Cost-effectiveness of anticoagulants for suspected heparin-induced thrombocytopenia in the United States.

Despite the availability of multiple nonheparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT), few data are available comparing the cost-effectiveness of these agents. This analysis is particularly important when considering differences in the risk of adverse effects, routes of administration, requirements for phlebotomy and laboratory monitoring, and overall drug costs. We conducted a cost-effectiveness analysis of argatroban, bivalirudin, and fondaparinux for the treatment of suspected HIT from the institutional perspective. A 3-arm decision-tree model was developed that employs standard practices for anticoagulation monitoring. We incorporated published data on drug efficacy and probability of HIT-related thromboembolism and major bleeding. We considered both institutional costs and average wholesale price (AWP) and performed probabilistic sensitivity analyses (PSA) to address any uncertainty in model parameters. Using institutional costs, fondaparinux prevailed over both argatroban and bivalirudin in terms of cost ($151 vs $1250 and $1466, respectively) and adverse events averted (0.9989 vs 0.9957 and 0.9947, respectively). Results were consistent when AWP was used, with fondaparinux being less expensive ($555 vs $3081 and $2187, respectively) and more effective in terms of adverse events averted (0.9989 vs 0.9957 and 0.9947, respectively). The PSA confirmed our findings using both institutional costs and AWP. In conclusion, fondaparinux subcutaneous injection afforded significant advantages in terms of cost savings and adverse events averted compared with IV argatroban or bivalirudin infusions. Our data strongly suggest potential cost savings with fondaparinux and underscore the critical need for larger clinical studies of fondaparinux in the treatment of suspected HIT.

Evaluation of Inpatient Opioid Prescribing Resulting in Outpatient Opioid Prescriptions for Previously Opioid-Naive Internal Medicine Patients.

BACKGROUND: Little data exist regarding inpatient opioid prescriptions as a potential contribution to the current opioid crisis. While pain management is essential to inpatient care, the ease of which opioids may be prescribed for all levels of pain may contribute to unnecessary inpatient exposure and new outpatient prescriptions. The aim of this study was to observe patterns of opioid prescribing potentially leading to new opioid prescriptions at hospital discharge for previously opioid-naive patients. METHODS: This study was a single-center observational study of opioid-naïve internal medicine patients who were prescribed inpatient opioids. Patient charts were reviewed to assess the patterns of inpatient opioid and non-opioid analgesic use, new opioid prescriptions upon discharge and medical record documentation justifying the need for outpatient therapy. RESULTS: Among the 101 patients included in this study, 71 were prescribed IV opioids and 45 were prescribed both IV and oral opioids. Non-opioid analgesics were available for 78 patients. Twenty patients were discharged with a new prescription. The mean duration of outpatient prescriptions was 3.85 +/- 1.85 days with mean morphine milligram equivalents (MME) of 44.25 +/- 22.16. Among patients receiving these outpatient prescriptions, 11 had reference to the therapy in the discharge summary. CONCLUSIONS: This observational study describes an opportunity to improve inpatient opioid prescribing practices which may reduce new prescriptions for continued outpatient therapy. Further work should focus on optimizing use of non-opioid analgesia, minimizing use of IV opioids and requiring prescribers to justify the indication for new opioid prescriptions upon hospital discharge.

Incidence of allergic reactions to Crotalidae polyvalent immune Fab.

CONTEXT: The administration of Crotalidae polyvalent immune Fab (FabAV) currently requires close observation, so patients can be monitored for hypersensitivity reactions. The objective of this study was to evaluate the occurrence of hypersensitivity reactions to FabAV. METHOD: This was a retrospective cohort study utilizing data from a statewide poison center database in the United States. Records of all patients envenomated by a rattlesnake and treated with FabAV between January 2002 and December 2014 were evaluated. Patients with acute hypersensitivity reactions were identified, and reactions were evaluated descriptively. RESULTS: A total of 1340 adult and pediatric patients received FabAV during the study period. Of these, 19 (1.4%) patients had a potential reaction to FabAV, with 10 requiring a reduction in infusion rate, but none requiring discontinuation of the antivenom. Reactions occurred during the loading dose (n = 10), maintenance doses (n = 4), or were delayed reactions (n = 6). Symptoms recorded included pruritus (n = 8), hives (n = 8), rash (n = 7), vomiting (n = 7), nausea (n = 6), dyspnea or wheezing (n = 4), diaphoresis (n = 3), throat irritation (n = 2), and mild hypotension (n = 2). One patient was given a concomitant administration of low dose epinephrine infusion until completion of the antivenom course. However, none of the reactions were considered to be life-threatening. CONCLUSION: FabAV appears to be associated with a low incidence of acute hypersensitivity reactions. Patients may not require placement in a location capable of detecting and rapidly responding to hemodynamic and/or airway issues for FabAV monitoring alone.

Impact of delayed initiation of erythropoietin in critically ill patients.

BACKGROUND: The purpose of this study was to evaluate the impact of recombinant human erythropoietin (rHuEPO) use for anemia of critical illness at a practice site where delayed initiation is common. METHODS: Retrospective medical record review involving patients treated with rHuEPO for anemia of critical illness. Those patients given rHuEPO or diagnosed with end-stage renal disease (ESRD) prior to ICU admission were excluded. The primary endpoints were rHuEPO use and RBC transfusion patterns. RESULTS: Complete data were collected for consecutive admissions of 126 patients. Average age (SD) and APACHE II score were 56.5 (18.6) years and 25 (7.8), respectively. The median ICU (IQR) and hospital length of stay (LOS) were 24 (11.25, 39) and 29 (17, 44.75) days, respectively. Treatment with rHuEPO was started an average of 12.5 +/- 10.5 days after ICU admission and given for 3.8 +/- 3.8 doses. Eighty percent of patients were transfused with an average total of 5.42 +/- 5.08 units received. RBC exposure inversely correlated with a lower mean hemoglobin response to rHuEPO. ICU LOS (p < 0.0001), hemoglobin at 24 hours (p = 0.055), transfusion within 48 hours of admit (p < 0.0001), and postoperative status (p = 0.019) were the best predictors of transfusion requirements (r2 = 0.37). CONCLUSION: Delayed initiation of rHuEPO for anemia of critical illness resulted in comparable hemoglobin and transfusion benefits. Future studies are needed to establish clinical benefit and role in therapy. RBC exposure may blunt the erythropoietic effects of rHuEPO, potentially frustrating benefits to those of greatest apparent need.

Evaluation of Deprescribing Amiodarone After New-Onset Atrial Fibrillation in Critical Illness.

BACKGROUND: Recent studies have shed light on the continued prescription of inpatient medications upon hospital discharge, despite the original intent of short-term inpatient therapy. Amiodarone, an antiarrhythmic associated with significant adverse effects with long-term use, is commonly used for new-onset atrial fibrillation in critical illness (NAFCI). Although it is often preferred in this setting of hemodynamic instability, a prescription for long-term use should be carefully considered, preferably by a cardiologist. This study was conducted to evaluate the incidence of patients discharged on amiodarone without a cardiology consult or referral after being initiated on amiodarone for NAFCI. METHODS: We conducted a retrospective review of all patients newly prescribed amiodarone for NAFCI over a 2-year period. The primary outcome was the percentage of patients who were continued on amiodarone upon hospital discharge without review by or outpatient referral to a cardiologist. RESULTS: Of the 100 patients who met inclusion criteria, 59 patients were prescribed amiodarone upon hospital discharge. Of these, 48 patients (81.4%) had converted to normal sinus rhythm with the resolution of critical illness. Of 100 patients, 23 received prescriptions for amiodarone upon discharge without a cardiology consult or referral. CONCLUSION: Amiodarone was frequently continued upon discharge without referral to a cardiologist in patients initiated on this therapy for NAFCI. This may contribute to unnecessary long-term therapy, thereby increasing the risk for significant side effects, drug interactions, and increased healthcare costs. This study suggests that careful medication reconciliation through all transitions of care, including discharge, is essential.

Pharmacologic management of constipation in the critically ill patient.

STUDY OBJECTIVE: To compare the effectiveness of common laxatives in producing a bowel movement in patients admitted to a medical intensive care unit (MICU). DESIGN: Retrospective medical record review. SETTING: MICU of an academic medical center. PATIENTS: Ninety-five patients admitted to the MICU from July 1-October 31, 2004. MEASUREMENTS AND MAIN RESULTS: Fifty patients satisfied the inclusion criteria. Patient-specific data such as age, weight, sex, length of MICU stay, Acute Physiology and Chronic Health Evaluation (APACHE) II score, dietary intake, opioid intake, laxative intake, and bowel movements were recorded during the first 96 hours of admission. Logistic regression analysis was used to compare patients who did and did not have a bowel movement. Of the 50 patients, 25 did not have a bowel movement during the first 96 hours of MICU admission. Patients given a stimulant laxative (senna, bisacodyl) and/or an osmotic laxative (lactulose, milk of magnesia) were more likely to have a bowel movement (odds ratio [OR] 26.6, 95% confidence interval [CI] 3.2-221, p=0.002). Opioid intake, expressed as logarithmic morphine equivalents, was negatively associated with occurrence of a bowel movement (OR 0.76, 95% CI 0.59-0.97, p=0.027). Disease severity, as determined by APACHE II score, was also negatively associated with a bowel movement (OR 0.84, 95% CI 0.7-0.99, p=0.04). CONCLUSION: Critically ill patients have a high frequency of constipation, and opioid therapy is a significant risk factor. Routine administration of stimulant or osmotic laxatives should be considered for this patient population.

Nutritional support and the surgical patient.

PURPOSE: Data on the impact of nutritional support (NS) on outcomes in surgical patients are reviewed. SUMMARY: While most patients will progress to oral nutrition after surgery and require little or no intervention, major surgery or postoperative complications can delay the prescription of an oral diet. In such patients, nutritional requirements are often increased to support wound healing and hypermetabolism associated with surgical recovery. Without adequate nutrition, muscle wasting, immune dysfunction, and declining visceral protein status are observed. While it would seem intuitive that early nutritional intervention is warranted for most patients, the literature to date suggests that early parenteral nutrition (PN) does not improve clinical outcomes. An exception may be for severely malnourished patients if NS is provided for at least seven days preoperatively. Such patients should be identified early through nutritional assessment. Early enteral nutrition (EN) may potentially improve patient outcomes compared with PN, but there are insufficient data to confirm this. High-dose parenteral glutamine may reduce infectious complications and the length of hospitalization for surgical patients, but a significant reduction in mortality has not been observed. Early EN with immune-enhancing formulas appears promising for general surgery patients. However, their use in the critically ill surgical patient is not unanimously supported, and some studies suggest potential harm. CONCLUSION: Surprisingly little evidence is available to support a significant impact of early NS on postoperative clinical outcomes.

Non-cardiogenic pulmonary edema and life-threatening shock due to calcium channel blocker overdose: a case report and clinical review.

Calcium channel blockers (CCBs) overdose can be life-threatening when manifest as catastrophic shock and non-cardiogenic pulmonary edema. We describe a case of massive overdose of multiple medications, including sustained-release verapamil, which was resistant to conventional support. Initial treatment for CCB overdose is primarily supportive, and includes fluid resuscitation. The mechanism of non-cardiogenic pulmonary edema is not well known, and reported cases have been successfully treated with mechanical ventilation. Circulatory shock may fail to respond to atropine, glucagon, and calcium in severely poisoned patients, and vasopressors are usually required. Attempting to overcome calcium-channel antagonism with the supra-therapeutic doses of calcium salts is clinically indicated to reverse hypotension and bradycardia. There is evidence that hyperinsulinemia-euglycemia therapy is superior to other therapies for CCB poisoning, and the mechanism is thought to be the insulin-mediated active transport of glucose into the cells, which counters the CCB-induced intra-cellular carbohydrate-deficient state. Conventional decontamination measures are ineffective in accelerating clearance of CCB. Experience with intravenous lipid emulsion for lipophilic drug overdose, such as verapamil, is limited, but has been proposed as a rescue therapy and might improve cardiac inotropy through intravascular sequestration of the lipophilic CCB.

Cost savings with interventions to reduce aerosolized bronchodilator use in mechanically ventilated patients.

PURPOSE: The purpose of this evaluation is to describe the cost savings associated with multimodal interventions aimed at reducing aerosolized bronchodilator use in mechanically ventilated patients without adversely affecting costs associated with length of stay (LOS). MATERIALS AND METHODS: Subjects were included in the analysis if they were aged more than 18 years, on mechanical ventilation in the intensive care unit, and received aerosolized bronchodilators. Patients were excluded if they had reversible airway disease, an indication needing bronchodilator therapy. Patient data were obtained using the University Health System Consortium Clinical Data Base/Resource Manager (Chicago, IL) to compare outcomes during two 6-month periods separated by a 4-month intervention phase aimed to reduce bronchodilator use. RESULTS: There were no significant differences in age, sex, and LOS (observed and expected) between the preintervention and postintervention phases. Based on whole acquisition costs, the total cost of bronchodilators dispensed to the adult intensive care units over the 6-month postintervention phase was reduced by $56960 compared with the 6-month preintervention phase ($120562 vs $63602, respectively). CONCLUSIONS: Multimodal efforts to restrict aerosolized bronchodilator therapy in mechanically ventilated patients were successful and led to sustained reductions in use that was associated with substantial reductions in cost, without affecting LOS.

Evaluation of discontinuation of atypical antipsychotics prescribed for ICU delirium.

A number of trials suggest that short-term use of atypical antipsychotics may be useful in the treatment of delirium associated with critical illness. However, long-term use of such agents for this indication has not been studied and may be associated with risks of adverse effects as well as unnecessary health care costs. A retrospective study of prescribing patterns of atypical antipsychotics initiated for the treatment of intensive care unit (ICU) delirium was performed to identify whether these agents were being discontinued prior to or upon hospital discharge. Of the 59 patients who met inclusion criteria and survived to hospital discharge, 28 (47%) were continued on the atypical antipsychotic upon discharge from the medical ICU. For those continued on the agent, 20 patients (71.4%) were prescribed continued therapy as an outpatient. Inpatient costs for atypical antipsychotics during the 9-month study period were increased by approximately $888. Annual cost of the medication as outpatient therapy is assessed at approximately $45,107. Although short-term trials of atypical antipsychotics may be useful for ICU delirium, caution is advised regarding potential adverse effects and added health care costs when use is prolonged.

Effect of albumin on diuretic response to furosemide in patients with hypoalbuminemia.

BACKGROUND: Albumin is broadly prescribed for critically ill patients although it does not have a mortality benefit over crystalloids. One common use of albumin is to promote diuresis. Objectives To compare urine output in patients treated with furosemide with and without albumin and to assess other variables possibly associated with enhanced diuresis. METHODS: A retrospective study was conducted on patients in a medical intensive care unit who received furosemide therapy as a continuous infusion with and without 25% albumin for more than 6 hours. Primary end points were urine output and net fluid loss. RESULTS: A total of 31 patients were included in the final analysis. Mean urine output in patients treated with furosemide alone did not differ significantly from output in patients treated with furo-semide plus albumin at 6, 24, and 48 hours: mean output, 1119 (SD, 597) mL vs 1201 (SD, 612) mL, P = .56; 4323 (SD, 1717) mL vs 4615 (SD, 1741) mL, P = .42; and 7563 mL (SD, 2766) vs 7432 (SD, 2324) mL, P = .94, respectively. Additionally, net fluid loss did not differ significantly between the 2 groups at 6, 24, and 48 hours. Higher concentrations of serum albumin did not improve urine output. The only independent variable significantly associated with enhanced urine output at 24 and 48 hours was increased fluid intake. CONCLUSION: Addition of albumin to a furosemide infusion did not enhance diuresis obtained with furosemide alone in critically ill patients.