Ketamine vs. haloperidol for prevention of cognitive dysfunction and postoperative delirium: A phase IV multicentre randomised placebo-controlled double-blind clinical trial

Study objectiveDelirium is frequently observed in the postoperative and intensive care unit (ICU) population. Due to the multifactorial origin of delirium and according to international guidelines (e.g., American Geriatrics Society; Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) guideline), there are several but no incontestable options for prevention and symptomatic treatment.The purpose of the Baden PRIDe (Prevention and Reduction of Incidence of postoperative Delirium) trial was to determine whether postoperative cognitive dysfunction and delirium could be prevented by the combination of possible preventive agents such as haloperidol and ketamine. In addition, pre- and postoperative levels of the biomarkers cortisol, neuron specific enolase (NSE) and S100β were measured to investigate their dynamics in delirious and non-delirious patients after surgery.DesignThe Baden PRIDe Trial was an investigator-initiated, phase IV, two-centre, randomised, placebo-controlled, double-blind clinical trial.SettingPerioperative care.Patients182 adult patients that underwent elective or emergency surgery under general or combined (i.e., general and regional) anaesthesia.InterventionsPre-anaesthetic, pharmacologic prevention of postoperative brain dysfunction with haloperidol, ketamine, and the combination of both vs. placebo.MeasurementsAssessment of cognitive performance pre- and postoperatively with the MMSE, the DOS, the Nursing Delirium Screening Scale (Nu-DESC) or the Intensive Care Delirium Screening Checklist (ICDSC) during ICU stay.Main resultsNone of the three study arms – haloperidol, ketamine, or both drugs combined - was significantly superior to placebo for prevention of postoperative brain dysfunction and delirium (P = 0.39). Measured levels of postoperative cortisol were significantly higher in delirious patients. S-100β levels were significantly higher in all postoperative outcome groups (cognitive impairment, delirium, no cognitive decline), whereas postoperative NSE levels declined in all groups.ConclusionsThe study results offer no possibility for a novel recommendation for prevention of postoperative cognitive decline including delirium. Perioperative S-100β trajectories in patients with cognitive deterioration suggest affection of glial cells in particular.Trial registrationClinicalTrials.gov NCT02433041; registered on April 7, 2015.     

The impact of social media presence,age, and patient reported wait times on physician review websites for sports medicine surgeons

BackgroundWhen choosing physicians, patients often review options online via physician review websites, which may influence decisions on providers.PurposeThe purpose of this study is to investigate the impacts of social media usage, age, and patient reported wait times on online ratings for three popular review websites.Study designCross-sectional study.MethodsThe American Orthopaedic Society for Sports Medicine database was used to extract demographic information for all listed sports medicine surgeons in Florida. Overall ratings, number of ratings and comments, and patient reported wait-times were recorded from three leading review websites (Healthgrades.com, Vitals.com, Google.com). Professionally focused SM accounts were searched for each physician on Facebook.com, Twitter.com, Instagram, and LinkedIn.com.Results102 orthopaedic sports medicine surgeons were included. At least one form of social media was used by 62.4% of our cohort. Those with social media had higher overall online physician ratings out of 5.00 across all review websites (Google:4.65vs4.44, p = 0.05; Healthgrades:4.41vs4.15, p = 0.03; Vitals:4.43vs4.14, p = 0.01). In bivariate analysis, older age was associated with lower ratings on Health Grades (Absolute difference (AD) −0.26, p < 0.0001), and social media was linked to higher ratings (Google: AD 0.21, p = 0.05; Healthgrades: AD 0.26, p = 0.03; Vitals: AD 0.29, p = 0.008). Longer wait times were associated with lower ratings in a dose-dependent manner in both bivariate and multivariable analysis.ConclusionsSocial media use among sports medicine surgeons correlated with higher overall physician ratings. Potentially, younger surgeons increase social media use because of a heightened concern for online image, whereas older surgeons may have less value in using online platforms to capitalize on an online presence. Older age and increased patient reported wait times in office had a negative correlation with online reviews, which highlights that factors beyond the surgeon's skill sets can influence overall ratings.     

A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY)

Study objectiveTo evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.DesignMulticenter, open-label, phase 3, randomized trial (PLAY; NCT03682302).SettingOperating room.PatientsTwo separate age groups were evaluated (age group 1: patients 12 to <17 years undergoing spine surgery; age group 2: patients 6 to <12 years undergoing spine or cardiac surgery).InterventionRandomized allocation of liposomal bupivacaine 4 mg/kg or bupivacaine hydrochloride (HCl) 2 mg/kg via local infiltration at the end of spine surgery (age group 1); liposomal bupivacaine 4 mg/kg via local infiltration at the end of spine or cardiac surgery (age group 2).MeasurementsThe primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations [C_max], time to C_max) and safety of liposomal bupivacaine, respectively.Main resultsBaseline characteristics were comparable across groups. Mean C_max after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean C_max in age group 2 was 320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to C_max of liposomal bupivacaine occurred later with cardiac surgery versus spine surgery (22.7 vs 7.4 h). In age group 1, the incidence of adverse events (AEs) was comparable between liposomal bupivacaine (61% [19/31]) and bupivacaine HCl (73% [22/30]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing spine and cardiac surgery experienced AEs, respectively. AEs were generally mild or moderate, with no discontinuations due to AEs or deaths.ConclusionsPlasma bupivacaine levels following local infiltration with liposomal bupivacaine remained below the toxic threshold in adults (~2000–4000 ng/mL) across age groups and procedures. AEs were mild to moderate, supporting the safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.Clinical trial number and registry URL: ClinicalTrials.gov identifier: NCT03682302     

Intraoperative hypotension is not associated with postoperative cognitive dysfunction in elderly patients undergoing general anesthesia for surgery: results of a randomized controlled pilot trial

Study objectiveTo assess the effect of different intraoperative blood pressure targets on the development of POCD and test the feasibility of a larger trial.DesignRandomized controlled pilot trial.SettingPerioperative care in a tertiary care teaching hospital with outpatient follow-up.PatientsOne hundred one patients aged ≥75 years with ASA physical status <4, undergoing elective, non-cardiac surgery under general anesthesia and 33 age-matched healthy controls.InterventionsRandomization to a personalized intraoperative blood pressure target, mean arterial pressure (MAP) ≥ 90% of preoperative values (Target group), or to a more liberal intraoperative blood pressure management (No-Target group). Strategies to reach intraoperative blood pressure target were at discretion of anesthesiologists.MeasurementsAn experienced neuropsychologist performed a validated battery of neurocognitive tests preoperatively and 3 months after surgery. Incidence of POCD at three months and postoperative delirium were assessed. Intraoperative time spent with MAP ≥ 90% of preoperative values, recruitment and drop-out rate at 3 months were feasibility outcomes.Main resultsThe Target group spent a higher percentage of intraoperative time with MAP ≥90% of preoperative values (65 ± 25% vs. 49 ± 28%, p < 0.01). Incidence of POCD (11% vs. 7%, relative risk 1.52; 95% CI, 0.41 to 6.3; p = 0.56) and delirium (6% vs. 14%, relative risk, 0.44; 95% CI, 0.12 to 1.60; p = 0.21) did not differ between groups. No correlation was found between intraoperative hypotension and postoperative cognitive performance (p = 0.75) or delirium (p = 0.19). Recruitment rate was of 6 patients/month (95% confidential interval (CI), 5 to 7) and drop-out rate at 3 months was 24% (95% CI, 14 to 33%).ConclusionsIntraoperative hypotension did not correlate with postoperative cognitive dysfunction or delirium occurrence in elderly patients undergoing general anesthesia for non-cardiac surgery.A multicenter randomized controlled trial is needed in order to confirm the effect of intraoperative blood pressure on the development of POCD.Trial registration numberNCT02428062 www.clinicaltrials.gov.     

Preoperative oximetry-derived hypoxemia predicts postoperative cardiovascular events in surgical patients with unrecognized obstructive sleep apnea

Study objectiveObstructive sleep apnea (OSA) is known to be associated with postoperative cardiovascular events in patients undergoing major non-cardiac surgery. The objective of the study is to determine whether preoperative oximetry-derived hypoxemia predicts postoperative cardiovascular events in surgical patients with unrecognized obstructive sleep apnea.Design and settingThe study was a planned post hoc analyses of a multicenter prospective cohort study.PatientsThe inclusion criteria were patients ≥45 years old undergoing major non-cardiac surgery with cardiovascular risk factors.Interventions and measurementsAll patients underwent pre-operative pulse oximetry (PULSOX-300i, Konica-Minolta Sensing, Inc). The severity of OSA was classified based on oxygen desaturation index (ODI) (mild: ≥5 to <15, moderate: ≥15 to <30, and severe OSA: ≥30 events/h). The 30 days cardiovascular events were a composite of myocardial injury, cardiac death, congestive heart failure, thromboembolism, atrial fibrillation, and stroke.Main resultsFor 1218 patients with mild, moderate, or severe OSA (mean age: 67.2 ± 9.3 years; body mass index: 27.0 ± 5.3 kg/m²), the rate of postoperative cardiovascular events was 16.4%, 25.2%, and 29.8% respectively. The multivariable analysis showed that preoperative oxygen desaturation index (ODI) ≥30 events per hour {adjusted hazard ratio (aHR) 1.63 [95% confidence interval (CI): 1.05–2.53]}, and cumulative time spent during sleep with oxygen saturation below 80% (CT80) ≥10 min {aHR 1.79 [95% CI: 1.28–2.50]} were independent predictors of 30-day postoperative cardiovascular events.ConclusionsPreoperative ODI ≥30 events per hour and CT80 ≥ 10 min are associated with increased risk of postoperative cardiovascular events. Preoperative screening using oximetry helps in risk stratification for unrecognized sleep apnea.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01494181     

Outcomes of individualized goal-directed therapy based on cerebral oxygen balance in high-risk patients undergoing cardiac surgery: A randomized controlled trial

Study objectiveTo investigate whether optimizing individualized goal-directed therapy (GDT) based on cerebral oxygen balance in high-risk surgical patients would reduce postoperative morbidity.DesignThis was a prospective, randomized, controlled study.SettingThe study was performed in the First Affiliated Hospital of Anhui Medical University, Hefei, China, from April 2017 to July 2018.Patients146 high-risk adult patients undergoing valve replacements or coronary artery bypass surgery with cardiopulmonary bypass (CPB) were enrolled.InterventionPatients were randomized to an individualized GDT group or usual care group. Individualized GDT was targeted to achieve the following goals: A less than 20% decline in the regional cerebral oxygen saturation (rScO₂) level from baseline; a less than 20% decline in the mean arterial pressure (MAP) from baseline, as well as a bispectral index (BIS) of 45–60 before and after CPB and 40–45 during CPB.MeasurementsThe primary outcome was a composite endpoint of 30-day mortality and major postoperative complications.Main results128 completed the trial and were included in the modified intention-to-treat analysis. Early morbidity was similar between the GDT (25 [39%] of 65 patients) and usual care groups (33 [53%] of 63 patients) (relative risk 0.73, 95% CI 0.50–1.08; P = 0.15). Secondary analysis showed that 75 (59%) of 128 patients achieved individual targets (irrespective of intervention) and sustained less morbidity (relative risk 3.41, 95% CI 2.19–5.31; P < 0.001).ConclusionsIn high-risk patients undergoing cardiac surgery, individualized GDT therapy did not yield better outcomes, however, the achievement of preoperative individual targets may be associated with less morbidity.Trial registrationClinicaltrials.gov identifier: NCT03103633. Registered on 1 April 2017.     

Critical care management of adult traumatic brain injury

Severe traumatic brain injury (TBI) is associated with significant morbidity and mortality. The critical care management of TBI requires a coordinated and comprehensive approach to treatment, including strategies to prevent secondary brain injury by avoidance of systemic physiological disturbances, such as hypotension, hypoxaemia, hypo- and hyperglycaemia and hyperthermia, and maintenance of adequate cerebral perfusion and oxygenation. Management protocols have evolved with international consensus, providing guidelines that assist clinicians in delivering optimal care. Those from the Brain Trauma Foundation are continuously updated to incorporate new trial data (https://braintrauma.org/coma/guidelines).     

Perioperative supplemental oxygen and oxidative stress in patients undergoing moderate- to high-risk major abdominal surgery – A subanalysis of randomized clinical trial

Study objectiveOxidative stress plays a pivotal role in the development and aggravation of cardiovascular diseases. The influence of intraoperative inspired oxygen concentrations on oxidative stress is still not entirely known. Therefore, we evaluated in this sub-study if supplemental oxygen affects the oxidation-reduction potential in patients at-risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery.DesignSub-study of a prospective parallel-arm double-blinded single-center superiority randomized trial.SettingOperating room and postoperative recovery area.InterventionAdministration of 0.8 FiO₂ versus 0.3 FiO₂ throughout surgery and for the first two postoperative hours.MeasurementsThe primary outcome was the static oxidation-reduction potential (sORP) and the oxidation-reduction potential capacity (cORP) between both groups. The secondary outcome was the trend of sORP and cORP in the overall study population. We assessed sORP and cORP before induction of anesthesia, 2 h after induction of anesthesia, within 2 h after surgery and on the first and third postoperative day.Main results258 patients were analyzed. 128 patients were randomly assigned to the 80% oxygen group and 130 patients were randomly assigned to the 30% oxygen group. Postoperative sORP values did not differ significantly between the 80% and 30% oxygen group (effect estimate: −1.162 mV,95% CI: −2.584 to 0.260; p = 0.109). On average, we observed a change in sORP of 5.288 mV (95% CI:4.633 to 5.913, p < 0.001) per day. cORP values did not differ significantly between the 80% and 30% oxygen group (effect estimate: −0.015μC, (95%CI: −0.062 to 0.032; p = 0.524). On average, we observed a change in cORP values of −0.170μC (95%CI: −0.194 to −0.147, p < 0.001) per day.ConclusionIn contrast to previous reports, we could not find any evidence of an association between intraoperative supplemental oxygen and perioperative oxidative stress assessed by sORP and cORP.Trial registrationclinicaltrials.gov: NCT03366857 https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1     

Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial

IntroductionThis report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND).MethodsThe ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1–2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQ-C30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.ResultsOverall, 976 questionnaires (501 in the SLN biopsy only group and 475 in the completion ALND group) were analysed, corresponding to a response rate of 82.6%. No significant group differences in overall HRQoL were identified. Participants receiving SLN biopsy only, reported significantly lower symptom scores on the EORTC subscales of pain, arm symptoms and breast symptoms. The Lymph-ICF domain scores of physical function, mental function and mobility activities were significantly in favour of the SLN biopsy only group.ConclusionOne year after surgery, arm morbidity is significantly worse affected by ALND than by SLN biopsy only. The results underline the importance of ongoing attempts to safely de-escalate axillary surgery.Trial registrationThe trial was registered at clinicaltrials.gov prior to initiation (https://clinicaltrials.gov/ct2/show/NCT 02240472).     

Perioperative supplemental oxygen and NT-proBNP concentrations after major abdominal surgery – A prospective randomized clinical trial

Study objectiveSupplemental oxygen is a simple method to improve arterial oxygen saturation and might therefore improve myocardial oxygenation. Thus, we tested whether intraoperative supplemental oxygen reduces the risk of impaired cardiac function diagnosed with NT-proBNP and myocardial injury after noncardiac surgery (MINS) diagnosed with high-sensitivity Troponin T.DesignParallel-arm double-blinded single-centre superiority randomized trial.SettingOperating room and postoperative recovery area.Patients260 patients over the age of 45 years at-risk for cardiovascular complications undergoing major abdominal surgery.InterventionAdministration of 80% versus 30% oxygen throughout surgery and for the first two postoperative hours.MeasurementsThe primary outcome was the postoperative maximum NT-proBNP concentration in both groups, which was assessed within 2 h after surgery, and on the first and third postoperative day. The secondary outcome was the incidence of MINS in both groups.Main results128 patients received 80% oxygen and 130 received 30% oxygen throughout surgery and for the first two postoperative hours. There was no significant difference in the median postoperative maximum NT-proBNP concentration between the 80% and the 30% oxygen group (989 pg.mL⁻¹ [IQR 499; 2005] and 810 pg.mL⁻¹ [IQR 409; 2386], effect estimate: 159 pg.mL⁻¹, 95%CI -123, 431, p = 0.704). There was no difference in the incidence of MINS between both groups. (p = 0.703).ConclusionsThere was no beneficial effect of perioperative supplemental oxygen administration on postoperative NT-proBNP concentration and MINS. It seems likely that supplemental oxygen has no effect on the release of NT-proBNP in patients at-risk for cardiovascular complications undergoing major abdominal surgery.Trial registrationClinicalTrials.gov: NCT 03366857.https://clinicaltrials.gov/ct2/results?cond=NCT+03366857&term=&cntry=&state=&city=&dist=     

Anticholinergic burden of long-term medication is an independent risk factor for the development of postoperative delirium: A clinical trial

BackgroundPostoperative delirium (POD) is a common complication after surgery.ObjectiveWe sought to determine the association between preoperative anticholinergic load calculated using the anticholinergic drug scale (ADS) and POD in cancer patients over 65 years of age.DesignA retrospective sub-investigation of a randomised controlled interventional trial.SettingTwo tertiary university hospitals.PatientsOverall, patients aged 65 years and older scheduled for surgical treatment of gastrointestinary, genitourinary or gynaecological cancers.Main outcome measuresThe primary outcome was the interaction between anticholinergic drug scale and occurrence of postoperative delirium. Patient clinical parameters and ADS scores were assessed preoperatively. POD screening was conducted for a total of 7 days following surgery using validated measures. Independent associations between ADS and POD were assessed using multivariate logistical regression analyses.ResultsA total of 651 patients (mean age, 71.8 years; 68.5% males) were included. Of those, 66 patients (10.1%) developed POD. The ADS score was independently associated with the occurrence of POD (higher ADS per point OR 1.496; 95% CI 1.09–2.05; p = 0.01). Additionally, age (per year OR 1.06; CI 95% CI 1.01–1.11; p = 0.03) and ASA state (OR 2.16; 95% CI 1.22–3.83; p = 0.01), as well as stay on ICU (yes vs. no OR 2.8; 95% CI 1.57–4.998; p < 0.01), were independently associated with POD.ConclusionsADS assessment according to chronic medication use is a cost-effective, non-invasive method of identifying elderly cancer patients at risk for POD.Trial registry: www.clinicaltrials.gov. Identifier NCT01278537.Ethics: IRB of Charité University-Medicine Berlin, Germany; EA2/241/08.     

Evaluation of atelectasis using electrical impedance tomography during procedural deep sedation for MRI in small children: A prospective observational trial

Study objectiveTo investigate the variation of poorly ventilated lung units (i.e., silent spaces) in children undergoing procedural sedation in a day-hospital setting, until discharge home from the Post-Anesthesia Care Unit (PACU).DesignProspective, single-center, observational cohort trial.SettingThis study was conducted at the radiology department and in PACU at Bern University Hospital (Switzerland), a tertiary care hospital.PatientsWe included 25 children (1–6 years, ASA I-III) scheduled for cerebral magnetic resonance imaging scan, spontaneously breathing under deep sedation. Children planned for tracheal intubation, supraglottic airway insertion, or with contraindication for propofol were excluded.InterventionAfter intravenous or inhaled induction, deep sedation was performed with 10 mg/kg/h Propofol. All children received nasal oxygen 0.3 ml/kg/min.MeasurementsThe proportion of silent spaces and the global inhomogeneity index were determined at each of five procedural points, using electrical impedance tomography: before induction (T1); before (T2) and after (T3) magnetic resonance imaging; at the end of sedation before transport to the PACU (T4); and before hospital discharge (T5).Main resultsThe median [interquartile range (IQR)] proportion of silent spaces at the five analysis points were: T1, 5% [2%–14%]; T2, 10% [7%–14%]; T3, 12% [5%–23%]; T4, 12% [7%–24%]; and T5, 3% [2%–11%]. These defined significant changes in silent spaces over the course of sedation (p = 0.009), but no differences in silent spaces from before induction to before discharge from the PACU (T1 vs. T5; p = 0.29). Median [IQR] global inhomogeneity indices were 0.57 [0.55–0.58], 0.56 [0.53–0.59], 0.56 [0.54–0.59], 0.57 [0.54–0.60] and 0.56 [0.54–0.57], respectively (p = 0.93). None of the children reported anesthesia-related complications.ConclusionDeep sedation results in significantly increased poorly ventilated lung units during sedation. However, this does not significantly affect ventilation homogeneity, which was fully resolved at discharge from the PACU.Trial registration: clinicaltrials.gov, identifier NCT04507581     

How to Develop and Validate Prediction Models for Orthopedic Outcomes

Prediction models are common in medicine for predicting outcomes such as mortality, complications, or response to treatment. Despite the growing interest in these models in arthroplasty (and orthopaedics in general), few have been adopted in clinical practice. If robustly built and validated, prediction models can be excellent tools to support surgical decision making. In this paper, we provide an overview of the statistical concepts surrounding prediction models and outline practical steps for prediction model development and validation in arthroplasty research. Please visit the following https://www.youtube.com/watch?v=9Yrit23Rkic for a video that explains the highlights of the paper in practical terms.     

Propensity Scores: Confounder Adjustment When Comparing Nonrandomized Groups in Orthopaedic Surgery

Many studies in arthroplasty research are based on nonrandomized, retrospective, registry-based cohorts. In these types of studies, patients belonging to different treatment or exposure groups often differ with respect to patient characteristics, medical histories, surgical indications, or other factors. Consequently, comparisons of nonrandomized groups are often subject to treatment selection bias and confounding. Propensity scores can be used to balance cohort characteristics, thus helping to minimize potential bias and confounding. This article explains how propensity scores are created and describes multiple ways in which they can be applied in the analysis of nonrandomized studies. Please visit the following (https://www.youtube.com/watch?v=sqgxl_nZWS4&t=3s) for a video that explains the highlights of the paper in practical terms.     

Postoperative opioid administration characteristics associated with opioid-induced respiratory depression: Results from the PRODIGY trial

Study objectiveOpioid administration for pain in general care floor patients remains common, and can lead to adverse outcomes, including respiratory compromise. The PRODIGY trial found that among ward patients receiving parenteral opioids, 46% experienced ≥1 respiratory depression episode. The objective of this analysis was to evaluate the geographic differences of opioid administration and examine the association between opioid administration characteristics and the occurrence of respiratory depression.DesignProspective observational trial.Setting16 general care medical and surgical wards in Asia, Europe, and the United States.Patients1335 patients receiving parenteral opioids.InterventionsBlinded, alarm-silenced continuous capnography and pulse oximetry monitoring.MeasurementsOpioid-induced respiratory depression, defined as respiratory rate ≤ 5 bpm, SpO₂ ≤ 85%, or ETCO₂ ≤ 15 or ≥ 60 mmHg for ≥3 min; apnea episode lasting >30 s; or any respiratory opioid-related adverse event.ResultsAcross all patients, 58% received only long-acting opioids, 16% received only short-acting (<3 h) opioids, and 21% received a combination of short- and long-acting (≥3 h) opioids. The type and median total morphine milligram equivalent (MME) of opioid administered varied significantly by region, with 31.5 (12.5–76.7) MME, 31.0 (6.2–99.0) MME, and 7.2 (1.7–18.7) MME in the United States, Europe, and Asia, respectively (p < 0.001). Considering only postoperative opioids, 54% (N = 119/220) and 45% (N = 347/779) of patients receiving only short-acting opioids or only long-acting opioids experienced ≥1 episode of opioid-induced respiratory depression, respectively. Multivariable analysis identified post-procedure tramadol (OR 0.62, 95% CI 0.424–0.905, p = 0.0133) and post-procedure epidural opioids (OR 0.485, 95% CI 0.322–0.731, p = 0.0005) being associated with a significant reduction in opioid-induced respiratory depression.ConclusionsDespite varying opioid administration characteristics between Asia, Europe, and the United States, opioid-induced respiratory depression remains a common global problem on general care medical and surgical wards. While the use of post-procedure tramadol or post-procedure epidural opioids may reduce the incidence of respiratory depression, continuous monitoring is also necessary to ensure patient safety when receiving postoperative opioids.Registration numberwww.clinicaltrials.gov, ID: NCT02811302     

Exploratory study of VVZ-149, a novel analgesic molecule,in the affective component of acute postoperative pain after laparoscopic colorectal surgery

Study objectiveVVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A. In the present study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after colorectal surgery.DesignRandomized, parallel group, double-blind Phase 2 clinical trial (NCT02489526).Setting3 academic institutions in the United States.Patients60 patients undergoing laparoscopic colorectal surgery.InterventionsA continuous 8-h intravenous infusion of VVZ-149 Injections (n = 40) or placebo (n = 20) administered after emergence from anesthesia.MeasurementsThe outcome measures included pain intensity (PI), opioid consumption via patient-controlled analgesia (PCA), and rescue dosing provided “as needed”. Early rescue dosing with opioids postoperatively was associated with preoperative negative affect (anxiety, depression, and pain catastrophizing), enabling it to be used as an indirect measure of the affective component of pain. Efficacy outcomes were compared between treatment groups based on preoperative negative affect and early rescue dosing of opioids.Main resultsPostoperative PI was non-significantly lower in patients receiving VVZ-149 compared to those receiving placebo. The VVZ-149 group had a 34.2% reduction in opioid consumption for 24 h post-dose, along with fewer PCA demands. Somnolence and headache was higher in the intervention group. For patients characterized by high levels of preoperative negative affect, the VVZ-149 group experienced a significant pain reduction and 40% less opioid use compared to the placebo group.ConclusionsVVZ-149 resulted in a non-significant reduction of postoperative pain during the first 8 h after surgery. Post hoc analysis indicates that VVZ-149 may benefit patients with negative affect who otherwise have higher postoperative opioid use.Registration numberwww.clinicaltrials.gov, ID: NCT02489526.     

Nuts and Bolts of Patient-Reported Outcomes in Orthopaedics

Patient-reported outcomes (PROs) are commonly used in orthopaedic clinical practice, comparative effectiveness research (CER), and label claims. In this paper, we provide an overview of PROs, their development, validation, and use in orthopaedic research with examples and conclude with practical guidelines for researchers and reviewers. We discuss considerations for conceptual framework, validity, reliability, factor analysis, and measurement of change with Knee Injury and Osteoarthritis Outcome score (KOOS), as an example. We also describe advantages of instruments developed based on item response theory and statistical analyses for data collected using PRO measures. Please visit the following (https://www.youtube.com/watch?v=4p-DtZgUHOA&t=354s) for a video that explains the highlights of the paper in practical terms.     

Transversus abdominis plane block with liposomal bupivacaine versus continuous epidural analgesia for major abdominal surgery: The EXPLANE randomized trial

ObjectiveCompare transversus abdominis plane (TAP) blocks with liposomal bupivacaine were to epidural analgesia for pain at rest and opioid consumption in patients recovering from abdominal surgery.BackgroundERAS pathways suggest TAP blocks in preference to epidural analgesia for abdominal surgery. However, the relative efficacies of TAP blocks and epidural analgesia remains unknown.MethodsPatients having major abdominal surgery were enrolled at six sites and randomly assigned 1:1 to thoracic epidural analgesia or bilateral/4-quadrant TAP blocks with liposomal bupivacaine. Intravenous opioids were used as needed. Non-inferiority margins were a priori set at 1 point on an 11-point pain numeric rating scale for pain at rest and at a 25% increase in postoperative opioid consumption.ResultsEnrollment was stopped per protocol at 3rd interim analysis after crossing an a priori futility boundary. 498 patients were analyzed (255 had TAP blocks and 243 had epidurals). Pain scores at rest in patients assigned to TAP blocks were significantly non-inferior to those given epidurals, with an estimated difference of 0.09 points (CI: −0.12, 0.30; noninferiority P < 0.001). Opioid consumption during the initial 3 postoperative days in TAP patients was not non-inferior to epidurals, with an estimated ratio of geometric means of 1.37 (CI: 1.05, 1.79; non-inferiority P = 0.754). However, the absolute difference was only 21 mg morphine equivalents over the 3 days. Patients with epidurals were more likely to experience mean arterial pressures <65 mmHg than those given TAP blocks: 48% versus 31%, P = 0.006.ConclusionPain scores at rest during the initial three days after major abdominal surgery were similar. Patients assigned to TAP blocks required more opioid then epidural patients but had less hypotension. Clinicians should reconsider epidural analgesia in patients at risk from hypotension.Trial Registration: ClinicalTrials.gov Identifier: NCT02996227.