Annals of Pharmacotherapy

Draper, Heather M; Eppert, J Alex

doi: 10.1345/aph.1K475pmid: 18349308

BACKGROUND:The pharmacist has many potential roles as part of the resuscitation team during cardiopulmonary arrest. Limited published research has evaluated the practice of advanced cardiac life support (ACLS) during in-hospital arrest. Recent reviews indicate that an audit of in-hospital resuscitation practices should be performed to guide future resuscitation training programs for hospital personnel.OBJECTIVE:To assess compliance with ACLS guidelines during in-hospital cardiopulmonary arrest in a community teaching hospital and evaluate the association of compliance with the presence of a pharmacist on the resuscitation team.METHODS:A retrospective analysis of the records of 74 consecutive in-hospital arrests occurring between January 1, 2003, and June 30, 2004, was conducted to evaluate compliance with American Heart Association ACLS guidelines.RESULTS:A total of 74 arrests were evaluated. Noncompliance was noted in 58.1% of all documented arrests; of the 650 treatment interventions identified, 10.6% were noncompliant with ACLS guidelines. The reasons cited for noncompliance included an incorrect medication dosage (20.3%), prolonged period of time between sequential interventions (26.1%), omission of an indicated treatment (17.4%), deviation from recommended treatment guidelines (26.1%), and incorrect energy for defibrillation (10.1%). A pharmacist was present at 36.5% of documented arrests. Compliance with ACLS treatment guidelines was more likely during resuscitations in which a pharmacist was present (59.3% vs 31.9%; p = 0.03).CONCLUSIONS:Noncompliance with resuscitation guidelines was common during in-hospital resuscitation. The presence of a pharmacist on the resuscitation team was associated with improved compliance with treatment guidelines. Despite institutional requirements for pharmacist participation during resuscitation efforts, participation rates remain low. Further evaluation of the role of the pharmacist on the resuscitation team and the impact of the pharmacist on resuscitation practices should be considered.

Ng, Tien MH; Bell, Adrienne M; Hong, Chandra; Hara, Jill M; Touchette, Daniel R; Danskey, Karine N; Lindsay, Tanya T; Puumala, Susan E

doi: 10.1345/aph.1K458pmid: 18319393

BACKGROUND:No data exist regarding the value of pharmacist monitoring of drugs associated with QTc interval prolongation.OBJECTIVE:To assess the capability, clinical impact, and economic impact of pharmacists monitoring for drug-induced QTc interval prolongation in critically ill medical adult patients.METHODS:In a prospective, parallel-group study, 149 consecutive medical intensive care unit (ICU) patients prescribed a QTc interval–prolonging drug at the Los Angeles County + University of Southern California Medical Center were assigned on alternating days to an intervention group (clinical pharmacist on physician team monitored drugs using a standardized algorithm) or a standard care group (team without pharmacist using an algorithm). The monitoring algorithm used daily assessments of electrocardiograms and laboratory data to generate pharmacotherapeutic recommendations. The primary endpoint was the frequency of QTc interval prolongation (>500 msec at any time or an increase ≥60 msec over baseline). Secondary endpoints included QTc interval greater than 470 msec in women or greater than 450 msec in men, mean increase in QTc interval at 48 hours, recommendation acceptance rate, and cost of care.RESULTS:QTc interval prolongation occurred less frequently in the intervention group compared with the standard care group (19% vs 39%, respectively; p = 0.006). Incidence of QTc interval greater than 500 msec (13% vs 33%, respectively; p = 0.003) was also lower in the intervention group. Incidence of QTc interval increase of 60 msec or more over baseline (12% vs 21%, respectively; p = 0.12) and increase in QTc interval at 48 hours over baseline (mean ± SD; 6.4 ± 40.8 vs 18.2 ± 42.3 msec, respectively; p = 0.097) were not significantly different between the groups. Algorithm-generated recommendations were accepted 70% of the time by the intervention group physician team. Total cost and cost per day were not significantly different between groups.CONCLUSIONS:In this preliminary study, pharmacist monitoring of QTc interval–prolonging drugs using a simple algorithm was feasible and reduced the risk of QTc interval prolongation. Further studies that monitor other proarrhythmic medications are warranted.

Moretti, Myla E; Rezvani, Massoud; Koren, Gideon

doi: 10.1345/aph.1K577pmid: 18349305

BACKGROUND:Gestational diabetes mellitus affects approximately 4% of all pregnancies. As with other oral hypoglycemics, the use of glyburide in pregnancy has been limited by fears of neonatal hypoglycemia following fetal exposure. Recent experimental and clinical studies have suggested, however, that the drug is not detectable in umbilical blood.OBJECTIVE:To determine the safety of glyburide use in pregnancy in the treatment of gestational diabetes compared with insulin therapy by analyzing all available human studies.METHODS:We conducted a systematic review and meta-analysis of all randomized and cohort studies that reported on the perinatal complications among women with gestational diabetes who received glyburide versus insulin. MEDLINE, EMBASE, and biological abstracts using BIOSIS previews were searched from inception of these databases through October 2006. The following outcomes were included: macrosomia, birthweight, gestational age, neonatal hypoglycemia, and intensive care unit (ICU) admissions. Odds ratios were calculated by the random effects method using Cochrane's Review Manager version 4.3.RESULTS:Nine studies met the inclusion criteria, including a total of 745 glyburide-exposed pregnancies and 637 insulin-exposed pregnancies, with each adverse perinatal outcome reported by 4–7 studies. The use of glyburide was not associated with risk of macrosomia (OR 1.07; 95% CI 0.78 to 1.47), differences in birth weight (weighted mean difference [WMD] OR 20.46 g; 95% CI −34.90 to 75.82), rate of large for gestational age (OR 1.04; 95% CI 0.75 to 1.43), differences in gestational age at birth (WMD 0.02 wk; 95% CI −0.23 to 0.26), ICU admission (OR 0.95; 95% CI 0.43 to 2.09), or increased risk of neonatal hypoglycemia (OR 1.24; 95% CI 0.91 to 1.69).CONCLUSIONS:The data shown here do not suggest increased perinatal risks with glyburide. The effectiveness and safety of glyburide require further evaluation, as most studies to date were not randomized.

Pastakia, Sonak D; Corbett, Amanda H; Raasch, Ralph H; Napravnik, Sonia; Correll, Todd A

doi: 10.1345/aph.1K547pmid: 18349307

BACKGROUND:Retrospective studies of hospitalized HIV-infected patients have noted a high occurrence of drug-related errors, ranging from 5% to 30%.OBJECTIVE:To prospectively evaluate errors in antiretroviral (ARV) prescribing in the inpatient setting of a hospital tertiary care center and the association of risk factors with the occurrence of errors.METHODS:HIV-infected patients who received care and continued their ARVs for HIV infection on admission to a large academic teaching hospital between January and April 2006 were included in this study. The care and assessment of these patients was conducted on a daily basis by an infectious diseases/HIV specialized clinical pharmacist. All errors were documented and classified based on a severity scale.RESULTS:Among the 68 patients who met the study's eligibility criteria, at least one error in the initial HIV regimen occurred in 72% of patients, and in 56% of patients, the error had the potential to cause moderate-to-severe discomfort or clinical deterioration. Patients on atazanavir-based therapy had a statistically significant increased occurrence of errors throughout their hospitalization (RR = 1.69; 95% CI 1.03 to 2.78; p = 0.02). Receiving nonformulary (combination) HIV medications increased patients' risk of having more than one error occur in their ARV regimen on admission and during hospitalization (RR = 1.95; 95% CI 1.25 to 3.04; p = 0.02). The clinical pharmacist recommendations had 100% acceptance.CONCLUSIONS:The alarmingly high frequency of potentially harmful errors uncovered in this study necessitates further investigation using larger sample sizes. Interventions to reduce and prevent these errors must be sought to eliminate the unintended harm associated with hospitalization.

Lesk, Mark R; Koulis, Theodoro; Sampalis, Fotini; Sampalis, John S; Bastien, Natacha R

doi: 10.1345/aph.1K565pmid: 18364402

BACKGROUND:Treatment of glaucoma is aimed at reducing intraocular pressure (IOP) to prevent further damage to the optic nerve. For patients who do not respond to monotherapy, combination treatment may be effective in achieving therapeutic reduction or target IOP.OBJECTIVE:To evaluate the effectiveness and safety of dorzolamide 2% with timolol 0.5% alone or combined with latanoprost in reducing IOP in a real-world setting.METHODS:A prospective, open-label, multicenter, nonrandomized interventional study was designed. Three hundred fifty patients with primary open-angle glaucoma or ocular hypertension and uncontrolled IOP after latanoprost monotherapy for 4 or more weeks were treated with combination dorzolamide–timolol twice daily added to their existing latanoprost therapy (D/T-Add-On; n = 280) or dorzolamide–timolol twice daily monotherapy (D/T-Switch; n = 70). The primary effectiveness outcome measure was the change in IOP after 6 and 12 weeks of treatment.RESULTS:Of the total population, 313 patients completed this trial (248 D/T-Add-On; 65 D/T-Switch). After 12 weeks, the mean ± SD IOP decrease was −6.3 ± 3.6 mm Hg (–28.1%) and −5.8 ± 4.9 mm Hg (–23.5%) in the D/T-Add-On and D/T-Switch groups, respectively (both p < 0.001). Therapeutic response rates (defined as IOP reduction >20%) after 12 weeks of treatment for the D/T-Add-On and the D/T-Switch groups were 66.4% (186/280) and 52.9% (37/70), respectively. There were 116 predominantly mild, nonserious adverse events attributed to the study drugs, reported by 86 (24.6%) patients. The most frequent adverse events were eye irritation (n = 42; 12.0%) and taste perversion (n = 15; 4.3%). No serious adverse events related to the study medications were reported.CONCLUSIONS:In patients with primary open-angle glaucoma or ocular hypertension and elevated IOP while on monotherapy with latanoprost, switching to dorzolamide–timolol or combining dorzolamide–timolol with latanoprost are effective and safe treatment options for reducing IOP and achieving therapeutic response.

Cates, Marshall E; Feldman, Jacqueline M; Boggs, Angela A; Woolley, Thomas W; Whaley, Nanci P

doi: 10.1345/aph.1K520pmid: 18364406

BACKGROUND:Weight gain is a common adverse effect of many psychotropic medications including antipsychotics, antidepressants, and mood stabilizers. There is a growing body of evidence that topiramate may be useful as an add-on therapy to induce weight loss in patients who have experienced psychotropic-induced weight gain.OBJECTIVE:To determine the efficacy and tolerability of topiramate for treatment of weight gain in a naturalistic mental health clinic setting.METHODS:A retrospective chart review was conducted at a community mental health clinic. Subjects were non-elderly adults who received topiramate therapy beginning in 2002–2005 for documented weight gain during treatment with psychotropic drugs. Primary outcome measures included response rate (based on weight loss of any magnitude) and mean changes in weight and body mass index (BMI).RESULTS:Forty-one patients were included in the study. There was a 58.5% (n = 24) response rate. Mean reductions in weight and BMI were approximately 2.2 kg and 0.5 points, respectively. Responders lost an average of 7.2 kg, whereas nonresponders gained an average of 5.0 kg. Patients with a baseline weight of at least 91 kg and those receiving a greater number of psychotropic medications were more likely to experience success with topiramate therapy. Of the 24 patients who responded to therapy, 22 experienced onset of weight reduction by the next clinic visit (1–4 mo) following either initiation of therapy or titration to the eventual therapeutic dose, and the usual rate of weight loss was 0.45–1.4 kg per month. Therapy was typically initiated at 50 mg/day. The mean maximum dose was 93.9 mg/day and the median maximum dose was 100 mg/day. Seven (17.1%) patients had documented adverse effects to topiramate therapy.CONCLUSIONS:Topiramate therapy resulted in overall modest (ie, <2%) decreases in weight and BMI, but many patients experienced more impressive weight loss. Therapy was generally well tolerated.

Goldenberg, Neil A; Jacobson, Linda; Hathaway, Hannah; Tripputi, Mark; Primeaux, Judy; Child, Jason

doi: 10.1345/aph.1K609pmid: 18349310

BACKGROUND:The low-molecular-weight heparin (LMWH) dalteparin is approved by the Food and Drug Administration for prophylaxis of venous thromboembolism (VTE) in adults and has recently received an indication for acute VTE therapy in adults with cancer. Published reports of experience with dalteparin use in European children suggest that this LMWH agent is safe and effective in the prophylaxis and treatment of VTE in the pediatric population. However, dalteparin is commonly available in the US in a concentrated form that requires dilution for accurate administration in infants and young children.OBJECTIVE:To investigate the in vitro stability of diluted dalteparin for pediatric use, as measured by serial anti-Xa activity assays over the course of 4 weeks.METHODS:At 2 clinical research pharmacies, dalteparin multidose vials (anti-Xa concentration 25,000 U/mL) of the 2 distinct lots presently available for clinical use were diluted 1:10 with preservative-free NaCl 0.9% and maintained in tuberculin syringes at 4 °C. Syringes were then sampled for anti-Xa activity by chromogenic assay at baseline and weekly over the course of 4 weeks.RESULTS:For each lot of dalteparin, there was strong agreement in anti-Xa activity between corresponding diluted syringes prepared at the 2 pharmacy sites. No statistically significant difference in anti-Xa activity was detected from baseline to any time point, nor was a trend of change detected in anti-Xa activity with time for either lot of dalteparin.CONCLUSIONS:These data indicate that the anti-Xa activity of diluted dalteparin for pediatric use is stable over the course of 4 weeks.

Stevens, Alison M; Then, Janine E; Frock, Karen M; Crookes, Bruce A; Commichau, Christopher; Marden, Brian T; Beynnon, Bonnie J; Rebuck, Jill A

doi: 10.1345/aph.1K555pmid: 18364404

BACKGROUND:There is considerable debate regarding the appropriateness of feeding patients by the enteral route in conjunction with pentobarbital coma therapy.OBJECTIVE:To determine the incidence of feeding intolerance (FI) in patients receiving pentobarbital in conjunction with enteral nutrition (EN).METHODS:A retrospective, observational evaluation of patients (>14 y of age) who received a therapeutic pentobarbital coma in combination with EN was conducted. Patients were divided into groups, based on the occurrence of FI defined as aspiration of gastric residuals greater than 75 mL for 2 consecutive measurements.RESULTS:Forty-eight percent (29 of 61) of patients experienced FI based on our definition. The median pentobarbital infusion rate did not differ significantly between patients who experienced FI versus those who did not (median [intraquartile range, IQR] 1.8 mg/kg/h [1.4, 2.1] vs 1.7 mg/kg/h [1.4, 2.5]; p = 0.680). The total pentobarbital bolus dose during the first 24 hours of therapy was lower in patients who experienced FI (700 mg [225, 980] vs 1000 mg [600, 1475]; p = 0.029). Median duration of pentobarbital therapy was comparable between groups (141.0 h [93.3, 217.3] vs 116.3 h [64.0, 174.8]; p = 0.115). Other factors with the potential to influence FI, such as catecholamines, neuromuscular blockade, and hyperglycemia, were similar between groups. The higher narcotic doses and greater percentage of patients receiving benzodiazepines in the FI group warrants further study.CONCLUSIONS:Pentobarbital therapy did not preclude use of EN in the entire study population. In addition, FI did not occur at a greater frequency in patients who received a higher dosage, a longer duration, or an earlier initiation of pentobarbital therapy.

Garwood, Candice L; Corbett, Tia L

doi: 10.1345/aph.1K498pmid: 18334606

OBJECTIVE:To evaluate data addressing use of anticoagulation in elderly patients with atrial fibrillation (AF), in particular those at risk of falls.DATA SOURCES:Primary literature was identified through PubMed MEDLINE (1966–December 2007) and EMBASE (1980–December 2007) using the search terms anticoagulation, warfarin, aspirin, elderly, falls, older persons, atrial fibrillation, bleeding, education, stroke, and use. Additional references were obtained through review of references from articles obtained.STUDY SELECTION AND DATA EXTRACTION:Clinical studies evaluating warfarin and aspirin efficacy in AF, as well as studies evaluating anticoagulation and falls, elderly patients, and bleeding were considered for inclusion. Selection emphasis was placed on randomized studies of AF and those evaluating anticoagulation and falls.DATA SYNTHESIS:Uncertainties over the optimal treatment for elderly patients with AF still exist. Variance in the guidelines is reflected in current practice, as some discrepancies are present. Warfarin is underprescribed in elderly patients, with only about 50% of eligible patients receiving therapy. Falls are most often cited as the reason for not using anticoagulants in an elderly patient. Three risk–benefit analyses have been performed, and all found that despite risks associated with warfarin, its benefits outweigh its risks even in patients who fall. Warfarin should be used rather than aspirin or no therapy in elderly patients at risk of falls. Anticoagulation education has been shown to reduce the risk of bleeding in the elderly and should be a vital part of warfarin management.CONCLUSIONS:The risk of falls alone should not automatically disqualify a person from being treated with warfarin. While falls should not dictate anticoagulant choice, assessment and management of fall risk should be an important part of anticoagulation management. Efforts should be made to minimize fall risk.

Cheng, Judy WM

doi: 10.1345/aph.1K542pmid: 18334607

OBJECTIVE:To review the pharmacology and clinical evidence of the use of vernakalant in the management of atrial fibrillation (AF).DATA SOURCES:Peer-reviewed articles published in the English language were identified from MEDLINE and Current Contents databases (both 1966–March 5, 2008) using the search terms RSD 1235 and vernakalant. Citations from available articles and recent meeting abstracts were reviewed for additional references. During the preparation of this article, vernakalant was being reviewed by the Food and Drug Administration (FDA). Therefore, information posted on the FDA Web site was also evaluated.STUDY SELECTION AND DATA EXTRACTION:Phase 2 and Phase 3 clinical studies of both intravenous and oral vernakalant were reviewed. The design and results of the studies were critically evaluated.DATA SYNTHESIS:Vernakalant is a sodium and ultra-rapid potassium channel blocker with atrial selective effects. In 2 clinical studies evaluating use of intravenous vernakalant in cardioversion of patients with recent-onset AF, vernakalant improved the chance of restoration of normal sinus rhythm (combined results 51% vs 3.8% with placebo; p < 0.001). In postoperative AF, intravenous vernakalant also improved the chance of restoration of normal sinus rhythm (45% vs 15% with placebo; p = 0.0002). Early Phase 2 studies demonstrated that oral vernakalant 300 mg or 600 mg twice daily successfully maintained sinus rhythm compared with placebo. No proarrhythmias relating to vernakalant have been reported to date. Common adverse effects include dysgeusia, sneezing, and paresthesia.CONCLUSIONS:Vernakalant is a new atrial-selective antiarrhythmic agent. Phase 3 clinical trials of the intravenous formulation and early Phase 2 studies of the oral formulation demonstrated vernakalant to be efficacious and safe in converting recent-onset AF to sinus rhythm. Further studies are needed to explore the efficacy and safety of vernakalant use in patients with severe heart failure and AF, as well as its relative efficacy and safety compared with other antiarrhythmic agents, especially with long-term use.