Lorazepam versus chlordiazepoxide for the treatment of alcohol withdrawal syndrome and prevention of delirium tremens in general medicine ward patients.

Alcohol withdrawal syndrome (AWS) is a serious complication of abrupt alcohol cessation. Severe AWS can develop into delirium tremens (DT), which is potentially life-threatening. Lorazepam (LOR) and chlordiazepoxide (CDE) are mainstays of therapy for AWS. Current literature lacks studies comparing outcomes between the two drugs for patients who are not in a de-addiction ward specifically for withdrawal treatment. The primary objective of the study was to determine the incidence rate of DT between the groups. Of 2112 patients screened, 142 met inclusion criteria (LOR = 74, CDE = 68). Baseline characteristics were similar between groups. No significant difference in the primary outcome of DT development was observed (7% LOR, 9% CDE; p = 0.76). No significant differences in cumulative doses of scheduled LOR or CDE were observed (LOR 14.6 ± 8 mg, CDE 15.4 ± 12; p = 0.64). However, significant differences were found in the amount of "as needed" (PRN) LOR required for the two groups (LOR 3.2 ± 4 mg, CDE 6.6 ± 13 mg; p = 0.03) and the amount of scheduled plus PRN LOR required (LOR 17.7 ± 10 mg, CDE 21.9 ± 14 mg; p = 0.04). Doses are reported in LOR equivalents. There were no observed differences in duration of treatment (LOR 3.6 ± 1.3 days, CDE 3.9 ± 2.1 days; p = 0.3) or length of stay (LOR 5.28 ± 3.8 days, CDE 4.73 ± 4.2 days p = 0.4). No adverse events related to BZD were noted in either group. Hospital outcomes did not differ between the groups, but patients treated with CDE may require more adjuvant therapy to control symptoms of AWS. Both agents appear equally effective at preventing the development of DT in those patients admitted to general medicine wards.

Comparison of Parenteral Opioid Dosing in Adult Sickle Cell Disease Patients With Vaso-occlusive Crisis.

Sickle cell disease (SCD) is a chronic condition characterized by multiple vaso-occlusive complications, including acute pain crisis. The mainstay of treatment for patients presenting with vaso-occlusive crisis (VOC) is pain control and adequate hydration. Currently, there are no studies to determine an optimal pain control regimen in adult SCD patients. The main objective of this study is to evaluate whether outcomes differ in patients with VOC based on pain management treatment modality. A retrospective review of admissions with a primary diagnosis of VOC admitted to our facility was conducted. The primary outcome was to compare the average length of stay (LOS) in patients treated with intermittent injection (INT) or patient-controlled analgesia (PCA). Secondary outcomes assessed included 30-day readmission, treatment failure, and impact on pain scores. Of 302 admissions screened, 150 met inclusion criteria (INT: n = 100; PCA: n = 50). Selection of initial pain control regimen showed no difference in average LOS (INT: 5.96 ± 4.19 days vs. PCA: 6.01 ± 3.47 days; P = .94) or 30-day readmission rates (INT: 21% vs. PCA: 16%; P = .52). Treatment failure was significantly higher in the INT group, occurring in 64% of patients vs. 14% in the PCA group (P < .0001). Pain scores were not significantly impacted by selection of pain regimen. Our study indicates that INT and PCA treatment modalities are both effective at controlling pain in VOC; however, more patients in the INT group were characterized as having a treatment failure. Based on our results, it is reasonable to initiate PCA as the primary pain treatment strategy in SCD patients presenting in VOC.

Underutilization of Aldosterone Antagonists in Heart Failure.

Background: Treatment with an aldosterone antagonist (AA) has been shown in multiple trials to reduce heart failure (HF)-related morbidity, mortality, and hospital readmission. American College of Cardiology Foundation (ACCF) and American Heart Association (AHA) treatment guidelines recommend the use of an AA in all HF patients with an ejection fraction ≤35% and no known contraindication. Several studies have documented underuse of AA. Objectives: To determine the proportion of patients who received AA therapy consistent with the ACCF/AHA guidelines. Secondary objectives included determining the proportion of patients who received an AA inconsistent with guidelines and 30- and 90-day readmission rates. Methods: A retrospective chart review was conducted of patients admitted to an inner city academic medical center with a diagnosis of HF between August 16, 2011, and June 5, 2013. Results: A total of 346 HF admissions (87.6% African American) were evaluated. Use of an AA at discharge was consistent with guidelines in 31% of patients. A total of 121 patients (35%) were discharged on an AA. Among the remaining 225 patients who were not discharged on an AA, 170 (75.6%) had no contraindication to therapy. Sixty-one patients were readmitted within 30 days, and a total of 108 patients were readmitted within 90 days. There were no significant differences in readmission rates between patients who were discharged on AA therapy and those who were not. Conclusion: AAs are still underutilized in the treatment of HF.

Fever as a risk factor for increased response to vitamin K antagonists: a review of the evidence and potential mechanisms.

Numerous factors affect the response to vitamin K antagonists (VKA) including age, dietary vitamin K, other drugs, pharmacogenetics, and disease states. In antithrombotic guidelines, fever is mentioned as a factor that may increase response to VKA. The purpose of this article is to review the available evidence regarding the effect of fever on response to VKA, and to discuss possible mechanisms of this effect. We performed a search of the English literature from 1943 to June 2014, using the key words fever AND warfarin, acenocoumarol, phenprocoumon, coumarin anticoagulants and VKA; fever AND vitamin K dependent clotting factors II, VII, IX, and X. One animal investigation and 6 studies in humans suggest fever increases response to VKA, but one study did not find a significant effect. The magnitude of this effect is variable. Possible mechanisms for the increased effect of VKA associated with fever are increased catabolism of vitamin K dependent clotting factors, decreased vitamin K intake, and inhibition of VKA metabolism. More rigorous studies are needed to confirm that fever increases response to warfarin and other VKA.

Analysis of gastrointestinal prophylaxis in patients receiving dual antiplatelet therapy with aspirin and clopidogrel.

BACKGROUND: Dual antiplatelet therapy (DAPT) has been found to reduce the risk of cardiac death, myocardial infarction, stroke, and stent thrombosis following acute coronary syndrome and percutaneous coronary intervention. However, this therapy has also been shown to increase the risk of gastrointestinal (GI) bleeding as high as 2-fold, especially in patients with multiple risk factors. Proton pump inhibitor (PPI) therapy decreases this risk. The current consensus document on reducing GI risks associated with antiplatelet agents no longer recommends PPI therapy for all patients receiving aspirin (ASA) and clopidogrel. The consensus recommendation reserves PPI therapy for patients receiving DAPT with a history of upper GI bleeding or prespecified risk factors for GI bleeding.   OBJECTIVES: To (a) describe the use of GI prophylaxis in patients on DAPT with ASA and clopidogrel and (b) assess the incidence of adverse outcomes that occurred during readmissions within 6 months of the index hospitalization.   METHODS: A retrospective chart review of patients receiving DAPT between February 1, 2011, and October 15, 2011, was performed to assess the appropriateness of GI prophylaxis based on the current consensus document. Therapy was defined as appropriate if an indication for prophylaxis was present and PPI therapy was prescribed, or if no indication was present and no GI prophylaxis was given. Inappropriate prophylaxis was defined as no indication for GI prophylaxis yet therapy received, or prophylaxis indicated but incorrect prophylaxis prescribed. Incorrect prophylaxis included no prophylaxis, histamine H2 blocker therapy, antacid, or combination therapy. During subsequent hospitalizations in the 6-month period following discharge from the index admission, patients were assessed for the development of vascular-, GI-, and PPI-related adverse events.   RESULTS: 250 patients receiving DAPT during the study period were evaluated. Gastrointestinal prophylaxis was appropriate in 48% (119/250) of patients. Of the remaining patients, 56.4% (74/131) met guideline criteria for GI prophylaxis but did not receive a PPI at discharge, whereas 43.5% (57/131) of patients received GI prophylaxis when not indicated. Thirty-three adverse events were identified during readmissions, with the most common type being vascular followed by GI and PPI adverse events, respectively.   CONCLUSION: More than half of the patients did not receive GI prophylaxis appropriately. The most common reason for nonadherence to the consensus document was no prophylaxis when indicated. Vascular events could not be directly attributed to PPI use, and GI events occurred despite prophylaxis. Overall, there was a low incidence of adverse events related to the use of PPI therapy. 

Supratherapeutic international normalized ratio due to reduced vitamin K intake secondary to prolonged vomiting in a patient on warfarin.

OBJECTIVE: To report a case of prolonged vomiting during warfarin therapy, leading to an elevated international normalized ratio (INR). CASE SUMMARY: A 32-year-old female with a history of cyclic vomiting syndrome since early childhood and bilateral pulmonary emboli diagnosed 4 months prior to this acute event presented to the clinic for routine monitoring of warfarin therapy. The warfarin dose had been maintained at 35 mg/wk for 3½ months (INR 2-3.5), but it was increased to 37.5 mg/wk because the INR had trended down to the low goal range over the preceding month. At presentation, the patient reported a 15-day history of vomiting with minimal oral intake that required intravenous fluids to prevent dehydration. The INR was 4.7; warfarin was withheld, and oral vitamin K 5 mg as well as subcutaneous vitamin K 10 mg was administered the following day. The INR then decreased to 1.3. Therapy was transitioned to subcutaneous enoxaparin 1 mg/kg every 12 hours for the duration of the patient's anticoagulation therapy. DISCUSSION: Multiple reports have demonstrated malabsorption of warfarin and decreased INR response in the presence of underlying gastrointestinal disease. Despite a prolonged episode of cyclic vomiting syndrome, our patient had an elevated INR. In normal circumstances, warfarin is rapidly absorbed from the gastrointestinal tract and reaches maximum serum concentrations in approximately 90 minutes. Studies have shown that although the presence of food does not affect overall absorption of the medication, it can decrease the rate of absorption. Our patient was vomiting 20-30 minutes after oral dose administration. Because the patient was not consuming food, absorption of warfarin was potentially prompt, thus contributing to the elevated INR. The variability of vitamin K in the diet also can have significant impact on the response to warfarin. Our patient's INR had been stable while she consumed 3 servings each week of foods rich in vitamin K. This consumption was abruptly discontinued with the onset of the cyclic vomiting syndrome. We believe that decreased intake and retention of oral vitamin K-containing foods from the diet due to the prolonged vomiting coupled with the rapid onset of absorption resulted in a notably increased INR and subsequent bruising in our patient. CONCLUSIONS: In the presence of prolonged vomiting, warfarin therapy requires more frequent monitoring than usual to detect fluctuations in INR that may increase the risk of adverse events.

Evaluation of antibiotic prescribing patterns in patients receiving sustained low-efficiency dialysis: opportunities for pharmacists.

OBJECTIVES: Sustained low-efficiency dialysis (SLED) is a 'hybrid' form of continuous renal replacement therapy; however, there is very limited information on drug disposition during this procedure. Individuals requiring SLED are often critically ill and require antibiotics. The study aim was to evaluate antibiotic orders for patients requiring SLED compared to literature-based recommendations. We also evaluated whether doses were administered as prescribed and assessed clinical and microbiologic cure. METHODS: A retrospective review was performed over a 2-year period for patients who received concurrent SLED and antibiotic therapy. Demographic data, prescribed antibiotic dosing regimens and doses delivered as prescribed were determined for 10 antibiotics: cefepime (C), daptomycin (Da), doripenem (D), gentamicin (G), imipenem-cilastatin (I), linezolid (L), meropenem (M), piperacillin-tazobactam (P), tobramycin (T) and vancomycin (V). Dosing regimens were compared to recommendations from the literature where available. The incidence of clinical and microbiologic cure was also evaluated. RESULTS: A total of 87 patients met inclusion criteria: mean age 54 ± 14 years, 60% male, 58% white. Prescribed doses were evidence-based for 37% of Da, 97% of L, 15% of M and 7% of V orders. The majority of discrepancies were due to under-dosing. There were 129 (11%) antibiotic doses missed. Of the 13 patients who met criteria for assessment of clinical and microbiologic cure, 10 achieved a microbiologic cure and none reached clinical cure. CONCLUSIONS: Prescribed antibiotic dosing regimens varied substantially and under-dosing was common. There is a need to further define appropriate dosing regimens for antibiotics administered during SLED and determine how pharmacists may help to ensure appropriate therapy.

Comparison of initial warfarin response in obese patients versus non-obese patients.

Achieving therapeutic anticoagulation with warfarin is complicated by substantial inter-patient and intra-patient variability with numerous factors known to influence dose requirements. Obesity is one factor for which there remains no study to date investigating its initial effect on warfarin response assessed by INR, stratified by BMI category in hospitalized patients. To compare initial warfarin response between obese and non-obese patients by evaluating average daily dose (ADD), time required to attain therapeutic INR, and mean discharge dose (MDD), stratified by BMI category. A retrospective review was conducted to evaluate initial warfarin response in hospitalized patients of different BMI categories initiated on warfarin with ≥4 consecutive days of therapy and managed by pharmacy dosing service. 211 patients were included (10 underweight, 45 normal weight, 48 overweight, 71 obese, 37 morbidly obese). Across BMI categories, the percentage of patients attaining therapeutic INR prior to discharge differed (p = 0.0004) with 71.1 % of normal weight therapeutic compared to 42.3 % of obese and 38 % of morbidly obese. Within BMI categories, when comparing ADD between patients therapeutic and subtherapeutic at discharge, no differences were observed, except among overweight patients (5.6 ± 0.3 vs. 7 ± 0.4 mg, p = 0.0143). Compared to normal weight, obese and morbidly obese required a significantly longer median time to achieve therapeutic INR (8 and 10 days vs. 6 days) and a higher ADD (6.6 ± 0.3 and 7.6 ± 0.5 vs. 5 ± 0.3 mg) and MDD (6.7 ± 0.5 and 6.7 ± 0.7 vs. 4.4 ± 0.5 mg). Compared to normal weight, obese and morbidly obese patients had a decreased initial response to warfarin.

Analysis of antithrombotic therapy after cardioembolic stroke due to atrial fibrillation or flutter.

BACKGROUND: Guidelines recommend that all patients with atrial fibrillation and a history of ischemic stroke should receive an anticoagulant. Prior analyses show that warfarin is underutilized in most populations. OBJECTIVE: To examine the use of antithrombotic and anticoagulant therapy in patients with atrial fibrillation or flutter during the index hospitalization for acute, ischemic stroke. METHODS: Retrospective electronic medical record review of 200 patients treated at a tertiary care hospital with a primary ICD-9 code for ischemic stroke and a secondary ICD-9 code for atrial fibrillation or flutter. Exclusion criteria were active bleeding, pregnancy, age less than 18, pre-existing warfarin allergy, or dabigatran use. RESULTS: Fifty-two percent of patients received at least one dose of warfarin during the index hospitalization. There was no relationship between CHADS2 score and likelihood of receiving warfarin (P > .05). There was no significant difference in adverse event rate in patients receiving warfarin compared to those receiving aspirin (3.8% vs 9.1%; P = .14), but the rate of hemorrhagic transformation was lower in patients receiving warfarin (1% vs 7%; P = .03). The composite of hemorrhagic stroke or hemorrhagic transformation was significantly lower in patients receiving bridging therapy (0% vs 11%; P = .03). Sixteen patients were readmitted for stroke within 3 months of discharge. Ten were readmitted for ischemic stroke, 3 for hemorrhagic stroke or hemorrhagic transformation, and 3 for systemic bleeding. Ten patients (62.5%) were receiving warfarin at readmission, but only one of these patients had a therapeutic INR. CONCLUSIONS: Warfarin was underutilized as secondary stroke prophylaxis in these high-risk patients. Bridging therapy appeared to be safe and was not associated with an increase in adverse events.

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.

Activities of Memphis-area hospitals to meet National Patient Safety Goals for warfarin therapy.

PURPOSE: The activities of Memphis hospitals to meet National Patient Safety Goals (NPSGs) for warfarin therapy are described. SUMMARY: In March 2008, leadership from the Mid-South College of Clinical Pharmacy (MSCCP), a local chapter of the American College of Clinical Pharmacy, commissioned a task force on anticoagulation, comprising pharmacy administrators, clinical pharmacy practitioners, and pharmacy faculty from local hospitals within the greater Memphis area. The charge of the task force was to (1) identify practice variations in regard to NPSG.03.05.01, (2) develop professional collaboration among both academic and nonacademic institutions to share policy and protocol development, and (3) facilitate all institutions in meeting the deadlines set forth by the Joint Commission. The MSCCP Task Force on Anticoagulation project was successful in promoting collaboration among multiple institutions and clinical practitioners in the Memphis area. There was no one-size-fits-all approach; however, meetings and discussions were beneficial and led to idea generation. Having input from multiple institutions in different clinical settings with varying levels of experience created a rich environment from which all institutions benefited. For example, smaller institutions felt that they drew support for physician acceptance with protocol approval based on the knowledge of the policies approved or lessons learned at larger institutions. In addition, the larger institutions felt that the working group was helpful in validating their interpretation of the NPSG elements. CONCLUSION: The MSCCP Task Force on Anticoagulation project was successful in promoting collaboration among multiple institutions and clinical practitioners to offer solutions to meet NPSG.03.05.01 as it related to the needs of each institution.

Risk of venous thromboembolism in hospitalized patients with peripherally inserted central catheters.

BACKGROUND: Peripherally inserted central catheters (PICC) are increasingly used in hospitalized patients. The benefit can be offset by complications such as upper extremity deep vein thrombosis (UEDVT). METHODS: Retrospective study of patients who received a PICC while hospitalized at the Methodist University Hospital (MUH) in Memphis, TN. All adult consecutive patients who had PICCs inserted during the study period and who did not have a UEDVT at the time of PICC insertion were included in the study. A UEDVT was defined as a symptomatic event in the ipsilateral extremity, leading to the performance of duplex ultrasonography, which confirmed the diagnosis of UEDVT. Pulmonary embolism (PE) was defined as a symptomatic event prompting the performance of ventilation-perfusion lung scan or spiral computed tomography (CT). RESULTS: Among 777 patients, 38 patients experienced 1 or more venous thromboembolisms (VTEs), yielding an incidence of 4.89%. A total of 7444 PICC-days were recorded for 777 patients. This yields a rate of 5.10 VTEs/1000 PICC-days. Compared to patients whose PICC was inserted in the SVC, patients whose PICC was in another location had an increased risk (odds ratio = 2.61 [95% CI = 1.28-5.35]) of VTE. PICC related VTE was significantly more common among patients with a past history of VTE (odds ratio = 10.83 [95% CI = 4.89-23.95]). CONCLUSIONS: About 5% of patients undergoing PICC placement in acute care hospitals will develop thromboembolic complications. Thromboembolic complications were especially common among persons with a past history of VTE. Catheter tip location at the time of insertion may be an important modifiable risk factor.

Does heart failure exacerbation increase response to warfarin? A critical review of the literature.

BACKGROUND: Numerous factors, such as other drugs, diet, and age, are well documented as altering response to warfarin. Less attention has been focused on the effect of disease states on the response to oral anticoagulants. Decompensated heart failure is reported to increase response to warfarin, but documentation is limited. OBJECTIVE: The purpose of this review is to critically examine the evidence of a possible effect of heart failure exacerbations on response to warfarin. RESEARCH DESIGN AND METHODS: A literature search was completed of the last 60 years using several databases, including PubMed, MEDLINE, EMBASE, and SCOPUS. Key terms in our search included 'warfarin' AND 'heart failure' and 'heart failure exacerbation' (or 'decompensated heart failure') AND 'effect on warfarin'. When relevant citations were found, the references cited by those authors were checked. RESULTS: Several reports from 1946-1989 suggested that decompensated heart failure increases response to oral anticoagulants. Unfortunately, these early reports have important limitations. More recent reports, since the widespread use of the international normalized ratio (INR), also suggest that heart failure exacerbations are associated with increased response to warfarin. Patient populations are small in these reports. CONCLUSIONS: Heart failure exacerbations may be associated with an increased response to warfarin and other vitamin K antagonists, but many reports are inadequate, and it appears that not all patients are susceptible to this effect. More frequent monitoring of INR in patients with decompensated heart failure is warranted. It is prudent to initiate warfarin at lower doses in patients with a history of heart failure and to monitor INR every 1-2 weeks during times of instability in ambulatory patients, and daily INRs in hospitalized patients. Given the large number of variables that impact on warfarin dose requirement, it is difficult to clearly establish the effect of decompensated heart failure on response to warfarin. Further studies must take all of these variables into account.