Perioperative copeptin: predictive value and risk stratification in patients undergoing major noncardiac surgery-a prospective observational cohort study.

PURPOSE: Biomarkers can aid in perioperative risk stratification. While preoperative copeptin has been associated with adverse events, intraoperative information is lacking and this association may rather reflect a baseline risk. Knowledge about correlations between postoperative copeptin measurements and clinically relevant outcomes is scarce. We examined the association of perioperative copeptin concentrations with postoperative all-cause mortality and/or major adverse cardiac and cerebrovascular events (MACCE) at 12 months and 30 days as well as with perioperative myocardial injury (PMI). METHODS: We conducted a prospective observational cohort study of adults undergoing noncardiac surgery with intermediate to high surgical risk in Basel, Switzerland, and Düsseldorf, Germany from February 2016 to December 2020. We measured copeptin and cardiac troponin before surgery, immediately after surgery (0 hr) and once between the second and fourth postoperative day (POD 2-4). RESULTS: A primary outcome event of a composite of all-cause mortality and/or MACCE at 12 months occurred in 48/502 patients (9.6%). Elevated preoperative copeptin (> 14 pmol·L-1), immediate postoperative copeptin (> 90 pmol·L-1), and copeptin on POD 2-4 (> 14 pmol·L-1) were associated with lower one-year MACCE-free and/or mortality-free survival (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.62 to 5.2; HR, 2.07; 95% CI, 1.17 to 3.66; and HR, 2.47; 95% CI, 1.36 to 4.46, respectively). Multivariable analysis continued to show an association for preoperative and postoperative copeptin on POD 2-4. Furthermore, elevated copeptin on POD 2-4 showed an association with 30-day MACCE-free survival (HR, 2.15; 95% CI, 1.18 to 3.91). A total of 64 of 489 patients showed PMI (13.1%). Elevated preoperative copeptin was not associated with PMI, while immediate postoperative copeptin was modestly associated with PMI. CONCLUSION: The results of the present prospective observational cohort study suggest that perioperative copeptin concentrations can help identify patients at risk for all-cause mortality and/or MACCE. Other identified risk factors were revised cardiac risk index, body mass index, surgical risk, and preoperative hemoglobin. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02687776); first submitted 9 February 2016.

RéSUMé: OBJECTIF: Les biomarqueurs peuvent aider à la stratification du risque périopératoire. Bien que la copeptine préopératoire ait été associée à des événements indésirables, les informations peropératoires font défaut; plutôt, cette association pourrait refléter un risque de base. Les connaissances sur les corrélations entre les mesures postopératoires de la copeptine et les résultats cliniquement pertinents sont rares. Nous avons examiné l'association entre les concentrations de copeptine périopératoires et la mortalité postopératoire toutes causes confondues et/ou les événements indésirables cardiaques et cérébrovasculaires majeurs (EICCM/MACCE) à 12 mois et 30 jours ainsi qu'en cas de lésion myocardique périopératoire (LMP/PMI). MéTHODE: Nous avons réalisé une étude de cohorte observationnelle prospective d'adultes bénéficiant d'une chirurgie non cardiaque à risque chirurgical intermédiaire à élevé à Bâle, en Suisse, et à Düsseldorf, en Allemagne, de février 2016 à décembre 2020. Nous avons mesuré la copeptine et la troponine cardiaque avant la chirurgie, immédiatement après la chirurgie (0 h) et une fois entre le deuxième et le quatrième jour postopératoire (JPO 2-4). RéSULTATS: Un événement constituant un critère d'évaluation principal d'un composite de mortalité toutes causes confondues et/ou de MACCE à 12 mois est survenu chez 48/502 patient·es (9,6 %). Une élévation de la copeptine préopératoire (> 14 pmol·L−1), de la copeptine postopératoire immédiate (> 90 pmol·L−1) et de la copeptine aux JPO 2 à 4 (> 14 pmol·L−1) était associée à une survie sans MACCE et/ou sans mortalité à un an plus faible (rapport de risque [RR], 2,89; intervalle de confiance [IC] à 95 %, 1,62 à 5,2; RR, 2,07; IC 95 %, 1,17 à 3,66; et RR, 2,47; IC 95 %, 1,36 à 4,46, respectivement). L'analyse multivariée a aussi montré une association entre la copeptine préopératoire et postopératoire aux JPO 2 à 4. De plus, un taux élevé de copeptine aux JPO 2 à 4 a montré une association avec la survie sans MACCE à 30 jours (RR, 2,15; IC 95 %, 1,18 à 3,91). Au total, 64 des 489 patient·es présentaient une LMP (13,1 %). Un taux élevé de copeptine préopératoire n'a pas été associé à la LMP, tandis que la copeptine postopératoire immédiate était modestement associée à la LMP. CONCLUSION: Les résultats de la présente étude de cohorte observationnelle prospective suggèrent que les concentrations périopératoires de copeptine peuvent aider à identifier les personnes à risque de mortalité toutes causes confondues et/ou de MACCE. Les autres facteurs de risque identifiés étaient l'indice de risque cardiaque révisé, l'indice de masse corporelle, le risque chirurgical et l'hémoglobine préopératoire. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT02687776); première soumission le 9 février 2016.

Rotational Thromboelastometry Values After On-Pump Cardiac Surgery - A Retrospective Cohort Study.

BACKGROUND: Viscoelastic coagulation monitoring is recommended for coagulation management after cardiac surgery, but optimum target values are poorly defined. AIMS: To determine "to-be-expected" values in rotational thromboelastometry (ROTEM) after heparin reversal, to correlate ROTEM parameters with fibrinogen levels and platelet count, and to estimate the effect of hemoglobin levels on these measurements. METHODS: We retrospectively analyzed 571 consecutive adult patients undergoing cardiac surgery with cardiopulmonary bypass from 12/2018 to 08/2020. ROTEM and conventional laboratory measurements were performed 5 to 10 minutes after protamine administration. RESULTS: Clotting times in EXTEM, INTEM, and FIBTEM were significantly prolonged (72.6%, 96.1%, and 31.8% above reference ranges, respectively). Clot firmness parameters in EXTEM and INTEM were relevantly reduced (7.9% to 14.4% and 9.1% to 32.3% below the reference ranges, respectively). There was an excellent linear correlation of FIBTEM amplitude after 10 min (A10) and of maximal clot firmness (MCF) with fibrinogen concentrations (r = .81 and .80). Areas under receiver operating characteristic (AUROC) for identifying hypofibrinogenemia <1.5 g/L were between .80 and .87. No effect of hematocrit was observed. We also found a linear correlation of EXTEM, INTEM, and EXTEM-FIBTEM at both A10 and MCF with platelet counts (.32 to .68). The AUROCs for identifying thrombocytopenia (<100,000/µL) were .79 to .84, and were greater for A10 than for MCF measurements (P=.074, .001, and <.001, respectively). CONCLUSIONS: "To-be-expected" ROTEM values after CPB are different from the published reference ranges. ROTEM parameters might allow for reliable estimation of fibrinogen level and platelet count without being influenced by hematocrit.

Quantification of metabolic equivalents (METs) by the MET-REPAIR questionnaire: A validation study in patients with a high cardiovascular burden.

STUDY OBJECTIVE: Quantifying functional capacity is a core component of preoperative cardiovascular risk assessment. Lower metabolic equivalents (METs) are associated with higher morbidity/mortality in non-surgical and surgical populations. However, actually measuring METs preoperatively is rare. We sought to determine the correlation of self-reported METs using the questionnaire of the MET: REevaluation for Perioperative cArdIac Risk (MET-REPAIR) study and objectively measured METs by gold-standard cardiopulmonary exercise testing (CPET). DESIGN: Single-center prospective validation study. SETTING: University hospital. PATIENTS: We enrolled adult patients aged ≥45 undergoing out-patient cardiac rehabilitation. INTERVENTION: Patients completed the MET-REPAIR Questionnaire and the Duke Activity Status Index (DASI), had blood samples drawn, and underwent undergoing routine CPET. MEASUREMENTS: We compared measured METs by CPET to 1) self-reported METs (the MET-REPAIR Questionnaire), 2) the DASI score, 3) stand-alone questions, and 4) N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations. MAIN RESULTS: 140 patients were recruited. Measured METs by CPET correlated with 1) self-reported METs by the MET-REPAIR Questionnaire (ρ = 0.489, "fair"), 2) self-reported physical activity by the DASI (ρ = 0.487, "fair"), 3) the self-reported continual stair climbing ability (one of the stand-alone questions; ρ = 0.587, "fair") and 4) NT-proBNP concentrations (ρ = -0.353, "poor"). The area under the receiver operating characteristic curve (AUROC) for the ability to perform more than 4 METs were: highest for flights of stairs (0.841 [95%CI 0.735-0.948], p < 0.05 to rest, optimum: 3 flights), not significantly different between MET-REPAIR Questionnaire and DASI (0.666 [95%CI 0.551-0.781], optimum: 6 METs vs. 0.704 [95%CI 0.578-0.829], optimum: 32.2 points or 6.7 METs, p = 0.405), and not significant for NT-proBNP: (0.623 [95%CI 0.483-0.763]). CONCLUSIONS: The MET-REPAIR Questionnaire correlates with measured METs; all utilized forms of self-reported physical activity overestimate measured METs. NT-proBNP correlates poorly with measured METs.

Peri-operative copeptin concentrations and their association with myocardial injury after vascular surgery: A prospective observational cohort study.

BACKGROUND: Copeptin levels in conjunction with cardiac troponin may be used to rule out early myocardial infarction in patients presenting with chest pain. Raised pre-operative copeptin has been shown to be associated with postoperative cardiac events. However, very little is known about the peri-operative time course of copeptin or the feasibility of very early postoperative copeptin measurement to diagnose or rule-out myocardial injury. OBJECTIVES: In this preparatory analysis for a larger trial, we sought to examine the time course of peri-operative copeptin and identify the time at which concentrations returned to pre-operative levels. Second, in an explorative analysis, we sought to examine the association of copeptin in general and at various time points with myocardial injury occurring within the first 48 h. DESIGN: Preparatory analysis of a prospective, observational cohort study. SETTING: Single university centre from February to July 2016. PATIENTS: A total of 30 consecutive adults undergoing vascular surgery. INTERVENTION: Serial peri-operative copeptin measurements. MAIN OUTCOME MEASURE: We measured copeptin concentrations before and immediately after surgery (0 h), then at 2, 4, 6 and 8 h after surgery and on the first and second postoperative day. Postoperative concentrations were compared with pre-operative levels with a Wilcoxon signed-rank test. Second, we explored an association between postoperative copeptin concentrations and myocardial injury by the second postoperative day. Myocardial injury was defined as a 5 ng l increase between pre-operative and postoperative high-sensitivity cardiac troponin T with an absolute peak of at least 20 ng l. RESULTS: Immediate postoperative copeptin concentrations (median [interquartile range]) increased nearly eight-fold from pre-operative values (8.5 [3.6 to 13.8] to 64.75 pmol l [29.6 to 258.7]; P < 0.001). Copeptin concentrations remained elevated until returning to baseline on the second postoperative day. Postoperative copeptin was significantly higher in patients experiencing myocardial injury than in those who did not (P = 0.02). The earliest most promising single time point for diagnosis may be immediately after surgery (0 h). The receiver-operating characteristics curve for immediate postoperative copeptin and myocardial injury by the second postoperative day was 0.743 (95% confidence interval 0.560 to 0.926). CONCLUSION: Copeptin concentrations are greatly increased after vascular surgery and remain so until the 2nd postoperative day. Postoperative copeptin concentrations appear to be higher in patients who go on to exhibit myocardial injury. Immediate postoperative copeptin concentrations show promise for eliminating or identifying those at risk of myocardial injury. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02687776, Mauermann/Lurati Buse.