Evaluation of Intraoperative Right Ventricular Myocardial Work Indices in Left Ventricular Assist Device Implantation: A Case Report.

Right ventricular myocardial work is an echocardiographic technique yielding significant insights into cardiac mechanics, energetics, and efficiency. Combining right ventricular myocardial strain with loading conditions correlates with invasively measured myocardial work and myocardial oxygen consumption. This method has not yet been described intraoperatively by transesophageal echocardiography. We describe this technique during a left ventricular assist device implantation. This case demonstrates that right ventricular myocardial work indices can be monitored intraoperatively and might assist decisions during left ventricular assist device implantation.

Factors affecting adherence to recommendations on pre-operative cardiac testing: A cohort study.

BACKGROUND: Cardiac risk evaluation prior to noncardiac surgery is fundamental to tailor peri-operative management to patient's estimated risk. Data on the degree of adherence to guidelines in patients at cardiovascular risk in Europe and factors influencing adherence are underexplored. OBJECTIVES: The aim of this analysis was to describe the degree of adherence to [2014 European Society of Cardiology (ESC)/European Society of Anaesthesiology (ESA) guidelines] recommendations on rest echocardiography [transthoracic echocardiography (TTE)] and to stress imaging prior to noncardiac surgery in a large European sample and to assess factors potentially affecting adherence. DESIGN: Secondary analysis of a multicentre, international, prospective cohort study (MET-REPAIR). SETTING: Twenty-five European centres of all levels of care that enrolled patients between 2017 and 2020. PATIENTS: With elevated cardiovascular risk undergoing in-hospital elective, noncardiac surgery. MAIN OUTCOME MEASURES: (Non)adherence to each pre-operative TTE and stress imaging recommendations classified as guideline-adherent, overuse and underuse. We performed descriptive analysis. To explore the impact of patients' sex, age, geographical region, and hospital teaching status, we conducted multivariate multinominal regression analysis. RESULTS: Out of 15 983 patients, 15 529 were analysed (61% men, mean age 72 ±â€Š8 years). Overuse (conduction in spite of class III) and underuse (nonconduction in spite of class I recommendation) for pre-operative TTE amounted to 16.6% (2542/15 344) and 6.6% (1015/15 344), respectively. Stress imaging overuse and underuse amounted to 1.7% (241/14 202) and 0.4% (52/14 202) respectively. Male sex, some age categories and some geographical regions were significantly associated with TTE overuse. Male sex and some regions were also associated with TTE underuse. Age and regions were associated with overuse of stress imaging. Male sex, age, and some regions were associated with stress imaging underuse. CONCLUSION: Adherence to pre-operative stress imaging recommendation was high. In contrast, adherence to TTE recommendations was moderate. Both patients' and geographical factors affected adherence to joint ESC/ESA guidelines. TRIAL REGISTRATION: NCT03016936.

A Multi-Country Survey on the Availability of Intraoperative Use of Echocardiography for Noncardiac Surgery.

BACKGROUND: This survey aimed to explore the availability and accessibility of echocardiography during noncardiac surgery worldwide. METHODS: An internet-based 45-item survey was sent, followed by reminders from August 30, 2021, to August 20, 2022. RESULTS: 1189 responses were received from 62 countries. Nearly seventy-one percent of respondents had intraoperatively used transesophageal or transthoracic echocardiography (TEE and TTE, respectively) for monitoring or examination. The unavailability of echocardiography machines (30.3%), lack of trained personnel (30.2%), and absence of clinical indications (22.6%) were the top 3 reasons for not using intraoperative echocardiography in noncardiac surgery. About 61.5% of participants had access to at least one echocardiography machine. About 41% had access to at least 1 TEE probe, and 62.2% had access to at least 1 TTE probe. Seventy-four percent of centers had a procedure to request intraoperative echocardiography if needed for noncardiac cases. Intraoperative echocardiography service was immediately available in 58% of centers. CONCLUSIONS: Echocardiography machines and skilled echocardiographers are still unavailable at many centers worldwide. National societies should aim to train a critical mass of certified TEE/TTE anesthesiologists and provide all anesthesiologists access to perioperative TEE/TTE machines in anesthesiology departments, considering the increasing number of older and sicker surgical patients scheduled for noncardiac surgery.

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.

NT-proBNP or Self-Reported Functional Capacity in Estimating Risk of Cardiovascular Events After Noncardiac Surgery.

Importance: Nearly 16 million surgical procedures are conducted in North America yearly, and postoperative cardiovascular events are frequent. Guidelines suggest functional capacity or B-type natriuretic peptides (BNP) to guide perioperative management. Data comparing the performance of these approaches are scarce. Objective: To compare the addition of either N-terminal pro-BNP (NT-proBNP) or self-reported functional capacity to clinical scores to estimate the risk of major adverse cardiac events (MACE). Design, Setting, and Participants: This cohort study included patients undergoing inpatient, elective, noncardiac surgery at 25 tertiary care hospitals in Europe between June 2017 and April 2020. Analysis was conducted in January 2023. Eligible patients were either aged 45 years or older with a Revised Cardiac Risk Index (RCRI) of 2 or higher or a National Surgical Quality Improvement Program, Risk Calculator for Myocardial Infarction and Cardiac (NSQIP MICA) above 1%, or they were aged 65 years or older and underwent intermediate or high-risk procedures. Exposures: Preoperative NT-proBNP and the following self-reported measures of functional capacity were the exposures: (1) questionnaire-estimated metabolic equivalents (METs), (2) ability to climb 1 floor, and (3) level of regular physical activity. Main Outcome and Measures: MACE was defined as a composite end point of in-hospital cardiovascular mortality, cardiac arrest, myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care. Results: A total of 3731 eligible patients undergoing noncardiac surgery were analyzed; 3597 patients had complete data (1258 women [35.0%]; 1463 (40.7%) aged 75 years or older; 86 [2.4%] experienced a MACE). Discrimination of NT-proBNP or functional capacity measures added to clinical scores did not significantly differ (Area under the receiver operating curve: RCRI, age, and 4MET, 0.704; 95% CI, 0.646-0.763; RCRI, age, and 4MET plus floor climbing, 0.702; 95% CI, 0.645-0.760; RCRI, age, and 4MET plus physical activity, 0.724; 95% CI, 0.672-0.775; RCRI, age, and 4MET plus NT-proBNP, 0.736; 95% CI, 0.682-0.790). Benefit analysis favored NT-proBNP at a threshold of 5% or below, ie, if true positives were valued 20 times or more compared with false positives. The findings were similar for NSQIP MICA as baseline clinical scores. Conclusions and relevance: In this cohort study of nearly 3600 patients with elevated cardiovascular risk undergoing noncardiac surgery, there was no conclusive evidence of a difference between a NT-proBNP-based and a self-reported functional capacity-based estimate of MACE risk. Trial Registration: ClinicalTrials.gov Identifier: NCT03016936.

Pressure-Volume Loops for Reviewing Right Ventricular Physiology and Failure in the Context of Left Ventricular Assist Device Implantation.

Right ventricular (RV) function is complex as a number of determinants beyond preload, inotropy and afterload play a fundamental role. In particular, arterial elastance (Ea), ventriculo-arterial coupling (VAC), and (systolic) ventricular interdependence play a vital role for the right ventricle. Understanding and actively visualizing these interactions in the failing RV as well as in the altered hemodynamic and morphological situation of left ventricular assist device (LVAD) implantation may aid clinicians in their understanding of RV dysfunction and failure. While, admittedly, hard data is scarce and invasive pressure-volume loop measurements will not become routine in cardiac surgery, we hope that clinicians will benefit from the comprehensive, simulation-based review of RV pathology. In particular, the aim of this article is to first, address and clarify the pathophysiologic hemodynamic factors that lead to RV dysfunction and then, second, expand upon this basis examining the changes occurring by LVAD implantation. This is illustrated using Harvi software which shows elastance, ventricular arterial coupling, and ventricular interdependence by simultaneously showing pressure volume loops of the right and left ventricle.

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.

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.

Analgesic benefit of metamizole and ibuprofen vs. either medication alone: a randomized clinical trial.

BACKGROUND: Postoperative pain relief remains a key problem after surgery. Multimodal pain therapy has proven beneficial in alleviating pain to a certain extent. However, when combining non-opioids, the focus has been on NSAIDs and paracetamol, but effects of combined use are only moderate. Metamizole could be a potent adjunct, due to its preclusion in several countries, data on its combined use are sparse, despite its common use in many countries. The aim of this study was to examine whether the combination of metamizole and ibuprofen is superior in relieving postoperative pain to either drug alone. METHODS: For this randomized, placebo-controlled, cross-over study, 35 patients undergoing bilateral lower third molar extraction were randomized. Each patient received three applications of 1000 mg metamizole + 400 mg ibuprofen for surgery on one side and either 1000 mg metamizole + placebo or 400 mg ibuprofen + placebo on the other side. Pain ratings, rescue-medication (tramadol), and sleep were assessed for 18 hours. RESULTS: The combined treatment of metamizole and ibuprofen showed lower mean pain scores over 12 hours than ibuprofen (2.4±1.3 vs 3.8±1.6; P=0.005). Further, combined treatment showed lower mean pain scores over 6 hours than ibuprofen (2.0±1.2 vs. 3.1±1.6; P=0.022) or metamizole alone (2.0±1.2 vs. 3.3±1.7; P=0.015). Consumption of rescue medication was lowest in the combination-group (25% vs. 46%-metamizole; 50%-ibuprofen). The trial was stopped prematurely as the COVID-pandemic halted elective surgeries. CONCLUSIONS: Combined use enables superior pain control compared to ibuprofen after molar extraction and tends to be superior to metamizole alone. The premature study-termination may overestimate this effect.

Pain response to cannabidiol in opioid-induced hyperalgesia, acute nociceptive pain, and allodynia using a model mimicking acute pain in healthy adults in a randomized trial (CANAB II).

ABSTRACT: Opioids in general and remifentanil in particular can induce hyperalgesia. Preclinical data suggest that cannabidiol might have the capacity to reduce opioid-induced hyperalgesia (OIH). Thus, we investigated the effect of oral cannabidiol on OIH in healthy volunteers using an established pain model. Twenty-four healthy participants were included in this randomized, double-blinded, crossover study and received either a 1600-mg single-dose oral cannabidiol or placebo. Hyperalgesia, allodynia, and pain were induced by intracutaneous electrical stimulation. To provoke OIH, participants recieved an infusion of 0.1 µg/kg/min remifentanil over a time frame of 30 minutes, starting 100 minutes after oral cannabidiol ingestion. The primary outcome was the area of hyperalgesia (in square centimetres) up to 60 minutes after remifentanil administration. The area of allodynia (in square centimetres) and pain (numeric rating scale) were also assessed.Cannabidiol had no significant effect on hyperalgesia, allodynia, or pain at any time point of measurement compared with placebo. The area of hyperalgesia after remifentanil administration significantly increased compared with baseline (17.0 cm 2 [8.1-28.7] vs 25.3 cm 2 [15.1-39.6]; P = 0.013). Mean cannabidiol blood levels were 4.1 ± 3.0 µg/L (mean ± SD) at 130 minutes after ingestion and were 8.2 µg/L ± 6.9 µg/L (mean ± SD) at 200 minutes. Cannabidiol was well tolerated. We conclude that a high single-oral dose of 1600-mg cannabidiol is not effective in reducing OIH. Before excluding an effect of cannabidiol on OIH, research should focus on drug formulations enabling higher cannabidiol concentrations.

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.

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.

Pain response to cannabidiol in induced acute nociceptive pain, allodynia, and hyperalgesia by using a model mimicking acute pain in healthy adults in a randomized trial (CANAB I).

ABSTRACT: Preclinical studies have demonstrated the analgesic potential of cannabidiol (CBD). Those suggesting an effect on pain-processing receptors have brought CBD back into focus. This study assessed the effect of CBD on acute pain, hyperalgesia, and allodynia compared with placebo. Twenty healthy volunteers were included in this randomized, placebo-controlled, double-blinded, crossover study assessing pain intensities (using numeric rating scale), secondary hyperalgesia (von Frey filament), and allodynia (dry cotton swab) in a well-established acute pain model with intradermal electrical stimulation. The authors compared the effect of 800-mg orally administered CBD on pain compared with placebo. They further examined the effect on hyperalgesia and allodynia. Cannabidiol whole blood levels were also measured. Pain ratings (mean ± SD) did not differ significantly after CBD application compared with placebo (5.2 ± 0.7 vs 5.3 ± 0.7, P-value 0.928), neither did the areas of hyperalgesia and allodynia differ significantly after CBD application compared with placebo (hyperalgesia 23.9 ± 19.2 cm2 vs 27.4 ± 17.0 cm2, P-value 0.597; allodynia 16.6 ± 13.1 cm2 vs 17.3 ± 14.1 cm2, P-value 0.884). The CBD whole blood level (median, first to third quartile) was 2.0 µg/L (1.5-5.1) 60 minutes and 5.0 µg/L (4.0-10.4) 130 minutes after CBD application. Although the oral application of 800-mg CBD failed to show a significant effect, it is important to focus future research on different dosing, routes of administration, and CBD as a part of multimodal treatment strategies before negating its effects on acute pain.