Safety and efficacy of repeated doses of 14.6 or 23.4 % hypertonic saline for refractory intracranial hypertension.

BACKGROUND: The efficacy of administering single bolus doses of 14.6 or 23.4 % hypertonic saline (HTS) to treat refractory intracranial hypertension has been demonstrated in the literature and has emerged as an important therapeutic option in treating these patients. However, many institutions lack experience with this therapy and there are few published studies evaluating the safety of repeated bolus dosing of HTS. METHODS: A retrospective review of patients admitted between January 2008 and July 2012 was conducted to evaluate the use of repeated dosing of HTS in patients with refractory intracranial hypertension. The primary objective was to evaluate the safety of repeated dosing of HTS assessed by documented adverse effects such as central pontine myelinolysis (CPM) and severe fluctuations in serum sodium concentrations. Secondary objectives were to evaluate the efficacy of repeated dosing HTS in reducing intracranial pressure (ICP) and to compare the dose-response relationship of 14.6 and 23.4 % doses. RESULTS: Fifty-five patients were included for evaluation, each receiving an average of 8.9 (range 2-61) doses of HTS. A statistically significant increase in mean serum sodium concentration occurred with the administration of HTS (p < 0.0001). No cases of CPM were identified. The use of HTS was found to be effective based on decreases in ICP after administration (p < 0.0001, mean ICP reduction: 10.1 mmHg, range 3-23.6 mmHg). The efficacy of 23.4 % saline in decreasing ICP was not found to be significantly different than 14.6 % saline (p = 0.23). CONCLUSIONS: Repeat bolus dosing of 14.6 or 23.4 % HTS appears to be relatively safe and effective for treating refractory intracranial hypertension assuming there is frequent electrolyte monitoring and concomitant fluid management.

Clopidogrel Resistance by P2Y12 Platelet Function Testing in Patients Undergoing Neuroendovascular Procedures: Incidence of Ischemic and Hemorrhagic Complications.

PURPOSE: The purpose of the study was to assess clopidogrel resistance and whether "intensified" antiplatelet therapy guided by platelet inhibition tests during neuroendovascular procedures would reduce ischemic complications. METHODS: We conducted a retrospective review of patients at Mayo Clinic in Jacksonville, Florida, who underwent neuroendovascular (NV) procedures and had P2Y12 platelet function testing from October 1, 2009, to September 30, 2010. The primary end-point was to determine P2Y12 resistance to antiplatelet therapy in patients who underwent NV procedures. Secondary objectives included incidence of hemorrhagic and ischemic events and a correlation between resistance and genetic CYP2C19 testing. RESULTS: 160 patients underwent P2Y12 platelet function tests. Eighty-one patients (81/160, 50.6%) met inclusion criteria. Platelet function tests identified 64 patients (79%) as non-resistant (≥20% P2Y12 inhibition) and 17 (21%) as resistant (<20% inhibition) after initial clopidogrel loading. There was an increased rate of death when a complication occurred in the resistant group by 30 day (17% versus 3%; p=0.059) and 90 day follow-up (23% versus 4%; p=0.032). There was no significant association found between complication and loading dose (p=0.0721). CONCLUSIONS: 21% of patients undergoing NV procedures were resistant to clopidogrel. Intensifying antiplatelet therapy to achieve ≥20% inhibition on platelet function testing did not result in higher numbers of ischemic or hemorrhagic events, but there was a trend toward more death in the resistant group by 30 and 90 days of those experiencing complication(s). AUTHOR JUSTIFICATIONS: Jerah D. Nordeen, Pharm.D.: Primary author Alden V. Patel, Pharm.D.: Contributor of professional content, study design Robert M. Darracott, Pharm.D.: Contributor of professional content, study design Gretchen S. Johns, M.D.: Contributor of professional content, study design Philipp Taussky, M.D.: Contributor of professional content, study design Rabih G. Tawk, M.D.: Contributor of professional content, study design David A. Miller, M.D.: Contributor of professional content, study design William D. Freeman, M.D.: Contributor of professional content, study design Ricardo A. Hanel, MD, PhD: Contributor of professional content, study design. LIST OF ABBREVIATIONS: (NV)neuroendovascular(CYP)cytochrome P-450(PPI)proton pump inhibitors(PCI)percutaneous coronary intervention. LIST OF COMMERCIAL PRODUCTS: Aspirin (Acetylsalicylic Acid) (Bayer Corp, Morristown, NJ, USA) Clopidogrel (Plavix®) (Bristol Myers Squibb/Sanofi Pharmaceuticals, Princeton, NJ, USA) VerifyNow® (Accumetrics Inc., San Diego, CA, USA) Ticlopidine (Ticlid®) (Roche Laboratories, Basel, Switzerland) Prasugrel (Effient®) (Eli Lilly & Co., Indianapolis, IN, USA) Eptifibatide (Integrilin®) (Merck & Co., Inc., Whitehouse Station, NJ, USA) Abciximab (Reopro®) (Janssen Pharmaceuticals, Inc., Titusville, NJ, USA) Tirofiban (Aggrastat®) (MGI Pharma, Inc., Bloomington, MN, USA) Pantoprazole (Protonix®) (Pfizer Inc., New York, NY, USA) Omeprazole (Prilosec®) (Procter and Gamble Pharmaceuticals, Mason, OH, USA) Famotidine (Pepcid®) (McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PA, USA) Ticagrelor (Brilinta®) (AstraZeneca Pharmaceuticals, Wilmington, NC, USA).

Safety of intraventricular hemorrhage (IVH) thrombolysis based on CT localization of external ventricular drain (EVD) fenestrations and analysis of EVD tract hemorrhage.

BACKGROUND: The purpose of the study is to review the CT findings associated with ventriculostomy placement in regards to the safety of an EVD plus recombinant tissue plasminogen activator (rt-PA) for IVH. METHODS: A retrospective review was conducted for patients receiving intraventricular rt-PA for IVH from January 2004 to September 2009. Safety was assessed by the presence of EVD tract hemorrhage by CT at baseline after EVD placement, worsening hemorrhage after rt-PA, and CSF infection. IVH volumetrics were assessed by the Le Roux score and outcomes by Glasgow Outcome Scale and modified Rankin Scale. RESULTS: Twenty-seven patients received rt-PA for IVH. Median dose was 2 mg (range 0.3-8) and a median of two doses (range 1-17) were given. Worsening EVD catheter tract hemorrhage after rt-PA was 46.7 %, with a significantly higher incidence of worsening tract hemorrhage seen with incorrectly placed EVDs (p = 0.04). IVH hematoma burden decreased by a median Le Roux score of 10 (range 3-16) prior to rt-PA to 4 (range 0-16) after rt-PA. There were no central nervous system bacterial infections. CONCLUSION: Intraventricular rt-PA appears to be relatively safe especially when all EVD fenestrations are within the ventricle and reduces IVH burden similar to other studies. We describe a CT-based EVD tract hemorrhage grading scale to evaluate EVD tract hemorrhage before and after thrombolysis, and a bone-window technique to evaluate EVD fenestrations prior to IVH thrombolysis. Further research is needed evaluating these imaging techniques in regard to intraventricular thrombolytic safety and EVD tract hemorrhage.

The safety of lacosamide for treatment of seizures and seizure prophylaxis in adult hospitalized patients.

BACKGROUND: Lacosamide (LCM) is a newer antiepileptic drug (AED) with favorable properties for hospitalized patients including intravenous formulation, minimal hepatic metabolism, and no adverse respiratory effects. We sought to determine the safety profile of LCM in hospitalized patients. METHODS: We performed a retrospective medical record review of patients who received LCM between July 1, 2009, and January 31, 2010, at Mayo Clinic Hospital. Data included demographics, LCM dosing, concomitant AED therapy, documented seizure activity, hemodynamic variables, electrocardiogram (ECG), and laboratory data. Adverse drug reaction and drug-drug interactions were reviewed. RESULTS: Thirty-two patients were identified. No major hypotension or serious cardiac arrhythmias occurred. Heart rate increased, however, in seizure group compared with the prophylaxis group 2 hours postdrug infusion (median heart rate = 86 vs 164). The ECGs demonstrated a mean PR interval prolongation of about 6 milliseconds (ms) after LCM initiation (mean PR 185.5 ms, compared with baseline ECG mean of 179.3 ms). Laboratory data revealed no clinically significant changes 24 hours after LCM initiation. Three patients developed adverse events (9.4%): One with altered mental state and exceptionally prolonged ECG PR interval (212 vs 178 ms baseline); One with unexplained thrombocytopenia; and a third patient with dizziness, all of which resolved after drug discontinuation. CONCLUSION: The LCM demonstrated ECG PR prolongation as previously reported without systemic hypotension, with no discernable drug-drug interactions in hospitalized patients. About 9% of patients had transient adverse drug reactions after LCM, namely alteration in mental state, unexplained thrombocytopenia, and dizziness, which stopped after discontinuation of the drug.

Inpatient warfarin management: pharmacist management using a detailed dosing protocol.

Hospitalized patients receiving anticoagulants such as warfarin are at increased risk for adverse events because of difficulties maintaining a therapeutic international normalized ratio (INR). We sought to determine whether a detailed warfarin dosing protocol administered by pharmacists with minimal physician oversight significantly reduced the proportion of hospitalized patients with a supratherapeutic INR. We conducted a prospective, nonrandomized trial with patients on cardiology, internal medicine, and family medicine inpatient services who received at least 1 dose of warfarin while hospitalized. The baseline group included 293 patients, and the intervention group comprised 217 patients. Baseline characteristics were similar in each group, except that more patients received antibiotics in the intervention group. The defect rate (INR > 5 after receiving warfarin) in the baseline group was significantly higher than in the intervention group (7.85 vs. 1.85%). Conversely, the percentage of patients with an INR less than 1.7 after 4 warfarin doses was lower in the intervention patients, indicating overall improvement in therapeutic levels. Dosing discussions were required between the pharmacist and a physician for only 6% of intervention patients. The protocol effectively reduced overanticoagulation without increasing under anticoagulation during hospitalization and reduced the need for close physician oversight.