Prasad Abraham

Sodium nitroprusside-associated cyanide toxicity in adult patients – fact or fiction? A critical review of the evidence and clinical relevance

Correspondence: Prasad Abraham Department of Pharmacy and Drug information, Box 2061, Grady Health System, 80 Jesse Hill Jr Dr Se, Atlanta, GA 30303, USA Tel +1 404-616-3246 Fax +1 404-616-2228 email pabraham@gmh.edu Abstract: Since its US Food and Drug Administration (FDA) approval in 1974, sodium nitroprusside (SNP) has been fraught with controversy in regards to its safety. Over the years, a growing concern related to SNPs propensity to cause cyanide (CN) toxicity culminated into a series of case reports that led the FDA to develop a black-box warning with dose limitations of ,2 μg/kg/min. These recommendations stemmed also from the reality of the difficulty of obtaining CN levels in a timely manner, as well as the presumed poor correlation of metabolic markers (lactate levels and pH) as it related to the severity of CN toxicity. All these issues have driven practitioners to the use of alternative agents. In this paper, we critically review the cases and the data that led to the development of these restrictive dosing recommendations and reveal several limitations of the data and assumptions that led to these recommendations. We conclude that SNP is still a reasonable agent to use in the management of patients with hypertension today and can safely be used beyond doses of 2 μg/kg/min. Furthermore, in lieu of CN levels, monitoring of lactic acid levels is also a reasonable measure to ensure safety.

Effect of Electronic Health Record Implementation in Critical Care on Survival and Medication Errors

Background: Electronic health records (EHR) with computerized physician order entry have become exceedingly common and government incentives have urged implementation. The purpose of this study was to ascertain the effect of EHR implementation on medical intensive care unit (MICU) mortality, length of stay (LOS), hospital LOS and medication errors. Materials and Methods: Prospective, observational study from July 2010‐June 2011 in MICU at an urban teaching hospital in Atlanta, Georgia of 797 patients admitted to the MICU; 281 patients before the EHR implementation and 516 patients post‐EHR implementation. Results: Compared with the preimplementation period (N = 43 per 281), the mortality risk at 4 months post‐EHR implementation (N = 41 per 247) and at 8 months post‐EHR implementation (N = 26 per 269) significantly decreased (P < 0.001). In addition, the mean MICU LOS statistically decreased from 4.03 ± 1.06 days pre‐EHR to 3.26 ± 1.06 days 4 months post‐EHR and to 3.12 ± 1.05 days 8 months post‐EHR (P = 0.002). However, the mean hospital LOS was not statistically decreased. Although medication errors increased after implementation (P = 0.002), this was attributable to less severe errors and there was actually a decrease in the number of severe medication errors (both P < 0.001). Conclusions: We report a survival benefit following the implementation of EHR with computerized physician order entry in a critical care setting and a concomitant decrease in the number of severe medication errors. Although overall hospital LOS was not shortened, this study proposes that EHR implementation in a busy urban hospital was associated with improved ICU outcomes.

Evaluating Simulation-Based ACLS Education on Patient Outcomes: A Randomized, Controlled Pilot Study

BACKGROUND Simulation training is widely accepted as an effective teaching tool, especially for dealing with high-risk situations. OBJECTIVE We assessed whether standardized, simulation-based advanced cardiac life support (ACLS) training improved performance in managing simulated and actual cardiac arrests. METHODS A total of 103 second- and third-year internal medicine residents were randomized to 2 groups. The first group underwent conventional ACLS training. The second group underwent two 2 1/2-hour sessions of standardized simulation ACLS teaching. The groups were assessed by evaluators blinded to their assignment during in-hospital monthly mock codes and actual inpatient code sheets at 3 large academic hospitals. Primary outcomes were time to initiation of cardiopulmonary resuscitation, time to administration of first epinephrine/vasopressin, time to delivery of first defibrillation, and adherence to American Heart Association guidelines. RESULTS There were no differences in primary outcomes among the study arms and hospital sites. During 21 mock codes, the most common error was misidentification of the initial rhythm (67% [6 of 9] and 58% [7 of 12] control and simulation arms, respectively, P  =  .70). There were no differences in primary outcome among groups in 147 actual inpatient codes. CONCLUSIONS This blinded, randomized study found no effect on primary outcomes. A notable finding was the percentage of internal medicine residents who misidentified cardiac arrest rhythms.

A review of current agents for anticoagulation for the critical care practitioner

There has been a tremendous boom in the arena of anticoagulant therapy recently. Although the indications for these agents reside in the noncritical care environment, over time, the impact of these agents have infiltrated the critical care environment particularly due to devastating complications with associated use. With so many newer agents on the market or coming down the pipeline, it is easy to become overwhelmed. It is important that the critical care practitioner does not ignore these agents but becomes familiar with them to better prepare for the management of patients on one or more anticoagulant agents in the intensive care unit. To equip the critical care practitioners with the knowledge about commonly used anticoagulants, we provide an extensive review of the pharmacology, indications, and adverse effects related to these agents as well as suggestions on preventing or managing complications.

Evaluation of medication errors with implementation of electronic health record technology in the medical intensive care unit

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Development of the Critical Care Pharmacotherapy Trials Network

Purpose. The development of the Critical Care Pharmacotherapy Trials Network (CCPTN) as a model for practice‐based pharmacotherapy research is described. Summary. The CCPTN was formed in 2010 as a collaborative research network dedicated to scientific investigation in the field of critical care pharmacotherapy. The CCPTN organizational structure is consistent with many professional pharmacy and interdisciplinary organizations and organized into 3 primary domains: executive committee, working committees, and network membership. The network membership consists of critical care investigators dedicated to the mission and vision of the CCPTN and is open to anyone expressing an interest in contributing to high‐level research. Network member sites represent the breadth of U.S. critical care practice environments. In addition, network members include individuals with demonstrated expertise in patient safety, administration, research design, grantsmanship, database management, peer review, and scientific writing. In 2015, there were more than 100 site investigators from around the United States and Canada. Projects to date have yielded numerous abstracts, platform presentations, and peer‐reviewed publications in high‐impact journals. The CCPTN has expanded to form collaborations with researchers in the United Kingdom, Australia, and New Zealand. The CCPTN has identified new potential partnerships and field‐based areas for inquiry. Numerous opportunities for continued growth and scientific inquiry in the field of critical care pharmacotherapy research exist for the CCPTN to foster in the coming years. Conclusion. The CCPTN has been a successful model for practice‐based pharmacotherapy research and assists its members in expanding critical care pharmacotherapy knowledge.

Prevalence and factors associated with the absence of pharmacologic venous thromboembolism prophylaxis: A cross-sectional study of Georgia intensive care units.

PURPOSE The need for venous thromboembolism prophylaxis is well accepted in the intensive care unit (ICU) and supported by a variety of guideline recommendations. Several studies have highlighted poor adherence to these recommendations, but it is unknown why this discrepancy exists. The aim of this study is assess the prevalence of pharmacoprophylaxis and characterize the practice of withholding prophylaxis. MATERIALS AND METHODS Multicenter, cross-sectional study conducted in adults admitted to a Georgia ICU at participating institutions on March 12, 2014. Data were collected on eligible patients regarding need for and omission of pharmacoprophylaxis. RESULTS Three hundred sixty-four patients across 9 institutions were included in the study. Patients had a mean age of 58 years and a median Sequential Organ Failure Assessment score of 5. Physical activity was completely bedridden or restricted in 87% of the cohort. Forty-five percent of patients were not receiving pharmacoprophylaxis. The most common reasons for withholding prophylaxis were receipt of mechanical prophylaxis, recent surgery or central nervous system bleed, and thrombocytopenia. Over 16% of the cohort was inappropriately not receiving thromboprophylaxis. Patients with an elevated international normalized ratio had lower odds of receiving prophylaxis (0.2). CONCLUSIONS Venous thromboembolism prophylaxis is commonly omitted in ICU patients, and reasons for omission vary. An elevated international normalized ratio is associated with withholding of pharmacologic prophylaxis.

108: THE DEVELOPMENT AND DESCRIPTION OF A PHARMACOTHERAPY RESEARCH NETWORK

Introduction: Over the last decade several critical care clinical trial groups (CCCTG, ANZICS, USCIITG) have been created to foster critical care research. Complex critical care pharmacotherapy issues are often a secondary consideration of these groups. The Critical Care Pharmacotherapy Trials Netwo

Case Report: Persistent Elevation in Creatine Phosphokinase Associated With High-Dose Daptomycin Therapy

Objective To report a persistent elevation in creatine phosphokinase (CPK) associated with high-dose daptomycin therapy that did not resolve following discontinuation of daptomycin. Summary A 34-year-old male with HIV/AIDS and stage IV Burkitt lymphoma was admitted for pain management. The patients initial hospital course was complicated by left brachial deep vein thrombosis (DVT), Clostridium difficile colitis, and pancytopenia. The patient later developed severe sepsis and septic shock secondary to methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), Candida albicans, and Escherichia coli infection. High-dose daptomycin (12 mg/kg) was initiated to treat MRSA and VRE bacteremia. The patients baseline CPK was 118 U/L, which increased to 327 U/L following 2 days of therapy. The patients CPK continued to increase to 1648 U/L on day 10 of daptomycin, thereby necessitating a discontinuation of daptomycin and the initiation of linezolid. Six days after discontinuation of therapy, the patients CPK remained elevated at 1940 U/L. Discussion A Naranjo scale score of 6 was calculated, indicating that daptomycin was the probable cause for the increase in CPK. Although daptomycin is known to cause elevations in CPK, there are limited published data describing this adverse event with high-dose daptomycin therapy. Conclusion High-dose daptomycin is becoming more frequently used in clinical practice, so clinicians should monitor for and report any adverse events associated with this dosing strategy.

Candida Guilliermondii Fungemia in a Critically III Trauma Patient

Objective: To report a case of fungemia caused by Candida guilliermondii in a non-neutropenic 17-year-old critically ill trauma patient. Case Summary: Few case reports and small surveys have reported invasive infection caused by C. guilliermondii, most of which has occurred in immunocompromised populations. We present the case of a 17-year-old trauma patient who developed fungemia with C. guilliermondii during his intensive care unit stay. While he had multiple risk factors for the development of candidemia, this was an atypical finding, considering that this patient was not neutropenic. Due to the variable resistance patterns with this species of Candida, mean inhibitory concentration testing was requested, which demonstrated susceptibility to fluconazole. The patient was thus treated with fluconazole and his fungemia resolved without relapse. Discussion: C. guilliermondii accounts for 1–5% of cases of non-albicans Candida. While C. guilliermondii typically does not cause invasive infection, it has been associated with severe, life-threatening candidiasis in immunocompromised patients. Due to its low incidence, guidelines for the management of C. guilliermondii infections have not been well established and specific risk factors have not been identified. While risk factors specific to C. guilliermondii may mimic established risk factors for candidal fungemia in general, an important aspect to consider in the treatment of this fungus is its unique resistance profile compared with other non-albicans species. Conclusions: This case illustrates the development of an uncommon fungal pathogen in a non-immunocompromised host, compared with previously published cases series. Susceptibility testing is recommended to prevent therapeutic failures due to varying resistance patterns with C. guilliermondii.