A comparison of proximal tibia, distal femur, and proximal humerus infusion rates using the EZ-IO intraosseous device on the adult swine (Sus scrofa) model.

OBJECTIVE: We sought to compare the flow rates of the proximal tibia, the distal femur, and the proximal humerus using high pressure (greater than 300 mmHg) through an intraosseous (IO) infusion needle in an adult swine model. METHODS: We performed a prospective interventional study in 11 swine. After placement of central vein and arterial lines, blood was removed via the central line until the animal's mean arterial pressure decreased 25% from the recorded baseline. We inserted a 25-mm IO needle into the proximal tibia and 45-mm needles into the distal femur and proximal humerus. All extremities were utilized in each study animal. We infused normal saline at each site for 10 minutes with a pressure bag inflated to the highest achievable pressure (greater than 300 mmHg) as measured at the infusion site with a calibrated portable inline pressure gauge. We measured the volume of normal saline remaining and we calculated infusion rates for each site. We then compared infusion flow rates between the three locations. Statistical analysis and comparison of the infusion rates of all three study arms were as performed using analysis of variance (ANOVA). RESULTS: The average weight of the swine was 71 kg (range 64-84 kg). Successful placement of the IO needle was confirmed at all three sites. The mean infusion flow rate was 213 mL/min (standard deviation [SD] 53.2 mL/min) for the proximal humerus, 138 mL/min (SD 65.3 mL/min) for the distal femur, and 103 mL/min (SD 48.1 mL/min) for the proximal tibia (p < 0.001). The flow rate through the proximal humerus was statistically greater than that for the proximal tibia and the distal femur (p < 0.001). The flow rates through the proximal tibia and distal femur were similar. CONCLUSION: The humerus is a suitable alternative site for IO placement, with a potential for higher flow rates than the proximal tibia and distal femur when resuscitating a patient.

Hydroxocobalamin versus sodium thiosulfate for the treatment of acute cyanide toxicity in a swine (Sus scrofa) model.

STUDY OBJECTIVE: We compare the efficacy of hydroxocobalamin to sodium thiosulfate to reverse the depressive effects on mean arterial pressure in a swine model of acute cyanide toxicity and gain a better understanding of the mechanism of action of the hydroxocobalamin in reversal of the toxicity. METHODS: Swine were intubated, anesthetized, and instrumented with central arterial and venous lines and a pulmonary artery catheter. Animals (n=36) were randomly assigned to one of 3 groups: hydroxocobalamin alone (150 mg/kg), sodium thiosulfate alone (413 mg/kg), or hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 60 minutes after the start of antidotal infusion. Cyanide was infused until severe hypotension developed, defined as blood pressure 50% of baseline mean arterial pressure. Repeated-measures ANOVA was used to determine statistically significant changes between groups over time. RESULTS: Time to hypotension (25, 28, and 33 minutes), cyanide dose at hypotension (4.7, 5.0, and 5.6 mg/kg), and mean cyanide blood levels (3.2, 3.7, and 3.8 µg/mL) and lactate levels (7, 8.2, 8.3 and mmol/L) were similar. All 12 animals in the sodium thiosulfate group died compared with 2 of 12 in the hydroxocobalamin/sodium thiosulfate group and 1 of 12 in hydroxocobalamin group. No statistically significant differences were detected between the hydroxocobalamin and hydroxocobalamin/sodium thiosulfate groups for carbon monoxide, mean arterial pressure, cyanide levels, or mortality at 60 minutes. Lactate level (2.6 versus 2.1 mmol/L), pH (7.44 versus 7.42), and bicarbonate level (25 versus 26 mEq/L) at 60 minutes were also similar between groups. CONCLUSION: Sodium thiosulfate failed to reverse cyanide-induced shock in our swine model of severe cyanide toxicity. Further, sodium thiosulfate was not found to be effective when added to hydroxocobalamin in the treatment of cyanide-induced shock. Hydroxocobalamin alone was again found to be effective for severe cyanide toxicity.

Hydroxocobalamin and epinephrine both improve survival in a swine model of cyanide-induced cardiac arrest.

STUDY OBJECTIVE: To determine whether hydroxocobalamin will improve survival compared with epinephrine and saline solution controls in a model of cyanide-induced cardiac arrest. METHODS: Forty-five swine (38 to 42 kg) were tracheally intubated, anesthetized, and central venous and arterial continuous cardiovascular monitoring catheters were inserted. Potassium cyanide was infused until cardiac arrest developed, defined as mean arterial pressure less than 30 mm Hg. Animals were treated with standardized mechanical chest compressions and were randomly assigned to receive one of 3 intravenous bolus therapies: hydroxocobalamin, epinephrine, or saline solution (control). All animals were monitored for 60 minutes after cardiac arrest. Additional epinephrine infusions were used in all arms of the study after return of spontaneous circulation for systolic blood pressure less than 90 mm Hg. A sample size of 15 animals per group was determined according to a power of 80%, a survival difference of 0.5, and an α of 0.05. Repeated-measure ANOVA was used to determine statistically significant changes between groups over time. RESULTS: Baseline weight, time to arrest, and cyanide dose at cardiac arrest were similar in the 3 groups. Coronary perfusion pressures with chest compressions were greater than 15 mm Hg in both treatment groups indicating sufficient compression depth. Zero of 15 (95% confidence interval [CI] 0% to 25%) animals in the control group, 11 of 15 (73%; 95% CI 48% to 90%) in the hydroxocobalamin group, and 11 of 15 (73%; 95% CI 48% to 90%) in the epinephrine group survived to the conclusion of the study (P<.001). The proportion of animals with return of spontaneous circulation at 5 minutes was 4 of 15 (27%; 95% CI 10% to 52%), and that of return of spontaneous circulation at 10 minutes was 11 of 15 (73%; 95% CI 48% to 90%) in the 2 treatment groups. Additional epinephrine infusion after return of spontaneous circulation was administered for hypotension in 2 of 11 (18%; 95% CI 4% to 48%) hydroxocobalamin animals and in 11 of 11 (100%; 95% CI 70% to 100%) of the epinephrine animals (P<.001). At 60 minutes, serum lactate was significantly lower in the hydroxocobalamin group compared with the epinephrine group (4.9 [SD 2.2] versus 12.3 [SD 2.2] mmol/L), and the pH was significantly higher (7.34 [SD 0.03] versus 7.15 [SD 0.07]). Serial blood cyanide levels in the hydroxocobalamin group were also lower than that of the epinephrine group from cardiac arrest through the conclusion of the study. CONCLUSION: Intravenous hydroxocobalamin and epinephrine both independently improved survival compared with saline solution control in our swine model of cyanide-induced cardiac arrest. Hydroxocobalamin improved mean arterial pressure and pH, decreased blood lactate and cyanide levels, and decreased the use of rescue epinephrine therapy compared with that in the epinephrine group.

Reasons military patients with primary care access leave an emergency department waiting room before seeing a provider.

OBJECTIVES: Our objective was to assess patients' understanding of emergency department (ED) wait times and why patients may leave the waiting room before seeing a provider. METHODS: Survey of patients in the ED waiting room of an urban tertiary care military hospital where civilian and military patients are treated. RESULTS: A total of 508/517 surveys (98%) were completed. Age ranges were 18 to 35 years (49%), 36 to 60 (31%), or older than 60 (20%). Education levels were high school (20%), some college (37%), or college graduate (39%). Of 503 respondents, 125 (25%) had left an ED waiting room before seeing a provider. The reasons included excessive wait times (91%) and family responsibilities (5%). Five hundred eight reported the factors that would motivate them to wait to see the physician (not leave without being seen [LWOBS]) were the severity of illness (64%), and if they received an update of wait times (26%); 82% (391/480) understood that severely ill patients were seen first. Patients attributed long wait times to doctors and nurses caring for other patients (292/583, 50%) and insufficient physician and nurse staffing (245, 42%). Of 802 responses for ideas to improve the wait, 34% said regular updates on estimated wait times, 21% said television shows or movies to view, 20% said books and magazines to read, and 11% said computers to access. CONCLUSIONS: Long wait times were the primary reason that patients left before seeing a provider, despite having ready access to care. Respondents attributed long wait times to patient volume and inadequate staffing. Regular updates on wait times and material for entertainment may improve the waiting experience and reduce LWOBS.

Survey in the emergency department of parents' understanding of cough and cold medication use in children younger than 2 years.

OBJECTIVES: In August 2007, the Food and Drug Administration (FDA) released a public health advisory recommending that over-the-counter cough and cold medications (CCMs) not be used in children younger than 2 years. Our objective was to assess parents' awareness and understanding of the guidelines. METHODS: We surveyed caregivers of children younger than 2 years in the emergency department of an urban tertiary care military hospital where civilian patients are also treated. After completing the survey, caregivers received a handout explaining the FDA's recommendations. RESULTS: Our response rate was 99% (264/265). First-time parents constituted 45% (114/251) of responders. Education level was high school, 21%; some college, 36%; and college graduate, 40%. Thirty-one percent (77/247) were aware of the FDA guidelines. Of these 77, 44 (57%) reported the guidelines indicated CCMs were not safe in children younger than 2 years, and 18 (23%) said CCMs have caused death. Twenty-six percent (68/264) did not give CCMs to their children younger than 2 years, and 40% of these reported it was because of learning about the guidelines; 63% (165/264) reported CCMs were effective, 11% ineffective, and 27% did not know. Fifty-seven percent (151/263) reported CCMs were safe, 12% unsafe, and 31% unsure. Twenty-two percent (31/143) planned to use or continue to use CCMs in their children, 34% did not, 23% not sure, and 21% only if their doctor advised it. CONCLUSIONS: The majority of caregivers were not aware of the FDA guidelines on CCM use in children younger than 2 years. Most thought CCMs were safe and effective.

Seven years of cyanide ingestions in the USA: critically ill patients are common, but antidote use is not.

BACKGROUND: Cyanide is a common toxin in structural fires and a salt that is ingested for suicide. However, most studies have focused on the effects of inhaled cyanide. The objective of this study was to describe the incidence of cyanide ingestions, symptoms, cardiac arrest and antidotal therapy used as reported to all US poison centres over 7 years. METHODS: A retrospective review of cases over 7 years as reported to 61 poison centres in the USA was performed. Sole ingestions of cyanide were identified. A trained reviewer used a standard data collection sheet within a secured electronic database. Age, intent, clinical effects, treatments, antidotes and outcomes were recorded. One investigator audited a random sample of charts. RESULTS: Out of 1741 exposures, 435 ingestions were identified. Most were male (68%) and the mean age was 34 years (range 1 month-83 years). 45% of cases were intentional, most commonly as a suicide attempt. 8.3% of cases died and 9% (38/435) of patients had cardiac arrest or hypotension. 13% of all cases and 26% of cases arriving at a healthcare facility received an antidote. In 35% of cases of cardiac arrest or hypotension, and in 74% of intentional ingestions, antidotes were not given. CONCLUSIONS: Suicide attempt was the most common reason for cyanide ingestion. Most of these patients died. Cardiac arrest or hypotension was common, but antidote use was not, particularly in critically ill patients. Research is needed to improve outcomes of cyanide-induced hypotension and cardiac arrest and to reduce barriers to antidote use.

Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection.

STUDY OBJECTIVE: Community-associated methicillin-resistant Staphylococcus aureus is now the leading cause of uncomplicated skin abscesses in the United States, and the role of antibiotics is controversial. We evaluate whether trimethoprim-sulfamethoxazole reduces the rate of treatment failures during the 7 days after incision and drainage and whether it reduces new lesion formation within 30 days. METHODS: In this multicenter, double-blind, randomized, placebo-controlled trial, we randomized adults to oral trimethoprim-sulfamethoxazole or placebo after uncomplicated abscess incision and drainage. Using emergency department rechecks at 2 and 7 days and telephone follow-up, we assessed treatment failure within 7 days, and using clinical follow-up, telephone follow-up, and medical record review, we recorded the development of new lesions within 30 days. RESULTS: We randomized 212 patients, and 190 (90%) were available for 7-day follow-up. We observed a statistically similar incidence of treatment failure in patients receiving trimethoprim-sulfamethoxazole (15/88; 17%) versus placebo (27/102; 26%), difference 9%, 95% confidence interval -2% to 21%; P=.12. On 30-day follow-up (successful in 69% of patients), we observed fewer new lesions in the antibiotic (4/46; 9%) versus placebo (14/50; 28%) groups, difference 19%, 95% confidence interval 4% to 34%, P=.02. CONCLUSION: After the incision and drainage of uncomplicated abscesses in adults, treatment with trimethoprim-sulfamethoxazole does not reduce treatment failure but may decrease the formation of subsequent lesions.

Intraosseous versus intravenous infusion of hydroxocobalamin for the treatment of acute severe cyanide toxicity in a Swine model.

OBJECTIVES: Easily administrated cyanide antidotes are needed for first responders, military troops, and emergency department staff after cyanide exposure in mass casualty incidents or due to smoke inhalation during fires involving many victims. Hydroxocobalamin has proven to be an effective antidote, but cannot be given intramuscularly because the volume of diluent needed is too large. Thus, intraosseous (IO) infusion may be an alternative, as it is simple and has been recommended for the administration of other resuscitation drugs. The primary objective of this study was to compare the efficacy of IO delivery of hydroxocobalamin to intravenous (IV) injection for the management of acute cyanide toxicity in a well-described porcine model. METHODS: Twenty-four swine (45 to 55 kg) were anesthetized, intubated, and instrumented with continuous mean arterial pressure (MAP) and cardiac output monitoring. Cyanide was continuously infused until severe hypotension (50% of baseline MAP), followed by IO or IV hydroxocobalamin treatment. Animals were randomly assigned to receive IV (150 mg/kg) or IO (150 mg/kg) hydroxocobalamin and monitored for 60 minutes after start of antidotal infusion. The primary outcome measure was the change in MAP after antidotal treatment from onset of hypotension (time zero) to 60 minutes. A sample size of 12 animals per group was determined by group size analysis based on power of 80% to detect a one standard deviation of the mean MAP between the groups with an alpha of 0.05. Whole blood cyanide, lactate, pH, nitrotyrosine (nitric oxide marker) levels, cerebral and renal near infrared spectrometry (NIRS) oxygenation, and inflammatory markers were also measured. Repeated-measures analysis of variance was used to determine statistically significant changes between groups over time. RESULTS: At baseline and at the point of hypotension, physiologic parameters were similar between groups. At the conclusion of the study, 10 out of 12 animals in the IV group and 10 out of 12 in IO group survived (p = 1.0). Both groups demonstrated a similar return to baseline MAP (p = 0.997). Cardiac output, oxygen saturation, and systemic vascular resistance were also found to be similar between groups (p > 0.4), and no difference was detected between bicarbonate, pH, and lactate levels (p > 0.8). Cyanide levels were undetectable after the hydroxocobalamin infusion throughout the study in both groups (p = 1.0). Cerebral and renal NIRS oxygenation decreased in parallel to MAP during cyanide infusion and increased after antidote infusion in both groups. Serum nitrotyrosine increased during cyanide infusion in all animals and then decreased in both study arms after hydroxocobalamin infusion (p > 0.5). Serum cytokines increased starting at cyanide infusion and no difference was detected between groups (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, and IL-10). CONCLUSIONS: The authors found no difference in the efficacy of IV versus IO hydroxocobalamin in the treatment of severe cyanide toxicity in a validated porcine model.

Acute electrocardiographic ST segment elevation may predict hypotension in a swine model of severe cyanide toxicity.

Cyanide causes severe cardiac toxicity resulting in tachycardia, hypotension, and cardiac arrest; however, the clinical diagnosis can be difficult to make. A clinical finding that may precede or predict cyanide-induced hypotension may be a trigger to provide treatment earlier and improve outcomes in cyanide toxicity. Our primary objective was to determine if there is a clinically significant change in ST segment deviation measured on ECG during intravenous cyanide infusion that may predict cyanide-induced hypotension. As part of a larger study comparing antidotes for cyanide-induced shock, 30 swine were anesthetized and monitored and then intoxicated with a continuous cyanide infusion until severe hypotension (50 % of baseline mean arterial pressure) occurred. ECGs were obtained at baseline, every 5 min during infusion, and at the development of hypotension. Repeated measures of analysis of variance were used to determine significance. The mean weight for the 30 swine at baseline was 48 kg (range 45-52), pulse rate 86 beats/min (range 55-121), and systolic blood pressure 109 mmHg (range 90-121). The mean time to hypotension was 31 min (range 16-39). The mean amount of cyanide infused was 5 mg/kg (range 2.5-6.3 mg/kg). All animals (30/30) had ECG changes in repolarization or depolarization during cyanide infusion. Significant rhythm, repolarization, and conduction changes from baseline were observed prior to severe hypotension (p < 0.05). Normal sinus rhythm and sinus tachycardia were the most common rhythms preceding hypotension. We observed ST segment elevation in leads V3, V4, III, and aVF and ST segment depression in leads aVL and aVR. The most pronounced ST segment elevation was observed in leads V3 and V4. We also detected significant changes with increased pulse rate, prolonged PR interval, and shortened QTc interval. Other significant changes were increased T axis and reduced QRS axis. We detected ST segment deviations occurring just before the onset of cyanide-induced hypotension in our swine model. Leads V3 and V4 had the most pronounced with ST elevation, but we also detected electrocardiographic ST elevation inferiorly. Shortening of the QTc and lengthening of the PR interval were also detected before hypotension.