Is Two Better Than Three? A Systematic Review of Two-bag Intravenous N-acetylcysteine Regimens for Acetaminophen Poisoning.

Introduction: Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration (FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion duration. Recently, simplified, off-label two-bag NAC infusion protocols have become more common. The purpose of this review is to summarize the effectiveness and safety of two-bag NAC. Methods: We undertook a comprehensive search of PubMed, EMBASE, and MEDLINE from inception to December 13, 2022, for articles describing human acetaminophen poisonings treated with two-bag NAC, defined as any regimen involving two discrete infusions in two separate bags. Outcomes included effectiveness (measured by incidence of liver injury); incidence of non-allergic anaphylactoid reactions (NAAR); gastrointestinal, cutaneous, and systemic reactions; treatments for NAARs; incidence of NAC-related medication errors; and delays or interruptions in NAC administration. Results: Twelve articles met final inclusion, 10 of which compared two-bag NAC to the three-bag regimen. Nine articles evaluated the two-bag/20-hour regimen, a simplified version of the FDA-approved three-bag regimen in which the traditional first and second bags are combined into a single four-hour infusion. Nine articles assessed comparative effectiveness of two-bag NAC in terms of liver injury, most commonly assessed for by incidence of hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1,000 international units per liter). No difference in liver injury was observed between two-bag and three-bag regimens. Of nine articles comparing incidence of NAARs, eight demonstrated statistically fewer NAARs with two-bag regimens, and one showed no difference. In seven articles evaluating treatment for NAARs (antihistamines, corticosteroids, epinephrine), all showed that patients received fewer medications for NAARs with two-bag NAC. Three articles evaluated NAC-related medication errors; two demonstrated no difference, while one study evaluating only children showed fewer errors with two-bag NAC. Two studies evaluated delays and/or interruptions in NAC infusions; both favored two-bag NAC. Conclusion: For patients with acetaminophen poisoning, two-bag NAC regimens appear to have similar outcomes to the traditional three-bag regimen in terms of liver injury. Two-bag NAC regimens are associated with fewer adverse events and fewer treatments for those events than the three-bag regimen and fewer interruptions in antidotal therapy.

Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage: A Systematic Review and Meta-analysis.

Importance: Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited. Objective: To evaluate the safety and outcomes of DOAC reversal agents among patients with ICH. Data Sources: PubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022. Study Selection: The eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model. Main Outcomes and Measures: The primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent. Results: A total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events. Conclusions and Relevance: In the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.

Prevalence and Categorization of Drug-Related Problems in the Emergency Department.

BACKGROUND: Drug-related problems (DRPs) are common among patients seen in the emergency department (ED), but the true incidence is not clear. OBJECTIVES: The primary objective of this study was to determine the prevalence of DRPs among patients seen in a U.S. ED. The secondary objective was to categorize these DRPs by problem type and by medication class. METHODS: This was a prospective observational cohort study of a random sample of ED patients between December 2011 and March 2013. ED pharmacists screened randomly selected patients for the presence of a DRP contributing to the ED visit. Four independent auditors evaluated the results to achieve consensus for the presence or absence of DRPs and categorization of the DRPs. RESULTS: Among 1039 patients screened for DRPs, 308 (29.6%) were found to have at least 1 DRP contributing to the ED visit. Among a total of 443 DRPs, the most commonly identified categories were adverse drug reaction (n = 193 [43.6%]), ineffective medication (n = 69 [15.6%]), and subtherapeutic dosage (n = 68 [15.3%]). The most commonly implicated drug classes were cardiovascular medications (n = 113 [26.5%]), anti-infective medications (n = 52 [12.2%]), and analgesic medications (n = 58 [13.6%]). CONCLUSIONS: A substantial proportion of ED visits are associated in part or in total with DRPs. Adverse drug reactions and cardiovascular medications are the most common category and medication class implicated, respectively.

Pediatric Emergency Department Interventions of Pharmacy Residents.

OBJECTIVE: We sought to assess the frequency and types of interventions performed by pharmacy residents in a pediatric emergency department (ED). METHODS: The study was conducted in an academic ED with 77,000 annual visits, of which 17% are pediatric. Six pharmacy residents completed a total of 9 two-week rotations in the pediatric ED as part of their pharmacy residency programs from February 2016 to December 2018. Pharmacy residents recorded pharmacy intervention data in real time. We quantified the number and type of interventions and time spent making the interventions. RESULTS: Of 1608 pediatric patients present during the ED shifts when pharmacy residents were on service, pharmacy residents intervened on 294 patients (18.3%). A total of 400 activities and interventions were recorded. The majority (72%) of patients required 1 intervention, whereas the remaining 28% had 2 or more interventions documented. The median time spent per patient was 15 minutes (interquartile range, 10-20 minutes). Pharmacy residents were most commonly involved with medication selection and dosing. CONCLUSIONS: The presence of a dedicated pharmacy team member in the pediatric area of the ED allows for a high level of involvement and interaction with other members of the health care team primarily through providing recommendations regarding medication selection, dosing, optimization, and answering drug information and medication administration questions.

Autoinjectors Preferred for Intramuscular Epinephrine in Anaphylaxis and Allergic Reactions.

INTRODUCTION: Epinephrine is the treatment of choice for anaphylaxis. We surveyed emergency department (ED) healthcare providers regarding two methods of intramuscular (IM) epinephrine administration (autoinjector and manual injection) for the management of anaphylaxis and allergic reactions and identified provider perceptions and preferred method of medication delivery. METHODS: This observational study adhered to survey reporting guidelines. It was performed through a Web-based survey completed by healthcare providers at an academic ED. The primary outcomes were assessment of provider perceptions and identification of the preferred IM epinephrine administration method by ED healthcare providers. RESULTS: Of 217 ED healthcare providers invited to participate, 172 (79%) completed the survey. Overall, 82% of respondents preferred the autoinjector method of epinephrine administration. Providers rated the autoinjector method more favorably for time required for training, ease of use, convenience, satisfaction with weight-based dosing, risk of dosing errors, and speed of administration (p<0.001 for all comparisons). However, manual injection use was rated more favorably for risk of provider self-injury and patient cost (p<0.001 for both comparisons). Three participants (2%) reported a finger stick injury from an epinephrine autoinjector. CONCLUSION: ED healthcare providers preferred the autoinjector method of IM epinephrine administration for the management of anaphylaxis or allergic reactions. Epinephrine autoinjector use may reduce barriers to epinephrine administration for the management of anaphylaxis in the ED.

Medication supply chain management through implementation of a hospital pharmacy computerized inventory program in Haiti.

BACKGROUND: In the aftermath of the 2010 earthquake in Haiti, St. Luke Hospital was built to help manage the mass casualties and subsequent cholera epidemic. A major problem faced by the hospital system was the lack of an available and sustainable supply of medications. Long-term viability of the hospital system depended largely on developing an uninterrupted medication supply chain. OBJECTIVE: We hypothesized that the implementation of a new Pharmacy Computerized Inventory Program (PCIP) would optimize medication availability and decrease medication shortages. DESIGN: We conducted the research by examining how medications were being utilized and distributed before and after the implementation of PCIP. We measured the number of documented medication transactions in both Phase 1 and Phase 2 as well as user logins to determine if a computerized inventory system would be beneficial in providing a sustainable, long-term solution to their medication management needs. RESULTS: The PCIP incorporated drug ordering, filling the drug requests, distribution, and dispensing of the medications in multiple settings; inventory of currently shelved medications; and graphic reporting of 'real-time' medication usage. During the PCIP initiation and establishment periods, the number of medication transactions increased from 219.6 to 359.5 (p=0.055), respectively, and the mean logins per day increased from 24.3 to 31.5, p<0.0001, respectively. The PCIP allows the hospital staff to identify and order medications with a critically low supply as well as track usage for future medication needs. The pharmacy and nursing staff found the PCIP to be efficient and a significant improvement in their medication utilization. CONCLUSIONS: An efficient, customizable, and cost-sensitive PCIP can improve drug inventory management in a simplified and sustainable manner within a resource-constrained hospital.

Emergency medicine pharmacy practice.

Emergency medicine (EM) pharmacy practice has existed for over 30 years. In recent years, however, the specialty has grown significantly. A large number of health care systems have either a dedicated EM pharmacist or other clinical pharmacist presence in the Emergency department (ED). Over the past decade, the role of the EM pharmacist as a critical member of the health care team has expanded significantly and many innovative practices have evolved throughout the country. There is also some heterogeneity between different EM pharmacy practice sites. This article reviews the history and general concepts of EM pharmacy practice as well as illustrate some of the established benefits of an EM pharmacist.

The role of the emergency pharmacist in trauma resuscitation.

The clinical pharmacist in the emergency department is now commonly incorporated as a member of the emergency department trauma team. As such, the emergency pharmacist needs to have detailed knowledge of the pharmacotherapy of resuscitation and be able to apply the skills needed to function as a valuable member of this team. In addition to the traditional skills of the discipline of clinical pharmacy, the emergency pharmacist must be familiar with the intricacies of treating life-threatening injuries in an emergent setting and be able to anticipate the direction of the patient's care. The ability to provide valuable pharmacological interventions throughout the resuscitation and stabilization process requires familiarity with the process of resuscitation, including rapid sequence induction, analgesia and sedation, seizure prophylaxis, appropriate antibiotic and tetanus prophylaxis, intracranial pressure control, hemodynamic stabilization, and any other specific drug therapy that the clinical situation demands. This article discusses the aforementioned pharmacotherapeutic topics and describes the role of the Emergency Pharmacist on the ED trauma team.

Assessment of the pharmacogenomics educational needs of pharmacists.

OBJECTIVES: To evaluate the self-perceived knowledge and confidence of inpatient and outpatient pharmacists in applying pharmacogenomics information to clinical practice. METHODS: A 19-question multiple-choice, electronic needs-assessment survey instrument was distributed to 480 inpatient and outpatient pharmacists in a large, academic, multi-campus healthcare system. RESULTS: The survey response rate was 64% (303). Most respondents (85%) agreed that pharmacists should be required to be knowledgeable about pharmacogenomics, and 65% agreed that pharmacists should be capable of providing information on the appropriate use of pharmacogenomics testing. Sixty-three percent felt they could not accurately apply the results of pharmacogenomics tests to drug-therapy selection, dosing, or monitoring. CONCLUSION: Pharmacists believe pharmacogenomics knowledge is important to the profession, but they lack the knowledge and self-confidence to act on the results of pharmacogenomics testing and may benefit from pharmacogenomics education.

Comparing intravenous amiodarone or lidocaine, or both, outcomes for inpatients with pulseless ventricular arrhythmias.

OBJECTIVE: To compare survival rates of patients with in-hospital cardiac arrest due to pulseless ventricular tachycardia/ventricular fibrillation treated with lidocaine, amiodarone, or amiodarone plus lidocaine. DESIGN: Multicenter retrospective medical record review. SETTING: Three academic medical centers in the United States. PATIENTS: Hospitalized adult patients who received amiodarone, lidocaine, or a combination for pulseless ventricular tachycardia/ventricular fibrillation between August 1, 2000, and July 31, 2002. MEASUREMENTS AND MAIN RESULTS: Data were collected according to the Utstein style. In-hospital proportion of patients living at 24 hrs and discharge were analyzed using chi-square analysis. Of the 605 patient medical records reviewed, 194 met criteria for inclusion (n=79 for lidocaine, n=74 for amiodarone, n=41 for combination). Available data showed no difference in proportion of patients alive 24 hrs post-cardiac arrest (p=.39). Cox regression analysis indicated a decreased likelihood of survival in patients with pulseless ventricular tachycardia/ventricular fibrillation as an initial rhythm as compared with those who presented with bradycardia followed by pulseless ventricular tachycardia/ventricular fibrillation and in those patients who received amiodarone as compared with lidocaine. However, only 14 patients (25%) in the amiodarone group received the recommended initial 300-mg intravenous bolus, and amiodarone was administered an average of 8 mins later in the code compared with lidocaine (p<.001). CONCLUSIONS: These results generate the hypothesis that inpatients with cardiac arrest may have different benefits from lidocaine and amiodarone than previously demonstrated. Inadequate dosing and later administration of amiodarone in the code were two confounding factors in this study. Prospective studies evaluating these agents are warranted.

Critical care pharmacy services in United States hospitals.

BACKGROUND: Critical care pharmacy activities have been described as fundamental, desirable, and optimal, but actual services provided have not been evaluated. OBJECTIVE: To characterize the type and level of pharmacy services provided to intensive care units (ICUs). METHODS: A 38 question survey was sent in 2 consecutive mailings to all US institutions (N = 3238) with an ICU. Questions were categorized according to clinical, educational, administrative, and scholarly activities, with levels of services stratified as fundamental, desirable, or optimal. RESULTS: Completed surveys were received from 382 (11.8%) institutions encompassing 1034 ICUs. Direct clinical pharmacy activities were provided at 62.2% of ICUs. The pharmacists in those programs attended rounds 4.4 +/- 1.5 days/wk, mean +/- SD, and had a workweek that consisted of patient care (43% of hours worked), drug distribution (26.2%), administration (12.6%), education (10.9%), and scholarly activities (7.3%). Fundamental clinical activities performed during at least 75% of patient ICU days were providing drug information, drug therapy evaluation, drug therapy intervention, and pharmacokinetic monitoring. Conducting in-services (92.8%), a fundamental service, was the only educational activity frequently provided. Most respondents were involved with at least one multidisciplinary committee, and 45.5% conducted scholarly activities. Desirable or optimal activities were not frequently provided across all service categories. CONCLUSIONS: Clinical pharmacists are directly involved as caregivers in nearly two-thirds of ICUs in the US. Although they provide a range of clinical and administrative services, involvement in educational and scholarly activities is variable. The level of services provided is consistent with the criteria deemed fundamental for improving patient care. Higher-order services are far less likely to be provided.

Pneumococcal vaccination in the emergency department: an assessment of need.

STUDY OBJECTIVES: Immunization against Streptococcus pneumoniae with the 23-valent pneumococcal polysaccharide vaccine has been shown to be cost-effective for prevention of invasive pneumococcal disease. Yet 23-valent pneumococcal polysaccharide vaccine is widely underused, particularly among ethnic minorities. The objectives of this survey are to determine the rate of 23-valent pneumococcal polysaccharide vaccine vaccination among all adult patients presenting to the emergency department (ED) of a county-based, urban, tertiary care medical center; the willingness of patients to receive 23-valent pneumococcal polysaccharide vaccine; and reasons for nonvaccination. METHODS: A quality assurance survey was performed in the ED during 3 days in September 2002. A survey was developed to determine 23-valent pneumococcal polysaccharide vaccine vaccination rates and eligibility according to indications and contraindications established by the Centers for Disease Control and Prevention (CDC). Descriptive statistics were performed to quantify the proportion of patients who were immunized, eligible, and willing to receive 23-valent pneumococcal polysaccharide vaccine and reasons for nonvaccination. RESULTS: A total of 250 patients of 1,535 registered in the ED were surveyed during the 3-day period. Only 48 (19%) had a primary care provider. The majority of patients were Hispanic (73%). Only 22 (9%) patients had received the vaccine. A total of 66 (26%) patients fit the CDC eligibility criteria for 23-valent pneumococcal polysaccharide vaccine, and 59 (89%) of these patients were willing to receive the vaccine during their ED visit. Most patients (79%) were eligible to receive 23-valent pneumococcal polysaccharide vaccine due to their comorbid illnesses. CONCLUSION: In the ED of our county-based urban medical center, 26% of patients were eligible for 23-valent pneumococcal polysaccharide vaccine; the majority of patients were Hispanic, unaware of the vaccine's existence, and willing to receive it during their ED visit. These data underscore a large unmet public health need among ethnic minorities in the ED.

Effect of once-daily dosing vs. multiple daily dosing of tobramycin on enzyme markers of nephrotoxicity.

OBJECTIVE: To determine the incidence of nephrotoxicity of once-daily dosing (ODD) and multiple daily dosing (MDD) regimens of tobramycin in critically ill patients. DESIGN: Randomized, prospective clinical trial. SETTING: : Adult intensive care units at two university hospitals. PATIENTS: Fifty-eight critically ill patients with a suspected or documented aerobic Gram-negative infection. INTERVENTIONS: Patients were randomized to receive tobramycin by ODD (7 mg/kg) or MDD. Baseline urine aliquots and 24-hr urine collections were collected on days 3, 7, and 11 during therapy and on days 3, 7, and 11 following discontinuation of therapy for measurement of alanine aminopeptidase (AAP), N-acetyl-beta-d-glucosaminidase (NAG), and creatinine. MEASUREMENTS AND MAIN RESULTS: Fifty-four patients were evaluable (ODD n = 25; MDD n = 29). The groups were similar with regard to demographic and clinical variables. The tobramycin dose was higher in the ODD group compared with the MDD group (425 +/- 122.5 mg vs. 312.8 +/- 116.6 mg, p <.001). Patients in the MDD group received a mean of 3.89 +/- 1.14 mg.kg(-1)day(-1) at intervals of 11.92 +/- 3.12 hrs. In the ODD group, patients had a higher measured creatinine clearance at the end of therapy compared with MDD group (70 +/- 18.6 vs. 64.8 +/- 17.5 mL/min, p =.047). Fewer patients in the ODD group developed nephrotoxicity than the MDD group (5 vs. 12, p =.142). Although there were increases in urinary enzymes in both treatment groups (AAP, 8.7 +/- 2.9 vs. 5.2 +/- 2.1 units/24 hrs, p <.01 MDD vs. ODD; NAG, 14.7 +/- 4.9 vs. 6.8 +/- 3.1, p <.01 MDD vs. ODD), the increases in the ODD group were significantly lower than in the MDD group. CONCLUSIONS: : The ODD tobramycin regimen appeared to be less nephrotoxic than the MDD regimen despite significantly higher doses. Tobramycin administered by ODD may be the preferred dosing method in selected critically ill medical patients to reduce the incidence and extent of renal damage.

A comparison of phenytoin-loading techniques in the emergency department.

OBJECTIVES: To compare the effectivenesses of three phenytoin-loading techniques. METHODS: Patients with subtherapeutic phenytoin concentrations who presented within 48 hours of a seizure were randomized to receive either 20 mg/kg of oral phenytoin (PO), divided in maximum doses of 400 mg every two hours, 18 mg/kg of intravenous phenytoin (IVP) at an initial infusion rate of 50 mg/min, or 18 mg/kg (phenytoin equivalents) of intravenous fosphenytoin (IVF) at an initial infusion rate of 150 mg/min. RESULTS: A total of 45 patients were enrolled: 16 in the PO group, 14 in the IVP group, and 15 in the IVF group. The times required to reach therapeutic drug concentrations were (mean +/- standard deviation [SD]) 5.62 +/- 0.28 hours, 0.24 +/- 0.3 hours, and 0.21 +/- 0.28 hours, respectively. A total of 17, 27, and 32 adverse drug events were observed in the PO, IVP, and IVF groups, respectively, with significantly fewer events in the PO group (p = 0.02, p = 0.01). No significant difference was found between the numbers of necessary adjustments to the infusions in the two IV groups. The average time to safe emergency department discharge was significantly shorter for the IV groups compared with the PO group (p < 0.001). CONCLUSIONS: Oral loading has fewer adverse drug events than either IV loading method, but its use may be limited when therapeutic concentrations are required quickly. Although IVF loading is faster, from an adverse-drug event perspective, no advantage of IVF over IVP was apparent.

Managing anemia in the critically ill patient.

Anemia of critical illness is a multifactorial condition caused by phlebotomy, ongoing blood loss, and inadequate production of red blood cells. It occurs early in the course of critical illness. Although red blood cell transfusion is the treatment of choice for immediate management of anemia in the intensive care unit, controversy surrounds the most appropriate hemoglobin concentration or hematocrit "trigger." Therapeutic options, including blood-conservation tools, minimization of phlebotomy, erythropoietic agents, and investigational oxygen-carrying agents, may be alternatives to red blood cell transfusions in critically ill patients with anemia. Patient selection for erythropoietic agents will depend on further work dealing with outcomes and the total cost of care in managing the anemia of critical illness.

Cost-effectiveness of oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin in the emergency department.

STUDY OBJECTIVE: Oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin are all commonly used for loading phenytoin in the emergency department (ED). The cost-effectiveness of each was compared for patients presenting with seizures and subtherapeutic phenytoin concentrations. METHODS: A simple decision tree was developed to determine the treatment costs associated with each of 3 loading techniques. We determined effectiveness by comparing adverse event rates and by calculating the time to safe ED discharge. Time to safe ED discharge was defined as the time at which therapeutic concentrations of phenytoin (>or=10 mg/L) were achieved with an absence of any adverse events that precluded discharge. The comparative cost-effectiveness of alternatives to oral phenytoin was determined by combining net costs and number of adverse events, expressed as cost per adverse events avoided. Cost-effectiveness was also determined by comparing the net costs of each loading technique required to achieve the time to safe ED discharge, expressed as cost per hour of ED time saved. The outcomes and costs were primarily derived from a prospective, randomized controlled trial, augmented by time-motion studies and alternate-cost sources. Costs included the cost of drugs, supplies, and personnel. Analyses were also performed in scenarios incorporating labor costs and savings from using a lower-urgency area of the ED. RESULTS: The mean number of adverse events per patient for oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin was 1.06, 1.93, and 2.13, respectively. Mean time to safe ED discharge in the 3 groups was 6.4 hours, 1.7 hours, and 1.3 hours. Cost per patient was 2.83 dollars, 21.16 dollars, and 175.19 dollars, respectively, and did not differ substantially in the Labor and Triage (lower-urgency area of ED) scenarios. When the measure of effectiveness was adverse events, oral phenytoin dominated intravenous phenytoin and intravenous fosphenytoin, with a lower cost and number of adverse events. With time to safe ED discharge as the outcome measure, the incremental cost-effectiveness ratios were 3.90 dollars and 387.27 dollars per hour of ED time saved for oral phenytoin versus intravenous phenytoin and for intravenous fosphenytoin versus intravenous phenytoin, respectively. CONCLUSION: Oral phenytoin is the most cost-effective loading method in most settings. Intravenous phenytoin is preferred if one is willing to pay an additional 20.65 dollars to 44.25 dollars per patient and willing to have more adverse events for a quicker average time to safe ED discharge. It is unlikely that intravenous fosphenytoin is justifiable in any setting.

Surgical issues in the poisoned patient.

Some toxicologic emergencies require immediate or urgent surgical intervention in addition to routine medical care. The EP must be familiar with the indications for operative care, even though many of these poisonings and exposures are relatively rare. The EP must also be knowledgeable regarding the various means of surgical decontamination that are available, including temporary cardiopulmonary bypass. Finally, a high level of vigilance must be maintained for patients who have delayed presentation and fulminant organ failure necessitating early involvement of the transplantation team.

Pharmacology, clinical efficacy, and safety of drotrecogin alfa (activated).

The protein C pathway, which plays an important role in maintaining normal hemostasis and is a critical link between the inflammatory and procoagulant host responses to infection, is involved in modulating the coagulation and inflammation associated with severe sepsis. Recombinant human activated protein C (APC), or drotrecogin alfa (activated), shares the intrinsic pharmacologic activity of endogenous APC. In the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, drotrecogin alfa (activated) decreased absolute mortality by 6% and relative risk of mortality by 19% compared with placebo. Drotrecogin alfa (activated) is an important advancement in the treatment of adult patients with severe sepsis.