Subdissociative Ketamine Use in the Emergency Department.

Ketamine is an anesthetic known globally both for its potent dissociative properties and potential for abuse. More recently, ketamine demonstrates utility in a variety of disease states such as treatment-resistant depression, status asthmaticus, and acute agitation. In addition, ketamine has been shown to demonstrate various effects at different doses, which adds to its pharmacological benefit. As these new indications continue to come to light, it is important to stay current with the dosing for these indications as well as the adverse effects associated with ketamine's use. This review highlights the history and mechanism of ketamine as well as addressing the use of the different dosing ranges of ketamine.

Effect of positive perioperative donor and recipient respiratory bacterial cultures on early post-transplant outcomes in lung transplant recipients.

BACKGROUND: It is standard practice to administer prophylactic antibiotics post lung transplantation. However, no studies have evaluated the impact of culture positivity. The purpose of this study was to evaluate early post-transplant outcomes of culture-positive and culture-negative lung transplant (LT) recipients and the appropriateness of the empiric regimens used. METHODS: Adult patients who received an LT at Emory University Hospital between January 1, 2010 and August 31, 2015 were reviewed and stratified into three groups: (i) culture-positive appropriate empiric treatment, (ii) culture-positive inappropriate empiric treatment, and (iii) culture-negative. Antibiotics were defined as appropriate if bacteria were sensitive to the empiric regimen. The primary endpoint was 30-day mortality. Secondary endpoints included hospital length of stay (LOS), intensive care unit (ICU) LOS, percent neutrophil count in a bronchoalveolar lavage (BAL) sample, presence of airway ischemia, and appropriateness of the empiric antibiotic regimen. RESULTS: Nine, zero, and four patients died within 30 days in the culture-positive appropriate (n = 113), culture-positive inappropriate (n = 5), and culture-negative groups (n = 29) (P = .564) respectively. The median hospital LOS was 19, 16, and 15 days respectively. Median ICU LOS was 6, 5, and 7 respectively. The respective percent neutrophil counts in the BAL fluid were 79, 83, and 65. The presence of airway ischemia was only documented in eight patients, all in the culture-positive appropriate group. CONCLUSION: We did not identify an association between antibiotic appropriateness and 30-day mortality, hospital LOS, or ICU LOS in post-LT recipients.

Rapid Development and Implementation of an ECMO Program.

Extracorporeal membrane oxygenation (ECMO) is an established therapy in the management of patients with refractory cardiogenic shock or acute respiratory failure. In this report, we describe the rapid development and implementation of an organized ECMO program at a facility that previously provided ad hoc support. The program provides care for patients within the Emory Healthcare system and throughout the Southeastern United States. From September 2014 to February 2015, 16 patients were treated with either venovenous or venoarterial ECMO with a survival to decannulation of 53.3% and survival to intensive care unit discharge of 40%. Of the 16 patients, 10 were transfers from outside facilities of which 2 were remotely cannulated and initiated on ECMO support by our ECMO transport team. Complications included intracerebral hemorrhage, bleeding from other sites, and limb ischemia. The results suggest that a rapidly developed ECMO program can provide safe transport services and provide outcomes similar to those in the existing literature. Key components appear to be an institutional commitment, a physician champion, multidisciplinary leadership, and organized training. Further study is required to determine whether outcomes will continue to improve.

Multidrug-Resistant Organism Infections in Patients with Left Ventricular Assist Devices.

Left ventricular assist devices improve survival prospects in patients with end-stage heart failure; however, infection complicates up to 59% of implantation cases. How many of these infections are caused by multidrug-resistant organisms is unknown. We sought to identify the incidence, risk factors, and outcomes of multidrug-resistant organism infection in patients who have left ventricular assist devices. We retrospectively evaluated the incidence of multidrug-resistant organisms and the independent risk factors associated with them in 57 patients who had permanent left ventricular assist devices implanted at our institution from May 2007 through October 2011. Outcomes included death, transplantation, device explantation, number of subsequent hospital admissions, and number of subsequent admissions related to infection. Infections were categorized in accordance with criteria from the Infectious Diseases Council of the International Society for Heart and Lung Transplantation. Multidrug-resistant organism infections developed in 18 of 57 patients (31.6%)-a high incidence. We found 3 independent risk factors: therapeutic goal (destination therapy vs bridging), P=0.01; body mass index, P=0.04; and exposed velour at driveline exit sites, P=0.004. We found no significant differences in mortality, transplantation, or device explantation rates; however, there was a statistically significant increase in postimplantation hospital admissions in patients with multidrug-resistant organism infection. To our knowledge, this is the first report in the medical literature concerning multidrug-resistant organism infection in patients who have permanent left ventricular assist devices.

Alteplase for the Treatment of Pulmonary Embolism: A Review.

Pulmonary embolism can present with a wide range of symptoms, from asymptomatic to cardiac arrest, making diagnosis challenging. Alteplase is a fibrinolytic that is indicated for the treatment of pulmonary embolism in intermediate- and high-risk patients. Controversy exists as to the patient population that will benefit most from fibrinolytic therapy, as well as the proper dose and administration technique. The patient's risk of bleeding should be weighed against the potential benefits of treatment in light of the clinical presentation because of the high mortality rate associated with pulmonary embolism. Nurses at the bedside must monitor for signs of bleeding when alteplase is administered. Fibrinolytic therapy will frequently be started in the emergency department, and the nurse must ensure that alteplase is administered in a safe and effective manner. This review discusses the clinical evidence for alteplase in pulmonary embolism and its specific role in treatment.

Coagulation and complications of left ventricular assist device therapy: a primer for emergency nurses.

Implantation of left ventricular assist devices (LVADs) is becoming more common with the advancement of mechanical circulatory support technology and the continued insufficient number of organ donors available for heart transplantation. Modern LVADs provide a mechanically induced, nonpulsatile, continuous blood flow that drastically alters the hemodynamic and coagulation profile of patients using these devices. In addition to the risk of bleeding and thrombotic events, LVAD support can also lead to arrhythmias and infection. Although LVAD therapy can prolong life, the majority of patients will experience an adverse event following implantation and many of these complications can result in emergency department visits. By understanding the pathophysiology and management of LVAD complications, emergency nurses will be able to provide prompt and quality care for this unique patient population.

Vancomycin clearance in high-volume venovenous hemofiltration.

OBJECTIVE: To report the pharmacokinetic and pharmacodynamic properties of vancomycin in 4 patients undergoing high-volume continuous venovenous hemofiltration (CVVH). CASE SUMMARY: Data from 4 patients prescribed high-volume CVVH for acute renal failure treated with vancomycin were analyzed. Vancomycin plasma concentrations were measured 4 and 24 hours after the end of a 1-hour vancomycin infusion. The mean therapy fluid rate on initiation of vancomycin was 56.2 mL/kg/h (range 48.0-65.5). The mean loading dose of vancomycin was 18.3 mg/kg (range 14.7-19.7). Median vancomycin concentration 4 hours after the dose was 18.1 mg/L (range 13.1-30.0). At 24 hours after the dose, only 1 patient had a detectable vancomycin concentration (5.2 mg/L). DISCUSSION: There was a large variability in the clearance of vancomycin in this patient population. Current strategies for dosing vancomycin may lead to subtherapeutic trough concentrations. Vancomycin dosing in this patient population should be based on a detailed assessment of the CVVH prescription, vancomycin concentrations, and clinical needs and response. CONCLUSIONS: An initial vancomycin dose of 20-25 mg/kg with frequent monitoring and adjustment is recommended for patients receiving high-volume CVVH.

Use of the chromogenic factor X assay in patients transitioning from argatroban to warfarin therapy.

STUDY OBJECTIVE: To assess the correlation between the chromogenic factor X assay and the international normalized ratio (INR) in patients transitioning from argatroban to warfarin therapy. DESIGN: Retrospective medical record review. SETTING: Academic medical center and community-based teaching hospital. PATIENTS: One hundred thirty-nine patients who had chromogenic factor X levels measured during the transition from argatroban to warfarin therapy between January 1, 2006, and July 31, 2010. MEASUREMENTS AND MAIN RESULTS: The correlation between chromogenic factor X levels and INRs during the transition period was assessed by calculating the sensitivity, specificity, positive predictive value, and negative predictive value for chromogenic factor X levels that were less than or equal to 45% in predicting a therapeutic INR (2.0-3.5). Patients received an average of 4.4 doses of warfarin before argatroban was discontinued. In 60 patients (43.2%), chromogenic factor X levels were subtherapeutic at the time of argatroban discontinuation. Chromogenic factor X levels could predict a therapeutic INR with a sensitivity of 63.2%, a specificity of 80%, a positive predictive value of 93.5, and a negative predictive value of 32.3. In patients who received 5 or more days of warfarin overlap with argatroban, the sensitivity of chromogenic factor X levels to predict an INR greater than 2.0 was 78.2%, with a specificity of 77.8%, a positive predictive value of 95.6, and a negative predictive value of 36.8. The correlation of chromogenic factor X levels and a therapeutic INR was 18.1%; however, this poor correlation may have been due to increases in the INR values of the patients who received less than 5 days of warfarin overlap with argatroban. During the transition period, nine patients developed thrombi and eight patients experienced clinically significant bleeding. CONCLUSION: Measuring chromogenic factor X levels is recommended before transitioning patients from argatroban to warfarin therapy. Patients should receive at least 5 days of overlap with warfarin and have a chromogenic factor X level of 45% or less before discontinuing argatroban.

Recognition of heparin-induced thrombocytopenia and initiation of argatroban therapy after cardiothoracic surgery in the intensive care unit.

OBJECTIVE: Patients recovering from cardiothoracic surgery are known to be at increased risk of heparin-induced thrombocytopenia. Postoperatively, if heparin-induced thrombocytopenia is suspected, heparin is discontinued immediately and an alternative anticoagulant, such as the direct thrombin inhibitor argatroban, is administered. Current data regarding the safety and efficacy of argatroban in the postoperative cardiothoracic surgical patient in the intensive care setting are limited. METHODS: Data were collected retrospectively from January 1, 2007, to December 31, 2010, from patients tested for antiplatelet factor 4/heparin antibodies on clinical suspicion of heparin-induced thrombocytopenia after cardiothoracic surgery. We evaluated the use of argatroban as a therapeutic agent for the postoperative treatment of suspected heparin-induced thrombocytopenia by comparing thrombotic and bleeding events, platelet dynamics, antiplatelet factor 4/heparin antibody titer, and clinical probability score between patients who did and did not receive argatroban. RESULTS: Eighty-seven patients were included; 47 patients (54%) were treated with argatroban, and 40 patients (46%) were not treated with argatroban. There was no association between argatroban therapy and bleeding, mortality, length of stay, or pretreatment thrombotic events. Among all patients, antiplatelet factor 4/heparin antibody titer and clinical probability score were higher in patients treated with argatroban. CONCLUSIONS: Clinical suspicion of heparin-induced thrombocytopenia as detected by clinical probability score and thrombotic complications should prompt immediate cessation of heparin and initiation of an alternative anticoagulant such as argatroban. The results from this study demonstrate that argatroban should be considered without increased risk for adverse events, including bleeding, in the cardiothoracic intensive care unit after surgery.

Management of hypertensive emergency and urgency.

Severe hypertension is a frequent condition among patients presenting to emergency departments. Historically, this has been referred to as a hypertensive crisis. In addition, these hypertensive crises have been further divided into either hypertensive emergencies or urgencies depending on the presence or absence of target organ damage, respectively. The management differs between these crises in both the rapidity of blood pressure correction and the medications used. Hypertensive emergencies must be treated immediately with intravenous antihypertensive medications. However, hypertensive urgencies may be treated with oral antihypertensive agents to reduce the blood pressure to baseline or normal over a period of 24-48 hr. Appropriate identification, evaluation, and treatment of these conditions are of great importance in the emergency department to prevent progression of organ damage and death. The purpose of this article is to provide an overview of the hypertensive crises and their management.

Pharmacotherapy for mechanical circulatory support: a comprehensive review.

OBJECTIVE: To provide a comprehensive review of the pharmacotherapy associated with the provision of mechanical circulatory support (MCS) to patients with end-stage heart failure and guidance regarding the selection, assessment, and optimization of drug therapy for this population. DATA SOURCES: The MEDLINE/PubMed, EMBASE, and Cochrane databases were searched from 1960 to July 2010 for articles published in English using the search terms mechanical circulatory support, ventricular assist system, ventricular assist device, left ventricular assist device, right ventricular assist device, biventricular assist device, total artificial heart, pulsatile, positive displacement, axial, centrifugal, hemostasis, bleeding, hemodynamic, blood pressure, thrombosis, antithrombotic therapy, anticoagulant, antiplatelet, right ventricular failure, ventricular arrhythmia, anemia, arteriovenous malformation, stroke, infection, and clinical pharmacist. STUDY SELECTION AND DATA EXTRACTION: All relevant original studies, meta-analyses, systematic reviews, guidelines, and reviews were assessed for inclusion. References from pertinent articles were examined for content not found during the initial search. DATA SYNTHESIS: MCS has advanced significantly since the first left ventricular assist device was implanted in 1966. Further advancements in MCS technology that occurred in the latter decade are changing the overall management of endstage heart failure care and cardiac transplantation. These pumps allow for improved bridge-to-transplant rates, enhanced survival, and quality of life. Pharmacotherapy associated with MCS devices may optimize the performance of the pumps and improve patient outcomes, as well as minimize morbidity related to their adverse effects. This review highlights the knowledge needed to provide appropriate clinical pharmacy services for patients supported by MCS devices. CONCLUSIONS: The HeartMate II clinical investigators called for the involvement of pharmacists in MCS patient assessment and optimization. Pharmacotherapeutic management of patients supported with MCS devices requires individualized care, with pharmacists as part of the team, based on the characteristics of each pump and recipient.

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.

Impact of nicotine replacement therapy on postoperative mortality following coronary artery bypass graft surgery.

BACKGROUND: Nicotine replacement therapy (NRT) has recently been associated with increased mortality in patients in medical intensive care units (ICUs). Although NRT is frequently used in cardiothoracic surgery patients, no safety data exist for use in this population. OBJECTIVES: To ascertain the impact of NRT on in-hospital mortality following coronary artery bypass graft (CABG) surgery. METHODS: This was a retrospective matched cohort pilot study in a 22-bed cardiothoracic surgery ICU. Patients prescribed transdermal NRT after CABG were randomly selected and matched to current smokers not prescribed NRT according to Acute Physiology and Chronic Health Evaluation II scores (N = 134). Data on comorbid conditions and pack-year history were also obtained. To compare these patients with nonsmoking patients, a larger unmatched population was also evaluated. The total number of patients prescribed NRT, current smokers not prescribed NRT, and nonsmokers who were evaluated in our study was 2057. RESULTS: Sixty-seven NRT patients were well matched with 67 current smokers in terms of baseline demographics and procedures. Mortality was nonsignificantly higher in the NRT group versus the non-NRT smoker group (4.5% vs 0.0%; p = 0.080). In an evaluation of a larger population controlled for differences in baseline characteristics, an increase in mortality due to NRT was found (OR 6.06; 95% CI 1.65 to 22.21). In an a priori subgroup of the overall population, mortality was significantly higher in patients receiving NRT after off-pump CABG versus smokers not receiving NRT (OR 6.49; 95% CI 1.29 to 32.56). CONCLUSIONS: The use of NRT in a postoperative CABG surgery population resulted in a significant increase in mortality when adjusted for baseline characteristics. Patients receiving NRT after off-pump cardiac surgery may be particularly susceptible. Additional evaluation in large patient cohorts with prospective controls is warranted.

Fatal Outcome of Disseminated Strongyloidiasis despite Detectable Plasma and Cerebrospinal Levels of Orally Administered Ivermectin.

Strongyloides stercoralis affects over 100 million people worldwide. Those people most susceptible to infection are those with an immunocompromising condition, such as cancer or human immunodeficiency virus (HIV). Local disease may spread throughout the body of the host, causing a condition termed disseminated strongyloidiasis. Standard treatment for Strongyloides stercoralis infection is oral ivermectin. We describe a patient with chronic lymphocytic leukemia diagnosed with disseminated strongyloidiasis two weeks after initial presentation. After repeated dosing of oral ivermectin with no clinical response, serum and cerebral spinal fluid (CSF) concentrations of ivermectin were measured to assess absorption. The peak serum concentration of 49.3 ng/mL correlated with a CSF concentration of 0.14 ng/mL. Despite these concentrations, the patient eventually succumbed to multi-system organ failure. We discuss the reasons for treatment failure and explore the utility of measuring ivermectin concentrations.

Evaluating the association between clozapine and venous thromboembolism.

PURPOSE: The possible association between clozapine and venous thromboembolism (VTE) is discussed. SUMMARY: Twenty-two cases of VTE associated with clozapine have been published. The average patient age at the time of occurrence was 38 years in the reported cases. Of the published cases with a known outcome, the mortality rate of a clotting complication while on clozapine was approximately 44%. The manufacturer of clozapine has calculated a mortality rate from pulmonary embolism to be one death per 3450 person years of use, approximately 28 times higher than the rate in the general population. The possible mechanism for the association between clozapine and VTE is probably multifactorial. A VTE usually occurs when one of three factors is present: damage to the vessel wall, static blood flow, or coagulation abnormalities. Clozapine, as well as other antipsychotics, has not been shown to cause direct damage to the vasculature in humans. However, static blood flow may be influenced by sedation and the sedentary lifestyle commonly associated with psychiatric disorders, their treatment, or both. Clozapine is associated with significant sedation and an average weight gain of 7-11 kg. There is also increasing evidence that clozapine and other antipsychotics may cause a variety of different coagulation abnormalities. Clozapine has been found to increase platelet adhesion as well as aggregation. Avoidance of risk factors, such as weight gain and sedentary lifestyle, may alleviate some of the risk of clozapine-induced VTE. CONCLUSION: Available data indicate an association between clozapine and VTE; however, it is unknown whether the increased risk of VTE in patients receiving clozapine is because of prothrombotic effects of the drug. Risk of VTE versus the benefits of therapy should be considered when initiating clozapine therapy.