Three- versus four-factor prothrombin complex concentrate for the reversal of warfarin-induced bleeding.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of 3-factor prothrombin complex concentrate (3F-PCC) compared to 4-factor PCC (4F-PCC) in warfarin-associated bleeding. METHODS: This multicenter, retrospective, cohort study analyzed data from patients admitted between May 2011 and October 2014 who received PCC for warfarin-associated bleeding. The primary outcome was the rate of international normalized ratio (INR) normalization, defined as an INR ≤1.3, after administration of 3F-PCC compared to 4F-PCC. Other variables of interest included the incidence of additional reversal agents, new thromboembolic events, and mortality. RESULTS: A total of 134 patients were included in the analysis. The average dose of PCC administered was 24.6 ± 9.3 units/kg versus 36.3 ± 12.8 units/kg in the 3F-PCC and 4F-PCC groups, respectively, P < 0.001. Baseline INR in the 3F-PCC and 4F-PCC groups was 3.61 ± 2.3 and 6.87 ± 2.3, respectively P < 0.001. 4F-PCC had a higher rate of INR normalization at first INR check post-PCC administration compared to 3F-PCC (84.2% vs. 51.9%, P = 0.0001). Thromboembolic events, intensive care unit and hospital length of stay, and mortality were similar among both groups. CONCLUSION: The use of 4F-PCC leads to a more significant reduction in INR compared to 3F-PCC though no difference in mortality or length of stay was observed. Thromboembolism rates were similar among both groups.

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.

Physiologically-based, predictive analytics using the heart-rate-to-Systolic-Ratio significantly improves the timeliness and accuracy of sepsis prediction compared to SIRS.

BACKGROUND: Enhancing the efficiency of diagnosis and treatment of severe sepsis by using physiologically-based, predictive analytical strategies has not been fully explored. We hypothesize assessment of heart-rate-to-systolic-ratio significantly increases the timeliness and accuracy of sepsis prediction after emergency department (ED) presentation. METHODS: We evaluated the records of 53,313 ED patients from a large, urban teaching hospital between January and June 2015. The HR-to-systolic ratio was compared to SIRS criteria for sepsis prediction. There were 884 patients with discharge diagnoses of sepsis, severe sepsis, and/or septic shock. RESULTS: Variations in three presenting variables, heart rate, systolic BP and temperature were determined to be primary early predictors of sepsis with a 74% (654/884) accuracy compared to 34% (304/884) using SIRS criteria (p < 0.0001)in confirmed septic patients. CONCLUSION: Physiologically-based predictive analytics improved the accuracy and expediency of sepsis identification via detection of variations in HR-to-systolic ratio. This approach may lead to earlier sepsis workup and life-saving interventions.

Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients with Sepsis.

BACKGROUND: Doripenem is approved by the Food and Drug Administration for the treatment of patients with complicated intra-abdominal infections and complicated urinary tract infections. While studies have described the pharmacokinetics/pharmacodynamics (PK/PD) of doripenem in the critically ill, no study has described the probability of target attainment profile among trauma patients with sepsis. PATIENTS AND METHODS: This study was a prospective, open-label, pharmacokinetic study in the surgical intensive care unit (SICU) at Grady Health System. Thirty trauma patients with sepsis admitted to the SICU received doripenem 1 g infused over 4 hours every 8 hours for three doses. Blood samples were taken just before and after the third dose. A two-compartment model was fit to the data using non-parametric population PK modeling software. Embedded with the final PK model, a Monte Carlo Simulations (MCS) was performed to determine the PK/PD profile of doripenem 1 g, infused over 4 hours, every 8 hours after administration of the first and fourth doses. RESULTS: Overall, the model fit the data well, and mean (standard deviation) clearance and volume of the central compartment were 16.9 (11.4) L/h and 28.5 (16.0) L, respectively. In the MCS analyses, doripenem 1 g, infused over 4 hours, administered every 8 hours, conferred >90% probabilities of achieving 30-50% time greater than the minimum inhibitory concentration (30-50% T>MIC) for MICs ≤2 mg/L after infusion of both the first and fourth doses. The MCS indicated that more intensive doripenem dosing schemes should be considered for organisms with MIC values in excess of 2 mg/L. CONCLUSIONS: This is the first study to describe the doripenem PK/PD in critically ill patients with trauma. Among these patients, the MCS analyses suggest that current dosing strategies may be ineffective when the MIC value for the infecting pathogen is expected to be above 2 mg/L.

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.

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.

Evaluation of pharmacy resident alertness in an overnight on-call program.

PURPOSE: Results of a study to determine the impact of overnight on-call duty on pharmacy residents' alertness are presented. METHODS: A prospective single-site observational study was conducted to evaluate sleep patterns and alertness levels among pharmacy residents serving 24-hour on-call duty assignments at a large hospital. The study participants (n = 10) wore a wrist actigraph to allow continuous tracking of rest-activity patterns; in addition, study participants completed a validated three-minute psychomotor vigilance test (PVT) during designated time periods around the beginning and the end of each duty shift and several hours after the shift ended. Study participants also documented sleep quality and quantity in a sleep log and self-rated their level of alertness using the Karolinska sleepiness scale (KSS). RESULTS: Assessments were conducted for a total of 31 on-call duty shifts over one month. Paired comparisons of PVT data obtained at the three assessment periods indicated that on-call duty was not associated with significant changes in PVT performance measures (mean response speed and number of attention lapses). On average, on-call residents rated the quality of sleep during duty assignments as 5 on a 10-point Likert scale. CONCLUSION: On-call residents slept for a mean of six hours during overnight duty shifts, with half of the residents reporting sleep interruptions (a mean of 1.73 per shift). PVT results and KSS values indicated no overall decline in resident alertness during the study period.

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.

Randomized Controlled Trial of Ondansetron vs. Prochlorperazine in Adults in the Emergency Department.

OBJECTIVE: To compare the effectiveness of ondansetron and prochlorperazine to treat vomiting. Secondary objectives were the effectiveness of ondansetron and prochlorperazine to treat nausea and their tolerability. METHODS: This was a prospective, randomized, active controlled, double-blinded study. Using a convenience sample, patients were randomized to either intravenous ondansetron 4mg (n=32) or prochlorperazine 10mg (n=32). The primary outcome was the percentage of patients with vomiting at 0-30, 31-60, and 61-120 minutes after the administration of ondansetron or prochlorperazine. Secondary outcomes were nausea assessed by a visual analog scale (VAS) at baseline, 0-30, 31-60, and 61-120 minutes after the administration of ondansetron or prochlorperazine and the percentage of patients with adverse effects (sedation, headache, akathisia, dystonia) to either drug. We performed statistical analyses on the VAS scales at each time point and did a subgroup analysis to examine if nausea scores were affected if the patient had vomited at baseline. RESULTS: The primary identified cause for nausea and vomiting was flu-like illness or gastroenteritis (19%). The number of patients experiencing breakthrough vomiting at 0-30, 31-60, and 61-120 minutes was similar between groups for these time periods; however, more patients receiving ondansetron experienced vomiting overall (7 [22%] vs. 2[3.2%] patients, p=not significant). Nausea scores at baseline and 0-30 minutes were severe and similar between groups; however, at 31-60 and 61-120 minutes, patients receiving prochlorperazine had better control of nausea (24.9 vs. 43.7 mm, p=0.03; 16.8 vs. 34.3 mm, p=0.05). Sedation scores were similar between groups. There were no cases of extrapyramidal symptoms as assessed by the treating physician and there were four cases of akathisia (prochlorperazine=3 [9%], ondansetron=1[3%]). CONCLUSION: Prochlorperazine and ondansetron appear to be equally effective at treating vomiting in the emergency department.

A practical approach to understanding acid-base abnormalities in critical illness.

Acid-base disorders are common in the critically ill. Arterial blood gas (ABG) analysis is frequently used to identify and manage acid-base disturbances. Using a systematic problem-solving approach to acid-base disturbances will facilitate the identification and assess the progression and severity of the metabolic and respiratory abnormality. The intent of this review is to examine acid-base physiology and regulation, provide a method to evaluate a patient's acid-base disorder, and provide therapeutic interventions.

Tackling the devastating effects of heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia with associated thrombosis is a potentially catastrophic complication of heparin therapy. Heart failure patients often require heparin therapy in the setting of multiple comorbidities, particularly renal insufficiency. The authors report a case of heparin-induced thrombocytopenia with associated thrombosis in a patient with multisystem organ failure and discuss dosing regimens using lepirudin for the treatment of this disorder. The potential risk for excessive anticoagulation is highlighted and a conservative dosing strategy with frequent monitoring of this agent in the presence of renal failure is emphasized.