Severe Hypertriglyceridemia Induced by Sirolimus Treated With Medical Management Without Plasmapheresis: A Case Report.

Hypertriglyceridemia and hyperlipidemia are the most remarkable metabolic complications seen with long-term sirolimus therapy. We report the case of a 36-year-old woman status post bilateral lung transplantation on a maintenance immunosuppression regimen of sirolimus, tacrolimus, and prednisone who presented with status migrainosus, chest pain, abdominal discomfort, and triglyceride levels greater than 4425 mg/dL. In previously reported cases of severe hypertriglyceridemia that developed on maintenance sirolimus therapy, plasmapheresis has been utilized as an early strategy to rapidly lower triglycerides in order to minimize the risk of acute complications such as pancreatitis, but our case was managed medically without plasmapheresis. The most recent triglyceride was down to 520 mg/dL 2 months after discontinuation of sirolimus. We estimate the probability of this reaction to sirolimus as probable based on a score of 5 points on the Naranjo scale. This is the first case report to our knowledge that highlights the sole use of oral lipid-lowering drug agents to treat severe hypertriglyceridemia secondary to sirolimus without the use of plasmapheresis. CONCLUSION: Sirolimus-induced severe hypertriglyceridemia can be managed with oral lipid-lowering agents without plasmapheresis. Clinician needs to be aware of the importance of baseline and regular triglyceride monitoring in patients on sirolimus.

Impact of Pharmacist Intervention on Selection and Timing of Appropriate Antimicrobial Therapy in Septic Shock.

BACKGROUND: Current guidelines for septic shock management recommend administration of appropriate, broad-spectrum antimicrobials within 1 hour of recognition. OBJECTIVE: To evaluate the interventions pharmacists make as part of a sepsis response team and to determine if these interventions increase the proportion of patients with appropriate empiric antimicrobial therapy. METHODS: A retrospective cohort study was undertaken reviewing adult patients in a large, academic medical center with confirmed septic shock who had an order for a "sepsis bundle," which includes notification of a pharmacist to assess adequacy of empiric therapy. Pharmacist interventions with regard to selection of empiric antimicrobials were documented. The proportion of patients with initial successful selection of antimicrobial therapy (SSAT) before and after pharmacist intervention was assessed as well as the time to first antimicrobial administration and time to appropriate antimicrobial administration. RESULTS: A total of 76 patients were included. Pharmacist intervention increased the proportion of patients with SSAT from 66% to 80% ( P = .04). Median time to first antimicrobial administration was 43 minutes, and time to appropriate antimicrobial therapy was 1 hour, 34 minutes for the entire cohort, with pharmacist intervention decreasing the latter time significantly in patients without SSAT on initiation of the "sepsis bundle" ( P < .001). CONCLUSION: Pharmacist assessment of patients in septic shock offers the opportunity to improve SSAT. Systems designed to use a pharmacist responder for the care of patients with septic shock maximize the selection of antimicrobials, facilitate rapid administration, and improve surrogate outcomes for mortality in septic shock.

Managing the Rising Costs and High Drug Expenditures in Critical Care Pharmacy Practice.

Pharmaceutical costs for patients in the intensive care unit (ICU) constitute a large portion of hospital drug budgets. Unfortunately, prices for medications commonly used in the ICU are on the rise for a variety of reasons. In particular, the U.S. Food and Drug Administration's Unapproved Drugs Initiative, generic manufacturers cornering the marketplace, drug shortages, and regulatory device changes are major drivers of pharmaceutical price escalation affecting costs in the ICU. Furthermore, traditional high acquisition cost items still pose challenges to controlling costs. To offer strategies to mitigate the rising costs of pharmaceuticals in the ICU setting, we searched the PubMed/Medline and International Pharmaceutical Abstracts databases and other related sources to identify published cost-saving protocols concerning specific medications that are affected by rising prices or have traditional high acquisition costs. In the absence of specific protocols, we offer possible cost-saving initiatives based on published literature regarding specific agents or based on our own diverse set of experiences. Finally, we review suggested clinical and operational activities at an institutional level to address these rising drug costs in the ICU setting.

Utilization of Pharmacist Responders as a Component of a Multidisciplinary Sepsis Bundle.

BACKGROUND: Sepsis and septic shock remain a significant burden on the US health care system. A multidisciplinary response system (Coordinated Response to Sepsis, CaRTS) that included a pharmacist responder was implemented for patients with newly suspected sepsis. OBJECTIVE: To evaluate the time to appropriate antibiotic administration among patients with the CaRTS intervention compared with historical controls. METHOD: The CaRTS intervention included an electronic order set as well as activation of a multidisciplinary team of pharmacy and nursing personnel to coordinate resuscitation and medication administration. The CaRTS group was compared to historical controls. The primary outcome of the study was the proportion of patients with appropriate antibiotic administration within 1 hour of recognition of sepsis. Secondary outcomes included achievement of mean arterial pressure (MAP) ≥65 mm Hg and central venous pressure (CVP) of 8 to 12 mm Hg within 6 hours. RESULT: The CaRTS intervention was used for 49 patients and 59 historical controls were included for analysis. Patients with the CaRTS intervention had a greater than 20 times higher odds of antibiotic administration within 1 hour compared with controls (odds ratio [OR] 22.4, 95% confidence interval [CI] 7.5-69) and were more likely to have a CVP ≥8 mm Hg at 6 hours (OR 2.4, 95% CI 1.0-5.6) compared with controls. CaRTS patients achieved statistically nonsignificant increases in MAP ≥65 mm Hg (OR 2.2, 95% CI 0.7-7.7). CONCLUSION: Utilization of a multidisciplinary sepsis bundle that included a pharmacist responder improved the proportion of patients receiving appropriate antibiotics within 1 hour of recognition of sepsis compared to historical controls.

More questions than answers in ICU delirium: pressing issues for future research.

With the release of the updated pain, agitation, and delirium guidelines by the Society of Critical Care Medicine, a number of new and updated recommendations are provided regarding the pharmacological prevention and treatment of ICU delirium. Whereas this is important to understand the limitations of existing literature in interpreting the guideline recommendations, it also provides an opportunity to identify those areas of practice where we need further knowledge. We discuss 5 of the most critical questions in our view regarding pharmacological therapy for ICU delirium in an attempt to highlight areas of this ICU condition that are much deserving of further research, including the deliriogenic potential of dexmedetomidine, optimal sedative choices for the delirious ICU patient, pharmacological prophylaxis for ICU delirium, optimal treatment duration for ICU delirium, and the impact of pharmacotherapy on long-term cognitive outcomes in ICU survivors. A multitude of opportunities for further research exist in the above areas for clinicians and researchers interested in this ICU condition.

Pharmacotherapy of lung transplantation: an overview.

Lung transplantation has become a viable treatment therapy for end-stage lung disease patients. The most common etiologies of end-stage lung disease, which can require a transplant are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), and pulmonary fibrosis (PF). Listing criteria are institution and program specific. Approximately 1500 lung transplants were performed in 2008; and at 5 years post transplant, one-half are expected to survive. The surgery itself is associated with various complications, including surgical, infectious, and mechanical. Immunosuppression is paramount to the management of these patients, the goal being prevention of T cell activation to prevent rejection of the new organ. The patients commonly receive an induction agent with a T cell depleting antibody and high-dose corticosteroids. Maintenance immunosuppression begins immediately after the surgery, consisting of a combination of a calcineurin inhibitor, antimetabolite, and corticosteroids. Side effect profiles from the various agents will determine the choice of agents, and patients may have modifications throughout the therapy. The role of the pharmacist spans the inpatient management of acute complications to medication selection, management of maintenance immunosuppression, as well as monitoring for adverse drug reactions and drug-drug interactions. A multidisciplinary collaborative approach must be taken to ensure the best outcomes for this patient population.

Fungal infection in heart-lung transplant recipients receiving single-agent prophylaxis with itraconazole.

OBJECTIVES: Heart and lung transplant recipients are at risk for invasive fungal infections. This study evaluated the affect of single-agent antifungal prophylaxis with itraconazole on the rate of fungal infections after heart or lung transplant. MATERIALS AND METHODS: An observational, retrospective study was performed to evaluate the rate of fungal infections in heart and lung transplant recipients at the University of Kentucky Medical Center over 4.5 years who received itraconazole as a single therapy prophylaxis. RESULTS: Eighty-three recipients (42 heart, 41 lung) had an overall fungal infection incidence of 16.9% (14/83), while the incidence was 11.9% for heart recipients (5/42), and 22.0% for lung recipients (9/41). CONCLUSIONS: Single-agent use with itraconazole in heart or lung transplant recipients did not affect the rate of fungal infection as compared with previous reports. The incidence of fungal infection increased significantly within 3 months after escalation of immunosuppressant for treatment of acute rejection.

A clinical-laboratory algorithm incorporating optical density value to predict heparin-induced thrombocytopenia.

The diagnosis of heparin-induced thrombocytopenia (HIT) is complex and involves integrating both clinical and laboratory findings. Readily available diagnostic tests such as the heparin-dependant antibody assay (HDAA) lack desired specificity when utilised alone. A diagnostic algorithm incorporating the 4T pretest probability score, HDAA, and optical density (OD) value was implemented as a tool to assist in the diagnosis of HIT and with the decision to treat patients. Patients with a 4T score >3 and/or positive HDAA result with an OD ≥1 were considered positive. Utilisation of this algorithm was hypothesised to improve the identification of patients without SRA confirmed HIT and improve overall specificity compared to other diagnostic strategies. Retrospective chart review was conducted and included patients with a positive or equivocal HDAA result and a serotonin release assay result during a two-year period. Each patient was evaluated for the diagnosis of HIT using the algorithm. The specificity and sensitivity of the diagnostic algorithm to identify subjects with SRA confirmed HIT was evaluated. A total of 83 patients were identified for inclusion in the study. The diagnostic algorithm identified 22 patients for direct thrombin inhibitor (DTI) therapy. Nine of these patients were SRA positive. The sensitivity of the algorithm was 0.9 with a specificity of 0.822. The diagnostic algorithm was found to be both more specific and sensitive than other diagnostic strategies including the 4T score alone, HDAA alone, and the combination of the 4T score and HDAA results. This preliminary data suggest a diagnostic algorithm combining 4T score, HDAA, and OD value may be a tool to aid in the identification SRA positive patients for DTI therapy.

Evaluation of atrial arrhythmias following noncardiac thoracic surgery.

Atrial arrhythmias (AAs) after noncardiac thoracic surgery may be associated with increased mortality, length of stay (LOS), and health care expenditures. A retrospective analysis of adult patients who underwent thoracotomy at our institution from January 2002 to June 2008 was performed. Of 820 patients identified, 112 (14%) developed an AA. Overall mortality was 7.14% in the AA group and 3.11% in the non-AA group (relative risk, 2.30; 95% confidence interval, 1.06-4.91; P = 0.035). Median intensive care unit (ICU) LOS and total LOS were 4.0 and 7.0 days in the AA group and 3.0 and 5.0 days in the non-AA group (ICU LOS P < 0.01 and total LOS P < 0.001). Median health care expenditures in the AA group were approximately $37,000 versus $28,000 in the non-AA group (P < 0.001). The development of an AA in this patient population may be associated with increased mortality, ICU and total LOS, and health care expenditures.

Methylene blue for the treatment of septic shock.

Septic shock is a major cause of morbidity and mortality in the intensive care unit, and effective therapies are limited. Methylene blue is a selective inhibitor of guanylate cyclase, a second messenger involved in nitric oxide-mediated vasodilation. The use of methylene blue in the treatment of septic shock has been repeatedly evaluated over the past 20 years, but data remain scarce. To evaluate the safety and efficacy of methylene blue for the treatment of septic shock, we conducted a literature search of the EMBASE (1974-June 2009), MEDLINE (1966-June 2009), and International Pharmaceutical Abstracts (1970-June 2009) databases. All available studies published in English were reviewed. Observational studies with methylene blue have demonstrated beneficial effects on hemodynamic parameters and oxygen delivery, but use of methylene blue may be limited by adverse pulmonary effects. Methylene blue administration is associated with increases in mean arterial pressure while reducing catecholamine requirements in patients experiencing septic shock; however, its effects on morbidity and mortality remain unknown. Well-designed, prospective evaluations are needed to define the role of methylene blue as treatment of septic shock.

Fondaparinux as a treatment option for heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication that can occur after exposure to heparin products. Because patients with HIT are at increased risk for thrombosis, anticoagulation is warranted. The direct thrombin inhibitors lepirudin and argatroban are approved by the United States Food and Drug Administration (FDA) for this indication. Bivalirudin, another direct thrombin inhibitor, is approved for use in patients with HIT who must undergo percutaneous coronary intervention. The synthetic pentasaccharide fondaparinux lacks FDA approval for treating patients with HIT; however, a few published reports describe its use. Furthermore, various small-scale, in vitro studies have demonstrated a lack of cross-reactivity between fondaparinux and HIT antibodies. Large, in vivo comparison trials must be performed before fondaparinux can become a standard treatment option in the setting of HIT.

Interventions to improve guideline compliance following coronary artery bypass grafting.

BACKGROUND: Lifestyle modification and appropriate medical therapy improve long-term outcomes following coronary artery bypass grafting (CABG). Our institutional experience suggested that evidence-based recommendations were not being followed postdischarge after CABG. We undertook this study to document our rate of compliance with evidence-based guidelines and to correct deficiencies in our discharge practices. METHODS: Seven evidence-based interventions were studied after CABG: (1) institution of beta-blocker therapy, (2) angiotensin-converting enzyme (ACE) inhibitor therapy, (3) aspirin, (4) lipid-lowering therapy, (5) smoking cessation intervention, (6) heart-healthy diet therapy, and (7) physical activity recommendations. The rate of compliance with guidelines in 50 control patients was measured at discharge. A multidisciplinary team including cardiac surgeons, nurses, dieticians, physical therapists, and clinical pharmacists evaluated the guideline compliance in the control group and developed interventions to assure guideline compliance at the time of discharge. A subsequent study group of 50 patients was then assessed prospectively to measure the guideline compliance after institution of intervention programs. The multidisciplinary team agreed on predefined acceptable compliance limits as follows: (1) >80% of patients receive ACE inhibitors at discharge, (2) 100% of patients receive beta-blockers, aspirin, and lipid-lowering agents at discharge, and (3) 100% of patients receive lifestyle modification counseling at discharge. Compliance with guidelines was defined as documentation in the medical record of provision of medications and lifestyle counseling at the time of discharge. RESULTS: In the control group, the rate of guideline compliance was surprisingly low. Rates of compliance with guidelines increased significantly after the multidisciplinary interventions were undertaken. CONCLUSIONS: We conclude that compliance with guidelines known to improve long-term outcome is suboptimal after CABG. A multidisciplinary intervention program can improve compliance with currently accepted guidelines and quality indicators in patients following CABG.