Effect of P2Y12 inhibitors on organ support-free survival in critically ill patients hospitalized for COVID-19: A randomized clinical trial

IMPORTANCE: Platelet activation is a potential therapeutic target in patients with COVID-19. OBJECTIVE: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients. INTERVENTION: Participants were randomly assigned to receive a P2Y12 inhibitor or no P2Y12 inhibitor (usual care) for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death and, for participants who survived to hospital discharge, the number of days free of cardiovascular or respiratory organ support up to day 21 of the index hospitalization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Hemostasis. RESULTS: At the time of trial termination, 949 participants (median [IQR] age, 56 [46-65] years; 603 male [63.5%]) had been randomly assigned, 479 to the P2Y12 inhibitor group and 470 to usual care. In the P2Y12 inhibitor group, ticagrelor was used in 372 participants (78.8%) and clopidogrel in 100 participants (21.2%). The estimated adjusted odds ratio (AOR) for the effect of P2Y12 inhibitor on organ support-free days was 1.07 (95% credible interval, 0.85-1.33). The posterior probability of superiority (defined as an OR \u3e 1.0) was 72.9%. Overall, 354 participants (74.5%) in the P2Y12 inhibitor group and 339 participants (72.4%) in the usual care group survived to hospital discharge (median AOR, 1.15; 95% credible interval, 0.84-1.55; posterior probability of superiority, 80.8%). Major bleeding occurred in 13 participants (2.7%) in the P2Y12 inhibitor group and 13 (2.8%) in the usual care group. The estimated mortality rate at 90 days for the P2Y12 inhibitor group was 25.5% and for the usual care group was 27.0% (adjusted hazard ratio, 0.96; 95% CI, 0.76-1.23; P = .77). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of critically ill participants hospitalized for COVID-19, treatment with a P2Y12 inhibitor did not improve the number of days alive and free of cardiovascular or respiratory organ support. The use of the P2Y12 inhibitor did not increase major bleeding compared with usual care. These data do not support routine use of a P2Y12 inhibitor in critically ill patients hospitalized for COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04505774

Splenic Embolization Decreases Infectious Complications and Resource Utilization Compared to Splenectomy in Severely Injured Patients

Introduction. Increasing use of main coil angioembolization for splenic injury has raised concerns of increased complication rates and resource utilization compared to splenectomy. This study examined complication rates for severely injured patients undergoing splenectomy versus main coil angioembolization. Methods. Demographic data (age, sex, and race), Injury Severity Score (ISS), and splenic injury grade were collected prospectively on all patients admitted to the intensive care unit with blunt splenic injury treated with splenectomy or main coil angioembolization. Outcome measures (transfusion requirements, mechanical ventilation use and duration, mortality, intensive care unit and hospital length of stay, infection rate, and systemic inflammatory response syndrome or SIRS score) were reviewed daily. Results. Of 116 patients reviewed, 65 underwent splenectomy and 51 underwent main coil angioembolization. Groups were comparable for age, sex, race, and mechanism of injury. Splenectomized patients had a higher ISS (41 vs 31) and splenic injury grade (3.7 vs 3.2). The main coil angioembolization group had a lower transfusion requirement, hospital length of stay, incidence of mechanical ventilation, nosocomial infection rate, and SIRS score. Overall, mortality and ventilator days were lower but not statistically significant. Conclusions. Severely injured patients treated with splenectomy had significantly higher infection rates and resource utilization compared to those treated with main coil angioembolization

Utility of esophageal gastroduodenoscopy at the time of percutaneous endoscopic gastrostomy in trauma patients

<p>Abstract</p> <p>Background</p> <p>The utility of esophagogastroduodenoscopy (EGD) performed at the time of percutaneous endoscopic gastrostomy (PEG) is unclear. We examined whether EGD at time of PEG yielded clinically useful information important in patient care. We also reviewed the outcome and complication rates of EGD-PEG performed by trauma surgeons.</p> <p>Methods</p> <p>Retrospective review of all trauma patients undergoing EGD with PEG at a level I trauma center from 1/01–6/03.</p> <p>Results</p> <p>210 patients underwent combined EGD with PEG by the trauma team. A total of 37% of patients had unsuspected upper gastrointestinal lesions seen on EGD. Of these, 35% had traumatic brain injury, 10% suffered multisystem injury, and 47% had spinal cord injury. These included 15 esophageal, 61 gastric, and six duodenal lesions, mucosal or hemorrhagic findings on EGD. This finding led to a change in therapy in 90% of patients; either resumption/continuation of H₂-blockers or conversion to proton-pump inhibitors. One patient suffered an upper gastrointestinal bleed while on H2-blocker. It was treated endoscopically. Complication rates were low. There were no iatrogenic visceral perforations seen. Three PEGs were inadvertently removed by the patient (1.5%); one was replaced with a Foley, one replaced endoscopically, and one patient underwent gastric repair and open jejunostomy tube. One PEG leak was repaired during exploration for unrelated hemorrhage. Six patients had significant site infections (3%); four treated with local drainage and antibiotics, one requiring operative debridement and later closure, and one with antibiotics alone.</p> <p>Conclusion</p> <p>EGD at the time of PEG <b>may add </b>clinically useful data in the management of trauma patients. Only one patient treated with acid suppression therapy for EGD diagnosed lesions suffered delayed gastrointestinal bleeding. Trauma surgeons can perform EGD and PEG with acceptable outcomes and complication rates.</p

Percutaneous Endoscopic Gastrostomy in the Super-Morbidly Obese Patient

INTRODUCTION: Obesity is reaching epidemic proportions in the United States, and as patients at the extremes of morbid obesity come under the care of surgeons, routine procedures may become increasingly complex in the face of greater body mass. We prospectively evaluated the success rate of percutaneous endoscopic gastrostomy (PEG) placement in a group of morbidly obese patients outside the current classification systems used to stratify obesity. METHODS: Patients with a body mass index (BMI) greater than 60 kg/m2 who presented for PEG over a one year period were prospectively enrolled. Each patient underwent attempted PEG placement using the pull method by a single surgeon. Outcome variables included: successful PEG, wound infection, tube dislodgement, or bleeding. RESULTS: Six patients with BMI \u3e 60 kg/m2 presented for PEG. All patients were in a surgical critical care unit maintained on mechanical ventilation. All underwent successful PEG placement with standard techniques and sustained no post-procedural complications. CONCLUSION: In the hands of an experienced surgical endoscopist, percutaneous endoscopic gastrostomy can be safely performed in patients at the extremes of morbid obesity. Future studies are warranted to validate the results of our small series