PROTOCOL FOR HUMAN EXPOSURE TO OPIOIDS AND CONCENTRATED MEDETOMIDINE USED IN FIELD APPLICATIONS.

Wildlife professionals routinely use potent sedatives and anesthetics when chemically immobilizing wildlife and zoo species in remote environments. Accidental exposure to these prescription veterinary drugs is rare but could be rapidly fatal. Commonly used agents include opioids and α2 adrenoreceptor agonists. These drugs can be reversed with specific antagonists; however, they are often not approved for human use. The protocol created here can be used by wildlife health professionals in a field setting with basic human emergency medical response training in coordination with local Emergency Medical Services (EMS). Key components include, building local relationships between EMS and wildlife professionals, focused EMS training, administering opioid and α2 adrenergic antagonists off label, and local evacuation procedures. This framework could allow wildlife management agencies or zoos to mitigate the risk of human exposures to these commonly used drugs, significantly improving occupational safety in an otherwise high-risk environment.

National trends in emergency department occupancy, 2001 to 2008: effect of inpatient admissions versus emergency department practice intensity.

STUDY OBJECTIVE: We evaluate recent trends in emergency department (ED) crowding and its potential causes by analyzing ED occupancy, a proxy measure for ED crowding. METHODS: We analyzed data from the annual National Hospital Ambulatory Medical Care Surveys from 2001 to 2008. The surveys abstract patient records from a national sample of hospital EDs to generate nationally representative estimates of visits. We used time of ED arrival and length of ED visit to calculate mean and hourly ED occupancy. RESULTS: During the 8-year study period, the number of ED visits increased by 1.9% per year (95% confidence interval 1.2% to 2.5%), a rate 60% faster than population growth. Mean occupancy increased even more rapidly, at 3.1% per year (95% confidence interval 2.3% to 3.8%), or 27% during the 8 study years. Among potential factors associated with crowding, the use of advanced imaging increased most, by 140%. But advanced imaging had a smaller effect on the occupancy trend than other more common throughput factors, such as the use of intravenous fluids and blood tests, the performance of any clinical procedure, and the mention of 2 or more medications. Of patient characteristics, Medicare payer status and the age group 45 to 64 years accounted for small disproportionate increases in occupancy. CONCLUSION: Despite repeated calls for action, ED crowding is getting worse. Sociodemographic changes account for some of the increase, but practice intensity is the principal factor driving increasing occupancy levels. Although hospital admission generated longer ED stays than any other factor, it did not influence the steep trend in occupancy.

Web-based self-triage of influenza-like illness during the 2009 H1N1 influenza pandemic.

The sudden emergence of 2009 H1N1 influenza in the spring of that year sparked a surge in visits to emergency departments in New York City and other communities. A larger, second wave of cases was anticipated the following autumn. To reduce a potential surge of health system utilization without denying needed care, we enlisted the input of experts from medicine, public health, nursing, information technology, and other disciplines to design, test, and deploy clinical algorithms to help minimally trained health care workers and laypeople make informed decisions about care-seeking for influenza-like illness. The product of this collaboration, named Strategy for Off-Site Rapid Triage (SORT) was disseminated in 2 forms. Static algorithms, posted on the Centers for Disease Control and Prevention's Web site, offered guidance to clinicians and telephone call centers on how to manage adults and children with influenza-like illness. In addition, 2 interactive Web sites, http://www.Flu.gov and http://www.H1N1ResponseCenter.com, were created to help adults self-assess their condition and make an informed decision about their need for treatment. Although SORT was anchored in a previously validated clinical decision rule, incorporated the input of expert clinicians, and was subject to small-scale formative evaluations during rapid standup, prospective evaluation is lacking. If its utility and safety are confirmed, SORT may prove to be a useful tool to blunt health system surge and rapidly collect epidemiologic data on future disease outbreaks.

Implications of the Emergency Medical Treatment and Labor Act (EMTALA) during public health emergencies and on alternate sites of care.

Hospitals throughout the country are using innovative strategies to accommodate the surge of patients brought on by the novel H1N1 virus. One strategy has been to help decompress the amount of patients seeking care within emergency departments by using alternate sites of care, such as tents, parking lots, and community centers as triage, staging, and screening areas. As at any other time an individual presents on hospital property, hospitals and providers must be mindful of the requirements of the Emergency Medical Treatment and Labor Act. In this article we review the act and its implications during public health emergencies, with a particular focus on its implications on alternative sites of care.

C5-blocking antibody reduces fluid requirements and improves responsiveness to fluid infusion in hemorrhagic shock managed with hypotensive resuscitation.

Hypotensive resuscitation strategies and inhibition of complement may both be of benefit in hemorrhagic shock. We asked if C5-blocking antibody (anti-C5) could diminish the amount of fluid required and improve responsiveness to resuscitation from hemorrhage. Awake, male Sprague-Dawley rats underwent controlled hemorrhage followed by prolonged (3 h) hypotensive resuscitation with lactated Ringer's or Hextend, with or without anti-C5. Anti-C5 treatment led to an estimated 62.3 and 58.5% reduction in the volume of Hextend and lactated Ringer's, respectively. In the subgroup of animals with a positive mean arterial pressure (MAP) response to fluid infusion following prolonged hypotension, anti-C5 treatment led to an estimated 4.7- and 4.1-fold increase in mean arterial pressure response per unit Hextend and lactated Ringer's infused, respectively. We observed no significant postresuscitation metabolic differences between the anti-C5 groups and controls. Whether anti-C5 could serve as a volume-sparing adjunct that improves responsiveness to fluid administration in humans deserves further study.

Brisk production of nitric oxide and associated formation of S-nitrosothiols in early hemorrhage.

The results of previous inhibitor studies suggest that there is some increase in nitric oxide (NO) production from constitutive NO synthase in early hemorrhage (H), but the magnitude of NO production early after H has not been previously assessed. It is generally believed that only modest production rates are possible from the constitutively expressed NO synthases. To study this, anesthetized male Sprague-Dawley rats were subjected to 90 min of isobaric (40 mmHg) H. During this period of time, the dynamics of accumulation of NO intermediates in the arterial blood was assessed using electron paramagnetic resonance spectroscopy, chemiluminescence, fluorescence imaging, and mass spectrometry. Electron paramagnetic resonance-detectable NO adducts were also measured with spin traps in blood plasma and red blood cells. H led to an increase in the concentration of hemoglobin-NO from 0.9 +/- 0.2 to 4.8 +/- 0.7 microM. This accumulation was attenuated by a nonselective inhibitor of NO synthase, NG-nitro-L-argininemethyl ester (L-NAME), but not by NG-nitro-D-argininemethyl ester (D-NAME) or 1400W. Administration of L-NAME (but not 1400W or D-NAME) during H produced a short-term increase in mean arterial pressure ( approximately 90%). In H, the level of N oxides in red blood cells increased sevenfold. S-nitrosylation of plasma proteins was revealed with "biotin switch" techniques. The results provide compelling evidence that there is brisk production of NO in early H. The results indicate that the initial compensatory response to H is more complicated than previously realized, and it involves an orchestrated balance between intense vasoconstrictor and vasodilatory components.

Hydroxyethyl starch inhibits neutrophil adhesion and transendothelial migration.

A resuscitation strategy that significantly alters the state of neutrophil (PMN) activation may impact organ function and survivability after shock. Various resuscitative fluids have been shown to elicit a severe immune activation and an upregulation of cellular injury markers, whereas other fluids have been shown to be protective. Recent studies have demonstrated that hydroxyethyl starch (HES), an artificial colloid, may exert significant anti-inflammatory effects, whereas conflicting studies with the same substance have shown an increase in PMN activation. Successful manipulation of the early immune events associated with hemorrhage and resuscitation will require a better understanding of the possible pro- or anti-inflammatory effects of resuscitation fluids. Our study investigated the effect of HES directly on PMN and cultured vascular endothelial cells in vitro. The effect of HES on PMN surface expression of CD11b and L-selectin was measured by flow cytometry. PMN activation response to HES was measured using a shape-change assay in response to formyl-methionyl-leucyl-phenylalanine (f-MLP). The effect of HES on endothelial cell surface expression of E-selectin, P-selectin, vascular cell adhesion molecule-1(VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) was evaluated by enzyme-linked immunoabsorbant assay. PMN rolling, adhesion, and migration events were measured using direct microscopy under conditions simulating microvascular flow. PMN surface expression of CD11b and L-selectin in whole blood samples and isolated PMNs were unaffected by exposure to HES. HES had no effect on the normal f-MLP dose-dependent increase in PMN activation. In the absence of IL-1 stimulation, there was a small but statistically significant (P < 0.05) increase in ICAM-1 after exposure to HES. After stimulation with IL-1 (10 U/mL), HES had no effect on the expression of P-selectin, E-selectin, ICAM-1, or VCAM-1. Under simulated microvascular flow conditions in vitro, HES significantly diminished the PMN tethering rate (P < 0.05) and the transendothelial migration rate (P < 0.05) in a dose-dependent manner. HES significantly alters the function of the PMN at the interface of the PMN responding to activated endothelium. The effect occurs, surprisingly, without a coincident effect on the state of PMN activation or a significant change in the surface expression of the adhesion molecules responsible for PMN-endothelial interaction.

Choice of fluid influences outcome in prolonged hypotensive resuscitation after hemorrhage in awake rats.

Hypotensive resuscitation (Hypo) has been considered an alternate resuscitation strategy in clinical settings that prevent the application of standard Advanced Trauma Life Support care. However, validation of this approach when used for prolonged periods of time remains to be demonstrated. The purpose of this study was to evaluate prolonged Hypo as an alternative to standard resuscitation using various currently available resuscitative fluids. Unanesthetized, male Sprague-Dawley rats underwent computer-controlled hemorrhagic shock and resuscitation. There were six experimental groups; nonhemorrhage (NH), nonresuscitated control (C), Hypo with lactated Ringer's (HypoLR), Hypo with Hextend, 6% hydroxyethyl starch in a balanced salt solution (HEX), Hypo with PolyHeme, a polymerized hemoglobin solution (HBOC), or standard resuscitation with LR (StandLR). Animals were bled over 15 min to a mean arterial blood pressure (MAP) of 40 mmHg where the blood pressure (BP) was held for 30 min. Hypo groups were resuscitated to 60 mmHg for 4 h followed by further resuscitation to 80 mmHg. StandLR rats were resuscitated to 80 mmHg immediately after the hemorrhage period. Animals were monitored until death or they were sacrifice at 24 h. Prolonged Hypo with HEX or LR resulted in a trend toward improved 24-h survival compared with C (71%, 65%, and 48%, respectively), and performed at least as well as StandLR (58% survival). HEX required significantly less intravenous fluid (0.7x total estimated blood volume [EBV]) compared with HypoLR (1.9x EBV) and StandLR (3.2x EBV) (P < 0.05). Although HBOC required the smallest fluid volume (0.4x EBV), survival was no better than C and it resulted in the most significant acidosis. These results support the decision to use Hextend for Hypo, a strategy currently being applied on the battlefield.