Gregory M. Bogdan

Health care facility and community strategies for patient care surge capacity

Abstract Recent terrorist and epidemic events have underscored the potential for disasters to generate large numbers of casualties. Few surplus resources to accommodate these casualties exist in our current health care system. Plans for “surge capacity” must thus be made to accommodate a large number of patients. Surge planning should allow activation of multiple levels of capacity from the health care facility level to the federal level. Plans should be scalable and flexible to cope with the many types and varied timelines of disasters. Incident management systems and cooperative planning processes will facilitate maximal use of available resources. However, resource limitations may require implementation of triage strategies. Facility-based or “surge in place” solutions maximize health care facility capacity for patients during a disaster. When these resources are exceeded, community-based solutions, including the establishment of off-site hospital facilities, may be implemented. Selection criteria, logistics, and staffing of off-site care facilities is complex, and sample solutions from the United States, including use of local convention centers, prepackaged trailers, and state mental health and detention facilities, are reviewed. Proper pre-event planning and mechanisms for resource coordination are critical to the success of a response.

Active surveillance of abused and misused prescription opioids using poison center data: A pilot study and descriptive comparison

Background. Prescription opioids are abused throughout the United States. Several monitoring programs are in existence, however, none of these systems provide up-to-date information on prescription opioid abuse. This article describes the use of poison centers as a real-time, geographically specific, surveillance system for prescription opioid abuse and compares our system with an existing prescription drug abuse monitoring program, the Drug Abuse Warning Network (DAWN). Methods. Data were collected from eight geographically dispersed poison centers for a period of twelve months. Any call involving buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, and oxycodone was considered a case. Any case coded as intentional exposure (abuse, intentional misuse, suicide, or intentional unknown) was regarded as misuse and abuse. Comparative data were obtained from DAWN. Results. Poison center rates of abuse and misuse were highest for hydrocodone at 3.75 per 100,000 population, followed by oxycodone at 1.81 per 100,000 population. DAWN emergency department (ED) data illustrate a similar pattern of abuse with most mentions involving hydrocodone and oxycodone. Poison center data indicate that people aged 18 to 25 had the highest rates of abuse. DAWN reported the majority of ED mentions among 35 to 44-year-olds. Geographically, Kentucky had the uppermost rates of abuse and misuse for all opioids combined at 20.69 per 100,000 population. Conclusions. Comparing poison center data to DAWN yielded mostly comparable results, including hydrocodone as the most commonly mentioned drug. Our results suggest poison center data can be used as an indicator for prescription opioid abuse and misuse and can provide timely, geographically specific information on prescription drug abuse.

A multicenter comparison of the safety of oral versus intravenous acetylcysteine for treatment of acetaminophen overdose

Oral and intravenous (IV) N-acetylcysteine (NAC) are used for the treatment of acetaminophen poisoning. The objective of this multicenter study was to compare the safety of these two routes of administration. Methods. We conducted a multicenter chart review of all patients treated with NAC for acetaminophen poisoning. The primary safety outcome was the percentage of patients with NAC-related adverse events. Results. A total of 503 subjects were included in the safety analysis (306 IV-only, 145 oral-only, and 52 both routes). There were no serious adverse events related to NAC for either route. Nausea and vomiting were the most common related adverse events and were more common with oral treatment (23 vs. 9%). Anaphylactoid reactions were more common with IV administration (6 vs. 2%). Conclusions. IV and oral NAC are generally mild adverse drug reactions.

Neutralization of Latrodectus mactans and L.hesperus venom by redback spider (l.hasseltii) antivenom

Objective: To test the effectiveness of L. hasseltii (redback spider) antivenom in neutralizing the lethal effects of L. hesperus and L. mactans(North American black widow) venoms. Methods: LD50 values for the L. hesperus and L. mactans venom preparations were determined. A prospective, randomized, double-blind antivenom efficacy experiment was then performed for each venom using a mouse envenomation model. The following treatments were premixed and incubated at 25°C for 1 hour prior to intraperitoneal injection: 1) saline control + protein control, 2) saline control + L. hasseltii antivenom, 3)L. hesperus or L. mactans venom + protein control, and 4) L. hesperus or L. mactans venom + L. hasseltii antivenom. The study endpoints were time elapsed until death and survival at 24 hours. Results: The mouse LD50 values for L. hesperus and L. mactans venoms were 0.64 mg/kg and 0.26 mg/kg, respectively. In the efficacy trial, all mice in group 3 (L. hesperus or L. mactans venom and protein control) died. In both experiments, all mice in group 4 (L. hesperus or L. mactans venom + antivenom) survived (p < 0.0001). Conclusion: This is the first study to derive mouse LD50 values for L. hesperus and L. mactans venom obtained by electrical stimulation of live adult spiders. Redback spider antivenom is effective in neutralizing the lethal effects of L. hesperus and L. mactans venoms in a mouse envenomation model. While this study is limited by the optimized premixing of antigen with antibody, it generates the hypothesis that red-back antivenom would be effective in the treatment of latrodectism in humans caused by the two clinically relevant species of North American widow spiders.

Australian tiger snake (Notechis scutatus) and mexican coral snake (Micruris species) antivenoms prevent death from United States coral snake (Micrurus fulvius fulvius) venom in a mouse model.

Background: Wyeth-Ayerst has discontinued production of Antivenin (Micrurus fulvius). Currently, there is no other approved coral snake antivenom available in the United States. Methods: This study was a randomized, placebo-controlled and blinded determination of the ability of a Mexican Micrurus (coral snake) antivenom and an Australian Notechis (tiger snake) antivenom to prevent lethality from a United States Micrurus fulvius fulvius venom in a mouse model. Venom dosing was based on an LD50 determined for this experiment. Our comparison groups included: (1) M. f. fulvius venom+Micrurus antivenom, (2) M. f. fulvius venom+Notechis antivenom, (3) M. f. fulvius venom+protein control, (4) 0.9% normal saline+protein control, (5) saline+Notechis antivenom, (6) saline+Micrurus antivenom. Venom dose was 5 times the determined LD50. The antivenom amounts were capable of neutralizing 10 times the venom injected (50 times the LD50). Results: The LD50 of M. f. fulvius venom was determined to be 0.85 mg/kg. All mice in both antivenom test groups were protected from lethality for the entire 24-hour observation period. Six of the 7 mice in the venom test group died, with a survival time of 349±382 minutes (mean±s.d.) after the venom injection. All three groups of control mice survived the entire 24-hour observation period. Conclusions: Mexican Micrurus antivenom and Australian Notechis antivenom provide protection from lethality in mice envenomated with a United States M. f. fulvius venom.

Time to reconstitution: purified Fab antivenom vs. unpurified IgG antivenom.

We conducted prospective, randomized analytical and observational trials to assess reconstitution times of two lyophilized crotaline snake antivenoms, Antivenin (Crotalidae) Polyvalent [Wyeth-Ayerst] (ACP) and affinity-purified, mixed monospecific crotalid antivenom ovine Fab (CroTAb) (Fab antivenom). The analytical experiment indicated Fab antivenom and ACP reached their maximum protein concentration at 25 and 45min, respectively. In the observational experiment, Fab antivenom (median 40min) had a shorter reconstitution time than ACP (>90min, p<0.008).

Heat and motion stability of polyvalent Crotalidae antivenin, ovine Fab.

This study was conducted to test the hypothesis that a Fab-based crotalid antivenin (FabAV) in commercially packaged vials will remain effective under more extreme heat and motion conditions than would be expected in field settings. Vials containing FabAV were subjected to heat or motion. The effect of heat or motion on the ED50 of FabAV was determined using a mouse model of crotalid snake envenomation. The ED50 for the heat stability groups (expressed as a ratio of mg antivenin to mg venom) were as follows: 4 degrees C x 60 days (control) = 26.5, 70 degrees C x 60 days = 66.3, 70 degrees C x 30 days = 52.4, 50 degrees C x 60 days = 25.8, 50 degrees C x 30 days = 34.0. The ED50 for the two motion stability groups were similar: 4 degrees C x 60 days = 40.3 and 70 degrees C x 60 days = 48.3. These results indicate that FabAV is heat stable at 50 degrees C for 60 days, but had less potency when heated to 70 degrees C for 30 days. FabAV appears less potent after agitation, but remains effective in the mouse model. We conclude that FabAV can be safely stored for at least 60 days without refrigeration under most field conditions where snake envenomation may occur.

A Randomized, Double-Blind, Placebo-Controlled Trial of a Highly Purified Equine F(ab)2 Antibody Black Widow Spider Antivenom

STUDY OBJECTIVE Black widow spider antivenom has never been tested in a randomized clinical trial, to our knowledge. We explore various efficacy measures for a novel F(ab)2 antivenom in patients with moderate to severe pain caused by black widow spider envenomation. METHODS A randomized, placebo-controlled, double-blind, clinical trial was conducted in 12 academic emergency departments. We included patients at least 10 years old with moderate to severe latrodectism. Subjects received either a single intravenous infusion of antivenom or placebo. Pain was assessed with the visual analog scale. The primary efficacy outcome was the difference in pre- and posttreatment visual analog scale score. Prospectively defined secondary outcomes included treatment failures and time to clinically important decrease in pain. RESULTS Twenty-four subjects were enrolled between October 2005 and October 2006; 13 were randomized to antivenom and 11 to placebo. The median change in visual analog scale at 150 minutes posttreatment was -50.0 mm (Interquartile Range [IQR] -67, -41 mm) in the antivenom treatment group and -46.0 mm (IQR -51, 0 mm) in the placebo treatment group (P=.14). There were 7 treatment failures (64%; 95% confidence interval 35% to 92%) in the placebo group and 3 (23%; 95% confidence interval 0.2% to 46%) in the antivenom group (P=.06). The median time to a clinically important decrease in pain after treatment was shorter in the antivenom group compared with the placebo group (30 minutes [IQR 30, 60 minutes] versus 90 minutes [IQR 30, 90 minutes]; P=.03). No serious adverse events or deaths were reported. CONCLUSION Although the overall reduction in pain was similar for antivenom- and placebo-treated subjects, antivenom reduced pain more rapidly than placebo. No significant adverse events occurred in either group.

Effects of clinical laboratory choice on study outcome: an interlaboratory evaluation of aminotransferase levels.

Study Objective. To determine if laboratories with disparate alanine aminotransferase (ALT) reference ranges would report different rates of elevation greater than the upper limit of reference range (ULRR) and thus have the potential to alter study results.