Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Study of the effect of oral gabapentin used as preemptive analgesia to attenuate post-operative pain in patients undergoing abdominal surgery under general anesthesia

Aims: To study the effect of oral gabapentin used as preemptive analgesia to attenuate post operative pain in patients undergoing abdominal surgery under general anesthesia. Materials and Methods: In a randomized double blind study, 60 patients were divided into two groups. Group A received 600mg gabapentin and group B oral received placebo 1 h prior to surgery. Anesthesia was induced with Propofol 2 mg/kg and Vecuronium 0.1mg/kg and maintained with 60% N 2 O in O 2 and Vecuronium 0.02 mg/kg. All cases were given Fentanyl 2μg/kg as pre-medication and a repeat dose 1μg/kg at the end of the first hour. Assessment of post-operative pain was made with the visual analog score (VAS) at extubation (0 h), 2, 4, 6, 12, and 24 h post-operatively. Post-operative analgesia was provided with intravenous Tramadol. The first dose was given in the Post Anesthesia Care Unit as 2mg/kg, and repeated at 8 and 16 h. Rescue analgesia was given with Diclofenac 1.5mg/kg, slow intravenous. The number of doses of rescue analgesia in both the groups was noted. Results: The VAS scores at 0, 2, 4, 6, 12, and 24 h were 1.9 vs. 2.4 (P=0.002), 2.3 vs. 3.0 (P=0.000), 3.2 vs. 3.7 (P=0.006), 2.9 vs. 4.4 (P=0.000), 3.6 vs. 4.6 (P=0.000), and 3.7 vs.4.6 (P=0.000), respectively. Numbers of patients requiring rescue analgesia with Diclofenac were 3 vs. 14 (P=0.004). Conclusion: A single oral dose of gabapentin given pre-operatively enhanced the analgesic effect of Tramadol as it also reduced the requirement of rescue analgesia with Diclofenac

Role of Neuromuscular Junction Monitoring in Management of a Postpartum Eclamptic Patient with Iatrogenic Hypermagnesemia

Accidental hypermagnesemia is a common and often missed complication during treatment in a postpartum eclamptic patient. As symptomatic hypermagnesemia leads to neuromuscular junction blockade, neuromuscular junction monitoring serves the purpose of vigilant monitoring and prevents iatrogenic overdose of magnesium

Acute Reversal of Warfarin Therapy in Patient with Protein C and S Deficiency Presenting for Emergency Surgery

This is a case report of a 19 year young male presented with swelling and blackening of right upper limb and abdominal pain since 10 days. He was a known case of protein C and protein S deficiency on warfarin therapy, with deranged coagulation parameters posted for amputation fingers in emergenc

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc

Long-term (180-Day) outcomes in critically Ill patients with COVID-19 in the REMAP-CAP randomized clinical trial

Importance The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. Objective To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. Design, Setting, and Participants Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. Interventions Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). Main Outcomes and Measures The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. Results Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies. Conclusions and Relevance Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months

Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial

International audienc