, we will evaluate the association between postoperative inflammation and the occurrence of major cardiovascular complications in patients at-risk for cardiovascular complications undergoing non-cardiac surgery. We will further evaluate the association of postoperative inflammation and days-at-home within 30 days after surgery (DAH30), the incidence of acute kidney injury, postoperative N-terminal probrain natriuretic peptide (NT-proBNP) concentrations and neurocognitive decline. METHODS AND ANALYSIS: In this multicentre study, we will include 1400 patients at-risk for cardiovascular complications undergoing non-cardiac surgery. Our primary aim is to evaluate the association of postoperative maximum C-reactive protein concentration and the occurrence of a composite of five major cardiovascular complications (myocardial infarction, myocardial injury after non-cardiac surgery, new onset of atrial fibrillation, stroke and death) within 30 days after surgery using a Mann-Whitney-U test as well as a logistic regression model. As our secondary aim, we will evaluate the association of a composite of three inflammatory biomarkers (interleukin 6, procalcitonin and copeptin) on the occurrence of our composite of five cardiovascular complications within 30 days and 1 year after surgery, acute kidney injury, DAH30 and NT-proBNP concentrations using linear or logistic regression models. We will measure inflammatory biomarkers before surgery, and on the first, second, third and fifth postoperative day. We will check medical records and conduct a telephone survey 30 days and 1 year after surgery. We evaluate neurocognitive function, using a Montreal Cognitive Assessment, before and 1 year after surgery. ETHICS AND DISSEMINATION: This study was approved by the ethics committees at the Medical University of Vienna (2458/2020) and at the Medical University of Graz (33-274 ex 20/21). TRIAL REGISTRATION NUMBER: NCT04753307.

Hemodynamic effects of intraoperative 30% versus 80% oxygen concentrations: an exploratory analysis.

Background: Supplemental oxygen leads to an increase in peripheral vascular resistance which finally increases systemic blood pressure in healthy subjects and patients with coronary artery disease, heart failure, undergoing heart surgery, and with sepsis. However, it is unknown whether this effect can also be observed in anesthetized patients having surgery. Thus, we evaluated in this exploratory analysis of a randomized controlled trial the effect of 80% versus 30% oxygen on intraoperative blood pressure and heart rate. Methods: We present data from a previous study including 258 patients, who were randomized to a perioperative inspiratory FiO2 of 0.8 (128 patients) versus 0.3 (130 patients) for major abdominal surgery. Continuous arterial blood pressure values were recorded every three seconds and were exported from the electronic anesthesia record system. We calculated time-weighted average (TWA) and Average Real Variability (ARV) of mean arterial blood pressure and of heart rate. Results: There was no significant difference in TWA of mean arterial pressure between the 80% (80 mmHg [76, 85]) and 30% (81 mmHg [77, 86]) oxygen group (effect estimate -0.16 mmHg, CI -1.83 to 1.51; p = 0.85). There was also no significant difference in TWA of heart rate between the 80 and 30% oxygen group (median TWA of heart rate in the 80% oxygen group: 65 beats.min-1 [58, 72], and in the 30% oxygen group: 64 beats.min-1 [58; 70]; effect estimate: 0.12 beats.min-1, CI -2.55 to 2.8, p = 0.94). Also for ARV values, no significant differences between groups could be detected. Conclusion: In contrast to previous results, we did not observe a significant increase in blood pressure or a significant decrease in heart rate in patients, who received 80% oxygen as compared to patients, who received 30% oxygen during surgery and for the first two postoperative hours. Thus, hemodynamic effects of supplemental oxygen might play a negligible role in anesthetized patients. Clinical Trail Registration: https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1.

Prolonged Opioid Use and Pain Outcome and Associated Factors after Surgery under General Anesthesia: A Prospective Cohort Association Multicenter Study.

BACKGROUND: There is insufficient prospective evidence regarding the relationship between surgical experience and prolonged opioid use and pain. The authors investigated the association of patient characteristics, surgical procedure, and perioperative anesthetic course with postoperative opioid consumption and pain 3 months postsurgery. The authors hypothesized that patient characteristics and intraoperative factors predict opioid consumption and pain 3 months postsurgery. METHODS: Eleven U.S. and one European institution enrolled patients scheduled for spine, open thoracic, knee, hip, or abdominal surgery, or mastectomy, in this multicenter, prospective observational study. Preoperative and postoperative data were collected using patient surveys and electronic medical records. Intraoperative data were collected from the Multicenter Perioperative Outcomes Group database. The association between postoperative opioid consumption and surgical site pain at 3 months, elicited from a telephone survey conducted at 3 months postoperatively, and demographics, psychosocial scores, pain scores, pain management, and case characteristics, was analyzed. RESULTS: Between September and October 2017, 3,505 surgical procedures met inclusion criteria. A total of 1,093 cases were included; 413 patients were lost to follow-up, leaving 680 (64%) for outcome analysis. Preoperatively, 135 (20%) patients were taking opioids. Three months postsurgery, 96 (14%) patients were taking opioids, including 23 patients (4%) who had not taken opioids preoperatively. A total of 177 patients (27%) reported surgical site pain, including 45 (13%) patients who had not reported pain preoperatively. The adjusted odds ratio for 3-month opioid use was 18.6 (credible interval, 10.3 to 34.5) for patients who had taken opioids preoperatively. The adjusted odds ratio for 3-month surgical site pain was 2.58 (1.45 to 4.4), 4.1 (1.73 to 8.9), and 2.75 (1.39 to 5.0) for patients who had site pain preoperatively, knee replacement, or spine surgery, respectively. CONCLUSIONS: Preoperative opioid use was the strongest predictor of opioid use 3 months postsurgery. None of the other variables showed clinically significant association with opioid use at 3 months after surgery.

Systematic reviews and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: mortality, morbidity, and organ failure.

BACKGROUND: Mortality, morbidity, and organ failure are important and common serious harms after surgery. However, there are many candidate measures to describe these outcome domains. Definitions of these measures are highly variable, and validity is often unclear. As part of the International Standardised Endpoints in Perioperative Medicine (StEP) initiative, this study aimed to derive a set of standardised and valid measures of mortality, morbidity, and organ failure for use in perioperative clinical trials. METHODS: Three domains of endpoints (mortality, morbidity, and organ failure) were explored through systematic literature review and a three-stage Delphi consensus process using methods consistently applied across the StEP initiative. Reliability, feasibility, and patient-centredness were assessed in round 3 of the consensus process. RESULTS: A high level of consensus was achieved for two mortality time points, 30-day and 1-yr mortality, and these two measures are recommended. No organ failure endpoints achieved threshold criteria for consensus recommendation. The Clavien-Dindo classification of complications achieved threshold criteria for consensus in round 2 of the Delphi process but did not achieve the threshold criteria in round 3 where it scored equivalently to the Post Operative Morbidity Survey. Clavien-Dindo therefore received conditional endorsement as the most widely used measure. No composite measures of organ failure achieved an acceptable level of consensus. CONCLUSIONS: Both 30-day and 1-yr mortality measures are recommended. No measure is recommended for organ failure. One measure (Clavien-Dindo) is conditionally endorsed for postoperative morbidity, but our findings suggest that no single endpoint offers a reliable and valid measure to describe perioperative morbidity that is not dependent on the quality of deli-vered care. Further refinement of current measures, or development of novel measures, of postoperative morbidity might improve consensus in this area.

Intra-abdominal hypertension in cardiac surgery patients: a multicenter observational sub-study of the Accuryn registry.

Intra-abdominal hypertension (IAH) is frequently present in the critically ill and is associated with increased morbidity and mortality. Conventionally, intermittent 'spot-check' manual measurements of bladder pressure in those perceived as high risk are used as surrogates for intra-abdominal pressure (IAP). True patterns of IAH remain unknown. We explored the incidence of IAH in cardiac surgery patients and describe the intra-and postoperative course of IAP using a novel, high frequency, automated bladder pressure measurement system. Sub-analysis of a prospective, multicenter, observational study (NCT04669548) conducted in three large academic medical centers. Continuous urinary output (CUO) and IAP measurements were observed using the Accuryn Monitoring System (Potrero Medical, Hayward, CA). Data collected included demographics, hemodynamic support, and high-frequency IAP and CUO. One Hundred Thirty-Seven cardiac surgery patients were analyzed intraoperatively and followed 48 h postoperatively in the intensive care unit. Median age was 66.4 [58.3, 72.0] years, and 61% were men. Median Foley catheter dwell time was 56.0 [46.8, 77.5] hours, and median baseline IAP was 6.3 [4.0, 8.1] mmHg. 93% (128/137) of patients were in IAH grade I, 82% (113/137) in grade II, 39% (53/137) in grade III, and 5% (7/137) in grade IV for at least 12 cumulative hours. For maximum consecutive duration of IAH, 84% (115/137) of patients spent at least 12 h in grade I, 62% (85/137) in grade II, 18% (25/137) in grade III, and 2% (3/137) in grade IV IAH. During the first 48 h after cardiac surgery, IAH is common and persistent. Improved and automated monitoring of IAP will increase the detection of IAH-which normally would remain undetected using traditional intermittent monitoring methods.

Perioperative Supplemental Oxygen and Postoperative Nausea and Vomiting: Subanalysis of a Trial, Systematic Review, and Meta-analysis.

BACKGROUND: Intraoperative supplemental oxygen may reduce postoperative nausea and vomiting by mitigating hypoxic stress on the gastrointestinal tract. The authors therefore tested the hypothesis that supplemental oxygen reduces nausea and vomiting in adults recovering from colorectal surgery at the Cleveland Clinic between January 28, 2013, and March 11, 2016. METHODS: Initially, the authors conducted an unplanned subanalysis of a previous trial that evaluated the effect of 80% versus 30% intraoperative inspired oxygen on surgical site infection. Specifically, they assessed the effect of 80% versus 30% oxygen concentration on the incidence of postoperative nausea and/or vomiting. Thereafter, the authors conducted a systematic review and meta-analysis of the effect of supplemental oxygen on postoperative nausea and vomiting. RESULTS: The authors' underlying analysis included 5,057 colorectal surgeries on 4,001 patients. For 2,554 surgeries, assignment was to 80% oxygen, and in 2,503 surgeries, to 30%. Postoperative nausea and vomiting was 852 of 2,554 (33%) in 80% oxygen and 814 of 2,503 (33%) in 30% oxygen. The estimated relative risk (95% CI) of 80% versus 30% oxygen on postoperative nausea and vomiting was 1.04 (0.96 to 1.12) in a generalized estimating equation model adjusting for within-patient correlation for patients with multiple surgeries, P = 0.355. Furthermore, supplemental oxygen did not reduce antiemetic use (P = 0.911) or the severity of nausea and vomiting (P = 0.924). The authors' meta-analysis included 10 qualifying trials (6,749 patients) and did not find a difference in postoperative nausea and vomiting: relative risk, 0.97 [95% CI, 0.86 to 1.08], P = 0.55, I2 = 52%. CONCLUSIONS: The incidence of postoperative nausea and vomiting did not differ in patients assigned to 80% or 30% inspired oxygen. A meta-analysis of available trials similarly indicated that supplemental intraoperative oxygen does not reduce postoperative nausea and vomiting. Therefore, supplemental oxygen should not be given in the expectation that it will reduce nausea and vomiting.

Intraoperative Inspiratory Oxygen Fraction and Myocardial Injury After Noncardiac Surgery: Results From an International Observational Study in Relation to Recent Controlled Trials.

BACKGROUND: Two trials reported that a high inspiratory oxygen fraction (F io2 ) does not promote myocardial infarction or death. Observational studies can provide larger statistical strength, but associations can be due to unobserved confounding. Therefore, we evaluated the association between intraoperative F io2 and cardiovascular complications in a large international cohort study to see if spurious associations were observed. METHODS: We included patients from the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were ≥45 years of age, scheduled for overnight hospital admission, and had intraoperative F io2 recorded. The primary outcome was myocardial injury after noncardiac surgery (MINS), and secondary outcomes included mortality and pneumonia, all within 30 postoperative days. Data were analyzed with logistic regression, adjusted for many baseline cardiovascular risk factors, and illustrated in relation to findings from 2 recent controlled trials. RESULTS: We included 6588 patients with mean age of 62 years of whom 49% had hypertension. The median intraoperative F io2 was 0.46 (5%-95% range, 0.32-0.94). There were 808 patients (12%) with MINS. Each 0.10 increase in median F io2 was associated with a confounder-adjusted increase in odds for MINS: odds ratio (OR), 1.17 (95% confidence interval [CI], 1.12-1.23; P < .0001). MINS occurred in contrast with similar frequencies and no significant difference in controlled trials (2240 patients, 194 events), in which patients were given 80% vs 30% oxygen. Mortality was 2.4% and was not significantly associated with a median F io2 (OR, 1.07; 95% CI, 0.97-1.19 per 0.10 increase; P = .18), and 2.9% of patients had pneumonia (OR, 1.05; 95% CI, 0.95-1.15 per 0.10 increase; P = .34). CONCLUSIONS: We observed an association between intraoperative F io2 and risk of myocardial injury within 30 days after noncardiac surgery, which contrasts with recent controlled clinical trials. F io2 was not significantly associated with mortality or pneumonia. Unobserved confounding presumably contributed to the observed association between F io2 and myocardial injury that is not supported by trials.

Effect of intraoperative subhypnotic infusion of propofol on postoperative nausea and vomiting: A retrospective analysis.

STUDY OBJECTIVE: To measure the possible association between subhypnotic propofol infusion during general balanced anesthesia and the incidence of PONV. DESIGN: Retrospective Cohort Analysis Using Propensity Score Matching. SETTING: Postanesthesia care unit and inpatient unit. PATIENTS: Patients with American Society of Anesthesiologists (ASA) physical status I-IV, undergoing non-cardiac surgery lasting >2 h were included. Patients were excluded if transferred to the intensive care unit after surgery or received ketamine. Initially 70,976 patients were screened, and a cohort of 51,707 eligible adult patients undergoing non-cardiac surgery under general balanced anesthesia between 2015 and 2019 were included. Using a propensity score matching, 3185 patients who received subhypnotic propofol during general balanced anesthesia were matched with 5826 patients who did not receive subhypnotic propofol in a 1:2 ratio. INTERVENTIONS: None. MEASUREMENTS: The primary outcome was the incidence of PONV during PACU stay. The secondary outcome was the incidence of PONV within the first 24 h after surgery. Exploratory outcomes were time-to-extubation and length of hospital stay. MAIN RESULTS: A total of 9011 patients were included (3185 patients who received propofol infusion, and 5826 patients who did not receive propofol infusion) after propensity score matching. The adjusted odds ratio for PONV incidence was 1.03 (95% CI: 0.90, 1.18; p = 0.635) in PACU, and 1.05 (95% CI: 0.90, 1.23; P = 0.50) within 24 h after surgery. The length of hospital stay was 6 h shorter (ratio of means (95% CI) of 0.92, 0.89, 0.94), p < 0.001) and time-to-extubation was 2 min longer (ratio of means 1.24 (1.20, 1.28), p < 0.001) in patients receiving subhypnotic propofol infusion. CONCLUSIONS: Our study suggests that subhypnotic propofol infusion during general balanced anesthesia is not associated with a reduction in the incidence of PONV during PACU stay and within the first 24 h after surgery. However, it is associated with decreased LOS and increased time-to-extubation, but differences in neither outcome were clinically important.

Effect of a Perioperative Hypotension-Avoidance Strategy Versus a Hypertension-Avoidance Strategy on the Risk of Acute Kidney Injury: A Clinical Research Protocol for a Substudy of the POISE-3 Randomized Clinical Trial.

BACKGROUND: Most patients who take antihypertensive medications continue taking them on the morning of surgery and during the perioperative period. However, growing evidence suggests this practice may contribute to perioperative hypotension and a higher risk of complications. This protocol describes an acute kidney injury substudy of the Perioperative Ischemic Evaluation-3 (POISE-3) trial, which is testing the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy in patients undergoing noncardiac surgery. OBJECTIVE: To conduct a substudy of POISE-3 to determine whether a perioperative hypotension-avoidance strategy reduces the risk of acute kidney injury compared with a hypertension-avoidance strategy. DESIGN: Randomized clinical trial with 1:1 randomization to the intervention (a perioperative hypotension-avoidance strategy) or control (a hypertension-avoidance strategy). INTERVENTION: If the presurgery systolic blood pressure (SBP) is <130 mmHg, all antihypertensive medications are withheld on the morning of surgery. If the SBP is ≥130 mmHg, some medications (but not angiotensin receptor blockers [ACEIs], angiotensin receptor blockers [ARBs], or renin inhibitors) may be continued in a stepwise manner. During surgery, the patients' mean arterial pressure (MAP) is maintained at ≥80 mmHg. During the first 48 hours after surgery, some antihypertensive medications (but not ACEIs, ARBs, or renin inhibitors) may be restarted in a stepwise manner if the SBP is ≥130 mmHg. CONTROL: Patients receive their usual antihypertensive medications before and after surgery. The patients' MAP is maintained at ≥60 mmHg from anesthetic induction until the end of surgery. SETTING: Recruitment from 108 centers in 22 countries from 2018 to 2021. PATIENTS: Patients (~6800) aged ≥45 years having noncardiac surgery who have or are at risk of atherosclerotic disease and who routinely take antihypertensive medications. MEASUREMENTS: The primary outcome of the substudy is postoperative acute kidney injury, defined as an increase in serum creatinine concentration of either ≥26.5 µmol/L (≥0.3 mg/dL) within 48 hours of randomization or ≥50% within 7 days of randomization. METHODS: The primary analysis (intention-to-treat) will examine the relative risk and 95% confidence interval of acute kidney injury in the intervention versus control group. We will repeat the primary analysis using alternative definitions of acute kidney injury and examine effect modification by preexisting chronic kidney disease, defined as a prerandomization estimated glomerular filtration rate <60 mL/min/1.73 m2. RESULTS: Substudy results will be analyzed in 2022. LIMITATIONS: It is not possible to mask patients or providers to the intervention; however, objective measures will be used to assess acute kidney injury. CONCLUSIONS: This substudy will provide generalizable estimates of the effect of a perioperative hypotension-avoidance strategy on the risk of acute kidney injury.

CONTEXTE: La plupart des patients qui prennent des médicaments antihypertenseurs continuent de les prendre le matin d'une intervention chirurgicale et pendant la période périopératoire. De plus en plus de preuves suggèrent que cette pratique pourrait entraîner l'hypotension périopératoire et augmenter le risque de complications. Ce protocole décrit une sous-étude sur l'insuffisance rénale aiguë (IRA) découlant de l'essai Perioperative Ischemic Evaluation-3 (POISE-3). Cet essai teste l'effet d'une stratégie d'évitement de l'hypotension périopératoire par rapport à une stratégie d'évitement de l'hypertension chez des patients qui subissent une chirurgie non cardiaque. OBJECTIFS: Cette sous-étude de l'essai POISE-3 vise à déterminer si une stratégie d'évitement de l'hypotension périopératoire réduit le risque d'IRA comparativement à la stratégie d'évitement de l'hypertension. TYPE D'ÉTUDE: Essai clinique randomisé à répartition 1:1 au groupe intervention (stratégie d'évitement de l'hypotension périopératoire) ou au groupe témoin (stratégie d'évitement de l'hypertension). GROUPE INTERVENTION: Si la pression artérielle systolique (PAS) avant l'opération est <130 mmHg, tous les médicaments antihypertenseurs sont suspendus le matin de la chirurgie. Si la PAS est ≥130 mmHg, certains médicaments (excluant les inhibiteurs de l'enzyme de conversion de l'angiotensine [IECA], les antagonistes du récepteur de l'angiotensine [ARA] ou les inhibiteurs de la rénine) peuvent être poursuivis de façon graduelle. Pendant la chirurgie, la pression artérielle moyenne (PAM) du patient est maintenue à ≥80 mmHg. Dans les 48 heures suivant l'intervention chirurgicale, certains médicaments antihypertenseurs (excluant les IECA, les ARA ou les inhibiteurs de la rénine) peuvent être réintroduits par étapes si la PAS est ≥130 mmHg. GROUPE TÉMOIN: Les patients reçoivent leurs médicaments antihypertenseurs habituels avant et après la chirurgie. La PAM du patient est maintenue à ≥60 mmHg de l'induction de l'anesthésie à la fin de l'intervention chirurgicale. CADRE: Recrutement à partir de 108 centres dans 22 pays entre 2018 à 2021. SUJETS: Des patients (~6 800) âgés de 45 ans et plus atteints d'athérosclérose, ou présentant un risque de l'être, devant subir une chirurgie non cardiaque et prenant des médicaments antihypertenseurs sur une base régulière. MESURES: Le principal critère d'évaluation de cette sous-étude est une IRA postopératoire définie par une hausse d'au moins 26,5 µmol/L (≥0,3 mg/dL) de la créatinine sérique dans les 48 heures suivant la randomisation ou d'au moins 50 % dans les 7 jours suivant la randomisation. MÉTHODOLOGIE: L'analyse primaire (par intention de traiter) examinera le risque relatif d'une IRA et l'intervalle de confiance à 95 % dans le groupe intervention par rapport au groupe témoin. Nous répéterons l'analyse primaire en utilisant d'autres définitions de l'IRA et nous examinerons la modification de l'effet en présence d'une insuffisance rénale préexistante (définie par un DFGe prérandomisation <60 ml/min/1,73 m2). RÉSULTATS: Les résultats de cette sous-étude seront analysés en 2022. LIMITES: Il n'est pas possible de procéder à l'insu des patients ou des prestataires de soins pour cette intervention; des mesures objectives seront toutefois utilisées pour évaluer l'IRA. CONCLUSION: Cette sous-étude fournira des estimations généralisables de l'effet d'une stratégie visant à éviter l'hypotension périopératoire sur le risque d'insuffisance rénale aiguë.

Hemodynamic Responses to Crystalloid and Colloid Fluid Boluses during Noncardiac Surgery.

BACKGROUND: Colloids are thought to sustain blood pressure and cardiac index better than crystalloids. However, the relative effects of intraoperative hydroxyethyl starch and crystalloid administration on the cardiac index and blood pressure remain unclear. This study therefore tested in this subanalysis of a previously published large randomized trial the hypothesis that intraoperative goal-directed colloid administration increases the cardiac index more than goal-directed crystalloid administration. Further, the effects of crystalloid and colloid boluses on blood pressure were evaluated. METHODS: This planned subanalysis of a previous trial analyzed data from 973 patients, of whom 480 were randomized to colloids and 493 were randomized to crystalloids. Fluid administration was guided by esophageal Doppler. The primary outcome was the time-weighted average cardiac index during surgery between the colloid and crystalloid group. The secondary outcomes were the cardiac index just after bolus administration, time elapsed between boluses, and the average real variability during surgery. The study recorded cardiac index, corrected flow time, and blood pressure at 10-min intervals, as well as before and after each bolus. RESULTS: Time-weighted average of cardiac index over the duration of anesthesia was only slightly greater in patients given colloid than crystalloid, with the difference being just 0.20 l · min-1 · m-2 (95% CI, 0.11 to 0.29; P < 0.001). However, the hazard for needing additional boluses was lower after colloid administration (hazard ratio [95% CI], 0.60 [0.55 to 0.66]; P < 0.001) in a frailty time-to-event model accounting for within-subject correlation. The median [quartiles] number of boluses per patient was 4 [2, 6] for colloids and 6 [3, 8] for crystalloids, with a median difference (95% CI) of -1.5 (-2 to -1; P < 0.001). The average real mean arterial pressure variability did not differ significantly between the groups (difference in means [95% CI] of -0.03 (-0.07 to 0.02) mmHg, P = 0.229). CONCLUSIONS: There were not clinically meaningful differences in the cardiac index or mean pressure variability in patients given goal-directed colloid and crystalloids. As might be expected from longer intravascular dwell time, the interval between boluses was longer with colloids. However, on a case basis, the number of boluses differed only slightly. Colloids do not appear to provide substantial hemodynamic benefit.

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.

Prolonged Blood Storage and Risk of Posttransfusion Acute Kidney Injury.

BACKGROUND: Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury. METHODS: The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria. RESULTS: The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units. CONCLUSIONS: In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury.

Supplemental Intraoperative Oxygen and Long-term Mortality: Subanalysis of a Multiple Crossover Cluster Trial.

BACKGROUND: Whether supplemental oxygen worsens long-term mortality remains unclear, with contradictory trial results. The authors therefore tested the hypothesis that supplemental oxygen (80% vs. 30%) increases the hazard for long-term mortality. METHODS: The authors conducted a post hoc analysis of a large multiple crossover cluster trial in which more than 5,000 colorectal surgeries on 4,088 adults were allocated to receive either 30% or 80% inspired oxygen during general anesthesia. The authors assessed the effect of 80% versus 30% target-inspired oxygen on long-term mortality and calculated Kaplan-Meier survival estimates. Analysis was restricted to patients with a home address in Ohio because the authors could obtain reliable vital status information from the Ohio Department of Health (Columbus, Ohio) for them. RESULTS: A total of 3,471 qualifying colorectal surgeries performed in 2,801 patients were analyzed, including 1,753 (51%) surgeries in 1,577 patients given 80% oxygen and 1,718 surgeries in 1,551 patients given 30% oxygen. The observed incidence of death after a median of 3 yr was 13% (234 of 1,753) in the 80% oxygen group and 14% (245 of 1,718) in the 30% oxygen group. The estimated hazard ratio for mortality was 0.94 (95% CI, 0.78 to 1.13; P = 0.493). CONCLUSIONS: In this post hoc analysis of a large, controlled trial, supplemental oxygen did not increase postoperative mortality.

Systematic review and consensus definitions for the Standardized Endpoints in Perioperative Medicine (StEP) initiative: cardiovascular outcomes.

BACKGROUND: Adverse cardiovascular events are a leading cause of perioperative morbidity and mortality. The definitions of perioperative cardiovascular adverse events are heterogeneous. As part of the international Standardized Endpoints in Perioperative Medicine initiative, this study aimed to find consensus amongst clinical trialists on a set of standardised and valid cardiovascular outcomes for use in future perioperative clinical trials. METHODS: We identified currently used perioperative cardiovascular outcomes by a systematic review of the anaesthesia and perioperative medicine literature (PubMed/Ovid, Embase, and Cochrane Library). We performed a three-stage Delphi consensus-gaining process that involved 55 clinician researchers worldwide. Cardiovascular outcomes were first shortlisted and the most suitable definitions determined. These cardiovascular outcomes were then assessed for validity, reliability, feasibility, and clarity. RESULTS: We identified 18 cardiovascular outcomes. Participation in the three Delphi rounds was 100% (n=19), 71% (n=55), and 89% (n=17), respectively. A final list of nine cardiovascular outcomes was elicited from the consensus: myocardial infarction, myocardial injury, cardiovascular death, non-fatal cardiac arrest, coronary revascularisation, major adverse cardiac events, pulmonary embolism, deep vein thrombosis, and atrial fibrillation. These nine cardiovascular outcomes were rated by the majority of experts as valid, reliable, feasible, and clearly defined. CONCLUSIONS: These nine consensus cardiovascular outcomes can be confidently used as endpoints in clinical trials designed to evaluate perioperative interventions with the goal of improving perioperative outcomes.

Arterial Catheters for Early Detection and Treatment of Hypotension During Major Noncardiac Surgery: A Randomized Trial.

BACKGROUND: Continuous blood pressure monitoring may facilitate early detection and prompt treatment of hypotension. We tested the hypothesis that area under the curve (AUC) mean arterial pressure (MAP) <65 mm Hg is reduced by continuous invasive arterial pressure monitoring. METHODS: Adults having noncardiac surgery were randomly assigned to continuous invasive arterial pressure or intermittent oscillometric blood pressure monitoring. Arterial catheter pressures were recorded at 1-minute intervals; oscillometric pressures were typically recorded at 5-minute intervals. We estimated the arterial catheter effect on AUC-MAP <65 mm Hg using a multivariable proportional odds model adjusting for imbalanced baseline variables and duration of surgery. Pressures <65 mm Hg were categorized as 0, 1-17, 18-91, and >91 mm Hg × minutes of AUC-MAP <65 mm Hg (ie, no hypotension and 3 equally sized groups of increasing hypotension). RESULTS: One hundred fifty-two patients were randomly assigned to arterial catheter use and 154 to oscillometric monitoring. For various clinical reasons, 143 patients received an arterial catheter, while 163 were monitored oscillometrically. There were a median [Q1, Q3] of 246 [187, 308] pressure measurements in patients with arterial catheters versus 55 (46, 75) measurements in patients monitored oscillometrically. In the primary intent-to-treat analysis, catheter-based monitoring increased detection of AUC-MAP <65 mm Hg, with an estimated proportional odds ratio (ie, odds of being in a worse hypotension category) of 1.78 (95% confidence interval [CI], 1.18-2.70; P = .006). The result was robust over an as-treated analysis and for sensitivity analyses with thresholds of 60 and 70 mm Hg. CONCLUSIONS: Intraoperative blood pressure monitoring with arterial catheters detected nearly twice as much hypotension as oscillometric measurements.