Faculty Bibliography

PURPOSE/OBJECTIVE:Safety of remdesivir in patients with renal impairment is unknown. Incidence of liver injury secondary to remdesivir is also unknown. The objective of this study is to assess the incidence of acute kidney injury (AKI) and to trend the liver enzymes during remdesivir treatment and change in eGFR from baseline to end of treatment as well as 48 h post completion of remdesivir therapy. METHODS:This is a retrospective chart review study including adult patients admitted with COVID-19 receiving remdesivir with a baseline eGFR < 30 ml/min per 1.73 m^2 from December 2020 to May 2021. The primary outcome was to assess the incidence of AKI and hepatic injury. The secondary outcome was to assess the efficacy of remdesivir defined by change in oxygen requirement. RESULTS:Seventy-one patients were included in the study. Patients experienced an improvement in eGFR from baseline (T0) to end of remdesivir treatment (T1), as well as 48 h after the end of the treatment (T2) ( + 30.3% and + 30.6% respectively, P < .0001). Creatinine reduced from baseline (T0) to T1 and T2 (-20.9% and -20.5% respectively, P < .0001). Creatinine clearance improved from baseline to T1 and T2 ( + 26.6% and + 26.2% respectively, p < .0001). Elevation of aminotransferase (AST) was observed at T1 ( + 2.5%, P  =  .727), however, AST reduction was seen at T2 (-15.8%, P  =  .021). Elevation in alanine transaminase (ALT) was observed at T1 and T2 ( + 25% and + 12%, P  =  .004 and P  =  .137 respectively). Both direct and total bilirubin remained stable and were not significantly changed from baseline. CONCLUSION/CONCLUSIONS:Our study showed that remdesivir use in renally-impaired patients with eGFR < 30 ml/min is safe. Remdesivir may be considered as a therapeutic option in this population with COVID-19 infection.

BACKGROUND:Valproic acid (VPA) has been widely used to prevent epileptic seizures after neurosurgery in China. We have found that the incidence of liver injury (LI) in patients using VPA after neurosurgery is higher than that in other patients. OBJECTIVE:The objective of this study was to investigate the risk factors of LI in patients using VPA after neurosurgery. METHODS:A nested case-control study was conducted in patients using VPA after neurosurgery between September 2019 and March 2021. Cases of LI were matched to controls by age and body mass index (BMI). Conditional logistic regression was used to estimate matched odds ratios representing the odds of LI. A receiver operating characteristic curve was used to analyze the optimal cutoff condition. RESULTS:A total of 248 people (62 LI and 186 control) were enrolled. Among patients with vs without LI, the matched odds ratio for trough concentration of VPA was significant (matched odds ratio [OR], 1.09; 95% confidence interval [CI]: 1.01-1.19). The course of treatment (OR: 1.17, 95% CI: 1.02-1.33), Glasgow score (OR: 0.26, 95% CI: 0.10-0.67), gene polymorphisms of CYP2C19 (OR: 2.09, 95% CI: 1.03-146.93), and UGT1A6 (OR: 34.61, 95% CI: 1.19-1003.23) were all related to the outcome. The optimal cutoff of the course of treatment was 10 days, while the trough concentration of VPA was determined to be 66.16 mg/L. CONCLUSION/CONCLUSIONS:Length of treatment, VPA trough concentration, and Glasgow score were associated with LI in patients after neurosurgery. A gene test may be necessary for people who are prescribed VPA for a long time.

BACKGROUND/UNASSIGNED:The prevalence of direct oral anticoagulants (DOACs) has increased with continued evidence of their efficacy and ease of use. However, the rise in their utilization also surfaced a concern regarding their reversal in patients actively bleeding and/or those requiring invasive procedures. Up until 2018, there were several reversal options available including 4-factor prothrombin complex concentrate (4-factor PCC), activated charcoal, desmopressin, and tranexamic acid. Then, in 2018, andexanet alpha, a recombinant factor Xa, was approved for the reversal of apixaban and rivaroxaban in patients with life-threatening or uncontrolled bleeding. Nonetheless, because 4-factor PCC is more easily attainable and cost-effective, it continues to be the more favorable option for many health-care professionals. METHODS/UNASSIGNED:This retrospective chart review was conducted at NYU Winthrop Hospital in patients who received 4-factor PCC for the reversal of DOACs from January 2018 to July 2018. Patient charts were reviewed and relevant data was collected (admitting diagnosis, dose of 4-factor PCC utilized, etc). RESULTS/UNASSIGNED:Fifty-three patients were evaluated with 85% experiencing a positive response and complete recovery following the administration of 4-factor PCC; 8 (15%) patients died after receiving 4-factor PCC, none as a result of its administration; 3 patients died secondary to other underlying comorbidities, 4 patients died due to an intracranial hemorrhage, and 1 died due to hematoma of the tongue. CONCLUSION/UNASSIGNED:Based on the results thus far, the use of 4-factor PCC may be a good treatment option in patients requiring DOAC reversal.

OBJECTIVE: Traumatic brain injury (TBI) is the most common cause of death and disability in persons between 15 and 30 years of age. Although various pharmacological agents have been reported to enhance consciousness recovery, few trials have studied these medications in patients with acute TBI. The objective of this study was to determine the effect of modafinil, methylphenidate, amantadine, and zolpidem in improving wakefulness in patients with TBI in an intensive care unit (ICU) setting and to identify any adverse drug reactions. METHODS: Retrospective chart review identified all patients prescribed modafinil, methylphenidate, amantadine, or zolpidem; only patients older than 18 years with TBI in an ICU setting were further analyzed. The electronic medical record was used to retrieve clinical data including patient demographics, mechanism of TBI, drug dosage, treatment duration, Glasgow Coma Scale (GCS) score, length of time to improve GCS score, hospital length of stay, reported adverse drug reactions associated with above medications, and mortality. The primary outcome was the rate of positive response in the clinical neurological exam. Secondary outcomes included change in baseline and final GCS score, time to response, duration of treatment, change in GCS score over time, length of hospital stay, and in-hospital mortality. Descriptive statistics were used to analyze the data. RESULTS: The final analysis included a total of 53 patients. Median ages ranged from 44.0 to 61.5 years; 85% of patients were male. Baseline median GCS score was 8.0 in the amantadine group; 6.5, modafinil; 7.5, methylphenidate; and 7.0, zolpidem. The highest positive response rate was 90% in the amantadine group, followed by modafinil, 77%; methylphenidate, 50%; and zolpidem, 36%. The change in baseline GCS score and median final GCS score for amantadine, modafinil, methylphenidate, and zolpidem was 2.5, 3.0, 1.0, and 0, respectively (P = 0.20). The median time to response in days was 1.5, 1.0, 0.5, and 1.0, respectively. Change in GCS score over time for amantadine, modafinil, methylphenidate, and zolpidem was 0.16, 0.38, 0.12, and 0, respectively. Though rare, the most common adverse events were agitation, hypertension, and posturing. CONCLUSION: It remains to be determined if these medications have a role in reducing ICU and hospital length of stay, length of mechanical ventilation, tracheostomies, and overall medical costs in managing TBI patients. In our study amantadine was associated with the highest overall positive response rate when used as an awakening agent in TBI. Modafinil was associated with the largest change in GCS score over time.

Objective: To determine whether the concomitant administration of vitamin C, hydrocortisone, and thiamine improves sepsis-related organ failure assessment (SOFA) score and mortality in a patient with septic and cardiogenic shock, multiple organ dysfunction syndrome (MODS), acute respiratory distress syndrome (ARDS), gram negative bacteremia, cardiomyopathy, disseminated intravascular coagulation (DIC), and 95% mortality on presentation. Design: A case report and literature review. Setting: Surgical Intensive Care Unit at NYU Winthrop Hospital. Patient: Patient with 95% mortality received appropriate treatment for septic and cardiogenic shock with no clinical improvement. Intervention: Hydrocortisone 50 mg intravenous push (IVP) every 6 hours for four days, vitamin C 1,500 mg IV every 6 hours for four days, and thiamine 200 mg intravenous piggyback (IVPB) every 12 hours for four days. Measurements and results: As seen in a retro-. spective study by Marik and associates analyzing patients with severe sepsis with elevated procalcitonin levels, administration of vitamin C, hydrocortisone, and thiamine significantly reduced the SOFA score and mortality rates. Patient was treated with combination regimen and within 72 hours of administration, he had significant improvement in his cardiac dysfunction, kidney failure, liver failure, and respiratory failure. His SOFA score greatly improved from 18 and 95% mortality to 8 and <33% mortality. Conclusion: Our patient had a remarkable survival of what was thought to be indefinite mortality with the intervention of vitamin C, hydrocortisone, and thiamine. The administration of the vitamin C protocol warrants a randomized controlled trial to change management of septic shock and mortality. We are very optimistic that it will show similar results yielding a significant decrease in mortality rates in patients with septic shock.

Amiodarone (Cordarone^®, Pfizer Inc) is an antiarrhythmic medication with a well-known toxicity profile, including rare cases of hyponatremia as a result of syndrome of inappropriate antidiuretic hormone (SIADH). We report on such a case in which a patient was found to be hyponatremic after evaluation. An 88-year-old male who presented to the emergency department was found to be hyponatremic secondary to amiodarone-induced SIADH following a fall, with possible seizure and traumatic brain injury. He had a history of hypertension, paroxysmal atrial fibrillation, emphysema, myocardial infarction, benign prostatic hyperplasia, chronic kidney disease, Meniere's disease, anemia, and gastroesophageal reflux. Upon admission, his urine sodium level was elevated, and his serum sodium, urine osmolality, and anion gap were below normal. In the setting of hyponatremia, the patient's amiodarone was held: he had been taking amiodarone 200 mg once daily for nine months prior to admission. He was treated with intravenous (IV) normal saline over four days. He was fluid-restricted and his sodium levels were closely monitored every two hours. Within 19 hours, his serum sodium levels had improved. Amiodarone was restarted approximately three days later. Upon follow-up after discharge, the patient remained on amiodarone for the next two months. His serum sodium level ranged from 126 mEq/L to 131 mEq/L over a two-week period. He was supplemented with sodium chloride tablets and has been otherwise stable. Amiodarone may cause acute or chronic SIADH, with a wide range of symptoms. Seizures have not been reported in the literature but our patient had a witnessed seizure, although his electroencephalogram (EEG) was negative. Syndrome of inappropriate antidiuretic hormone can occur with any formulation of amiodarone in a dose-dependent fashion. Our patient's sodium levels stabilized within two weeks after amiodarone was resumed. The mechanism of amiodarone-induced SIADH remains unclear.