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Purpose Postoperative complications increase mortality, disability and costs. Advanced understanding of the risk factors for postoperative complications is needed to improve surgical outcomes. This paper discusses the rationale and profile of the BIGPROMISE (biomarkers to guide perioperative management and improve outcome in high-risk surgery) cohort, that aims to investigate risk factors, pathophysiology and outcomes related to postoperative complications.Participants Adult patients undergoing major surgery in two tertiary teaching hospitals. Clinical data and blood samples are collected before surgery, at the end of surgery and on the first, second and third postoperative day. At each time point a panel of cardiovascular, inflammatory, renal, haematological and metabolic biomarkers is assessed. Aliquots of plasma, serum and whole blood of each time point are frozen and stored. Data on severe complications are prospectively collected during 30 days after surgery. Functional status is assessed before surgery and after 120 days using the WHO Disability Assessment Schedule (WHODAS) 2.0. Mortality is followed up until 2 years after surgery.Findings to date The first patient was enrolled on 8 October 2021. Currently (1 January 2024) 3086 patients were screened for eligibility, of whom 1750 (57%) provided informed consent for study participation. Median age was 66 years (60; 73), 28% were female, and 68% of all patients were American Society of Anaesthesiologists (ASA) physical status class 3. Most common types of major surgery were cardiac (49%) and gastro-intestinal procedures (26%). The overall incidence of 30-day severe postoperative complications was 16%.Future plans By the end of the recruitment phase, expected in 2026, approximately 3000 patients with major surgery will have been enrolled. This cohort allows us to investigate the role of pathophysiological perioperative processes in the cause of postoperative complications, and to discover and develop new biomarkers to improve risk stratification for adverse postoperative outcomes.Trial registration number NCT05199025.

Purpose Although elective surgery is generally safe, some procedures remain associated with an increased risk of complications. Improved preoperative risk stratification and earlier recognition of these complications may ameliorate postoperative recovery and improve long-term outcomes. The perioperative longitudinal study of complications and long-term outcomes (PLUTO) cohort aims to establish a comprehensive biorepository that will facilitate research in this field. In this profile paper, we will discuss its design rationale and opportunities for future studies.Participants Patients undergoing elective intermediate to high-risk non-cardiac surgery are eligible for enrolment. For the first seven postoperative days, participants are subjected to daily bedside visits by dedicated observers, who adjudicate clinical events and perform non-invasive physiological measurements (including handheld spirometry and single-channel electroencephalography). Blood samples and microbiome specimens are collected at preselected time points. Primary study outcomes are the postoperative occurrence of nosocomial infections, major adverse cardiac events, pulmonary complications, acute kidney injury and delirium/acute encephalopathy. Secondary outcomes include mortality and quality of life, as well as the long-term occurrence of psychopathology, cognitive dysfunction and chronic pain.Findings to date Enrolment of the first participant occurred early 2020. During the inception phase of the project (first 2 years), 431 patients were eligible of whom 297 patients consented to participate (69%). Observed event rate was 42% overall, with the most frequent complication being infection.Future plans The main purpose of the PLUTO biorepository is to provide a framework for research in the field of perioperative medicine and anaesthesiology, by storing high-quality clinical data and biomaterials for future studies. In addition, PLUTO aims to establish a logistical platform for conducting embedded clinical trials.Trial registration number NCT05331118.

BackgroundContinuous monitoring of vital signs has the potential to assist in the recognition of deterioration of patients admitted to the general ward. However, methods to efficiently process and use continuously measured vital sign data remain unclear. ObjectiveThe aim of this study was to explore methods to summarize continuously measured vital sign data and evaluate their association with respiratory insufficiency in COVID-19 patients at the general ward. MethodsIn this retrospective cohort study, we included patients admitted to a designated COVID-19 cohort ward equipped with continuous vital sign monitoring. We collected continuously measured data of respiratory rate, heart rate, and oxygen saturation. For each patient, 7 metrics to summarize vital sign data were calculated: mean, slope, variance, occurrence of a threshold breach, number of episodes, total duration, and area above/under a threshold. These summary measures were calculated over timeframes of either 4 or 8 hours, with a pause between the last data point and the endpoint (the “lead”) of 4, 2, 1, or 0 hours, and with 3 predefined thresholds per vital sign. The association between each of the summary measures and the occurrence of respiratory insufficiency was calculated using logistic regression analysis. ResultsOf the 429 patients that were monitored, 334 were included for analysis. Of these, 66 (19.8%) patients developed respiratory insufficiency. Summarized continuously measured vital sign data in timeframes close to the endpoint showed stronger associations than data measured further in the past (ie, lead 0 vs 1, 2, or 4 hours), and summarized estimates over 4 hours of data had stronger associations than estimates taken over 8 hours of data. The mean was consistently strongly associated with respiratory insufficiency for the three vital signs: in a 4-hour timeframe without a lead, the standardized odds ratio for heart rate, respiratory rate, and oxygen saturation was 2.59 (99% CI 1.74-4.04), 5.05 (99% CI 2.87-10.03), and 3.16 (99% CI 1.78-6.26), respectively. The strength of associations of summary measures varied per vital sign, timeframe, and lead. ConclusionsThe mean of a vital sign showed a relatively strong association with respiratory insufficiency for the majority of vital signs and timeframes. The type of vital sign, length of the timeframe, and length of the lead influenced the strength of associations. Highly associated summary measures and their combinations could be used in a clinical prediction score or algorithm for an automatic alarm system.

Abstract Background An elevated cardiac troponin level after noncardiac surgery is associated with both morbidity and mortality. Guidelines suggest routine troponin monitoring in high-risk patients. We implemented a dedicated anesthesia team to conduct follow-up on patients with postoperative troponin elevation. We hypothesized that these visits would facilitate early detection of complications. Therefore, the aim of this study was to evaluate the effect of postoperative visits by dedicated anesthesiologists on early detection of complications and care utility. Methods This retrospective observational study included patients aged ≥ 60 years with an elevated troponin within the first 3 days after noncardiac surgery. Troponin elevation was detected by routine biomarker monitoring. The primary outcome was early detected myocardial infarctions by the dedicated anesthesiologist. Other outcomes were overall detected complications, additional diagnostic tests and treatment advised by the anesthesiologist, consultation of another medical specialist, and advised postoperative follow-up at the outpatient cardiac clinic within 1 week after surgery. Results Of the 811 patients, 509 (63%) received a postoperative consultation by the anesthesiologist. Anesthesiologists were involved in the early detection of 59% of all myocardial infarctions and in 12% of all complications. Besides cardiac ischemia, patients were also often diagnosed with noncardiac complications, including respiratory failure (8.9%), pneumonia (13.2%), and acute kidney injury (17.5%) within 1 week after surgery. In 75% of patients, anesthesiologists ordered additional diagnostics, most frequently existing of electrocardiograms and additional cardiac enzyme testing. Additionally, change in treatment was advised, most often a medication change, in 16% of patients. Conclusions Standard consultation of a dedicated anesthesiologist resulted in an early detection of 59% of all myocardial infarctions and involved a change in treatment in a considerable number of patients with postoperative troponin elevation. Whether this may improve patient outcomes remains to be elucidated.

Abstract To compare mental, cognitive and physical outcomes between COVID-19 and non-COVID-19 patients, 3–6 months after Intensive Care Unit (ICU) treatment during the COVID-19 pandemic and to compare mental outcomes between relatives of these patients. This retrospective cohort study included 209 ICU survivors (141 COVID-19 patients and 68 non-COVID-19 patients) and 168 of their relatives (maximum one per patient) during the COVID-19 pandemic. Primary outcomes were self-reported occurrence of mental, cognitive and/or physical symptoms 3–6 months after ICU discharge. The occurrence of mental symptoms did not differ between former COVID-19 patients (34.7% [43/124]) and non-COVID-19 patients (43.5% [27/62]) (p = 0.309), neither between relatives of COVID-19 patients (37.6% [38/101]) and relatives of non-COVID-19 patients (39.6% [21/53]) (p = 0.946). Depression scores on the Hospital Anxiety and Depression Scale were lower in former COVID-19 patients, compared to non-COVID-19 patients (p = 0.025). We found no differences between COVID-19 and non-COVID-19 patients in cognitive and physical outcomes. Mental, cognitive and physical outcomes in COVID-19 ICU survivors were similar to non-COVID-19 ICU survivors. Mental symptoms in relatives of COVID-19 ICU survivors did not differ from relatives of non-COVID-19 ICU survivors, within the same time frame.

Background: Intraoperative hypotension has been extensively studied for its association with adverse outcomes. However, small sample sizes and methodological issues limit the causal inference that can be drawn. Methods: In this multicentre, adaptive, randomised controlled trial, we will include 5000 adult inpatients scheduled for elective non-cardiac surgery under general or central neuraxial anaesthesia. Patients will be either randomly allocated to the intervention or care-as-usual group using computer-generated blocks of four, six, or eight, with an allocation ratio of 1:1. In the intervention arm patients will be divided into low-, intermediate-, and high-risk groups based on their likelihood to experience intraoperative hypotension, with resulting mean blood pressure targets of 70, 80, and 90 mm Hg, respectively. Anaesthesia teams will be provided with a clinical guideline on how to keep patients at their target blood pressure. During the first 6 months of the trial the intervention strategy will be evaluated and further revised in adaptation cycles of 3 weeks if necessary, to improve successful impact on the clinical process. The primary outcome is postoperative disability after 6 months measured with the World Health Organization Disability Assessment Score (WHODAS) 2.0 questionnaire. Ethics and dissemination: This study protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht (20–749) and all protocol amendments will be communicated to the Medical Ethics Committee. The study protocol is in adherence with the Declaration of Helsinki and the guideline of Good Clinical Practice. Dissemination plans include publication in a peer-reviewed journal. Clinical trial registration: The Dutch Trial Register, NL9391. Registered on 22 March 2021.

OBJECTIVES:. Although opioids are frequently used to treat pain, and are an important risk for ICU delirium, the association between ICU pain itself and delirium remains unclear. We sought to evaluate the relationship between ICU pain and delirium. DESIGN:. Prospective cohort study. SETTING:. A 32-bed academic medical-surgical ICU. PATIENTS:. Critically ill adults (n = 4,064) admitted greater than or equal to 24 hours without a condition hampering delirium assessment. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Daily mental status was classified as arousable without delirium, delirium, or unarousable. Pain was assessed six times daily in arousable patients using a 0–10 Numeric Rating Scale (NRS) or the Critical Care Pain Observation Tool (CPOT); daily peak pain score was categorized as no (NRS = 0/CPOT = 0), mild (NRS = 1–3/CPOT = 1–2), moderate (NRS = 4–6/CPOT = 3–4), or severe (NRS = 7–10/CPOT = 5–8) pain. To address missingness, a Multiple Imputation by Chained Equations approach that used available daily pain severity and 19 pain predictors was used to generate 25 complete datasets. Using a first-order Markov model with a multinomial logistic regression analysis, that controlled for 11 baseline/daily delirium risk factors and considered the competing risks of unarousability and ICU discharge/death, the association between peak daily pain and next-day delirium in each complete dataset was evaluated. RESULTS:. Among 14,013 ICU days (contributed by 4,064 adults), delirium occurred on 2,749 (19.6%). After pain severity imputation on 1,818 ICU days, mild, moderate, and severe pain were detected on 2,712 (34.1%), 1,682 (21.1%), and 894 (11.2%) of the no-delirium days, respectively, and 992 (36.1%), 513 (18.6%), and 27 (10.1%) of delirium days (p = 0.01). The presence of any pain (mild, moderate, or severe) was not associated with a transition from awake without delirium to delirium (aOR 0.96; 95% CI, 0.76–1.21). This association was similar when days with only mild, moderate, or severe pain were considered. All results were stable after controlling for daily opioid dose. CONCLUSIONS:. After controlling for multiple delirium risk factors, including daily opioid use, pain may not be a risk factor for delirium in the ICU. Future prospective research is required.

IMPORTANCE:. Failure to recognize and address data missingness in cohort studies may lead to biased results. Although Strengthening the Reporting of Observational Studies in Epidemiology reporting guidelines advocate data missingness reporting, the degree to which missingness is reported and addressed in the critical care literature remains unclear. OBJECTIVES:. To review published ICU cohort studies to characterize data missingness reporting and the use of methods to address it. DESIGN, SETTING, AND PARTICIPANTS:. We searched the 2022 table of contents of 29 critical care/critical care subspecialty journals having a 2021 impact factor greater than or equal to 3 to identify published prospective clinical or retrospective database cohort studies enrolling greater than or equal to 100 patients. MAIN OUTCOMES AND MEASURES:. In duplicate, two trained researchers conducted a manuscript/supplemental material PDF word search for “missing*” and extracted study type, patient age, ICU type, sample size, missingness reporting, and the use of methods to address it. RESULTS:. A total of 656 studies were reviewed. Of the 334 of 656 (50.9%) studies mentioning missingness, missingness was reported for greater than or equal to 1 variable in 234 (70.1%) and it exceeded 5% for at least one variable in 160 (47.9%). Among the 334 studies mentioning missingness, 88 (26.3%) used exclusion criteria, 36 (10.8%) used complete-case analysis, and 164 (49.1%) used a formal method to avoid missingness. In these 164 studies, imputation only was used in 100 (61.0%), an analytic strategy only in 24 (14.6%), and both in 40 (24.4%). Only missingness greater than 5% (in ≥ 1 variable) was independently associated with greater use of a missingness method (adjusted odds ratio 2.91; 95% CI, 1.85–4.60). Among 140 studies using imputation, multiple imputation was used in 87 studies (62.1%) and simple imputation in 49 studies (35.0%). For the 64 studies using an analytic method, 12 studies (18.8%) assigned missingness as an unknown category, whereas sensitivity analysis was used in 47 studies (73.4%). CONCLUSIONS AND RELEVANCE:. Among published critical care cohort studies, only half mentioned result missingness, one-third reported actual missingness and only one-quarter used a method to manage missingness. Educational strategies to promote missingness reporting and resolution methods are required.

Abstract Background Chronic pain after cardiac surgery, whether or not related to the operation, is common and has negative impact on health related quality of life (HRQL). Frailty is a risk factor for adverse surgical outcomes, but its relationship with chronic pain after cardiac surgery is unknown. This study aimed to address the association between frailty and chronic pain following cardiac surgery. Methods This sub-study of the Anesthesia Geriatric Evaluation study included 518 patients ≥ 70 years undergoing elective cardiac surgery. Pain was evaluated with the Short-Form 36 questionnaire prior to and one year after surgery. Associations between chronic postoperative pain and frailty domains, including medication use, nutritional status, mobility, physical functioning, cognition, HRQL, living situation and educational level, were investigated with multivariable regression analysis. Results Chronic pain one year after cardiac surgery was reported in 182 patients (35%). Medication use, living situation, mobility, gait speed, Nagi’s physical functioning and preoperative HRQL were frailty domains associated with chronic pain after surgery. For patients with chronic pain physical HRQL after one year was worse compared to patients without chronic pain (β –10.37, 99% CI –12.57 – –8.17). Conclusions Preoperative polypharmacy, living alone, physical frailty and lower mental HRQL are associated with chronic pain following cardiac surgery. Chronic postoperative pain is related to worse physical HRQL one year after cardiac surgery. These findings may guide future preoperative interventions to reduce chronic pain and poor HRQL after cardiac surgery in older patients. Trial Registration This trial has been registered before initiation under number NCT02535728 at clinicaltrials.gov.