Jeremy R. DeGrado

Use of antiepileptics for seizure prophylaxis after traumatic brain injury

PURPOSE Antiepileptics used for seizure prophylaxis after traumatic brain injury (TBI) are reviewed. SUMMARY Of the 275,000 people who are hospitalized with TBI each year, approximately 5-7% experience a posttraumatic seizure (PTS). According to the latest guidelines issued by the Brain Trauma Foundation and the American Academy of Neurology (AAN) for the management of severe TBI, PTS prophylaxis is recommended only during the first seven days after TBI. Of the available antiepileptic drugs, phenytoin has been the most extensively studied for the prophylaxis of PTS. Phenobarbital, valproate, and carbamazepine have not been as extensively researched, and, given their adverse-effect profiles and pharmacodynamic properties, there is no advantage to using these agents over phenytoin. Levetiracetam has demonstrated comparable efficacy to phenytoin for PTS prophylaxis and is associated with fewer adverse effects and monitoring considerations; it may be a reasonable alternative to phenytoin. However, levetiracetam has been associated with an increased seizure tendency. The Brain Trauma Foundation recommends using phenytoin for early PTS prophylaxis. The guidelines also state that valproate has demonstrated similar efficacy to phenytoin but warn that its use may be associated with increased mortality. CONCLUSION The available literature supports the use of antiepileptics for early PTS prophylaxis during the first week after a TBI. Phenytoin has been extensively studied for this indication and is recommended by the AAN and Brain Trauma Foundation guidelines for early PTS prophylaxis. Levetiracetam has demonstrated comparable efficacy to phenytoin for early PTS prophylaxis and may be a reasonable alternative to consider in this patient population.

Clevidipine: A Short-Acting Intravenous Dihydropyridine Calcium Channel Blocker for the Management of Hypertension

Drugs used to acutely lower blood pressure have specific indications and precautions for use. Clevidipine is a third‐generation parenteral dihydropyridine calcium channel blocker that received United States Food and Drug Administration approval in August 2008 for blood pressure reduction when oral therapy is not feasible or desirable. Formulated as an injectable oil‐in‐water emulsion, the drug is a short‐acting arterial‐selective vasodilator. Clinical efficacy and safety trials of clevidipine have primarily focused on blood pressure management during cardiac surgery and in patients with acute severe hypertension (in intensive care units and emergency departments). In phase III trials, clevidipine demonstrated efficacy in blood pressure lowering, with a relatively low occurrence of adverse events. Reflex tachycardia, atrial fibrillation, and acute renal failure were observed in these studies and merit additional analysis. The lack of specific clinical outcomes documenting improved morbidity and mortality rates as compared with other agents, the small numbers of treated patients, and concerns regarding the lipid formulation necessitate further investigation to help define the therapeutic role of clevidipine.

Early vasopressin reduces incidence of new onset arrhythmias

PURPOSE The objective of this study was to determine the effect of early vs late vasopressin therapy on catecholamine dose and duration. MATERIALS AND METHODS We conducted a single-center, retrospective chart review of adult patients admitted to the medical intensive care unit between January 2010 and December 2011 with septic shock requiring catecholamine and vasopressin therapy. Patients were included in the early group if vasopressin was initiated within 6 hours and the late group if vasopressin was initiated between 6 and 48 hours of catecholamine(s). RESULTS Duration of catecholamine and vasopressin therapy was similar between the 35 patients in the early group and the 36 in the late group. Vasopressin therapy was associated with a decrease in catecholamine requirements in both groups. Early vasopressin was associated with fewer new onset arrhythmias (37.1% vs 62.9%, P<.001). There was no difference in mortality, hospital, or intensive care unit length of stay between the early and late group vasopressin groups (88.6% vs 88.9%, P=1; 14 vs 10 days, P=.48; 9 vs 7 days, P=.71, respectively). CONCLUSIONS Early initiation of vasopressin therapy in adult critically ill patients with septic shock was associated with no difference in total catecholamine requirements but decreased incidence of new onset arrhythmias.

Evaluation of a Pharmacist-Directed Vancomycin Dosing and Monitoring Pilot Program at a Tertiary Academic Medical Center

Background: Consensus guidelines recommend vancomycin doses of 15 to 20 mg/kg every 8 to 12 hours in patients with normal renal function. Objective: To evaluate the effect of a pharmacist-directed vancomycin dosing and monitoring pilot program on the percentage of patients receiving targeted weight-based dosing recommendations. Methods: This was a pre-/postevaluation study, approved by the institutional review board at our institution, comparing retrospectively reviewed vancomycin dosing practices hospital-wide between September 1 and September 30, 2010 to patients prospectively managed by a pharmacist-directed vancomycin pilot program between February 1 and April 26, 2011. All adult inpatients receiving intravenous vancomycin were included, unless patients had a creatinine clearance less than or equal to 60 mL/min or indication for therapy was surgical prophylaxis or febrile neutropenia. The primary outcome was the percentage of patients who received optimal vancomycin dosing defined as ≥30 mg/kg/d within 24 hours of initiation of therapy. Secondary outcomes included number of pharmacist interventions, length of therapy and incidence of nephrotoxicity while receiving vancomycin. Results: A total of 319 patients were analyzed, 161 preimplementation and 158 postimplementation. The percentage of patients who received optimal vancomycin dosing was significantly higher postimplementation of the pilot program, 96.8 versus 40.4% (P < 0.001). Pharmacist-directed interventions postimplementation, resulted in 50% more patients being dosed optimally (P < 0.001). Patients in the pilot program also had a shorter length of therapy (10.0 vs 8.4 days, P < 0.003) and a lower incidence of nephrotoxicity (8.7% vs 3.2%, P = 0.006). Conclusions: This pharmacist-directed vancomycin pilot program significantly increased the percentage of patients optimally dosed according to consensus guidelines within 24 hours of initiation of therapy.

Evaluation of a local ICU sedation guideline on goal-directed administration of sedatives and analgesics

Purpose: Sedatives and analgesics are commonly used in mechanically ventilated patients in the intensive care unit. Sedation guidelines have been shown to improve sedation management as well as various patient outcomes. The main objective was to evaluate adherence to a sedation guideline with both sedative prescribing and documentation of Richmond Agitation-Sedation Scale (RASS) scores. Methods: In a retrospective chart review, data was collected on 111 medical intensive care unit patients mechanically ventilated via endotracheal tube for 12 hours or greater at Brigham and Women’s Hospital. Fifty-seven patients were evaluated pre-guideline implementation and 54 patients were evaluated post-guideline. Results: Significant increases were seen in the post-guideline group in goal-directed sedation with a patient-specific RASS goal in the sedation order: 21.3 vs 85.4% (P < 0.001), and mean number of sedation assessments per 24 hours using the RASS: 4.7 vs 11.4 (P < 0.001). Similarly, this group experienced a higher percentage of RASS scores at their sedation goal: 31.4 vs 44.1% (P < 0.001). No difference was seen in other clinical endpoints. Conclusion: Implementation and routine application of a hospital pain and sedation guideline was associated with significantly improved sedation metrics, such as goal-directed sedation, as well as frequency of sedation level assessment and documentation. An increase was observed in the time that post-guideline patients spent at or near their RASS goal.

Evaluation of sedatives, analgesics, and neuromuscular blocking agents in adults receiving extracorporeal membrane oxygenation

Purpose: The objective of this study was to evaluate the use of sedative, analgesic, and neuromuscular blocking agents (NMBAs) in patients undergoing extracorporeal membrane oxygenation (ECMO) support. Materials and methods: This was a 2‐year, prospective, observational study of adult intensive care unit patients on ECMO support for more than 48 hours. Results: We analyzed 32 patients, including 15 receiving VA (venoarterial) ECMO and 17 VV (venovenous) ECMO. The median daily dose of benzodiazepines (midazolam equivalents) was 24 mg, and the median daily dose of opioids (fentanyl equivalents) was 3875 &mgr;g. There was a moderate negative correlation between the day of ECMO and the median daily benzodiazepine dose (r = −0.5515) and a very weak negative correlation for the median daily opioid dose (r = −0.0053). On average, patients were sedated to Richmond Agitation Sedation Scale scores between 0 and −1. Continuous infusions of opioids, benzodiazepines, propofol, dexmedetomidine, and NMBAs were administered on 404 (85.1%), 199 (41.9%), 95 (20%), 32 (6.7%), and 60 (12.6%) ECMO days, respectively. Patients in the VA arm received a continuous infusion opioid (96.4% vs 81.6% days; P < .001) and benzodiazepine (58.2% vs 37.0% days; P < .001) more frequently. Conclusions: Patients received relatively low doses of sedatives and analgesics while at a light level of sedation on average. Patients rarely required neuromuscular blockade.

Safety of Propofol for Oxygenator Exchange in Extracorporeal Membrane Oxygenation

The purpose of this analysis is to describe the safety of propofol administration in adult extracorporeal membrane oxygenation (ECMO) patients. We performed a prospective cohort analysis of patients using ECMO at Brigham and Womens Hospital between February 2013 and October 2015. Patients were included if they used ECMO for at least 48 hours. The major end-point of the analysis was the median oxygenator lifespan. Oxygenator exchanges were analyzed by the number of patients requiring an oxygenator exchange and the number of oxygenator exchanges per ECMO day. A priori analysis was performed by comparing the outcomes between patients who did and did not receive propofol during their ECMO course. During the study, 43 patients were included in the analysis. Sixteen patients used propofol during their ECMO course. There were 12 oxygenator exchanges during therapy. Oxygenator exchange occurred on 1.8% of ECMO days. The median oxygenator lifespan was 7 days. Patients who used propofol had a significantly longer oxygenator lifespan (p = 0.02). Among patients who received propofol, patients who required oxygenator exchange used a significantly lower median daily dose of propofol (p < 0.001). The use of propofol appears safe in ECMO with regards to oxygenator viability. Contrary to expected, oxygenator lifespan was significantly longer among patients who received propofol.

Inpatient pharmacological sleep aid utilization is common at a tertiary medical center

BACKGROUND Sleep is known to be poor in the hospital. Patients frequently request pharmacological sleep aids, despite the risk of altered mental status (delirium) and falls. Little is known about the scope of pharmacological sleep aid use in hospitalized patients. METHODS We performed a single center, retrospective review of all patients admitted to the general adult (age >18 years) medical and surgical units of a tertiary care center during a recent 2-month period (January 2013-February 2013). Review of the electronic medication administration system was performed to assess for medications administered for sleep. RESULTS Of 642 unique admissions, 168 patients (26.2%) received a medication for sleep. Most (n = 115, 68.5%) had no known history of insomnia or regular prior sleep medication use. Patients most frequently were treated with trazodone (30.4%; median dose, 50 mg; range, 12.5-450 mg), lorazepam (24.4%; median, 0.5 mg; range, 0.25-2 mg), and zolpidem tartrate (17.9%; median, 10 mg; range, 2.5-10 mg). Of the medications given, 36.7% were given early (before 9 pm) or late (after midnight). Of patients not known to be previously taking a pharmacological sleep aid, 34.3% of them were discharged with a prescription for one. CONCLUSIONS Despite increasing evidence of risks such as delirium or falls, pharmacological sleep aid use in general wards remains common, even in elderly patients. Medication administration time is frequently suboptimal. Many previously sleep medication-naïve patients leave the hospital with a sleep aid prescription. Further research is needed to understand the factors that contribute to the high rate of sleep medication use in hospitalized patients.

Pharmacodynamic target attainment with high-dose extended-interval tobramycin therapy in patients with cystic fibrosis

Abstract Utilization of high-dose extended-interval aminoglycoside therapy (HEAT) in patients with cystic fibrosis (CF) is supported by primary literature and national guidelines. We sought to evaluate the effectiveness of a local aminoglycoside guideline to achieve pharmacodynamic goals in patients with CF that received ≧3 doses of HEAT from 2005 to 2011. Patients with renal dysfunction at baseline, status-post-lung transplant, or receiving inhaled tobramycin were excluded. In the 282 patient admissions, the average initial tobramycin dose was 10·3 mg/kg with an average initial peak of 21·5 mg/l. At least one dose titration was seen in 39% of patients. Patients who achieved the pharmacodynamic goal received a higher dose (10·4 mg/kg versus 9·7 mg/kg; P<0·001). A mean starting dose of tobramycin at 10·3 mg/kg every 24 hours achieved an average peak above goal. Higher initial dosing resulted in a higher likelihood of achieving the pharmacodynamic goal.

Risk factors for acute kidney injury associated with the treatment of bacterial endocarditis at a tertiary academic medical center

Background: Acute kidney injury (AKI) is a common complication of endocarditis. Objective: To determine risk factors for the development of AKI in patients treated for endocarditis. Methods: This single centre, retrospective univariate and multivariate analysis to determine risk factors for the development of AKI included patients diagnosed with endocarditis between January 2009 and October 2013. Results: Of 211 included patients, a total of 84 (39.8%) patients developed AKI. We identified multiple independent variables associated with the development of AKI, including: age ≥ 65 years, presence of hardware, chronic kidney disease, AKI on admission, infection with Staphylococcus spp, receipt of nafcillin or oxacillin or aminoglycoside and nafcillin or oxacillin or aminoglycoside and vancomycin, vancomycin trough level ≥ 20.0 mcg/ml, aminoglycoside total daily dose reduction, duration of vancomycin exceeding three days, receipt of loop diuretic or more than three concomitant nephrotoxins and duration of loop diuretic or non-steroidal anti-inflammatory drug therapy exceeding seven days. Conclusions: In patients treated for endocarditis, multiple risk factors for AKI were identified. Prospective studies are needed to evaluate these variables for causation of AKI in patients treated for endocarditis.