Pathological findings associated with the updated European Society of Cardiology 2022 guidelines for preoperative cardiac testing: an observational cohort modelling study.

BACKGROUND: In 2022, the European Society of Cardiology updated guidelines for preoperative evaluation. The aims of this study were to quantify: (1) the impact of the updated recommendations on the yield of pathological findings compared with the previous guidelines published in 2014; (2) the impact of preoperative B-type natriuretic peptide (NT-proBNP) use for risk estimation on the yield of pathological findings; and (3) the association between 2022 guideline adherence and outcomes. METHODS: This was a secondary analysis of MET-REPAIR, an international, prospective observational cohort study (NCT03016936). Primary endpoints were reduced ejection fraction (EF<40%), stress-induced ischaemia, and major adverse cardiovascular events (MACE). The explanatory variables were class of recommendations for transthoracic echocardiography (TTE), stress imaging, and guideline adherence. We conducted second-order Monte Carlo simulations and multivariable regression. RESULTS: In total, 15,529 patients (39% female, median age 72 [inter-quartile range: 67-78] yr) were included. The 2022 update changed the recommendation for preoperative TTE in 39.7% patients, and for preoperative stress imaging in 12.9% patients. The update resulted in missing 1 EF <40% every 3 fewer conducted TTE, and in 4 additional stress imaging per 1 additionally detected ischaemia events. For cardiac stress testing, four more investigations were performed for every 1 additionally detected ischaemia episodes. Use of NT-proBNP did not improve the yield of pathological findings. Multivariable regression analysis failed to find an association between adherence to the updated guidelines and MACE. CONCLUSIONS: The 2022 update for preoperative cardiac testing resulted in a relevant increase in tests receiving a stronger recommendation. The updated recommendations for TTE did not improve the yield of pathological cardiac testing.

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.

Risk assessment for major adverse cardiovascular events after noncardiac surgery using self-reported functional capacity: international prospective cohort study.

BACKGROUND: Guidelines endorse self-reported functional capacity for preoperative cardiovascular assessment, although evidence for its predictive value is inconsistent. We hypothesised that self-reported effort tolerance improves prediction of major adverse cardiovascular events (MACEs) after noncardiac surgery. METHODS: This is an international prospective cohort study (June 2017 to April 2020) in patients undergoing elective noncardiac surgery at elevated cardiovascular risk. Exposures were (i) questionnaire-estimated effort tolerance in metabolic equivalents (METs), (ii) number of floors climbed without resting, (iii) self-perceived cardiopulmonary fitness compared with peers, and (iv) level of regularly performed physical activity. The primary endpoint was in-hospital MACE consisting of cardiovascular mortality, non-fatal cardiac arrest, acute myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care or resulting in a prolongation of stay on ICU/intermediate care (≥24 h). Mixed-effects logistic regression models were calculated. RESULTS: In this study, 274 (1.8%) of 15 406 patients experienced MACE. Loss of follow-up was 2%. All self-reported functional capacity measures were independently associated with MACE but did not improve discrimination (area under the curve of receiver operating characteristic [ROC AUC]) over an internal clinical risk model (ROC AUCbaseline 0.74 [0.71-0.77], ROC AUCbaseline+4METs 0.74 [0.71-0.77], ROC AUCbaseline+floors climbed 0.75 [0.71-0.78], AUCbaseline+fitnessvspeers 0.74 [0.71-0.77], and AUCbaseline+physical activity 0.75 [0.72-0.78]). CONCLUSIONS: Assessment of self-reported functional capacity expressed in METs or using the other measures assessed here did not improve prognostic accuracy compared with clinical risk factors. Caution is needed in the use of self-reported functional capacity to guide clinical decisions resulting from risk assessment in patients undergoing noncardiac surgery. CLINICAL TRIAL REGISTRATION: NCT03016936.

Preoperative anaemia in cardiac surgery: preoperative assessment, treatment and outcome.

Preoperative anaemia is common and associated with increased postoperative morbidity and mortality after cardiac surgery. These findings are supported by a large Dutch cohort study including >35 000 patients published in this issue of the British Journal of Anaesthesia. Timely diagnosis and preoperative anaemia treatment seem to be reasonable targets for perioperative risk stratification and modification. However, implementation of anaemia therapy into clinical routines remains challenging, and evidence for improved outcome is currently limited.

Assessing Left Ventricular Early Diastolic Velocities With Tissue Doppler and Speckle Tracking by Transesophageal and Transthoracic Echocardiography.

BACKGROUND: Assessing diastolic dysfunction is essential and should be part of every routine echocardiography examination. However, clinicians routinely observe lower mitral annular velocities by transesophageal echocardiography (TEE) under anesthesia than described by awake transthoracic echocardiography (TTE). It would be important to know whether this difference persists under constant loading conditions. We hypothesized that mean early diastolic mitral annular velocity, measured by tissue Doppler imaging (TDI, JOURNAL/asag/04.03/00000539-202105000-00029/inline-graphic1/v/2021-04-15T211206Z/r/image-tiff) would be different in the midesophageal 4-chamber (ME 4Ch) than in the apical 4-chamber (AP 4Ch) view under unchanged or constant loading conditions. Secondarily we examined (1) JOURNAL/asag/04.03/00000539-202105000-00029/inline-graphic2/v/2021-04-15T211206Z/r/image-tiff in an alternative transesophageal view with presumed superior Doppler beam alignment, the deep transgastric view (DTG), compared to those in the AP 4Ch, and (2) early diastolic speckle tracking-based strain rate (JOURNAL/asag/04.03/00000539-202105000-00029/inline-graphic3/v/2021-04-15T211206Z/r/image-tiff), in the ME 4Ch and in the AP 4Ch. METHODS: Twenty-five consecutive adult patients undergoing on-pump cardiac surgery from February 2017 to July 2017 were included. Both TTE and TEE measurements were obtained under anesthesia in a randomized order in the AP 4Ch, ME 4Ch, and DTG views. Within-patient average values were compared by paired t tests with a Bonferroni adjustment. Box plots, correlation, and agreement by Bland-Altman were examined for all 3 comparisons. A second echocardiographer independently acquired and analyzed images; images were reanalyzed after 4 weeks. Image quality and reproducibility were also reported. RESULTS: Averaged JOURNAL/asag/04.03/00000539-202105000-00029/inline-graphic4/v/2021-04-15T211206Z/r/image-tiff measurements were lower in the ME 4Ch than in the AP 4Ch (6.6 ± 1.7 cm/s vs 7.0 ± 1.5 cm, P = .028; within-patient difference mean ± standard deviation: 0.6 ± 1.2 cm/s). An alternative TEE view for JOURNAL/asag/04.03/00000539-202105000-00029/inline-graphic5/v/2021-04-15T211206Z/r/image-tiff, the DTG, also exhibited lower mean values (6.0 ± 1.6 cm/s, P = .006; within-patient difference mean ± standard deviation: 1.1 ± 1.8 cm/s). JOURNAL/asag/04.03/00000539-202105000-00029/inline-graphic6/v/2021-04-15T211206Z/r/image-tiff strain rate showed a low degree of bias, but greater variability (ME 4Ch: 0.87 ± 0.32%/s vs AP 4Ch: 0.73 ± 0.18%/s, P = .078; within-patient difference mean ± standard deviation: -0.1 ± 0.2%/s). CONCLUSIONS: This study confirms that TEE modestly underestimates JOURNAL/asag/04.03/00000539-202105000-00029/inline-graphic7/v/2021-04-15T211206Z/r/image-tiff but not to a clinically relevant extent. While JOURNAL/asag/04.03/00000539-202105000-00029/inline-graphic8/v/2021-04-15T211206Z/r/image-tiff in the DTG is not a promising alternative, the future role for speckle tracking-based early diastolic strain rate is unknown.

Pain Response to Open Label Placebo in Induced Acute Pain in Healthy Adult Males.

BACKGROUND: Open label placebos with patient education are effective in reducing chronic pain, and recent studies on their effect on pain have established interest in this field. Nevertheless, data on their effect on acute pain are scarce, and on hyperalgesia and allodynia, absent. This study assessed the effect of open label placebos on acute pain in healthy adult males and the influence of placebo education. METHODS: Thirty-two healthy males were included in this prospective, randomized, assessor-blinded crossover, single-center study assessing pain intensities (via numeric rating scale), area of hyperalgesia (von Frey filament), and allodynia (dry cotton swab) in a pain model utilizing intracutaneous electrical stimulation. The authors compared the effect of intravenous open label placebo on pain compared to no treatment. The authors further examined the effect of placebo on hyperalgesia and allodynia, and the influence of education (short vs. detailed) before placebo application. Saliva cortisol concentrations were also measured. RESULTS: Pain ratings (median, first to third quartile) were 21% lower during placebo treatment compared to no treatment, 4.0 (3.2 to 4.9) versus 5.1 (4.7 to 5.4), respectively (P = 0.001). The areas of hyperalgesia and allodynia were lower during placebo treatment compared to no treatment (hyperalgesia, 30 cm [17 to 47] vs. 55 cm [42 to 68], P = 0.003; allodynia, 24 cm [11 to 39] vs. 45 cm [31 to 62], P = 0.007). This corresponds to reductions of 47%. The extent of placebo education had no effect on pain. Saliva cortisol decreased significantly over time and was under the limit of detectability in the majority of participants in postbaseline measurements in both treatment branches. Baseline cortisol was not associated with the placebo effect or strength applied of current to reach defined pain ratings. CONCLUSIONS: Open label placebos might play a role in multimodal analgesic concepts.

Right Ventricular Systolic Assessment by Transesophageal Versus Transthoracic Echocardiography: Displacement, Velocity, and Myocardial Deformation.

OBJECTIVE: First, to compare tricuspid annular displacement and velocity in transthoracic and transesophageal echocardiography (TTE, TEE) using conventional angle-dependent technologies. Second, to evaluate both alternative TEE views as well as an alternative technology (speckle tracking) for overcoming proposed differences in TTE and TEE. DESIGN: Prospective, comparative, cross-over study with a randomized order of image acquisition. SETTING: University hospital. PARTICIPANTS: Adults undergoing cardiac surgery. INTERVENTIONS: Postinduction standardized image acquisition and analysis in TTE and TEE by 2 echocardiographers. MEASUREMENTS AND MAIN RESULTS: The authors measured tricuspid annular plane systolic excursion (TAPSE) by M-mode and velocity by tissue Doppler (S') in the apical 4-chamber TTE view and midesophageal 4-chamber TEE view (AP4C, ME4C). They then examined (1) the same measurements in alternative TEE views with proposed better ultrasound angulation; and (2) speckle tracking-based endpoints (TAPSE by speckle tracking, strain, and strain rate). Data were available in 24 of 25 patients. Conventional TAPSE by M-mode and velocity by tissue Doppler (TDI) were underestimated in the ME4C compared with the AP4C reference (mean ± standard deviation: TAPSE: 13.1 ± 3.8 mm v 17.3 ± 4.0 mm; S': 6.7 ± 2.1 cm/s v 9.1 ± 2.2 cm/s; both p < 0.001). Neither a modified deep transgastric view (TAPSE 14.5 ± 4.7 mm, p = 0.017; S' 6.8 ± 1.8 cm/s, p < 0.001) nor a transgastric right ventricular inflow view (TAPSE 12.3 ± 4.0 mm, p = 0.001; S' 6.0 ± 1.3 cm/s, p < 0.001) was similar to the AP4C. Speckle tracking TAPSE was unbiased but with high variability (mean bias = -0.3 mm, 95% limits of agreement = -9.1 to 8.4); strain and strain rate were higher in TEE than for TTE (-17.7 ± 3.6 v -12.6 ± 2.1, p < 0.001; -1.0 ± 0.2/s v -0.7 ± 0.1/s, p < 0.001). CONCLUSIONS: Right ventricular displacement, velocity, and myocardial deformation measured by TEE versus TTE are different. Neither alternative transesophageal echocardiography views nor speckle tracking-based deformation is promising; TAPSE by speckle tracking is unbiased but imprecise.

Rapid, Single-View Speckle-Tracking-Based Method for Examining Left Ventricular Systolic and Diastolic Function in Point of Care Ultrasound.

OBJECTIVES: A rapid, reliable quantitative assessment of left ventricular systolic and diastolic function is important for patient treatment in urgent and dynamic settings. Quantification of annular velocities based on a single 2-dimensional image loop, rather than on Doppler velocities, could be useful in point-of-care or focused cardiac ultrasound. We hypothesized that novel speckle-tracking-based mitral annular velocities would correlate with reference standard tissue Doppler imaging (TDI) velocities in a focused cardiac ultrasound-esque setting. METHODS: Two echocardiographers each performed transthoracic echocardiographic measurements before and after induction of anesthesia in supine patients undergoing cardiac surgery. Speckle-tracking echocardiography (STE)-based systolic (S'STE ) and diastolic (E'STE and A'STE ) velocities were compared to TDI and global longitudinal strain/strain rate. We also compared mitral annular displacement by speckle tracking with M-mode imaging. RESULTS: Twenty-five patients were included and examined in both preinduction and postinduction states. Speckle-tracking-based velocities correlated with TDI measurements in both states (S', r = 0.73 and 0.76; E', r = 0.87 and 0.65; and A', r = 0.65 and 0.73), showing a mean bias of 25% to 30% of the reference standard measurement. The correlation of S'STE with strain and the strain rate (S-wave) and E'STE with the strain rate (E-wave) was good in awake, spontaneously breathing patients but was less strong in the ventilated state. Similarly, displacement by speckle tracking correlated with M-mode measurements in both states (r = 0.91 and 0.84). Measurements required medians of 31 and 34 seconds; reproducibility was acceptable for S'STE and E'STE . CONCLUSIONS: Speckle-tracking-based mitral annular velocities and displacement correlate well with conventional measures as well as with deformation imaging. They may be clinically useful in rapidly assessing both systolic and diastolic function from a single 2-dimensional image loop.

A Novel Speckle-Tracking Based Method for Quantifying Tricuspid Annular Velocities in TEE.

OBJECTIVES: A novel speckle-tracking-based option for measuring tricuspid annular velocities in the midesophageal 4-chamber view (ME4C) was compared with velocities measured by tissue Doppler in the apical-4 chamber view (AP4C). Because this method was based on a modified speckle-tracking-based measurement of tricuspid annular plane systolic excursion (TAPSE), the authors also compared TAPSE by speckle tracking in the ME4C with TAPSE by M-mode in the AP4C. The authors hypothesized that velocities measured by speckle tracking in transesophageal echocardiography (TEE) would be similar, correlate, and agree with those measured by tissue Doppler in transthoracic echocardiography (TTE). DESIGN: Prospective diagnostic study with randomization of the order of post-induction echocardiography views by TTE (AP4C) and TEE (ME4C). Images were both acquired and analyzed by 2 echocardiographers independently. The primary outcome was S'; secondary outcomes were E', A', and TAPSE. SETTING: Single university hospital. PARTICIPANTS: Consecutive adult patients undergoing cardiac surgery (mainly coronary artery bypass grafting). INTERVENTIONS: None. MAIN RESULTS: Complete data was available in 24 of 25 patients. For the primary outcome, S' measured by speckle tracking in the ME4C correlated and agreed with S' measured by tissue Doppler in the AP4C (S'STE = 0.87STDI + 0.60, p < 0.001, r = 0.78; mean bias -0.6 cm/s, 95% limits of agreement (LoA) -3.5 to 2.4 cm/s). Similarly results were found for E', but not A' (E'STE = 0.69E'TDI + 2.37, p < 0.001, r = 0.71; mean bias 0.1 cm/s, 95%LoA -2.5 to 2.8cm/s; A'STE = 0.15A'TDI + 11.17, p = 0.629). TAPSE measurements by the authors' modified speckle-tracking-based technique were similar to TAPSE by M-mode (18.2 ± 5.5 mm and 17.1 ± 3.9 mm, respectively). CONCLUSIONS: Tricuspid annular velocities (S'STE, E'STE) determined by speckle tracking in TEE seem to be promising surrogates for velocities measured in TTE. This may be important for perioperative assessment of the right ventricle.

Differences in Two- and Three-Dimensional Assessment of the Mitral Valve by Novices and Experts, Illustrated Using Anterior Mitral Valve Leaflet Length.

OBJECTIVES: In this measurement validation study, the authors evaluated agreement between 2-dimensional (2D) and three-dimensional (3D) transesophageal echocardiography (TEE), measuring anterior mitral valve leaflet length by both novice and experienced echocardiographers. DESIGN: This was a retrospective, observational study. SETTING: Single university hospital. PARTICIPANTS: Analyses on datasets from 44 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty datasets from 44 patients with mitral regurgitation were analyzed by 4 observers (2 novices, 2 experts). All observers measured the anterior mitral valve leaflet length from end-systolic 2D TEE images from the midesophageal longitudinal axis view and 3D software-augmented TEE images. The overall mean anterior mitral valve leaflet length was significantly shorter with 3D versus 2D TEE measurements (24.6 ± 4.5 mm v 26.2 ± 5.3 mm; p < 0.001), with novices measuring shorter leaflets than experts for both techniques (p < 0.001 and p = 0.005, respectively). Bland-Altman plots of 3D and 2D TEE measurements showed mean biases (95% limits of agreement) of -1.6 mm (-9.0 to 5.9 mm), -1.8 mm (-9.6 to 6.0 mm), and -1.3 mm (-8.4 to 5.7 mm) for all observers, novices, and experts, respectively. For 2D measurements, interobserver reliability was very strong among experts and strong among novices (Pearson's r = 0.83 v 0.66; p = 0.055). For 3D measurements, interobserver reliability was strong in experts and moderate in novices (Pearson's r = 0.69 v 0.51; p = 0.168). CONCLUSION: For both novices and experts, 3D TEE measurements of the anterior mitral valve leaflet were significantly shorter than 2D measurements. Interobserver reliability was lowest for novices making 3D TEE measurements, indicating that reliable, quantitative evaluation of 3D TEE may require a greater amount of practice.

Association between intra-operative fentanyl dosing and postoperative nausea/vomiting and pain: A prospective cohort study.

BACKGROUND: Postoperative nausea and/or vomiting (PONV) is one of the anaesthesia-related effects most dreaded by patients and may delay hospital discharge. Although scores and risk factors are established, many were developed before contemporary anaesthesia regimens and without focussing on modifiable anaesthesia-related variables. OBJECTIVE: To examine whether, in association with a contemporary anaesthesia regimen, there is an association between intra-operative fentanyl dose and PONV, and, second, postoperative pain within the first 24 h. DESIGN: Prospective, observational cohort. SETTING: Single-centre university hospital. PATIENTS: Inclusion criteria were opioid-naive patients without chronic pain and with a simplified Apfel score at least 2 undergoing abdominal, gynaecological or otorhinolaryngological inpatient surgery. INTERVENTION: None. MAIN OUTCOME MEASURE: With logistic regression, we examined three models of increasing complexity exploring the relationship between PONV and fentanyl dosing: Model 1, simplified Apfel score + intra-operative fentanyl; Model 2, Model 1 + pre-emptive antiemetic prophylaxis; Model 3, Model 2 + postoperative morphine. Model 1 was the primary analysis. Second, we explored whether or not postoperative pain scores were associated with intra-operative fentanyl dosing. RESULTS: From the 363 patients, 163 (45%) experienced PONV, despite the use of total intravenous anaesthesia with propofol in more than 80% of the cohort, and some 66% of patients receiving additional antiemetic agents. After adjusting for the simplified Apfel score, higher intra-operative fentanyl dose was associated with PONV: odds ratio per µg h, 1.006 [95% confidence interval (CI) 1.002 to 1.010]. Including intra-operative fentanyl in the simplified Apfel score also increased the area under the receiver operator characteristics curve [0.601 (95% CI 0.555 to 0.662) vs. 0.651 (95% CI 0.594 to 0.707); P = 0.016]. Finally, a higher intra-operative fentanyl dose was associated with higher 24 h pain scores (P = 0.001) and a trend towards higher 24 h morphine requirements (P = 0.055). CONCLUSION: Even when using propofol and antiemetic agents, PONV within the first 24 h remained higher than expected. Intra-operative fentanyl, a modifiable risk factor, is associated with the incidence of PONV and postoperative pain. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03201315.

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.

Absolute Postoperative B-Type Natriuretic Peptide Concentrations, but Not Their General Trend, Are Associated With 12-Month, All-Cause Mortality After On-Pump Cardiac Surgery.

BACKGROUND: B-type natriuretic peptide (BNP) is a predictor of mortality after on-pump cardiac surgery. However, previous limited and heterogeneous studies have focused on peak concentrations at 3 to 5 days after surgery and may not offer clinicians much help in early decision-making. After confirming the predictive value of first-postoperative-day BNP in a preliminary analysis, we explored the association between isolated second-postoperative-day BNP concentrations, second-day BNP concentrations in conjunction with first-day BNP concentrations, and the change in BNP (ie, ΔBNP) from the first to the second postoperative day and 12-month, all-cause mortality. METHODS: We included consecutive patients undergoing on-pump cardiac surgery in this observational, secondary analysis of prospectively collected data. We analyzed biomarkers on the first and second postoperative day. ΔBNP was defined as BNP on the second postoperative day minus BNP on the first postoperative day. The primary end point was 12-month, all-cause mortality. The secondary end point was a composite of major adverse cardiac events (MACEs) at 12 months and/or all-cause mortality at 12 months. MACE was defined as nonfatal cardiac arrest, myocardial infarction, and congestive heart failure. The association between BNP and outcomes was examined by receiver operating characteristic curves, as well as univariate and multivariable logistic regression, adjusting for the EuroSCORE II, cross-clamp time, and first-postoperative-day troponin T. RESULTS: We included 1199 patients in the preliminary analysis focused on BNP on postoperative day 1. In the analyses examining BNP variables requiring second-postoperative-day BNP measurement (n = 708), we observed 66 (9.3%) deaths, 48 (6.8%) MACE, and 104 (14.7%) deaths and/or MACE. Both first- and second-postoperative-day BNP were significant independent predictors of all-cause, 12-month mortality per 100 ng/L increase (adjusted odds ratio [aOR], 1.040 [95% confidence interval (CI), 1.019-1.065] and 1.064 [95% CI, 1.031-1.105], respectively). When used in conjunction with one another, first-day BNP was not significant (aOR, 1.021 [95% CI, 0.995-1.048]), while second-day BNP remained significant (aOR, 1.046 [95% CI, 1.008-1.091]). The ΔBNP per 100 ng/L increase was not associated with 12-month, all-cause mortality in the univariable (OR, 0.977 [95% CI, 0.951-1.007]) or multivariable analysis (aOR, 0.989 [95% CI, 0.962-1.021]). CONCLUSIONS: Both absolute concentrations of first- and second-postoperative-day BNP are independent predictors of 12-month, all-cause mortality. When modeled together, second-postoperative-day BNP is more predictive of 12-month, all-cause mortality. Although intuitively appealing, the change in BNP from the first to the second postoperative day is a complex variable and should not routinely be used for prognostication.

Postoperative High-Sensitivity Troponin and Its Association With 30-Day and 12-Month, All-Cause Mortality in Patients Undergoing On-Pump Cardiac Surgery.

BACKGROUND: Troponin T is a predictor of cardiac morbidity and mortality after cardiac surgery with most data examining fourth generational troponin T assays. We hypothesize that postoperative high-sensitivity troponin T (hsTnT) measured in increments of the upper limit of the norm independently predicts 30-day all-cause mortality. METHODS: We included consecutive patients undergoing on-pump cardiac surgery from February 2010 to March 2012 in a prospective cohort that measured hsTnT at 0600 of the first and second postoperative day. Our primary end point was 30-day, all-cause mortality. The secondary end point was 12-month, all-cause mortality in patients surviving the first 30 days. We divided hsTnT into 5 predetermined categorizes based on the upper limit of the norm (ULN). We used Cox regression to examine an association of hsTnT independent of the EuroSCORE II at both 30 days as well as at 12 months in patients surviving the first 30 days. We assessed the area under the receiver operating characteristics curve and the net reassignment improvement for examining the benefit of adding of hsTnT to the EuroSCORE II for prognostication and restratification of 30-day, all-cause mortality. RESULTS: We included 1122 of 1155 eligible patients (75% male; mean age 66 ± 11 years). We observed 58 (5.2%) deaths at 30 days and another 35 (3.4%) deaths at 12 months in patients surviving 30 days. HsTnT categorized by ULN exhibited a graded response for the mortality. Furthermore, hsTnT remained an independent predictor of all-cause mortality at 30 days (adjusted hazard ratio 1.019 [1.014-1.024] per 10-fold increase in ULN) as well as at 12 months (adjusted hazard ratio 1.019 [1.007-1.032]) in patients surviving the first 30 days. The addition of hsTnT to the EuroSCORE II significantly increased the area under the receiver operating characteristics curve (area under curve: 0.816 [95% confidence interval, 0.754-0.878] versus area under curve: 0.870 [95% confidence interval, 0.822-0.917], respectively; P = .012). Finally, adding hsTnT to the EuroSCORE II improved restratification by the net reassignment improvement, primarily by improving rule-out of events. CONCLUSIONS: This analysis suggests that, similar to previous assays, higher postoperative concentrations of hsTnT are independently associated with all-cause mortality in patients undergoing on-pump cardiac surgery.

Time course of copeptin during a model of experimental pain and hyperalgesia: A randomised volunteer crossover trial.

BACKGROUND: A reliable biomarker for quantifying pain or hyperalgesia has yet to be found. A surrogate marker of arginine vasopressin, copeptin, is elevated in a number of states of physiological and psychological stress and may have a role in quantifying pain and/or hyperalgesia. OBJECTIVES: To evaluate copeptin as a biomarker for pain or hyperalgesia developing after 120 min of sustained electrical stimulation. DESIGN: Secondary analysis of a randomised, double-blinded, crossover trial. SETTING: Single, tertiary university hospital from September 2014 to January 2015. PARTICIPANTS: A total of 16 healthy, opioid-naïve white men with no confounding medication or history of pain. INTERVENTIONS: Copeptin and cortisol were measured five times during an established model of transdermal electrical stimulation designed to assess pain and hyperalgesia. MAIN OUTCOME MEASURES: The primary outcome was the change in copeptin concentration after 120 min of sustained electrical stimulation. Secondary outcomes were copeptin and cortisol concentrations after a subsequent period of rest and analyses of copeptin and cortisol concentrations were made in high-dose and low-dose fentanyl groups separately. RESULTS: Total copeptin concentrations were not significantly elevated after 120 min [9.15 pmol l (interquartile ranges (IQR), 3.45 to 35.45 pmol l); P = 0.150] compared with baseline [6.15 pmol l (IQR, 3.60 to 10.62 pmol l)]. In the high-dose fentanyl group, there was a significant increase in copeptin within individuals [P = 0.001; median, 37.9 pmol l (IQR, 8.1 to 62 pmol l)] after 120 min, and in the low-dose fentanyl group a significant decrease in copeptin concentrations within individuals [P = 0.006; median, 4.7 pmol l (IQR, 3.13 to 9.35 pmol l)]. No correlation between copeptin concentration and either the area under the pain curve or area under the hyperalgesia curve could be found, indicating that the observed differences may be due to other fentanyl-mediated effects. CONCLUSION: Copeptin concentrations do not appear to be associated directly with pain and hyperalgesia. Instead, some fentanyl-mediated effect or effects appear to have greatly increased copeptin concentrations from baseline to 120 min. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02252458.