Nitrous oxide for the treatment of complex regional pain syndrome: a randomized blinded trial.

INTRODUCTION: Complex Regional Pain Syndrome (CRPS) is a debilitating neuropathic condition often refractory to conventional treatments. N-methyl-D-aspartate (NMDA) receptor antagonists have a well-established role in the development and modulation of chronic neuropathic pain. Nitrous oxide is widely used and generally safe anesthetic gas with NMDA receptor antagonist activity. We therefore tested the hypothesis that brief periods of nitrous oxide exposure reduce pain in patients with CRPS. METHODS: Patients with a diagnosis of CRPS were randomized to either 2 hours of nitrous oxide exposure on three alternating days (Nitrous Oxide) versus a placebo air/oxygen mixture (Air-Oxygen). Our primary outcome was patient-reported pain scores at 1 week and 1 month. Secondary and exploratory outcomes were physical and mental health (PRMOIS-29 v2 survey), specific neuropathic pain symptoms (McGill short-form questionnaire), and opioid consumption. RESULTS: 44 patients participated in the study; 20 were randomized to Nitrous Oxide and 24 were assigned to Air-Oxygen. Pain scores did not differ significantly, with the estimated difference in means (Nitrous Oxide-Air-Oxygen) of -0.57 (95% CI: -1.42 to 0.28) points, p=0.19. There were also no differences detected in secondary outcomes, with the estimated difference in mean Z-scores for physical health (Nitrous Oxide-Air-Oxygen) of 0.13 (95% CI: -0.16 to 0.43), mental health 0.087 (95% CI: -0.31 to 0.48), and Patient Global Impression of Change score -0.7 (95% CI: -1.85 to 0.46). CONCLUSIONS: Compared with air/oxygen, 2 hours of nitrous oxide/oxygen exposure for three sessions did not provide meaningful therapeutic potential for patients with chronic CRPS. Our results do not support using nitrous oxide for the treatment of CRPS.

Cooling vest improves surgeons' thermal comfort without affecting cognitive performance: a randomised cross-over trial.

OBJECTIVES: Surgeons become uncomfortable while performing surgery because heat transfer and evaporative cooling are restricted by insulating surgical gowns. Consequently, perceptions of thermal discomfort during surgery may impair cognitive performance. We, therefore, aimed to evaluate surgeons' thermal comfort, cognitive performance, core and mean skin temperatures, perceptions of sweat-soaked clothing, fatigue and exertion with and without a CoolSource cooling vest (Cardinal Health, Dublin, Ohio, USA). METHODS: Thirty orthopaedic surgeons participated in a randomised cross-over trial, each performing four total-joint arthroplasties with randomisation to one of four treatment sequences. The effects of cooling versus no cooling were measured using a repeated-measures linear model accounting for within-subject correlations. RESULTS: The cooling vest improved thermal comfort by a mean (95% CI) of -2.1 (-2.7 to -1.6) points on a 0-10 scale, p<0.001, with no evidence of treatment-by-period interaction (p=0.94). In contrast, cooling had no perceptible effect on cognition, with an estimated mean difference (95% CI) in Cleveland Clinic Cognitive Battery (C3B) Processing Speed Test score of 0.03 (95% CI -2.44 to 2.51), p=0.98, or in C3B Visual Memory Test score with difference of 0.88 (95% CI -2.25 to 4.01), p=0.57. Core temperature was not lower with the cooling vest, with mean difference (95% CI) of -0.13 (-0.33°C to 0.07°C), p=0.19, while mean skin temperature was lower, with mean difference of -0.23 (95% CI -0.40°C to -0.06°C) lower, p=0.011. The cooling vest significantly reduced surgeons' perceptions of sweat-soaked clothing, fatigue and exertion. CONCLUSIONS: A cooling vest worn during surgery lowered core and skin temperatures, improved thermal comfort, and decreased perceptions of sweating and fatigue, but did not improve cognition. Thermal discomfort during major orthopaedic surgery is thus largely preventable, but cooling does not affect cognition. TRIAL REGISTRATION NUMBER: NCT04511208.

Relative contributions of anaemia and hypotension to myocardial infarction and renal injury: Post hoc analysis of the POISE-2 trial.

BACKGROUND: Hypotension and postoperative anaemia are associated with myocardial and renal injury after noncardiac surgery, but the interaction between them remains unknown. OBJECTIVES: To test the hypothesis that a double-hit of postoperative anaemia and hypotension synergistically worsens a 30-day composite of myocardial infarction (MI) and mortality and acute kidney injury (AKI). Characterising the interaction when hypotension and anaemia occur at same time on myocardial infarction and acute kidney injury. DESIGN: Post hoc analysis of the POISE-2 trial. SETTING: Patients were enrolled between July 2010 and December 2013 at 135 hospitals in 23 countries. PATIENTS: Adults at least 45 years old with known or suspected cardiovascular disease. We excluded patients without available postoperative haemoglobin measurements or hypotension duration records. Exposures were the lowest haemoglobin concentration and the average daily duration of SBP less than 90 mmHg within the first four postoperative days. MAIN OUTCOME MEASURES: The primary outcome was a collapsed composite of nonfatal MI and all-cause mortality during the initial 30 postoperative days; our secondary outcome was AKI. RESULTS: We included 7940 patients. The mean ±â€ŠSD lowest postoperative haemoglobin was 10 ±â€Š2 g dl -1 , and 24% of the patients had SBP less than 90 mmHg with daily duration ranging from 0 to 15 h. Four hundred and nine (5.2%) patients had an infarction or died within 30 postoperative days, and 417 (6.4%) patients developed AKI. Lowest haemoglobin concentrations less than 11 g dl -1 , and duration of SBP less than 90 mmHg was associated with greater hazard of composite outcome of nonfatal MI and all-cause mortality, as well as with AKI. However, we did not find significant multiplicative interactions between haemoglobin splines and hypotension duration on the primary composite or on AKI. CONCLUSION: Postoperative anaemia and hypotension were meaningfully associated with both our primary composite and AKI. However, lack of significant interaction suggests that the effects of hypotension and anaemia are additive rather than multiplicative. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01082874.

Hypoventilation in the PACU is associated with hypoventilation in the surgical ward: Post-hoc analysis of a randomized clinical trial.

OBJECTIVE: To evaluate the association between early postoperative hypoventilation in the last hour of the post-anesthesia care unit (PACU) stay and hypoventilation during the rest of the first 48 postoperative hours in the surgical ward. DESIGN: Sub-analysis of a clinical trial. SETTING: PACU and surgical wards of a single medical center. PATIENTS: Adults having abdominal surgery under general anesthesia. INTERVENTIONS: Monitoring with a respiratory volume monitor from admission to PACU until the earlier of 48 h after surgery or discharge. MEASUREMENTS: The exposure was having at least one low minute-ventilation (MV) event during the last hour of PACU stay, defined as MV lower than 40% the predicted value lasting at least 1 min. The primary outcome was low MV events lasting at least 2 min during the rest of the first 48 postoperative hours, while in the surgical ward. The secondary outcome was the rate of low MV events per monitored hour. MAIN RESULTS: Data of 292 patients were analyzed, of which 20 (6.8%) patients had a low MV event in PACU. Low MV events in the surgical ward were found in 81 (28%) patients. All patients who had low MV events in PACU had events again in the ward, while 61/272 (22%) had an event in the ward but not in PACU. The incidence rate of low MV events per hour was 24 (95% CI: 13, 46) among patients having an event in the PACU, and 2 (1, 4) among those who did not. CONCLUSIONS: In adults recovering from abdominal surgery, events of hypoventilation during the first postoperative hour are associated with similar events during the rest of the first 48 postoperative hours, with positive predictive value approaching 100%. Sixty-one patients had ward hypoventilation that was not preceded by hypoventilation in PACU.

Effect of Intravenous Acetaminophen on Mean Arterial Blood Pressure: A Post Hoc Analysis of the EFfect of Intravenous ACetaminophen on PosToperative HypOxemia After Abdominal SurgeRy Trial.

BACKGROUND: Acetaminophen is commonly used as part of multimodal analgesia for acute pain. The intravenous formulation offers a more predictable bioavailability compared to oral and rectal acetaminophen. There have been reports of hypotension with intravenous acetaminophen attributable to centrally mediated and vasodilatory effects. We tested the hypothesis that in adults having abdominal surgery the use of intravenous acetaminophen versus placebo for postoperative pain management is associated with a decrease in mean arterial pressure (MAP) after its administration. METHODS: This is a substudy of eFfect of intravenous ACetaminophen on posToperative hypOxemia after abdominal surgeRy (FACTOR) trial (NCT02156154). FACTOR trial randomly assigned adults undergoing abdominal surgery to either 1 g of acetaminophen or placebo every 6 hours during the first postoperative 48 hours. Continuous monitoring of blood pressure was obtained by noninvasive ViSi Mobile device (Sotera Wireless, Inc, San Diego, CA) at 15-second intervals during initial 48 hours postoperatively. We excluded patients without continuous monitoring data available. The primary outcome was the MAP difference between MAP 5 minutes before study drug administration (baseline) and MAP 30 minutes poststudy drug administration initiation. We used a linear mixed effects model to assess the treatment effect on MAP change. The secondary outcome was MAP area under baseline (AUB) during the 30 minutes after treatment. In a sensitivity analysis of change in MAP from predrug to postdrug administration, we instead used postdrug MAP as the outcome adjusting for the baseline MAP in the model. RESULTS: Among 358 patients analyzed, 182 received acetaminophen and 176 placebo. The mean (standard deviation [SD]) of average MAP change was -0.75 (5.9) mm Hg for the treatment and 0.32 (6.3) mm Hg for the placebo. Acetaminophen was found to decrease the MAP from baseline more than placebo after drug administration. The estimated difference in mean change of MAP was -1.03 (95% confidence interval [CI] -1.60 to -0.47) mm Hg; P < .001. The sensitivity analysis showed postoperative MAP in the acetaminophen group was 1.33 (95% CI, 0.76-1.90) mm Hg lower than in the placebo group (P < .001). The median of MAP AUB was 33 [Q1 = 3.3, Q3 = 109] mm Hg × minutes for the treatment and 23 [1.6, 79] mm Hg × minutes for the placebo. Acetaminophen was found to increase the AUB with an estimated median difference of 15 (95% CI, 5-25) mm Hg × minutes (P = .003). CONCLUSIONS: Intravenous acetaminophen decreases MAP after its administration. However, this decrease does not appear to be clinically meaningful. Clinicians should not refrain to use intravenous acetaminophen for acute pain management because of worries of hypotension.

Association between In-hospital Mortality and Low Cardiac Output Syndrome with Morning versus Afternoon Cardiac Surgery.

BACKGROUND: Recent work suggests that having aortic valve surgery in the morning increases risk for cardiac-related complications. This study therefore explored whether mortality and cardiac complications, specifically low cardiac output syndrome, differ for morning and afternoon cardiac surgeries. METHODS: The study included adults who had aortic and/or mitral valve repair/replacement and/or coronary artery bypass grafting from 2011 to 2018. The components of the in-hospital composite outcome were in-hospital mortality and low cardiac output syndrome, defined by requirement for at least two inotropic agents at 24 to 48 h postoperatively or need for mechanical circulatory support. Patients who had aortic cross-clamping between 8 and 11 am (morning surgery) versus between 2 and 5 pm (afternoon surgery) were compared on the incidence of the composite outcome. RESULTS: Among 9,734 qualifying operations, 0.4% (29 of 6,859) died after morning, and 0.7% (20 of 2,875) died after afternoon surgery. The composite of in-hospital mortality and low cardiac output syndrome occurred in 2.8% (195 of 6,859) of morning patients and 3.4% (97 of 2,875) of afternoon patients: morning versus afternoon confounder-adjusted odds ratio, 0.96 (95% CI, 0.75 to 1.24; P = 0.770). There was no evidence of interaction between morning versus afternoon and surgery type (P = 0.965), and operation time was statistically nonsignificant for surgery subgroups. CONCLUSIONS: Patients having aortic valve surgery, mitral valve surgery, and/or coronary artery bypass grafting with aortic cross-clamping in the morning and afternoon did not have significantly different outcomes. No evidence was found to suggest that morning or afternoon surgical timing alters postoperative risk.

A guide to regional analgesia for Total Knee Arthroplasty.

Regional analgesia has been introduced successfully into the postoperative pain management after total knee arthroplasty, reducing pain scores, opioid use and adverse effects. Combination of regional analgesia techniques is associated with better pain management and lower side effects than single regional techniques. Adductor canal block provides good analgesia and considerably lower detrimental effect in muscular strength than femoral nerve block, enhancing surgical recovery. Infiltration techniques may have equivalent analgesic effect than epidural analgesia and peripheral nerve blocks, however there should be awareness of dose dependent toxicity. Novel long-acting local anesthetics role for regional analgesia is still to be determined, and will require larger randomized trials to support its advantage over traditional local anesthetics.