The effect of proactive versus reactive treatment of hypotension on postoperative disability and outcome in surgical patients under anaesthesia (PRETREAT): clinical trial protocol and considerations.

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.

Postoperative troponin surveillance to detect myocardial infarction: an observational cohort modelling study.

BACKGROUND: Clinical presentation of postoperative myocardial infarction (POMI) is often silent. Several international guidelines recommend routine troponin surveillance in patients at risk. We compared how these different guidelines select patients for surveillance after noncardiac surgery with our established risk stratification model. METHODS: We used outcome data from two prospective studies: Measurement of Exercise Tolerance before Surgery (METS) and Troponin Elevation After Major non-cardiac Surgery (TEAMS). We compared the major American, Canadian, and European guideline recommendations for troponin surveillance with our established risk stratification model. For each guideline and model, we quantified the number of patients requiring monitoring, % POMI detected, sensitivity, specificity, diagnostic odds ratio, and number needed to screen (NNS). RESULTS: METS and TEAMS contributed 2350 patients, of whom 319 (14%) had myocardial injury, 61 (2.5%) developed POMI, and 14 (0.6%) died. Our risk stratification model selected fewer patients for troponin monitoring (20%), compared with the Canadian (78%) and European (79%) guidelines. The sensitivity to detect POMI was highest with the Canadian and European guidelines (0.85; 95% confidence interval [CI] 0.74-0.92). Specificity was highest using the American guidelines (0.91; 95% CI 0.90-0.92). Our risk stratification model had the best diagnostic odds ratio (2.5; 95% CI 1.4-4.2) and a lower NNS (21 vs 35) compared with the guidelines. CONCLUSIONS: Most postoperative myocardial infarctions were detected by the Canadian and European guidelines but at the cost of low specificity and a higher number of patients undergoing screening. Patient selection based on our risk stratification model was optimal.

Postoperative myocardial injury phenotypes and self-reported disability in patients undergoing noncardiac surgery: a multicentre observational study.

BACKGROUND: Postoperative myocardial injury (PMI) comprises a spectrum of mechanisms resulting in troponin release. The impact of different PMI phenotypes on postoperative disability remains unknown. METHODS: This was a multicentre prospective cohort study including patients aged ≥50 yr undergoing elective major noncardiac surgery. Patients were stratified in five groups based on the occurrence of PMI and clinical information on postoperative adverse events: PMI classified as myocardial infarction (MI; according to fourth definition), PMI plus adverse event other than MI, clinically silent PMI (PMI without adverse events), adverse events without PMI, and neither PMI nor an adverse event (reference). The primary endpoint was 6-month self-reported disability (assessed by WHO Disability Assessment Schedule 2.0 [WHODAS]). Disability-free survival was defined as WHODAS ≤16%. RESULTS: We included 888 patients of mean age 69 (range 53-91) yr, of which 356 (40%) were women; 151 (17%) patients experienced PMI, and 625 (71%) experienced 6-month disability-free survival. Patients with PMI, regardless of its phenotype, had higher preoperative disability scores than patients without PMI (difference in WHODAS; ß: 3.3, 95% confidence interval [CI]: 0.5-6.2), but scores remained stable after surgery (ß: 1.2, 95% CI: -3.2-5.6). Before surgery, patients with MI (n=36, 4%) were more disabled compared with patients without PMI and no adverse events (ß: 5.5, 95% CI: 0.3-10.8). At 6 months, patients with MI and patients without PMI but with adverse events worsened in disability score (ß: 11.2, 95% CI: 2.3-20.2; ß: 8.1, 95% CI: 3.0-13.2, respectively). Patients with clinically silent PMI did not change in disability score at 6 months (ß: 1.39, 95% CI: -4.50-7.29, P=0.642). CONCLUSIONS: Although patients with postoperative myocardial injury had higher preoperative self-reported disability, disability scores did not change at 6 months after surgery. However, patients experiencing myocardial infarction worsened in disability score after surgery.

Effect of a national guideline on postoperative troponin surveillance: a retrospective cohort study.

PURPOSE: We aimed to evaluate the effect of the 2017 Canadian Cardiovascular Society (CCS) guidelines on troponin surveillance after noncardiac surgery. METHODS: This was a single-centre, retrospective, observational study. Patients aged 40 yr or older undergoing intermediate- to high-risk elective noncardiac surgery between 2016 and 2021 were included. We compared the number and percentage of troponin tests ordered before and after the guidelines were published and compared patient characteristics, specifically cardiovascular comorbidity, using odds ratio's (OR) with 95% confidence intervals (CIs). Outcomes were myocardial injury, myocardial infarction (MI), and in-hospital mortality. RESULTS: The cohort included 36,386 patients and the median age was 63 yr. Between 2016 and 2018, troponin surveillance was done in 2,461 (13%) of the 19,046 patients, compared with 2,398 (14%) of the 17,340 patients who had surgery between 2019 and 2021 (OR, 1.08; 95% CI, 1.02 to 1.15). Patients who had surgery in the second period had less cardiovascular comorbidity; the adjusted OR for troponin surveillance was 1.14 (95% CI, 1.07 to 1.21). In the two periods, troponin was elevated in 561 (2.9%) and 470 (2.7%) patients, an MI was documented in 54 (0.3%) and 36 (0.2%) patients, and 95 (0.5%) and 73 (0.4%) patients died, respectively. After adjustment for baseline differences in the two periods, the ORs for MI and mortality were 0.83 (95% CI, 0.54 to 1.27) and 0.88 (95% CI, 0.64 to 1.19), respectively. CONCLUSION: Although the odds of troponin ordering were slightly but significantly higher after publication of the CCS guidelines, the odds for detecting an MI and for mortality did not change.

RéSUMé: OBJECTIF: Notre objectif était d'évaluer l'effet des lignes directrices 2017 de la Société canadienne de cardiologie (SCC) sur le monitorage de la troponine après une chirurgie non cardiaque. MéTHODE: Il s'agissait d'une étude observationnelle rétrospective monocentrique. Les patient·es âgé·es de 40 ans ou plus bénéficiant d'une chirurgie non cardiaque non urgente à risque intermédiaire à élevé entre 2016 et 2021 ont été inclus·es. Nous avons comparé le nombre et le pourcentage de tests de troponine prescrits avant et après la publication des lignes directrices et comparé les caractéristiques des patient·es, en particulier la comorbidité cardiovasculaire, en utilisant le rapport de cotes (RC) avec des intervalles de confiance (IC) à 95 %. Les critères d'évaluation comprenaient les lésions myocardiques, l'infarctus du myocarde (IM) et la mortalité hospitalière. RéSULTATS: La cohorte comprenait 36 386 personnes et l'âge médian était de 63 ans. Entre 2016 et 2018, le monitorage de la troponine a été réalisé chez 2461 (13 %) des 19 046 patient·es, contre 2398 (14 %) des 17 340 patient·es opéré·es entre 2019 et 2021 (RC, 1,08; IC 95%, 1,02 à 1,15). Les patient·es qui ont bénéficié d'une intervention chirurgicale au cours de la deuxième période présentaient moins de comorbidité cardiovasculaire; le RC ajusté pour le monitorage de la troponine était de 1,14 (IC 95 %, 1,07 à 1,21). Au cours des deux périodes, la troponine était élevée chez 561 (2,9 %) et 470 (2,7 %) patient·es, un IM a été documenté chez 54 (0,3 %) et 36 (0,2 %) patient·es, et 95 (0,5 %) et 73 (0,4 %) patient·es sont décédé·es, respectivement. Après ajustement pour tenir compte des différences initiales au cours des deux périodes, les RC pour l'IM et la mortalité étaient de 0,83 (IC 95 %, 0,54 à 1,27) et de 0,88 (IC 95 %, 0,64 à 1,19), respectivement. CONCLUSION: Bien que les probabilités de commande de troponine aient été légèrement mais significativement plus élevées après la publication des lignes directrices de la SCC, les probabilités de détection d'un IM et de mortalité n'ont pas changé.

Complications of Factor V Leiden in Adults Undergoing Noncardiac Surgical Procedures: A Systematic Review.

Factor V Leiden is the commonest hereditary prothrombotic allele, affecting 1% to 5% of the world's population. The objective of this study was to characterize the perioperative and postoperative outcomes of patients with Factor V Leiden compared to patients without a diagnosis of hereditary thrombophilia. This was a focused systematic review of studies including adult (>18 years) patients with Factor V Leiden (heterozygous or homozygous) undergoing noncardiac surgery. Included studies were either randomized controlled trials or observational. The primary clinical outcomes of interest were thromboembolic events occurring from the perioperative period up to 1 year postoperatively, defined as deep venous thrombosis, pulmonary embolism, or other clinically significant thrombosis occurring during or after a surgical procedure. Secondary outcomes included cerebrovascular events, cardiac events, death, transplant-related outcomes, and surgery-specific morbidity. Pediatric and obstetrical patients were excluded, as were case reports and case series. Databases searched included MEDLINE and EMBASE from inception until August 2021. Study bias was assessed through the CLARITY (Collaboration of McMaster University researchers) Risk of Bias tools, and heterogeneity through analysis of study design and end points, as well as the I 2 statistic with its confidence interval and the Q statistic. A total of 5275 potentially relevant studies were identified, with 115 having full text assessed for eligibility and 32 included in the systematic review. On the whole, the literature suggests that patients with Factor V Leiden have an increased risk of perioperative and postoperative thromboembolic events compared to patients without the diagnosis. Increased risk was also seen in relation to surgery-specific morbidity and transplant-related outcomes, particularly arterial thrombotic events. The literature did not support an increased risk for mortality, cerebrovascular, or cardiac complications. Limitations of the data include predisposition toward bias due in many study designs and small sample sizes across the majority of published studies. Variable outcome definitions and durations of patient follow-up across different surgical procedures resulted in high study heterogeneity precluding the effective use of meta-analysis. Factor V Leiden status may confer additional risk for surgery-related adverse outcomes. Large, adequately powered studies are required to accurately estimate the degree of this risk by zygosity.

Association of a Liberal Fasting Policy of Clear Fluids Before Surgery With Fasting Duration and Patient Well-being and Safety.

Importance: Current fasting guidelines for procedures under anesthesia are poorly implemented, leading to negative metabolic sequelae. Recent studies in children showed support of liberal clear fluid intake; adult physiology can support clear fluid intake, but implementation studies are lacking. Objective: To evaluate the successfulness of implementation of a liberal clear fluid policy with regard to fasting duration, well-being, and safety in adults scheduled for anesthesia. Design, Setting, and Participants: This was a quality improvement study conducted from January 2016 to July 2021 at a tertiary referral hospital in the Netherlands. Adults scheduled for nonemergency procedures under anesthesia were included in the study. Patients undergoing obstetrics procedures or those who were intubated preoperatively were excluded. Interventions: Stepwise introduction of a liberal fluid fasting policy, allowing for ingestion of clear fluids until arrival at the operating room. Main Outcomes and Measures: The primary outcome was change in fasting duration. Secondary outcomes were patient well-being, measured as preoperative thirst, amount of fluid ingested, postoperative nausea and vomiting (PONV), and administration of antiemetics. Safety was measured as incidence of regurgitation and aspiration (pneumonia). Results: Of the 76 451 patients (mean [SD] age, 56 [17] years; 39 530 male individuals [52%] 36 921) included in the study, 59 036 (78%) followed the standard policy, and 16 815 (22%) followed the liberal policy. Time series analysis showed an estimated fasting duration decrease of 3:07 hours (IQR, 1:36-7:22; P < .001) after implementation of the liberal policy. Postimplementation median (IQR) fasting duration was 1:20 (0:48-2:24) hours. The incidence of regurgitation changed from 18 (95% CI, 14-21) to 24 (95% CI, 17-32) in 10 000 patients, and the incidence of aspiration changed from 1.7 (95% CI, 0.6-2.7) to 2.4 (95% CI, 0.5-4.7) in 10 000 patients. In the liberal policy, thirst feelings decreased (37% [4982 of 8615] vs 46% [3373 of 7362]; P < .001). PONV incidence decreased from 10.6% (6339 of 59 636) to 9.4% (1587 of 16 815; P < .001) and antiemetic administration decreased from 11.0% (6538 of 59 636) to 9.5% (1592 of 16 815; P < .001). Conclusions and Relevance: Results of this quality improvement study suggest that a liberal fasting policy was associated with a clinically relevant reduction in fasting duration and improved patient well-being with regard to preoperative thirst and PONV. Although a slightly higher incidence of regurgitation could not be ruled out, wider implementation of such a policy may be advocated as results are still within the clinically accepted risks margins. Results suggest that surgical procedures in patients who drink clear fluids within 2 hours before anticipated anesthesia should not be postponed or canceled.

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.

Preoperative frailty and one-year functional recovery in elderly cardiac surgery patients.

OBJECTIVE: Frailty increases risk for morbidity and mortality after cardiac surgery. Its influence on functional outcome is largely unknown. We studied the association of frailty with health-related quality of life and disability after cardiac surgery. METHODS: A prospective 2-center observational cohort of 555 patients aged 70 years or more undergoing cardiac surgery. A comprehensive frailty assessment was performed before surgery based on 11 individual assessments in physical, mental, and social domains. Frailty was defined as at least 1 positive test in each domain. The primary outcome was health-related quality of life over 1 year, and the secondary outcomes were severe in-hospital complications and disability over 1 year. Adverse functional outcome was defined as the composite of a decreased health-related quality of life and disability. RESULTS: Physical frailty was most common (91%) compared with mental (39%) or social frailty (42%). Adverse functional outcome occurred in 257 patients (46%) and consisted of decreased physical health-related quality of life in 134 (24%), decreased mental health-related quality of life in 141 (25%), and disability in 120 (22%). Frailty was more common in patients with adverse functional outcome (29%) compared with patients without adverse functional outcome (16%, P < .001). Poor mobility, malnutrition, and polypharmacy were associated with a decreased health-related quality of life over time, whereas impaired physical functioning and higher self-rated health were related to increased health-related quality of life. Disability after cardiac surgery was associated with poor mobility, polypharmacy, dependent living, living alone, and lower self-rated mental health before surgery. CONCLUSIONS: Mobility, nutrition, medication use, physical functioning, and self-rated health before surgery are associated with health-related quality of life in elderly patients 1 year after cardiac surgery.

Definitions of low cardiac output syndrome after cardiac surgery and their effect on the incidence of intraoperative LCOS: A literature review and cohort study.

Objectives: Low cardiac output syndrome (LCOS) is a serious complication after cardiac surgery. Despite scientific interest in LCOS, there is no uniform definition used in current research and clinicians cannot properly compare different study findings. We aimed to collect the LCOS definitions used in literature and subsequently applied the definitions obtained to existing data to estimate their effect on the intraoperative LCOS incidences in adults, children and infants. Design: This is a literature review, followed by a retrospective cohort study. Setting: This is a single-institutional study from a university hospital in the Netherlands. Participants: Patients from all ages undergoing cardiac surgery with cardiopulmonary bypass between June 2011 and August 2018. Interventions: We obtained different definitions of LCOS used in the literature and applied these to data obtained from an anesthesia information management system to estimate intraoperative incidences of LCOS. We compared intraoperative incidences of LCOS in different populations based on age (infants, children and adults). Measurements and main results: The literature search identified 262 LCOS definitions, that were applied to intraoperative data from 7,366 patients. Using the 10 most frequently published LCOS definitions, the obtained incidence estimates ranged from 0.4 to 82% in infants, from 0.6 to 56% in children and from 1.5 to 91% in adults. Conclusion: There is an important variety in definitions used to describe LCOS. When applied to data obtained from clinical care, these different definitions resulted in large distribution of intraoperative LCOS incidence rates. We therefore advocate for standardization of the LCOS definition to improve clinical understanding and enable adequate comparison of outcomes and treatment effects both in daily care and in research.

Associations between intraoperative hypotension, duration of surgery and postoperative myocardial injury after noncardiac surgery: a retrospective single-centre cohort study.

BACKGROUND: Studies of intraoperative hypotension typically specify a blood pressure threshold associated with adverse outcomes. Such thresholds are likely to be study-biased, investigator-biased, or both. We hypothesised that a newly developed modelling method without a threshold, which is biologically more plausible than a threshold-based approach, would reveal a continuous association between exposure to intraoperative hypotension and adverse outcomes. METHODS: Single-centre, retrospective cohort study of subjects ≥60 yr old undergoing noncardiac surgery. We modelled intraoperative hypotension using three different approaches: (1) unweighted, (2) weighted for degree of hypotension (depth), and (3) weighted for duration of hypotension. The primary outcome was myocardial injury, defined as elevated troponin I (>60 ng L-1) measured during the first 3 days after surgery. The associations between the three models, postoperative myocardial injury, and mortality (secondary outcome) were reported as penalised adjusted odds ratios (ORs) scaled between the 75th and 25th percentiles. RESULTS: Myocardial injury occurred in 1812/15 452 (12%) procedures, with 554/15 452 (3.6%) procedures resulting in death before discharge from hospital. The unweighted lower blood pressure measure (OR: 0.26, 95% confidence interval [CI]: 0.12-0.53) and the depth-weighted measure (OR: 4.4, 95% CI: 2.6-7.4) were associated with myocardial injury. The duration-weighted measure was not associated with myocardial injury (OR: 0.89, 95% CI: 0.61-1.3). The unweighted measure (OR 0.08, 95% CI: 0.01-0.40) and the depth-weighted measure (OR: 12, 95% CI, 3.8-35) were associated with in-hospital mortality, but not the duration-weighted measure (OR: 1.3, 95% CI: 0.53-3.0). CONCLUSIONS: Intraoperative hypotension appears to have a graded association with postoperative myocardial injury and mortality, with depth appearing to contribute more than duration.

Outlying End-Tidal Carbon Dioxide During General Anesthesia Is Associated With Postoperative Pulmonary Complications: A Multicenter Retrospective Observational Study From US Hospitals Between 2010 and 2017.

BACKGROUND: Postoperative pulmonary complications (PPCs) occur in up to 33% of patients who undergo noncardiothoracic surgery. Emerging evidence suggests that permissive hypercapnia may reduce the risk of lung injury. We hypothesized that higher intraoperative end-tidal carbon dioxide (Etco2) concentrations would be associated with a decreased risk of PPCs. METHODS: This retrospective, observational, multicenter study included patients undergoing general anesthesia for noncardiothoracic procedures (January 2010-December 2017). The primary outcome was PPC within 30 postoperative days. Secondary outcomes were PPC within 1 week, postoperative length of stay, and inhospital 30-day mortality. The association between these outcomes, median Etco2, and 4 time-weighted average area-under-the-curve (TWA-AUC) thresholds (<28, <35, <45, and >45 mm Hg) was explored using a multivariable mixed-effect model and by plotting associated risks. RESULTS: Among 143,769 cases across 11 hospitals, 10,276 (7.1%) experienced a PPC. When compared to a baseline median Etco2 of 35 to 40 mm Hg, a median Etco2 >40 mm Hg was associated with an increase in PPCs within 30 days (median Etco2, 40-45 mm Hg; adjusted OR, 1.16 [99% confidence interval {CI}, 1.00-1.33]; P value = .008 and median Etco2, >45 mm Hg; OR, 1.64 [99% CI, 1.33-2.02]; P value < .001). The occurrence of any Etco2 value <28 mm Hg (ie, a positive TWA-AUC < 28 mm Hg) was associated with PPCs (OR, 1.40 [95% CI, 1.33-1.49]; P value < .001), mortality, and length of stay. Any Etco2 value >45 mm Hg (ie, a positive TWA-AUC >45 mm Hg) was also associated with PPCs (OR, 1.24 [95% CI, 1.17-1.31]; P < .001). The Etco2 range with the lowest incidence of PPCs was 35 to 38 mm Hg. CONCLUSIONS: Both a very low (<28 mm Hg) and a high Etco2 (>45 mm Hg) were associated with PPCs within 30 days. The lowest PPC incidence was found in patients with an Etco2 of 35 to 38 mm Hg. Prospective studies are needed to clarify the relationship between postoperative PPCs and intraoperative Etco2.

Autonomous patient consent for anaesthesia without preoperative consultation: a qualitative feasibility study including low-risk procedures.

Background: Informed consent for anaesthesia is mandatory and requires provision of information and subsequent consent during consultation between anaesthesiologist and patient. Although information can be provided in an electronic format, it is unknown whether this a valid substitute for a consultation. We explored whether provision of digital information is equivalent to oral consultation and whether it enables patients to give electronic informed consent (e-consent) for anaesthesia. Methods: Qualitative feasibility study using semi-structured interviews in 20 low-risk adults scheduled for minor surgery under general anaesthesia or procedural sedation at a university hospital. Data were analysed using a thematic content analysis approach. During the interviews, patients followed an application that provides information and subsequent e-consenting. Results: The mean age was 50 yr and patients had good digital skills. Fifteen patients (75%) had previous experience of anaesthesia. The digital application provided enough information for all patients, but eight (40%) preferred consultation with an anaesthesiologist, mainly for personal contact. Patients had different information needs, with previous experiences leading to lower information needs. Nineteen patients had sufficient information to consent autonomously. Most patients considered separate anaesthesia consent superfluous to the surgical consent. Conclusion: The digital application provided sufficient information and patients valued the information offered and the advantage of processing information at their own pace. This information made patients feel empowered to autonomously consent to anaesthesia without consultation. Remarkably, consent for anaesthesia was considered unimportant, because patients felt they had 'no choice' if they wanted to undergo surgery.

Critical oxygen delivery threshold during cardiopulmonary bypass in older cardiac surgery patients with increased frailty risk.

OBJECTIVES: Older patients have a higher cardiac surgery-associated acute kidney injury (CSA-AKI) related mortality. Low oxygen delivery (DO2) during cardiopulmonary bypass (CPB) is a risk factor for CSA-AKI, but critical DO2 thresholds for older patients are unknown. This study investigated critical DO2 thresholds for CSA-AKI in patients ≥70 years undergoing on-pump cardiac surgery. METHODS: Patients were enrolled from July 2015 until August 2017. CPB data from 432 patients were collected, and DO2 values were calculated per minute. The primary outcome was CSA-AKI. The association between DO2 and CSA-AKI was analysed with multivariable regression analysis. Multiple DO2 thresholds were analysed. The association between CSA-AKI and the area below the DO2 thresholds (DO2 deficit) was evaluated, as was the association between frailty and CSA-AKI. RESULTS: CSA-AKI occurred in 63 (14.6%) patients. Mean and nadir (lowest) DO2 values were lower in patients with CSA-AKI (283 vs 312 ml/min/m2; P-value <0.001 and 238 vs 270 ml/min/m2; P-value <0.001, respectively). The adjusted relative risk for CSA-AKI was 1.006 [99% confidence interval (CI) 1.001-1.012] per ml/min/m2 nadir DO2 decrease. The critical DO2 threshold was 270 ml/min/m2 [adjusted relative risk 2.06 (99% CI 1.33-2.80)]. The DO2 deficit below 270 ml/min/m2 was associated with CSA-AKI [adjusted relative risk 2.84 (99% CI 1.87-3.81)]. No association between frailty and CSA-AKI was found (P = 0.82). CONCLUSIONS: Low DO2 increased the risk for CSA-AKI in older patients who had cardiac surgery. A critical DO2 threshold of 270 ml/min/m2 was applicable for frail and non-frail patients. The efficacy of a DO2 >270 ml/min/m2 to reduce CSA-AKI in older patients needs further evaluation.

The comparative and added prognostic value of biomarkers to the Revised Cardiac Risk Index for preoperative prediction of major adverse cardiac events and all-cause mortality in patients who undergo noncardiac surgery.

BACKGROUND: The Revised Cardiac Risk Index (RCRI) is a widely acknowledged prognostic model to estimate preoperatively the probability of developing in-hospital major adverse cardiac events (MACE) in patients undergoing noncardiac surgery. However, the RCRI does not always make accurate predictions, so various studies have investigated whether biomarkers added to or compared with the RCRI could improve this. OBJECTIVES: Primary: To investigate the added predictive value of biomarkers to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. Secondary: To investigate the prognostic value of biomarkers compared to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. Tertiary: To investigate the prognostic value of other prediction models compared to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. SEARCH METHODS: We searched MEDLINE and Embase from 1 January 1999 (the year that the RCRI was published) until 25 June 2020. We also searched ISI Web of Science and SCOPUS for articles referring to the original RCRI development study in that period. SELECTION CRITERIA: We included studies among adults who underwent noncardiac surgery, reporting on (external) validation of the RCRI and: - the addition of biomarker(s) to the RCRI; or - the comparison of the predictive accuracy of biomarker(s) to the RCRI; or - the comparison of the predictive accuracy of the RCRI to other models. Besides MACE, all other adverse outcomes were considered for inclusion. DATA COLLECTION AND ANALYSIS: We developed a data extraction form based on the CHARMS checklist. Independent pairs of authors screened references, extracted data and assessed risk of bias and concerns regarding applicability according to PROBAST. For biomarkers and prediction models that were added or compared to the RCRI in ≥ 3 different articles, we described study characteristics and findings in further detail. We did not apply GRADE as no guidance is available for prognostic model reviews. MAIN RESULTS: We screened 3960 records and included 107 articles.   Over all objectives we rated risk of bias as high in ≥ 1 domain in 90% of included studies, particularly in the analysis domain. Statistical pooling or meta-analysis of reported results was impossible due to heterogeneity in various aspects: outcomes used, scale by which the biomarker was added/compared to the RCRI, prediction horizons and studied populations.  Added predictive value of biomarkers to the RCRI Fifty-one studies reported on the added value of biomarkers to the RCRI. Sixty-nine different predictors were identified derived from blood (29%), imaging (33%) or other sources (38%). Addition of NT-proBNP, troponin or their combination improved the RCRI for predicting MACE (median delta c-statistics: 0.08, 0.14 and 0.12 for NT-proBNP, troponin and their combination, respectively). The median total net reclassification index (NRI) was 0.16 and 0.74 after addition of troponin and NT-proBNP to the RCRI, respectively. Calibration was not reported. To predict myocardial infarction, the median delta c-statistic when NT-proBNP was added to the RCRI was 0.09, and 0.06 for prediction of all-cause mortality and MACE combined. For BNP and copeptin, data were not sufficient to provide results on their added predictive performance, for any of the outcomes. Comparison of the predictive value of biomarkers to the RCRI  Fifty-one studies assessed the predictive performance of biomarkers alone compared to the RCRI. We identified 60 unique predictors derived from blood (38%), imaging (30%) or other sources, such as the American Society of Anesthesiologists (ASA) classification (32%). Predictions were similar between the ASA classification and the RCRI for all studied outcomes. In studies different from those identified in objective 1, the median delta c-statistic was 0.15 and 0.12 in favour of  BNP and NT-proBNP alone, respectively, when compared to the RCRI, for the prediction of MACE. For C-reactive protein, the predictive performance was similar to the RCRI. For other biomarkers and outcomes, data were insufficient to provide summary results. One study reported on calibration and none on reclassification. Comparison of the predictive value of other prognostic models to the RCRI   Fifty-two articles compared the predictive ability of the RCRI to other prognostic models. Of these, 42% developed a new prediction model, 22% updated the RCRI, or another prediction model, and 37% validated an existing prediction model. None of the other prediction models showed better performance in predicting MACE than the RCRI. To predict myocardial infarction and cardiac arrest, ACS-NSQIP-MICA had a higher median delta c-statistic of 0.11 compared to the RCRI. To predict all-cause mortality, the median delta c-statistic was 0.15 higher in favour of ACS-NSQIP-SRS compared to the RCRI. Predictive performance was not better for CHADS2, CHA2DS2-VASc, R2CHADS2, Goldman index, Detsky index or VSG-CRI compared to the RCRI for any of the outcomes. Calibration and reclassification were reported in only one and three studies, respectively. AUTHORS' CONCLUSIONS: Studies included in this review suggest that the predictive performance of the RCRI in predicting MACE is improved when NT-proBNP, troponin or their combination are added. Other studies indicate that BNP and NT-proBNP, when used in isolation, may even have a higher discriminative performance than the RCRI. There was insufficient evidence of a difference between the predictive accuracy of the RCRI and other prediction models in predicting MACE. However, ACS-NSQIP-MICA and ACS-NSQIP-SRS outperformed the RCRI in predicting myocardial infarction and cardiac arrest combined, and all-cause mortality, respectively. Nevertheless, the results cannot be interpreted as conclusive due to high risks of bias in a majority of papers, and pooling was impossible due to heterogeneity in outcomes, prediction horizons, biomarkers and studied populations. Future research on the added prognostic value of biomarkers to existing prediction models should focus on biomarkers with good predictive accuracy in other settings (e.g. diagnosis of myocardial infarction) and identification of biomarkers from omics data. They should be compared to novel biomarkers with so far insufficient evidence compared to established ones, including NT-proBNP or troponins. Adherence to recent guidance for prediction model studies (e.g. TRIPOD; PROBAST) and use of standardised outcome definitions in primary studies is highly recommended to facilitate systematic review and meta-analyses in the future.

Variation in perioperative cerebral and hemodynamic monitoring during carotid endarterectomy.

BACKGROUND: Hemodynamic disturbances cause half of the perioperative strokes following carotid endarterectomy (CEA). Guidelines strongly recommend strict pre- and postoperative blood pressure (BP) monitoring in CEA patients, but do not provide firm practical recommendations. Although in the Netherlands 50 centres perform CEA, no national protocol on perioperative hemodynamic, and cerebral monitoring exists. To assess current monitoring policies of all Dutch CEA-centres, a national survey was conducted. METHODS: Between May and July 2017 all 50 Dutch CEA-centres were invited to complete a 42-question survey addressing perioperative hemodynamic and cerebral monitoring during CEA. Nonresponders received a reminder after 1 and 2 months. By November 2017 the survey was completed by all centres. RESULTS: Preoperative baseline BP was based on a single bilateral BP-measurement at the outpatient-clinic in the majority of centres (n = 28). In 43 centres (86%) pre-operative monitoring (transcranial Doppler (TCD, n = 6), electroencephalography (EEG, n = 11), or TCD + EEG (n = 26)) was performed as a baseline reference. Intraoperatively, large diversity for type of anaesthesia (general: 45 vs. local [LA]:5) and target systolic BP (>100 mm hg - 160 mm hg [n = 12], based on preoperative outpatient-clinic or admission BP [n = 18], other [n = 20]) was reported. Intraoperative cerebral monitoring included EEG + TCD (n = 28), EEG alone (n = 13), clinical neurological examination with LA (n = 5), near-infrared spectroscopy with stump pressure (n = 1), and none due to standard shunting (n = 3). Postoperatively, significant variation was reported in standard duration of admission at a recovery or high-care unit (range 3-48 hr, mean:12 hr), maximum accepted systolic BP (range >100 mm hg - 180 mm Hg [n = 32]), postoperative cerebral monitoring (standard TCD [n = 16], TCD on indication [n = 5] or none [n = 24]) and in timing of postoperative cerebral monitoring (range directly postoperative - 24 hr postoperative; median 3 hr). CONCLUSIONS: In Dutch centres performing CEA the perioperative hemodynamic and cerebral monitoring policies are widely diverse. Diverse policies may theoretically lead to over- or under treatment. The results of this national audit may serve as the baseline dataset for development of a standardized and detailed (inter)national protocol on perioperative hemodynamic and cerebral monitoring during CEA.