Low dose vs high dose tocilizumab in COVID-19 patients with hypoxemic respiratory failure
PURPOSE/OBJECTIVE:Tocilizumab has been shown to decrease mortality when used concomitantly with steroids in COVID-19 with 8 mg/kg (max 800 mg) being the standard dose. Our study sought to assess whether a low dose (400 mg) shows similar benefit compared to a high dose for COVID patients concurrently on the same median dose of steroids. MATERIALS/METHODS/METHODS:A retrospective, multihospital observational study of COVID-19 patients who received tocilizumab in conjunction with steroids between March 2020 and August 2021 was conducted. RESULTS:A total of 407 patients were analyzed with low dose group being significantly more ill at baseline as a higher percentage of patients received vasopressors, were admitted to the ICU and on mechanical ventilation. In the propensity-matched analysis, both groups receiving a median dexamethasone equivalent dose of 10 mg showed no difference in 28-day mortality (p = 0.613). The high dose group had a higher rate of fungal and viral infections. CONCLUSION/CONCLUSIONS:Compared to low dose tocilizumab, the high dose did not provide additional efficacy and mortality benefit but resulted in higher fungal and viral infections. This study illustrates that low dose tocilizumab can be an alternative to high dose during a drug shortage of tocilizumab without compensating for efficacy and safety, conserving resources for more patients.
LOW-DOSE VERSUS HIGH-DOSE TOCILIZUMAB IN COVID-19 PATIENTS WITH HYPOXIC RESPIRATORY FAILURE [Meeting Abstract]
INTRODUCTION: Tocilizumab has been shown to decrease mortality when used concomitantly with steroids in COVID-19. Tocilizumab dose of 8 mg/kg (max: 800 mg), stemmed from the RECOVERY trial, has been the standard dose for COVID. Due to a drug shortage of tocilizumab, our study seeks to assess whether low dose (400 mg) shows similar benefit compared to high dose for COVID patients concurrently on same median dose of steroids.
METHOD(S): This was a retrospective observational study of COVID-19 patients who received tocilizumab in conjunction with steroids. Between March 2020 and August 2021, adult patients with positive COVID-19 PCR, hypoxic respiratory failure defined as FiO2>70%, and received a dose of tocilizumab in conjunction with steroids were included. Patients were excluded if they have died within 24 hours of treatment initiation. Primary outcome was 28-day mortality and secondary outcomes included biomarker improvement and relative risk of infection. Propensity matched analysis between groups was performed.
RESULT(S): A total of 407 patients met the study criteria and were analyzed. The low dose and high dose tocilizumab group had 222 and 185 patients respectively. Gender and age were similar between groups and all patients received steroids. The low dose group was significantly more ill at baseline as a higher percentage of patients received vasopressors, were admitted to the ICU and on mechanical ventilation. In the propensity-matched analysis of 56 patients in each group, with a median dose of steroid of 10 mg in both groups showed no difference in 28 day mortality (HR 0.82 [95% CI: 0.41-1.67]; p=0.6138). A greater decrease to normalization of CRP (p< 0.0001) and downtrend of ferritin (p=0.503) was observed in the high dose group at day 14. The high dose group trended a higher rate of fungal and viral infections.
CONCLUSION(S): Compared to low dose tocilizumab, high dose did not provide additional efficacy and mortality benefit but resulted in uptrend of fungal and viral infections. While a greater decrease in CRP was seen in the high dose group, it did not translate into lower mortality. This study illustrates that low dose tocilizumab can be an alternative to high dose during a drug shortage of tocilizumab without compensating for efficacy and safety, conserving resources for more patients
The incidence of propofol infusion syndrome in critically-ill patients
PURPOSE/OBJECTIVE:PRIS is a potentially fatal syndrome characterized by various clinical symptoms and abnormalities. Experts suggest that propofol treatment duration â‰¥48 h or dose â‰¥83 Î¼g/kg/min is associated with developing PRIS. We hypothesized PRIS might be underdiagnosed due to the overlap of PRIS clinical manifestations with critical illnesses. MATERIALS AND METHODS/METHODS:Multihospital, retrospective study of adult patients who received continuous propofol infusion â‰¥48 h or dose â‰¥60Î¼g/kg/min for >24 h since admission were assessed for the development of PRIS. RESULTS:The incidence of PRIS was 2.9% with a PRIS-associated mortality rate of 36.8%. In PRIS patients, propofol was administered at a median dose of 36.4 Î¼g/kg/min and over a median duration of 147.0 h. The development of PRIS was observed at a median of 125.0 h post-propofol initiation and a cumulative dose of 276.5 mg/kg. The development of metabolic acidosis (78.9%), cardiac dysfunction (52.6%), hypertriglyceridemia (100%), and rhabdomyolysis (26.3%) were observed in our PRIS patients. CONCLUSION/CONCLUSIONS:PRIS can often be overlooked and underdiagnosed. It is important to monitor for early signs of PRIS in patients who are on prolonged propofol infusion. Prompt recognition and interventions can minimize the dangers resulting from PRIS.
The Use of High-Dose Corticosteroids Versus Low-Dose Corticosteroids With and Without Tocilizumab in COVID-19 Acute Respiratory Distress Syndrome
BACKGROUND/UNASSIGNED:Corticosteroids and tocilizumab have been shown to improve survival in patients who require supplemental oxygen from coronavirus disease 2019 (COVID-19) pneumonia. The optimal dose of immunosuppression for the treatment of COVID-19 acute respiratory distress syndrome (ARDS) is still unknown. OBJECTIVE/UNASSIGNED:The objective of this study was to evaluate the effectiveness and safety of high- versus low-dose corticosteroids with or without tocilizumab for the treatment of COVID-19 ARDS. METHODS/UNASSIGNED:This was a retrospective study of patients admitted to the intensive care unit (ICU) requiring mechanical ventilation who received high- versus low-dose corticosteroids with or without tocilizumab. The primary outcome was survival to discharge. Safety outcomes included infections and incidence of hyperglycemia. RESULTS/UNASSIGNED:= 0.01). The highest rate of a bacterial pneumonia was in patients who received high-dose corticosteroids with tocilizumab. CONCLUSIONS/UNASSIGNED:In critically ill patients with COVID-19 ARDS requiring mechanical ventilation, we found no difference in high- versus low-dose corticosteroids with regard to survival to hospital discharge. However, patients receiving only low-dose corticosteroids without tocilizumab did worse than the other groups. Larger prospective studies are needed to determine the optimal immunosuppression dosing strategy in this patient population.
Reply: Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk [Comment]
Prevalence of propofol infusion syndrome in critically ill patients [Meeting Abstract]
INTRODUCTION: Propofol has been widely used in the ICU for sedation and refractory status epilepticus. PRIS is a serious and potentially fatal condition that is characterized by a spectrum of clinical symptoms and abnormalities. Literature suggests that a longer duration of propofol >= 48 hours or a dose >= 83 mcg/kg/min is associated with a higher risk of PRIS. Many of the critically ill patients in our health system required a larger dose of propofol and prolonged duration of infusion for sedation in the ICU, especially during Covid-19. Delayed treatment of PRIS can lead to death. It is very likely that patients who develop PRIS may often go unrecognized as the manifestations of PRIS can overlap with common ICU conditions. The current prevalence of PRIS is unknown, however, a prospective study has reported a prevalence of 1.1% in critically ill patients.
METHOD(S): Patients were identified by querying the NYU Langone Health COVID clinical data mart from March 2020 till February 2021. The inclusion criteria included patients receiving propofol infusion for >= 48 hours or receiving a dose >= 60 mcg/kg/min for more than 24 hours. Pregnant patients, children, and patients with rhabdomyolysis prior to the start of infusion were excluded. PRIS was defined by the development of metabolic acidosis and cardiac dysfunction with 2 or more minor criteria (rhabdomyolysis, hypertriglyceridemia, renal failure, and hepatic transaminitis) or developing 3 or more minor criteria.
RESULT(S): 424 patients were included in our study. Of the 424 patients, 21 patients were found to have developed PRIS. The occurrence of PRIS was observed at the median infusion rate of 36.1 mcg/kg/min and a median duration of infusion of 147 hours. The prevalence of PRIS was found to be 4.9%.
CONCLUSION(S): The prevalence of PRIS in our study was found to be 4.9%. The occurrence of PRIS was observed at the median infusion rate of 36.1 mcg/kg/min suggesting that PRIS can be developed at a lower rate of infusion than previously reported. We suggest that patients - especially those receiving a duration >= 48 hours and a higher dose of 60 mcg/kg/min - should be monitored for signs and symptoms of PRIS during propofol infusion as it may be underrecognized because PRIS is characterized by multiple clinical manifestations that overlap with critical illness
Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk
BACKGROUND:Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven. OBJECTIVES/OBJECTIVE:The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure. METHODS:A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit. RESULTS:= 0.005] without increasing the risk of infection. CONCLUSION AND RELEVANCE/UNASSIGNED:Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.
Real-World Experience Using Cefpodoxime and Cefuroxime Axetil for Urinary Tract Infections at a Large Academic Medical Center
Safety of intravenous push administration of beta-lactams within a healthcare system
PURPOSE:A critical shortage of small-volume parenteral solutions in late 2017 led hospitals to develop strategies to ensure availability for critical patients, including administration of antibiotics as intravenous push (IVP). Minimal literature has been published to date that assesses the safety of administration of beta-lactams via this route. Therefore, the purpose of this study was to evaluate the safety of IVP administration of select beta-lactam antibiotics. METHODS:We performed a retrospective review of IVP administrations of aztreonam, ceftriaxone, cefepime, and meropenem at two campuses of the New York University Langone Health system after October 2017. Patients receiving surgical prophylaxis or more than one IVP antibiotic simultaneously were excluded. The primary endpoint was adverse events (ADE) following IVP administration of antibiotics. RESULTS:We evaluated 1000 patients who received IVP aztreonam (n = 43), ceftriaxone (n = 544), cefepime (n = 368) or meropenem (n = 45). There were 10 (1%) ADE observed, 5 of which were allergic reactions. Four ADE were neurotoxicity related to IVP cefepime. Based on the Naranjo score, 1 adverse event was "probably" and 3 were "possibly" related to cefepime IVP administration. Lastly, only 1 report of phlebitis was observed with the use of IVP ceftriaxone. CONCLUSIONS:The use of IVP as an alternative to intravenous piggyback (IVPB) during times of drug shortage for select beta-lactam antibiotics appears to be safe, and ADE are similar to those previously described for IVPB administration. Future studies evaluating clinical outcomes between IVP and IVPB administration may be of benefit.
The Safety of Midline Catheters for Intravenous Therapy at a Large Academic Medical Center
Background: Midline catheters (MCs) have arisen as alternatives to peripherally inserted central catheters (PICCs) for both general intravenous therapy and extended outpatient parenteral therapy. However, there is a lack of data concerning the safety of medication therapy through midline for extended durations. Objective: The purpose of this study is to evaluate the safety of MCs for extended intravenous use. Methods: This was a retrospective cohort study evaluating patients who received intravenous therapy through an MC at a tertiary care academic medical center. The primary end point was the incidence of composite catheter-related adverse events that included local events, catheter dislodgment, infiltration, catheter occlusion, catheter-related venous thromboembolism, extravasation, and line-associated infection. Results: A total of 82 MC placements and 50 PICC placements were included; 50 MCs were for outpatient parenteral antimicrobial therapy, and 32 were for inpatient intravenous use. There were 21 complications per 1000 catheter-days in the outpatient group and 7 complications per 1000 catheter-days in the PICC group (P = 0.91). The median time to complication in both groups was 8 days. The antimicrobial classes commonly associated with complications were cephalosporins, carbapenems, and penicillins. Conclusion and Relevance: Our results suggest that intravenous therapy with MCs is generally safe for prolonged courses that do not exceed 14 days as compared with PICC lines, which can be placed for months. There is still limited evidence for the use of MCs between 14 and 28 days of therapy. This study can help guide our selection of intravenous catheters for the purpose of outpatient antimicrobial therapy.