Early Versus Delayed Initiation of Pharmacological Venous Thromboembolism Prophylaxis After an Intracranial Hemorrhage.

BACKGROUND: Intracranial hemorrhage (ICH) accounts for up to 20% of all strokes with and carries an approximate 50% 30-day mortality. The risk of venous thromboembolism (VTE) is markedly higher in patients with ICH compared with ischemic strokes, but the optimal time to initiate pharmacological prophylaxis is ill-defined. DESIGN: Retrospective analysis. SETTING: University-affiliated, tertiary care center. PATIENTS: Patients admitted for a nontraumatic ICH who received pharmacological VTE prophylaxis during their first 30 hospital days. RESULTS: Of the 793 patients evaluated, 400 were included [142 (35.5%) early]. Rebleeding event rates were similar for early versus late [8 (5.6%) vs. 13 (5.0%), P=0.80] and rates of hospital-acquired VTEs were not statistically different [1 (0.7%) vs. 8 (3.1%), P=0.17]. The median time from admission to the first dose of pharmacological prophylaxis was similar in patients who experienced rebleeding versus those that did not [74 h (range, 38 to 110.5 h) vs. 63 h (range, 45 to 90.5 h), P=0.69]. There was a longer median time from admission to the first dose of pharmacological prophylaxis in patients who developed a VTE during the initial hospitalization versus those who did not [108 h (range, 73.3 to 187 h) vs. 63 h (range, 44.5 to 90 h), P=0.005]. CONCLUSIONS: Initiation of early pharmacological prophylaxis in ICH patients did not appear to increase the risk of rebleeding nor decrease the risk of VTE. Among those patients who did develop VTE during hospitalization, there was a longer median time from admission to the first dose of pharmacological prophylaxis.

Evaluation of venous thromboembolism prophylaxis in patients with chronic liver disease.

BACKGROUND: The incidence of venous thromboembolism (VTE) in chronic liver disease (CLD) patients has been reported to be 0.5% to 6.3%. Studies report the use of thromboprophylaxis in CLD patients as suboptimal, with at least 75% of patients receiving no prophylaxis. OBJECTIVE: To describe the use of VTE prophylaxis in CLD patients. DESIGN: A retrospective review. SETTING: Tertiary-care academic medical center. PATIENTS: Inpatient admissions from August 2009 through July 2011 with CLD diagnosis. INTERVENTION: None. MEASUREMENTS: Initiation and type of thromboprophylaxis, incidence of VTE, bleeding events, hospital length of stay, in-hospital mortality, 30-day readmission for VTE. RESULTS: Of the 410 patients included, 225 (55%) patients received thromboprophylaxis. For patients with international normalized ratio (INR) >2.0, a significant decrease in overall thromboprophylaxis use and pharmacologic prophylaxis use was seen compared to those with INR 1.4 to 2.0 (P = 0.013 and P < 0.001, respectively). Overall incidence of VTE was 0.7%. Fifteen bleeding events occurred (3.7%): 9 on mechanical prophylaxis, 1 on pharmacologic, 3 on combination, and 2 with no prophylaxis. The majority of patients experiencing a bleeding event had an INR >2.0 (P = 0.001). CONCLUSION: The use of thromboprophylaxis in CLD patients is higher in our study than previous reports but remains suboptimal. Use of VTE pharmacologic prophylaxis does not appear to increase bleeding in CLD patients with INR ≤2.0. Further studies are needed to provide additional safety data.

Phenytoin-rifampin drug interaction in a hypoalbuminemic, renal failure patient: a complex clinical case.

Phenytoin, a commonly used antiepileptic, is difficult to dose optimally due to its narrow therapeutic window, nonlinear pharmacokinetics, extensive protein binding, and participation in clinically significant drug interactions. Although clinicians are aware of the interaction with two widely used antituberculosis agents, rifampin and isoniazid, few reports have described the implications for managing phenytoin dosing in this situation. To our knowledge, only two reports of the clinical experience with this interaction have been published, and only one of these reports involved the addition of isoniazid. We present a case of a 60-year-old man treated with triple antiepileptic therapy, including phenytoin, who experienced seizures shortly after hospital admission. Dosing of phenytoin proved difficult in this patient due to an acute kidney injury and severe hypoalbuminemia requiring hemodialysis. A further complexity was the addition of antituberculosis therapy (rifampin, isoniazid, pyrazinamide, and ethambutol [RIPE]) for suspected tuberculosis meningitis after the patient experienced persistent encephalopathy. Phenytoin concentrations decreased steadily after rifampin and isoniazid initiation despite dose increases, and the free concentration of phenytoin reached a low of less than 0.5 µg/ml on day 8 of RIPE therapy. The patient continued on a stable dose of phenytoin and RIPE therapy for unconfirmed tuberculosis meningitis until discharge. This report is the first description of this drug interaction in 20 years and highlights the need for appropriate management of phenytoin in a patient with complicated needs for pharmacotherapy.

Early vs delayed enteral nutrition in critically ill medical patients.

This study was conducted to identify current practice in provision of enteral nutrition (EN) and to determine effects of early enteral nutrition (EEN) on length of stay in the medical intensive care unit (ICU). In this prospective, observational study, medical ICU patients were evaluated to determine their candidacy for EEN. If patients were candidates for EN and expected to remain nothing-by-mouth for 48 hours, they were classified as receiving EEN (within 24 hours of admission) or delayed EN. Thirty-six patients were candidates for EEN. Eighteen received EEN and 18 received delayed EN. In the delayed group, the median time to start of EN was 2.1 +/- 4.8 days. Median ICU length of stay was 4.7 +/- 3.5 days in the EEN group compared with 8.5 +/- 8.3 days in the delayed group. Although hospital length of stay was shorter in the EEN group, this was not statistically significant (10.4 +/- 6.9 vs 16.9 +/- 11.5 days). Time on the ventilator was significantly shorter in the EEN group vs delayed (n = 30, 3.0 +/- 4.2 vs 6.0 +/- 9.2 days). The incidence of new pneumonia was lower in the EEN group (5.5% vs 44%), but no difference was found in the incidence of bacteremia. Hospital mortality was lower in the EEN group (1 vs 7 deaths). Given its association with numerous benefits, EEN within 24 hours of admission should be encouraged and implemented by clinicians in medical ICU patients, but additional research is needed.

Treatment of warfarin-related intracranial hemorrhage: a comparison of prothrombin complex concentrate and recombinant activated factor VII.

OBJECTIVE: Warfarin-related intracranial hemorrhage (ICH) is a devastating complication of warfarin therapy. Several studies have demonstrated successful correction of the international normalized ratio (INR) using prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa). To our knowledge, no study has directly compared these agents for treatment of warfarin-related ICH. METHODS: We retrospectively reviewed the charts of 15 patients who received rFVIIa and 9 who received PCC for treatment of warfarin-related ICH over a 2-year period. The primary objective was to compare the efficacy of rFVIIa and PCC in correcting the INR to 1.3 or less. Baseline INR was compared to INR obtained within 1, 3, 6, 12, and 24 hours after rFVIIa or PCC administration. RESULTS: Six patients in the rFVIIa group and five in the PCC group had a follow-up INR within 1 hour of agent administration. In the rFVIIa group, the mean INR decreased from 6.1 to 1.1 and from 2.3 to 1.48 in the PCC group. At 6 hours, all rFVIIa patients and six (67%) PCC patients had at least one subsequent INR, with 93% and 50% correcting to an INR of 1.3 or less. Mean dose for all patients included was 53.4 ± 17.5 µg/kg and 27.8 ± 15.4 units/kg for rFVIIa and PCC, respectively. CONCLUSION: Correction of the INR is more reliably obtained with rFVIIa when compared to PCC. Larger, prospective studies comparing these therapies for warfarin-related ICH are needed.

Unrecognized valproic acid intoxication.

We report the case of a patient with schizophrenia who presented to the emergency department (ED) with a mental status change. He was initially treated for nonconvulsive seizures until a valproic acid (VPA) serum concentration test was performed and indicated acute intoxication. To report a case of acute intoxication with VPA that was unrecognized and treated as nonconvulsive seizure. A 28-year old man presented to the ED after being assaulted. A computed tomography scan of his head showed no intracranial injury. While still in the ED, the patient became increasingly difficult to arouse. Because nonconvulsive seizures were suspected, an electroencephalogram was performed, which indicated mild encephalopathy but no epileptogenic activity. Despite these results, the patient was given VPA 1000 mg intravenously. A VPA level was obtained before the dose was given, but the results were not available at the time the dose was ordered and administered. It was later determined to be greater than 300 microg/mL and increased to 423 microg/mL. The patient was admitted to the hospital and later reported that he had attempted to commit suicide by taking an unknown amount of VPA, which was prescribed for a history of schizophrenia. Emergency physicians should be aware that anticonvulsant medications are used for a variety of medical conditions in addition to the treatment of seizure disorders. Especially when anticonvulsant medications are used for psychiatric conditions, acute intoxication should be a differential diagnosis in any patient presenting with mental status changes.

Intracerebral hemorrhage secondary to a warfarin-metronidazole interaction.

BACKGROUND: It has been >25 years since the interaction between warfarin and metronidazole was last reported in the literature. The current case report represents the first documentation of this interaction associated with intracerebral hemorrhage. CASE SUMMARY: We present a case of a 78-year-old white woman started on metronidazole (250 mg every 8 hours for 5 days) and levofloxacin (500 mg QD for 6 days) for an upper respiratory tract infection after visiting a walk-in clinic. The patient did not notify any of the health care professionals involved that she was on concomitant warfarin therapy, which had been stable over the last 3 months. Her warfarin dose was 7 mg daily, and her most recent international normalized ratio (INR) reading was 2.5. Nine days after her clinic visit, the patient was admitted to the hospital for a profuse nosebleed with an INR of 8.0 and was found to have an intraparenchymal hemorrhage of the left occipital lobe. The Naranjo adverse drug reaction probability scale indicated that the association with metronidazole was probable and the association with levofloxacin was possible (scores of 7 and 4, respectively). After a 1-week hospital stay, she was discharged. CONCLUSIONS: This adverse event is highly suggestive of a drug interaction caused primarily by metronidazole, which produces an increase in S-warfarin concentrations. Treatment provided by health care providers who were not familiar with the patient and the use of a different pharmacy (where the pharmacist was unaware of her current medications) likely contributed to the event.