Search

Purpose: Cytarabine is considered the standard of care for induction therapy in patients with acute myeloid leukemia (AML) who are preparing for bone marrow transplant. Summary: We report a case of a 72-year-old female presenting to the intensive care unit with hepatic failure after high-dose cytarabine (HiDAC) for the treatment of relapsed AML. The patient's liver function tests (LFTs) were elevated acutely, with a mildly elevated bilirubin and a normal alkaline phosphatase. HiDAC was discontinued but her LFTs remained high for 9 days post discontinuation, and the patient eventually expired due to sepsis and multiple organ failure. We estimated the probability of the hepatotoxicity observed with HiDAC as probable based on a score of 5 on the Naranjo scale. Conclusion: Clinicians should be aware of the potential hepatotoxicity associated with HiDAC for patients with AML, specifically in the elderly population., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The impact of vasopressin and norepinephrine discontinuation order in the recovery phase of septic shock remains controversial. This systematic review and patient-level meta-analysis were performed to determine the impact of vasopressin and norepinephrine discontinuation order on clinically significant outcomes in the recovery phase of septic shock., Methods: Cumulative Index to Nursing and Allied Health Literature, Embase, PubMed, and ClinicalTrials.gov were searched from inception through November 2018 for studies comparing outcomes after the discontinuation of vasopressin or norepinephrine in septic shock. Individual patient-level data were obtained from included studies and combined using a two-stage meta-analysis., Results: Six studies of low or moderate risk of bias with 957 patients were included. Clinically significant hypotension occurred more frequently when vasopressin was discontinued first compared to norepinephrine (60.7% versus 43.3%, respectively). First discontinuation of norepinephrine compared to vasopressin had lower pooled odds of developing clinically significant hypotension (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07-0.68, I 2 87%). No differences were detected in short-term mortality (OR 1.12, 95% CI 0.67-1.86, I 2 45%), intensive care unit length of stay (mean difference 0.15 day, 95% CI -1.58 to 1.88, I 2 21%), or hospital length of stay (mean difference 1.65 days, 95% CI -0.47 to 3.76, I 2 0%)., Conclusions: Discontinuation of norepinephrine prior to vasopressin during the recovery phase of septic shock resulted in less clinically significant hypotension but no difference in mortality or lengths of stay. Larger, prospective studies evaluating the impact of relative vasopressin deficiency and norepinephrine and vasopressin discontinuation order and timing on patient-centered outcomes are needed., (© 2019 Pharmacotherapy Publications, Inc.)

A framework for evaluating pharmacists' impact on cost avoidance in the intensive care unit (ICU) and emergency department (ED) has not been established. This scoping review was registered (CRD42018091217) and conducted to identify, aggregate, and qualitatively describe the highest quality evidence for cost avoidance generated by clinical pharmacists on interventions performed in an ICU or ED. Searches were conducted in PubMed, Scopus, CINAHL, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews from inception until April 2018. The level of evidence (LOE) for each specific category of intervention was evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation evidence-to-decision framework. The risks of bias for articles were evaluated using Newcastle Ottawa and Cochrane Collaboration tools. The values from all interventions were inflated to 2018 U.S. dollars using the consumer price index for medical care. Of the 464 articles initially identified, 371 were excluded and 93 were included. After reviewing references from the articles included, an additional 71 articles were also reviewed. The 38 cost intervention categories were supported by varying LOEs: IA (0 categories), IB (1 category), IIA (4 categories), IIB (0 categories), III (27 categories), and IV (6 categories), and articles mostly displayed low to moderate risks of bias. Pharmacists generate cost avoidance through a variety of interventions in critically and emergently ill patients. The quality of evidence supporting specific cost avoidance values is generally low. Quantification of and factors associated with the cost avoidance generated from pharmacists caring for these patients are of paramount importance., (© 2019 Pharmacotherapy Publications, Inc.)

Objectives: Mounting evidence has shown that critically ill patients are commonly thiamine deficient. We sought to test the hypothesis that critically ill patients with septic shock exposed to thiamine would demonstrate improved lactate clearance and more favorable clinical outcomes compared with those not receiving thiamine., Design: Retrospective, single-center, matched cohort study., Setting: Tertiary care academic medical center., Patients: Adult patients admitted with an International Classification of Diseases, 9th Edition, or International Classification of Diseases, 10th Edition, diagnosis code of septic shock to either the medicine or surgery ICU., Interventions: None., Measurements and Main Results: Patients who received IV thiamine supplementation within 24 hours of hospital admission were identified and compared with a matched cohort of patients not receiving thiamine. The primary objective was to determine if thiamine administration was associated with a reduced time to lactate clearance in septic shock. Secondary outcomes included 28-day mortality, acute kidney injury, and need for renal replacement therapy, and vasopressor and mechanical ventilation-free days. Two-thousand two-hundred seventy-two patients were screened, of whom 1,049 were eligible. The study consisted of 123 thiamine-treated patients matched with 246 patients who did not receive thiamine. Based on the Fine-Gray survival model, treatment with thiamine was associated with an improved likelihood of lactate clearance (subdistribution hazard ratio, 1.307; 95% CI, 1.002-1.704). Thiamine administration was also associated with a reduction in 28-day mortality (hazard ratio, 0.666; 95% CI, 0.490-0.905). There were no differences in any secondary outcomes., Conclusions: Thiamine administration within 24 hours of admission in patients presenting with septic shock was associated with improved lactate clearance and a reduction in 28-day mortality compared with matched controls.

Objective: To review and summarize data on angiotensin II (AT-II), approved by the Food and Drug Administration (FDA) in December 2017 to increase blood pressure in adults with septic or other distributive shock., Data Sources: A PubMed/MEDLINE search was conducted using the following terms: (angiotensin ii OR angiotensin 2) AND (shock) from 1966 to February 2018., Study Selection and Data Extraction: A total of 691 citations were reviewed with only relevant clinical data extracted., Data Synthesis: AT-II is a peptide hormone with a multitude of physiological effects-namely, vasoconstriction of venous and arterial smooth muscle. The priority approval granted by the FDA was secondary to a phase 3 study of patients receiving at least 0.2 µg/kg/min of norepinephrine or equivalent for vasodilatory shock. Compared with placebo, AT-II had a significantly higher rate of response, defined as a mean arterial pressure of 75 mm Hg or an increase of 10 mm Hg. No significant difference was found in death by day 28., Conclusions: AT-II is a newly available vasoactive agent with a novel mechanism for the treatment of distributive shock. Further research is needed to define its exact role in therapy of shock states, identify patients most likely to benefit, and further study its safety profile in critical illness.

Objectives: Although the potential dangers of hyperchloremia from resuscitation fluids continue to emerge, no study to date has considered the contribution of medication diluents to cumulative volume and hyperchloremia. This study compares saline versus dextrose 5% in water as the primary medication diluent and the occurrence of hyperchloremia in critically ill patients., Design: Prospective, open-label, sequential period pilot study., Setting: Medical ICU of a large academic medical center., Patients: Adult patients admitted to the medical ICU were eligible for inclusion. Patients who were admitted for less than 48 hours, less than 18 years old, pregnant, incarcerated, or who had brain injury were excluded., Interventions: Saline as the primary medication diluent for 2 months followed by dextrose 5% in water as the primary medication diluent for 2 months., Measurements and Main Results: A total of 426 patients were included, 216 in the saline group and 210 in the dextrose 5% in water group. Medication diluents accounted for 63% of the total IV volume over the observation period. In the saline group, 17.9% developed hyperchloremia compared with 10.5% in the dextrose 5% in water group (p = 0.037), which was statistically significant in multivariable analysis (odds ratio, 0.50; 95% CI, 0.26-0.94; p = 0.031). In the saline group, 34.2% developed acute kidney injury versus 24.5% in the dextrose 5% in water group (p = 0.035); however, this was not statistically significant when adjusting for baseline covariates. No other significant differences in dysnatremias, insulin requirements, glucose control, ICU length of stay, or ICU mortality were observed., Conclusions: This study identified that medication diluents contribute substantially to the total IV volume received by critically ill patients. Saline as the primary medication diluent compared with dextrose 5% in water is associated with hyperchloremia, a possible risk factor for acute kidney injury.

Acute liver failure secondary to acetaminophen overdose can be a life-threatening condition, characterized by severe electrolyte derangements. Hepatocyte regeneration is associated with phosphorous utilization and is a known complication of liver recovery following injury. We report the case of profound, life-threatening hypophosphatemia following recovery from acute fulminant liver failure. As the liver enzymes normalized, serum phosphorous levels plummeted. Our patient required an aggressive, individualized phosphorus replacement regimen, which resulted in a continuous infusion of intravenous (IV) sodium phosphate, titrated to a maximum rate of 30 mmol/h or 0.5 mmol/kg/h. The patient required over 400 mmol of total IV and oral phosphorous over the course of 48 hours. An aggressive approach to phosphorous replacement was done safely and effectively. Traditional replacement protocols are not adequate to sustain patients with this degree of hypophosphatemia. This is the first report to utilize a continuous infusion of phosphate with a maximum reported rate (0.5 mmol/kg/h). Our report summarizes a novel and safe approach for clinicians to maximally support these patients through high-dose, continuous infusion phosphorous administration.

Purpose: This single-center, retrospective cohort study investigated the effects of timing of initiating home neuropsychiatric medications (NPMs) on sedation-related outcomes., Materials and Methods: Subjects included adult medical intensive care unit (MICU) patients who had an NPM on their admission medication list; intubated before or on arrival to the intensive care unit (ICU); and were on benzodiazepine-based sedation. The intervention assessed was the timing of the initiation of home NPMs: early (≤5days) vs. late (>5days) into the ICU stay., Results: There were 56 and 53 patients in the early and late restart groups, respectively. Early cohort patients maintained a median daily RASS of -1.5, while late cohort patients had a median daily RASS of -2.0 (p=0.02). The effect was driven by the subgroup of patients on home anti-depressant therapy who were restarted early on these agents. The early restart group had a higher percentage of days with RASS scores within goal (p=0.01) and less delirium (p=0.02). Early restarting of home NPMs was associated with a non-significant decrease in ventilator days compared with late restarting (p=0.11)., Conclusions: Restarting home NPMs was associated with lighter sedation levels and less delirium., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

Background: Limited data support high-dose oseltamivir in critically ill patients with influenza. In several recent influenza seasons, there were oseltamivir drug shortages., Methods: This was a retrospective cohort analysis of 57 patients admitted to the intensive care unit (ICU) with confirmed influenza. Patients receiving high-dose oseltamivir were compared to those receiving standard dosing., Results: When adjusted for clinically relevant predictors of disease severity, including age, duration of therapy, Acute Physiology and Chronic Health Evaluation II score, and receipt of extracorporeal membrane oxygenation, there was no difference in the duration of mechanical ventilation, oxygenation, ICU length of stay, or hospital length of stay between the high-dose and standard dose groups., Conclusions: As compared to the standard doses of oseltamivir, higher-dose (ie, double dose) oseltamivir was not associated with improvement in any clinical outcomes. Using higher doses empirically on all patients during influenza season may exacerbate local drug shortages.

Objective: Norepinephrine is the first-line vasopressor recommended for patients in septic shock. Weight-based dosing may increase drug exposure and the risk of adverse effects in obese patients. The objective was to evaluate the safety and efficacy of weight-based norepinephrine dosing using actual body weight in the morbidly obese compared with normal weight patients., Methods: This was a single centre, retrospective study of adult patients admitted with septic shock requiring norepinephrine for at least 12hours. The primary endpoint was the incidence of tachycardia within 48hours after norepinephrine initiation. Secondary endpoints included timing and dosing of norepinephrine when adjunctive agents were added., Results: The incidence of tachycardia was similar between groups. Total norepinephrine exposure was significantly greater in obese patients on day 1 (p=0.02). Obese patients were more likely to be started on vasopressin (p<0.001) and steroids at a lower weight-based norepinephrine dose (p=0.016)., Conclusions: Weight-based norepinephrine dosing using actual body weight did not result in more tachycardia in the morbidly obese compared to normal weight patients, despite greater total exposure. These results were limited by the low doses used and a small cohort. However, use of actual body weight in morbidly obese patients appears to be safe., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Rabson-Mendenhall syndrome is a rare genetic disorder resulting from mutations in the insulin receptor and is associated with high degrees of insulin resistance. These patients are prone to complications secondary to their hyperglycemia including diabetic ketoacidosis (DKA). We report the case of a 19-year-old male with Rabson-Mendenhall syndrome presenting with DKA who required doses of up to 500 U/h (10.6 U/kg/h) of insulin. The patient's insulin infusion was originally compounded with U-100 regular insulin, although to minimize volume, the product was compounded with U-500 insulin. The DKA eventually resolved requiring infusion rates ranging from 400 to 500 U/h. Although numerous opportunities for medication errors exist with the use of U-500 insulin, this case outlines the safe use of concentrated intravenous insulin when clinically indicated for patients requiring extremely high doses of insulin to control blood glucose.

Whether for temporary or long term use, mechanical circulatory support (MCS) has seen increased utilization and interest over the past several years. Even though these devices innately cause thrombocytopenia, co-administration of heparin anticoagulation carries the risk for heparin-induced thrombocytopenia (HIT). This poses challenges for practitioners as very few studies provide guidance for the management of this condition, particularly in this population. This has led to a wide spectrum of treatment protocols within current practice. This review was developed to bring together available literature on the management of HIT in patients with MCS along with practical experience and clinical opinion in order to help guide the management of these patients.

Purpose: The use of high-fidelity simulation training for preparing pharmacy residents for various high-stress and high-impact medical emergencies and the impact of this training on pharmacy residents' perception of preparedness are described., Summary: During the 2015-16 residency year at the University of Kentucky Medical Center, simulation training, in addition to lecture-based orientation training, was chosen as a method to reinforce skills and knowledge learned throughout the orientation, before residents began working on-call shifts. Three different simulation exercises were developed to cover five selected topics over the course of 3 different days: sepsis as its own session, a surgical-themed session combining bleeding reversal and malignant hyperthermia, and a neurologic-themed session combining stroke and status epilepticus. Postgraduate year 2 (PGY2) specialty residents in critical care and emergency medicine helped facilitate the cases. The specialty residents played the role of the physician or nurse for the case and were allowed to answer questions asked of the pharmacy residents, appropriate to their respective roles. Following completion of the simulation exercise, a survey tool was sent to pharmacy residents to rate their perception of preparedness before and after the training for each scenario and again at 6 months after the simulation training to assess sustainability of the training. Participants generally responded that the simulations met their expectations and that the PGY2 residents facilitated the simulations fairly well (scores of 68.5-80 on a scale of 0-100). The resident-reported that beneficial effects of simulation training persisted at 6 months following the simulation exercises., Conclusion: Simulation training increased pharmacy residents' self-reported preparedness for high-stress, high-impact clinical scenarios and medical emergencies., (Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

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., (© 2016 Pharmacotherapy Publications, Inc.)

Objective: This study aimed to assess whether interventions targeted at improving sleep in the ICU were associated with reductions in ICU delirium. Secondary outcomes include duration of delirium and ICU length of stay., Data Sources: MEDLINE, CINAHL, Web of Science, Scopus, WorldCat, and International Pharmaceutical Abstracts were searched from inception to January 2016., Study Selection: Studies investigating any type of sleep intervention (nonpharmacologic or pharmacologic) and assessing the impact on ICU delirium were included. Any type of study design was permitted so long as the delirium assessment was made at least daily with a validated delirium assessment tool., Data Extraction: The following data were extracted: first author, year of publication, study design, ICU type, components of sleep intervention, use of sleep assessment tool, patient age, sex, severity of illness, sleep measures, delirium assessment tool, incidence of delirium, duration of delirium, and ICU length of stay. The incidence of delirium was used to compare rates of ICU delirium across studies. Methodologic quality of included studies was evaluated using the Effective Public Health Practice Project quality assessment tool., Data Synthesis: Of 488 citations screened, 10 studies were identified for inclusion in the final review; six of which demonstrated a statistically significant reduction in the incidence of ICU delirium associated with sleep intervention. Four studies assessed duration of delirium; of which, three reported a shorter duration of delirium with sleep intervention. Two studies associated sleep intervention with a reduced ICU length of stay. In regard to quality assessment and risk of bias, only one study was assessed as strong. Multiple identified confounders and the significant qualitative assessment of heterogeneity limit both the conclusions that can be drawn from these findings and the quantitative pooling of data., Conclusions: Although sleep interventions seem to be a promising approach for improving delirium-related outcomes, studies are limited by bias issues, varying methodologies, and multiple confounders, making the evidence base for this conclusion limited at best. Future studies would benefit from a systematic approach to studying the link between sleep intervention and delirium-related outcomes, which is outlined in the context of reviewing the existing literature.

Salmonella species are facultative intracellular pathogens that most frequently cause self-limiting gastrointestinal disease, often acquired through the ingestion of contaminated food. We report the case of a 33-year-old otherwise healthy, not overtly immunosuppressed, man who was transferred to our facility with the chief complaint of respiratory failure and septic shock. Computed tomography of the chest revealed multifocal pneumonia in both lungs. A bronchial alveolar lavage was performed in the right middle lobe and cultures predominantly grew Salmonella enterica serovar Enteritidis. The patient received a prolonged course of antimicrobials, ultimately changing to oral levofloxacin. The etiology of the salmonella infection likely occurred through an aspiration event. Salmonella species are not a typical respiratory pathogen in immunocompetent hosts; however, clinicians should be aware of the possibility that salmonella species may be a pathogenic source of infection in the lungs; a prolonged course of antimicrobials may be warranted.

Objective: Patients with a chronic alcohol use disorder presenting to the ICU may be deficient in important vitamins and electrolytes and are often prescribed a "banana bag" as a reflexive standard of therapy. The difficulty of diagnosing Wernicke's encephalopathy in the critical care setting is reviewed. Furthermore, whether the contents and doses of micronutrients and electrolytes in standard banana bags meet the needs of critically ill patients with an alcohol use disorder is assessed based on available evidence., Data Source: MEDLINE/PubMed (1966 to June 2015) database search, the Cochrane Database of Systematic Reviews, and manual selection of bibliographies from selected articles., Study Selection and Data Extraction: Articles relevant to Wernicke's encephalopathy, vitamin and electrolyte deficiencies in patients with alcohol use disorders, and alcoholic ketoacidosis were selected. Articles were narratively synthesized for this review., Data Synthesis: Of these deficiencies, thiamine is the most important for the practicing clinician to assess and prescribe replacement in a timely manner. Based on a pharmacokinetic assessment of thiamine, the banana bag approach likely fails to optimize delivery of thiamine to the central nervous system. Folic acid and magnesium may also merit supplementation although the available data do not allow for as strong a recommendation as for prescribing thiamine in this setting. There is no available evidence supporting the prescription of a multivitamin., Conclusions: Based on the published literature, for patients with a chronic alcohol use disorder admitted to the ICU with symptoms that may mimic or mask Wernicke's encephalopathy, we suggest abandoning the banana bag and utilizing the following formula for routine supplementation during the first day of admission: 200-500 mg IV thiamine every 8 hours, 64 mg/kg magnesium sulfate (approximately 4-5 g for most adult patients), and 400-1,000 μg IV folate. If alcoholic ketoacidosis is suspected, dextrose-containing fluids are recommended over normal saline.

We report the case of capecitabine-induced ventricular fibrillation arrest, possibly secondary to type I Kounis syndrome. A 47-year-old man with a history of T3N1 moderately differentiated adenocarcinoma of the colon, status-post sigmoid resection, was started on adjuvant capecitabine approximately five months prior to presentation of cardiac arrest secondary to ventricular fibrillation. An electrocardiogram (EKG) revealed ST segment elevation on the lateral leads and the patient was taken emergently to the cardiac catheterization laboratory. The catheterization revealed no angiographically significant stenosis and coronary artery disease was ruled out. After ruling out other causes of cardiac arrest, the working diagnosis was capecitabine-induced ventricular fibrillation arrest. As such, an inflammatory work up was sent to evaluate for the possibility of a capecitabine hypersensitivity, or Kounis syndrome, and is the first documented report in the literature to do so when evaluating Kounis syndrome. Immunoglobulin E (IgE), tryptase, and C-reactive protein were normal but histamine, interleukin (IL)-6, and IL-10 were elevated. Histamine elevation supports the suspicion that our patient had type I Kounis syndrome. Naranjo adverse drug reaction probability scale indicates a probable adverse effect due to capecitabine with seven points. A case of capecitabine-induced ventricular fibrillation arrest is reported, with a potential for type 1 Kounis syndrome as an underlying pathology supported by immunologic work up., (© The Author(s) 2014.)

PubMed/MEDLINE (1966-November 2014) was searched to identify relevant published studies on the overall frequency, types, and examples of medication errors during medical emergencies involving cardiopulmonary resuscitation and related situations, and the breakdown by type of error. The overall frequency of medication errors during medical emergencies, specifically situations related to resuscitation, is highly variable. Medication errors during such emergencies, particularly cardiopulmonary resuscitation and surrounding events, are not well characterized in the literature but may be more frequent than previously thought. Depending on whether research methods included database mining, simulation, or prospective observation of clinical practice, reported occurrence of medication errors during cardiopulmonary resuscitation and surrounding events has ranged from less than 1% to 50%. Because of the chaos of the resuscitation environment, errors in prescribing, dosing, preparing, labeling, and administering drugs are prone to occur. System-based strategies, such as infusion pump policies and code cart management, as well as personal strategies exist to minimize medication errors during emergency situations., (©2016 American Association of Critical-Care Nurses.)

Levetiracetam is considered by many clinicians to be one of the most benign antiepileptic medications available. We report the case of a 24-year-old man presenting with seizures for which he was started on levetiracetam. Despite an extensive work-up and treatment of possible infectious and noninfectious issues, the patient remained intermittently febrile. When a marked peripheral eosinophilia was noted, the patient's levetiracetam was discontinued and phenytoin prescribed. The fever resolved within 24 hours, and the patient's eosinophilia count returned to normal limits following discharge back to his long-term care facility. We estimate the probability of this reaction related to levetiracetam as probable based on a score of 7 on the Naranjo scale. Clinicians should be aware of the possibility that levetiracetam may be an offending agent in a patient with unexplained fever and eosinophilia. These may be early signs of the progression to a more serious drug hypersensitivity reaction, such as drug rash, eosinophilia, and systemic symptoms (DRESS) syndrome., (© 2015 Pharmacotherapy Publications, Inc.)

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., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2014.)

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.