An Evaluation of the Incidence of Nephrotoxicity After a Loading Dose of Vancomycin in Patients With Severe Renal Impairment.

BACKGROUND: Loading doses of vancomycin assist in the rapid achievement of target trough concentrations. Patients with renal dysfunction have been excluded from studies evaluating loading doses. OBJECTIVE: The purpose of this study was to investigate nephrotoxicity related to initial vancomycin dose in patients with severe renal dysfunction. METHODS: A retrospective cohort study was approved by the Institutional Review Board of a large, academic health system. Adults were included if they received intravenous vancomycin in the emergency department and presented with creatinine clearance < 30 mL/min. Chronic dialysis patients were excluded. The primary outcome was incidence of nephrotoxicity after an initial high (>20 mg/kg) vs. low (≤20 mg/kg) dose of vancomycin. Secondary outcomes included dialysis, vancomycin concentrations, length of stay, in-hospital mortality, and a composite outcome of nephrotoxicity or dialysis. RESULTS: Of the 927 patients included in the analysis, nephrotoxicity occurred in 7.2% and 13.8% of patients in the high- and low-dose groups, respectively (p < 0.01). Patients in the high-dose group had a reduced risk of nephrotoxicity (relative risk 0.53; 95% confidence interval 0.35-0.78). The reduction in risk remained after fitting a generalized linear model adjusting for weight, age, sex, initial serum creatinine, diabetes, and chronic kidney disease (relative risk 0.61; 95% confidence interval 0.39-0.93). Limitations of this study include its retrospective design and single-center population. CONCLUSION: These data suggest that vancomycin loading doses do not increase nephrotoxicity compared with lower doses in patients with severe renal dysfunction. These patients should be included in future studies relating to vancomycin loading doses.

Even Faster Door-to-Alteplase Times and Associated Outcomes in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The timely administration of thrombolytic therapy for acute ischemic stroke has been associated with good functional outcomes. Current guidelines recommend alteplase administration within 60 minutes in 75% of eligible patients and within 45 minutes in 50% of patients. There is limited evidence guiding these measures and their effect on outcomes. We report a single-center, retrospective assessment of the safety and efficacy of alteplase treatment within 45 minutes. METHODS: Five hundred and eighty-six patients were treated with alteplase in our emergency departments (EDs) between January 2014 and October 2016; 368 patients were included for analysis. Multivariate regression analysis was used to assess the association between door-to-alteplase (DTA) times and 90-day modified Rankin scale (mRS) scores. Incidence of intracerebral hemorrhage (ICH) was also documented. RESULTS: The median DTA time was 29 minutes versus 64 minutes in the DTA less than or equal to 45 minutes arm and more than 45 minutes arm, respectively. The primary outcome of 90-day mRS 0-1 was achieved in 56% of patients in the less than or equal to 45 minutes group versus 58% in more than 45 minutes group (P = .67). Odds of achieving mRS 0-1 were not significantly impacted by DTA times. In the multivariate regression analysis, patient characteristics associated with achieving mRS 0-1 were: younger age, male sex, not requiring intubation in the ED, and without prior history of hypertension, atrial fibrillation, or stroke. There was no significant difference in rates of ICH for patients less than or equal to 45 minutes versus more than 45 minutes. CONCLUSIONS: Rapid administration of alteplase was not associated with significantly better outcomes nor increased risk of ICH. Conclusions about efficacy are limited due to the retrospective nature of the study, small sample size, and incomplete data points.

A randomized trial of loading vancomycin in the emergency department.

BACKGROUND: Optimizing vancomycin dosing may help eradicate bacteria while avoiding resistance. The guidelines recommend loading doses; however, there are no data to demonstrate that this may result in a more rapid achievement of therapeutic troughs. OBJECTIVE: To evaluate the percentage of troughs reaching therapeutic levels at 12, 24, and 36 hours following an initial vancomycin dose of 30 mg/kg compared with 15 mg/kg. METHODS: This prospective, randomized study was performed in a community academic medical center. Patients who were to receive vancomycin in the emergency department were randomized to an initial traditional dose of 15 mg/kg or a 30-mg/kg loading dose followed by 15 mg/kg every 12 hours for 3 doses. Patients weighing >120 kg or with creatinine clearances <50 mL/min were excluded. RESULTS: In total, 99 patients were enrolled; 12 hours after the initial dose of vancomycin, there was a significantly greater proportion of patients reaching target trough levels of 15 mg/L among the patients who received a loading dose as compared with a traditional dose (34% vs 3%, P < 0.01). This trend continued at 24 hours but was not statistically significant. At 36 hours, there was no difference in the percentage of patients reaching target levels between the 2 groups. No statistically significant difference in nephrotoxicity or adverse events among the 2 groups was demonstrated. CONCLUSION: A loading dose of 30 mg/kg of vancomycin achieved a higher percentage of therapeutic levels at 12 hours when compared with the traditional dose of 15 mg/kg, without increased nephrotoxicity or adverse events.

Delayed cardiac dysrhythmias after fingolimod administration.

A 51-year-old woman with relapsing-remitting multiple sclerosis was initiated on fingolimod. She developed a Mobitz Type I (Wenckebach)second-degree atrioventricular (AV) heart block during the initial 6-hour monitoring. She was transferred to the emergency department for further monitoring, where she went into a junctional tachycardia then went back into a Mobitz Type I AV block. The patient was symptomatic with a heart rate nadir of 38 beats per minute and treated with atropine. Junctional tachycardia has not been previously reported with fingolimod use. Patients may require extended cardiac monitoring after fingolimod administration.

Use of C1 Inhibitor for Angiotensin-Converting Enzyme (ACE) Inhibitor-Induced Angioedema Decreases Mechanical Ventilation Time.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitor-induced angioedema is a rare, albeit serious emergency that can result in airway compromise and potentially death if not treated promptly. Currently, there are no agents approved by the Food and Drug Administration to target ACE inhibitor angioedema and to prevent intubation. C1 inhibitors are approved for hereditary angioedema but may show promise in alleviating inflammation associated with ACE inhibitor angioedema. CASE REPORT: A 41-year-old man presented to the emergency department with swelling of his lips a few days after starting lisinopril for hypertension. Despite receiving diphenhydramine, ranitidine, and methylprednisolone, the swelling progressed to the patient's tongue. A C1 inhibitor was ordered in an effort to prevent intubation. Before the arrival of the medication, the patient was intubated emergently for airway protection. After receipt of the C1 inhibitor, the swelling dramatically improved, and the patient was successfully extubated after less than 18 hours from presentation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case illustrates a potential role for C1 inhibitors in the emergency setting for treating drug-induced angioedema, which may prevent or minimize mechanical ventilation time.

Hemorrhagic gastritis with dabigatran in a patient with renal insufficiency.

BACKGROUND: Dabigatran etexilate is the first oral direct thrombin inhibitor approved in the United States. Unlike warfarin, dabigatran has no known antidote. Providers should be aware of patients that may be at risk for dabigatran coagulopathies and recognize potential treatment options. OBJECTIVE: To report a case of hemorrhagic gastritis in a patient with chronic renal insufficiency recently initiated on dabigatran etexilate. CASE SUMMARY: An 85-year-old white man with a known history of hypertension and stage III chronic kidney disease presented to the Emergency Department complaining of dark stools, shortness of breath, and abdominal pain. The patient recently started dabigatran 150mg twice daily for new-onset atrial fibrillation. An upper gastrointestinal endoscopy identified non-specific gastritis with hemorrhage. It was determined to be probable using the Naranjo Probability Scale that gastrointestinal hemorrhaging was a result of dabigatran therapy. Fresh frozen plasma was used to reverse the dabigatran-induced coagulopathy. CONCLUSION: This case highlights the challenges that providers may face when dealing with life-threatening bleeding in patients receiving dabigatran.

Prescribing habits of vancomycin in the Emergency Department: are we dosing appropriately?

BACKGROUND: To prevent the development of bacterial resistance, current guidelines recommend vancomycin dosages of 15-20 mg/kg based on actual body weight. OBJECTIVE: Our aim was to determine if two community teaching Emergency Departments followed the new recommendations for a weight-based dosing regimen for vancomycin. METHODS: A retrospective cohort study was conducted on the prescribing habits of vancomycin in the Emergency Department. During a 6-month time period, 1,734 doses of vancomycin were dispensed and a subsequent random sample of 240 doses was reviewed. Data collection included age, gender, weight, creatinine clearance, vancomycin dose, and indication for vancomycin therapy. Mean values, standard deviations, and ranges were computed to illustrate current prescribing practices. RESULTS: The mean vancomycin dose was 1,117 ± 325 mg. Based on actual body weight, the calculated mean dose was 14.6 ± 5.7 mg/kg. Only 19.6% (47 of 240) of all patients received an appropriate dose based on the recommended 15-20 mg/kg vancomycin dose. CONCLUSIONS: Our Emergency Department is inappropriately dosing vancomycin in the majority of patients. Educating clinicians regarding appropriate vancomycin dosing is recommended to achieve compliance with the latest consensus guidelines.