Emergency Medicine Journal

Is Hot Water Immersion an Effective Treatment for Marine Envenomation?

Marine envenomations generally occur by 1 of 2 mechanisms: surface stings (eg, via nematocysts) and puncture wounds/bites. Examples of organisms with nematocysts include the Portuguese man-of-war (Physalia), anemones, jellyfish, and corals. Introduction of venom via puncture wounds with either spines or teeth occurs with sea urchins, starfish, stingrays, weever fish, sea snakes, and certain octopi.

Multiple treatment options currently exist for both types of injury, including application of heat, cold, vinegar, fig juice, and urine. However, according to most first-aid manuals and textbooks, common treatment for surface stings has been cold applications (ice) and vinegar, whereas treatment for puncture wounds has been hot water immersion (HWI). In order to evaluate HWI as a treatment for both kinds of injuries, this report's authors compiled a review of the literature and databases, as well as correspondences and private files of experts in marine envenomations.

Methods of heat application include showers, basins of hot water, and thermal packs. Showering is thought to be the most effective because it may also act to remove any remaining intact nematocysts. Authors caution against the possibility of burns and advise to use as high a temperature as “is tolerable.”

Hot water immersion is thought to work via 1 of 2 mechanisms: 1) denaturing of proteins and enzymes by temperatures greater than 50°C, thereby deactivating the venom (some studies suggest that lower temperatures are effective as well, but these authors could not find evidence of effectiveness at less than 39°C); 2) modulation of pain receptors by heat, thereby lessening the sensation of pain.

These authors found that randomized controlled trials have not yet been completed to show evidence of efficacy for HWI in puncture wounds. One experimental trial and 99 reports of effectiveness in 110 cases do suggest its effectiveness and have led to its widespread use. Three randomized trials and 1 abstracted randomized control trial have shown HWI to be effective in surface stings. Pain relief was greater in jellyfish and Physalia stings when HWI was used. In addition to describing each of the randomized studies, the authors also described multiple crossover studies, case series (122 of 135 patients reported complete pain relief after HWI), reviews, summaries, and correspondences suggesting that HWI may emerge as a treatment of choice not only for puncture wounds but also for surface stings. However, first-aid guidelines for treatment of surface stings still advocate the use of vinegar to inactivate nematocysts, immobilization, and ice packs as definitive treatment. Based on the mounting evidence towards the effectiveness of HWI as an effective treatment, new clinical guidelines may be developed.

(Emerg Med J. 2006;23:503–508) PRT Atkinson, A Boyle, D Hartin, D McAuley. Prepared by Karen Nolan Kuehl, MD, FACEP Carilion Emergency Medicine, Roanoke, VA, USA

Circulation

Role of Endothelin-1 in Exposure to High Altitude: Acute Mountain Sickness and Endothelin-1 (ACME-1) Study

Multiple studies have shown increases in pulmonary artery pressures (PAP) in mountaineers ascending to high altitude. Although the true pathophysiology of this remains unclear, a well-described hypothesis is that plasma concentrations of endothelin-1 (ET-1), a vasoactive substance, cause pulmonary arterial and venous constriction. Eventual adaptation to high altitude occurs via various mechanisms, including increased urine output and decreased renal sensitivity to arginine vasopressin (AVP), with resultant free water clearance. Endothelin-1 antagonism has been used with success in patients with pulmonary hypertension, an idea that triggered this study. This study was designed to test the effects of ET-1 antagonism at high altitude using an ET-1 antagonist, bosentan, with particular focus on the effects of pulmonary hypertension, renal water, and electrolytes.

This double-blind study was completed in Italy using 20 healthy volunteer mountaineers. Exclusion criteria included smoking or taking any regular medications. Baseline measurements were completed 2 to 4 weeks prior to the study at sea level. On the first day of testing, subjects received either bosentan 62.5 mg on day 1 followed by bosentan 125 mg on days 2 and 3 or placebo. Laboratory testing included levels of ET-1, creatinine, sodium, potassium, and osmolality in blood and urine, and echocardiography was performed. Subjects then ascended from 1130 to 4554 m in less than 24 hours with 1 overnight stay at 3611 m. Testing was then repeated over the next 3 days. In addition to physiologic tests, the subjects completed Lake Louise questionnaires daily to evaluate for acute mountain sickness (AMS).

Bosentan was found not to change hemodynamic or renal parameters in healthy subjects at sea level. It did significantly reduce PAP (P < .03) and slightly increase arterial oxygen saturation when compared with placebo at altitude. Although the PAP remained significantly lower in the bosentan group throughout the study, the arterial oxygen concentrations became comparable in the 2 groups on the second day of testing. Importantly, urinary volume and free water clearance were significantly reduced in the bosentan group after 2 days of treatment (P < .05). None of the subjects in either group met criteria for AMS by Lake Louise scores.

Study results indicate that ET-1 antagonism may exert a positive effect on PAP at altitude, thus possibly lessening the likelihood of high-altitude pulmonary edema. However, this benefit is accompanied by a subsequent decrease in urinary output and eventual acclimatization. These researchers went on to suggest that this decreased urine output could eventually lead to worsening overload and an increased risk of high-altitude pulmonary edema. This small study was unable to fully define the risks of the use of ET-1 antagonists at altitude. Dr Lewis Rubin from the University of California, San Diego, did contribute an editorial that hypothesized that the addition of a diuretic could prevent this volume overload, but obviously additional studies need to be completed in order to evaluate the safety of this theory. Until that time, bosentan should not be used to prevent or treat altitude-related illnesses.

(Circulation. 2006;114:1410–1416) PA Modesti, S Vanni, M Morabito, et al. Prepared by Karen Nolan Kuehl, MD, FACEP Carilion Emergency Medicine, Roanoke, VA, USA

New England Journal of Medicine

Single-Dose Azithromycin for the Treatment of Cholera in Adults

Although the mainstay of treatment of cholera (Vibrio cholera) has long been oral rehydration therapy (ORT) and intravenous fluids (IVF), antibiotics when available have been used in the treatment of severe cases. Single-dose tetracycline has been used for more than 40 years but cannot be used in children or pregnant women. Erythromycin is an alternative that must be used as a 3-day regimen. Azithromycin has been shown to be effective in a single dose in children in one previous study and has been applauded for its longer half-life and less gastrointestinal toxicity than erythromycin. This study was designed to evaluate the effectiveness of azithromycin in adults, when compared with ciprofloxacin, an antibiotic that has also been shown in past studies to treat cholera with a single-dose regimen.

This double-blind, randomized trial was completed using men who presented to a Bangladesh hospital with severe cholera. Inclusion criteria included age 18 to 60 years, severe dehydration, large volume of stool with or without vomiting, and V cholera obtained via either stool culture or rectal swab. Patients were randomized to a single dose of either azithromycin (1 g orally) or ciprofloxacin (1 g orally) at the onset of the study and were then admitted for 5 days. Patients were evaluated every 6 hours for vital signs, presence of watery stool, and fluid balance. Oral rehydration therapy was utilized, and IVF was reserved for those unable to maintain hydration. At discharge, patients were asked to return in 7 to 10 days for reevaluation and culture. Stool specimens were analyzed at day 0, day 3, and at follow-up visits, and all V cholera isolates were tested for sensitivities to azithromycin, ciprofloxacin, and other antibiotics. Outcomes included clinical success (no diarrhea at 48 hours) and bacterial success (no V cholera at 48 hours).

A total of 195 men were enrolled in the study. Clinical success was achieved in 73% (71/97) in the azithromycin group and 27% (26/98) of the ciprofloxacin group (P < .0001). Bacterial success was achieved in 78% (76/97) of the azithromycin subjects and 10% (10/98) of the ciprofloxacin subjects (P < .0001). Secondary success was seen in the azithromycin group, who had shorter duration of diarrhea, less vomiting, fewer stools, and smaller stool volume than the ciprofloxacin group. No patients in either group had clinical or bacterial cholera at the recheck, although only three quarters of each group returned for recheck. Factors associated with treatment failure included use of ciprofloxacin, longer duration of diarrhea prior to admission, and larger amounts of stool volume during the study course. Cultured organisms were sensitive to both ciprofloxacin and azithromycin, but a much larger median minimal inhibitory concentration was required for ciprofloxacin, suggesting increased resistance.

This study showed the effectiveness of single-dose azithromycin in the treatment of men with cholera. The data also suggest that the area of Bangladesh in which the study was completed has increased rates of ciprofloxacin-resistant V cholera. Although ORT is often the only treatment available in desolate and impoverished areas of Asia and Africa, single-dose azithromycin, when available, could be a helpful adjunct to ORT, at least until increasing microbial resistance develops to this antibiotic as well.

(N Engl J Med. 2006;354(23);2452–2461) D Saha, MM Karim, WA Khan, et al. Prepared by Karen Nolan Kuehl, MD, FACEP Carilion Emergency Medicine, Roanoke, VA, USA

The American Journal of Sports Medicine

Effect of Functional Bracing on Knee Injury in Skiers With Anterior Cruciate Ligament Reconstruction: A Prospective Cohort Study

The role of knee bracing in anterior cruciate ligament (ACL) injury is controversial; studies of bracing suggest that some functional knee orthotics do increase stability under low-impact conditions. However, the effect of bracing on stability under physiologic conditions has not yet been established, and clinical evidence of efficacy for bracing in the ACL-reconstructed (ACLr) knee is lacking. The aim of this study was to determine the effect of functional bracing on subsequent knee injury in ACLr skiers.

From 1991 to 1997, 11 606 skiers employed at a major ski resort underwent preseason knee screening. This group was composed of various employees who ski as a part of their job, including ski instructors, lift operators, ski patrol, and mountain skier services. All employees completed a pre-employment questionnaire and a screening exam that included Lachman and pivot-shift tests performed by an orthopedic sports medicine fellow. The ACLr group was defined as individuals who had undergone ACL reconstruction at least 2 years prior to the current ski season. All ACLr individuals were counseled by one of the staff surgeons, and, if recommended, a CTi2 brace (Innovation Sports, Irvine, CA) was provided free of charge. The employees were not required to use the recommended brace, and there was no formal protocol to evaluate compliance. Knee injuries during the ski season were defined as an injury that prevented the employee from working and identified as such through workers’ compensation records when the ski season was over.

The study population comprised 820 ACLr skiers at risk of injury for 1 ski season, with bracing selected by 257 (31%) individuals. There were 61 (7.4%) subsequent injuries; 28 required knee surgery (25 of these in the nonbraced group), and 11 of the 28 required ACLr revision (all in the nonbraced group). The injury rate in nonbraced skiers was 9% (51/563) and 4% (10/257) in the braced skiers (P = .009). After controlling for Lachman, pivot shift, and age, regression modeling identified nonbracing as a significant risk factor for subsequent knee injury.

The results of this study show that the use of bracing after ACL reconstruction resulted in a lower injury rate. The study did not look at the effect of rehabilitative or postoperative bracing in the first 2 years, but rather the effect of bracing on the fully rehabilitated knee. The study's major limitations included the decision-making scheme of brace use, the method of identification of injuries, and the inability to closely monitor the use of the brace during a high-risk sport. Nonetheless, the study showed that the ACLr skiers without a brace were almost 3 times more likely to sustain a subsequent knee injury. The authors recommend functional bracing for ACLr skiers with evidence of increased laxity.

(Am J Sports Med. 2006;34(10):1581–1585) WI Sterett, KK Briggs, T Farley, JR Steadman. Prepared by Michael Wallace, MS3 Oregon Health & Science University, Portland, OR, USA

Journal of Allergy and Clinical Immunology

Sublingual Epinephrine Tablets Versus Intramuscular Injection of Epinephrine: Dose Equivalence For Potential Treatment of Anaphylaxis

Anaphylactic reactions to such stimuli as food, insect stings, and medications are common occurrences in the community and wilderness. The mainstay of out-of-hospital treatment for anaphylaxis is use of an autoinjectable device containing epinephrine (eg, EpiPen [Dey, L.P., Napa]). It is thought that epinephrine may be underused or improperly used by patients during anaphylactic reactions for a variety of reasons, including a fear of needles. Improper use of such devices could expose patients to dosage variability. Current formulations of the EpiPen include the standard EpiPen for adults, which delivers 0.3 mg of epinephrine, and the EpiPen Jr, which delivers 0.15 mg for children.

Sublingual administration has been offered as an alternative and more palatable means of giving epinephrine. This study was designed to evaluate the feasibility of sublingual epinephrine absorption and to determine the sublingual dose that might achieve equivalent plasma concentrations to subcutaneous administration.

This study was a prospective, controlled, 5-way crossover study involving 5 New Zealand white rabbits. The animals were each administered sublingual tablets containing 0, 10, 20, and 40 mg of epinephrine and an intramuscular injection of 0.3 mg of epinephrine on 5 different study days, each separated by at least 4 weeks. Plasma epinephrine levels were obtained from each subject at 30 minutes pre-epinephrine administration and at 5, 10, 15, 20, 30, 40, 60, 90, and 120 minutes postepinephrine administration.

The average dose of epinephrine administered from the EpiPen was measured to be 0.34 mg. The mean area under the curve (AUC), maximum plasma concentration (C_max), and time to maximum plasma concentration (T_max) of the intramuscular injection of epinephrine did not differ significantly from the 40-mg sublingual epinephrine dose, whereas the other doses (0, 10, and 20 mg) had at least 1 of these 3 variables (mean AUC, C_max, and T_max) that significantly differed from the EpiPen values. The AUC values for 10, 20, and 40 mg of sublingual epinephrine (335 ng/mL/min, 801 ng/mL/min, and 1861 ng/mL/min, respectively) showed absorption is dose dependent in a near-linear fashion. No adverse effects were observed during the study.

Anaphylactic reactions necessitating the use of epinephrine are recognized as a true medical emergency; however, the fear of needles and other factors culminating in the underuse of this treatment modality speak to the need for different delivery devices. This study confirms the feasibility of sublingual epinephrine absorption while providing an equivalent sublingual dose (40 mg) to the standard 0.3-mg intramuscular dose in New Zealand white rabbits. Further research into sublingual administration of epinephrine in humans is warranted and necessary.

(J Allergy Clin Immunol. 2006;117(2):398–403) MM Rawas-Qalaji, FE Simons, KJ Simons. Prepared by David Stenstrom, MS3 Oregon Health & Science University, Portland, OR, USA