Comparison of thromboelastography versus conventional coagulation tests in simulated Crotalus atrox envenomation using human blood.

INTRODUCTION: Pit viper bites are a source of significant morbidity and mortality. Pit viper bites can cause venom-induced consumptive coagulopathy (VICC), typically evaluated with laboratory-based conventional coagulation tests (CCTs). However, CCTs require a laboratory and average 1 h to conduct. Thromboelastography (TEG) provides real-time, point-of-care tests of coagulation that are fast and require no separate laboratory facilities, which could be advantageous in both hospital and austere settings. However, the relative efficacy of TEG versus CCTs was unclear, particularly at low venom concentrations. Therefore, the objectives of this study were to test human blood with various concentrations of pit viper venom using CCTs and TEG to determine dose-dependent changes, lowest observed effect concentration (LOEC), and sensitivity to detecting samples out of normal diagnostic range. METHODS: Blood samples from 20 volunteers were mixed with varying concentrations of western diamond back rattlesnake (Crotalus atrox) venom based on the mouse LD50IV (none, 0.5%, 1%, 2%, 33%, 66%, and 100% LD50IV). Samples were split and assessed with both CCTs including prothrombin time (PT), international normalized ratio (INR), partial thromboplastin time (PTT), fibrinogen, and D-dimer, along with TEG measures of reaction time (R), kinetic time (K), rate of clot formation (α-angle), and clot strength (MA). Data were analyzed as dose-dependent concentration-based changes in raw values and in percent of samples exceeding diagnostic thresholds using ANOVA and nonparametric statistics at the p < .05 threshold. RESULTS: All evaluations showed significant concentration-dependent changes, and 100% of samples exceeded diagnostic thresholds at 33%LD50IV and above, save D-dimer. At 0.5%LD50IV, R, K, α-angle, PT, and INR were significantly different from controls, and at 1%LD50IV, mean values exceeded diagnostic thresholds for R, K, α-angle, MA, PT, and INR, but not for PTT, D-dimer, or fibrinogen. At 2%LD50IV, 100% of samples were out of normal range for K, α-angle, and PT. CONCLUSION: TEG is effective in coagulopathy evaluations of in vitro simulated pit viper envenomation. At low venom concentrations, TEG performed as well or better than the majority of CCTs. These findings provide empirical evidence supporting the use of TEG to rapidly and accurately evaluate VICC.

Field Expedient Vasopressors During Aeromedical Evacuation: A Case Series from the Puerto Rico Disaster Response.

IntroductionEmergency physicians are using bolus-dose vasopressors to temporize hypotensive patients until more definitive blood pressure support can be established. Despite a paucity of clinical outcome data, emergency department applications are expanding into the prehospital setting. This series presents two cases of field expedient vasopressor use by emergency medicine providers for preflight stabilization during aeromedical evacuation to a hospital ship as part of the United States Navy disaster response in Puerto Rico. A critical approach and review of the literature are discussed.Case ReportTwo critically ill patients were managed in an austere environment as a result of the devastation from Hurricane Maria (Yabucoa, Puerto Rico; 2017). They both exhibited signs of respiratory distress, hemodynamic instability, and distributive shock requiring definitive airway management and hemodynamic support prior to aeromedical evacuation.DiscussionThe novel use of field expedient vasopressors prior to induction for rapid sequence intubation was successfully and safely employed in both cases. Both patients had multiple risk factors for peri-induction cardiac arrest given their presenting hemodynamics. Despite their illness severity, both patients were induced, transported, and ultimately admitted to the intensive care unit (ICU) in stable condition following administration of the field expedient vasopressors.Conclusion:Field expedient vasopressors were safely and effectively employed in an austere field environment during a disaster response. This case series contributes to the growing body of literature of safe bolus-dose vasopressor use by emergency physicians to temporize hypotensive patients in resource-constrained situations. HardwickJM, MurnanSD, Morrison-PonceDP, DevlinJJ. Field expedient vasopressors during aeromedical evacuation: a case series from the Puerto Rico disaster response. Prehosp Disaster Med. 2018;33(6):668-672.

Detection of ingested nitromethane and reliable creatinine assessment using multiple common analytical methods.

AIM: Nitromethane, found in fuels used for short distance racing, model cars, and model airplanes, produces a falsely elevated serum creatinine with standard creatinine analysis via the Jaffé method. Erroneous creatinine elevation often triggers extensive testing, leads to inaccurate diagnoses, and delayed or inappropriate medical interventions. Multiple reports in the literature identify "enzymatic assays" as an alternative method to detect the true value of creatinine, but this ambiguity does not help providers translate what type of enzymatic assay testing can be done in real time to determine if there is indeed false elevation. METHODS: We report seven cases of ingested nitromethane where creatinine was determined via Beckman Coulter® analyser using the Jaffé method, Vitros® analyser, or i-Stat® point-of-care testing. Nitromethane was detected and semi-quantified using a common clinical toxic alcohol analysis method, and quantified by headspace-gas chromatography-mass spectrometry. RESULTS: When creatinine was determined using i-Stat® point-of-care testing or a Vitros® analyser, levels were within the normal range. Comparatively, all initial creatinine levels obtained via the Jaffé method were elevated. Nitromethane concentrations ranged from 42 to 310 µg/mL. CONCLUSIONS: These cases demonstrate reliable assessment of creatinine through other enzymatic methods using a Vitros® analyser or i-STAT®. Additionally, nitromethane is detectable and quantifiable using routine alcohols gas chromatography analysis and by headspace-gas chromatography-mass spectrometry.

Medical toxicologists' practice patterns regarding drug-induced QT prolongation in overdose patients: a survey in the United States of America, Europe, and Asia Pacific region.

OBJECTIVE: To describe practice patterns of medical toxicologists in the United States of America (USA), Europe, and Asia Pacific Region regarding management of drug induced QT prolongation and torsades de pointes in overdose. METHODS: A survey was developed to assess current practice patterns and consistency with guidelines published by the American Heart Association (AHA), American College of Cardiology (ACC), and European Society of Cardiology (ESC). It was reviewed by our department research committee and the American College of Medical Toxicology (ACMT). The ACMT, European Association of Poisons Centres and Clinical Toxicologists, and Asia Pacific Association of Medical Toxicology electronically disseminated the survey to their physician members in the USA, Europe and Asia Pacific Region. RESULTS: The overall response rate was 37% (229/617) (36% USA; 32% Europe; 52% Asia Pacific Region). Twelve toxicologists from Asia Pacific Region and Europe used the QT nomogram (Australia-5, New Zealand-1, United Kingdom-1) or QT alone (France-1, Russia-1, Romania-1, Germany-1, Philippines-1), in lieu of the corrected QT (QTc) to determine risks of developing torsades de pointes. Because only those who used QTc could proceed through the remainder of the survey, only 217 could do so. Approximately half of the respondents (52%) did not calculate QTc manually and based decisions on the electrocardiogram machines automated measurement. For those who corrected the QT interval themselves, the most common formula used was Bazett's (40%). There is great variation in the QTc value considered prolonged. Most responders considered QTc greater than 450 ms in men (28%) and 460 ms in women (25%) to be prolonged. Interestingly, approximately 15% of participants did not consider the QTc prolonged until it exceeded 500 ms in both men and women. Given an overdose scenario of a male patient with a QTc of 560 ms, heart rate of 90 beats/minute, 59% would not recommend administering intravenous magnesium sulfate. Forty-five percent and 36% believed magnesium could shorten QTc and prevent torsades de pointes, respectively. In addition, almost 90% believed administering 1-2 boluses of intravenous magnesium is safe, even when serum magnesium is not available. In regards to cardiac pacing of patients with QT prolongation and torsades de pointes, only 38% of the participating toxicologists' responses agreed with AHA/ACC/ESC recommendations. Furthermore, 21% would not pace a patient who developed torsades de pointes regardless of the scenario. DISCUSSION AND CONCLUSIONS: The results indicate that medical toxicologists have considerable heterogeneity in terms of management practices for overdose patients with QT prolongation and torsades de pointes. Medical toxicologists may benefit from developing evidence-based consensus guidelines for the management of this relatively common finding in overdose of QT-prolonging drugs.

A case of abrin toxin poisoning, confirmed via quantitation of L-abrine (N-methyl-L-tryptophan) biomarker.

INTRODUCTION: The seeds of Abrus precatorius contain the highly toxic plant protein abrin. There is no antidote for abrin poisoning. Management, largely supportive, may consist of administering intravenous fluids, anti-emetics, and activated charcoal depending on the time of exposure. We report the presentation of a single case of unintentional abrin poisoning confirmed by the quantitation of L-abrine biomarker. CASE REPORT: A previously healthy 22-month-old, 11.5-kg female presented to the hospital after ingesting approximately 20 rosary peas (A. precatorius) sold as a "peace bracelet". Her primary manifestations were episodes of forceful emesis that included food particles progressing to clear gastric fluid. The patient was tachycardic (HR = 134 bpm) but had brisk capillary refill and normal blood pressure (96/60 mmHg). Laboratory testing revealed elevated blood urea nitrogen (16 mg/dL) and serum creatinine (0.4 mg/dL). In the emergency department, the patient was resuscitated with 40 mL/kg normal saline via peripheral IV and received ondansetron (0.15 mg/kg IV) to control retching. The patient was discharged well 24 h after the ingestion. DISCUSSION: This is the first case of human abrin toxin poisoning confirmed by the quantitation of L-abrine as a biomarker. Quantifying the levels of abrin toxin in the body after exposure can help clinicians make informed decisions when managing patients with symptomatic exposures to seeds of A. precatorius.

Clinical features, testing, and management of patients with suspected prosthetic hip-associated cobalt toxicity: a systematic review of cases.

Safety concerns regarding cobalt-containing metal alloy hip prosthetics (Co-HP) have resulted in product recalls, a medical device alert, and issuance of guidance for clinicians. Recently, cases of suspected prosthetic hip-associated cobalt toxicity (PHACT) from Co-HP have been reported. Although little is known about suspected PHACT, these patients may be referred to medical toxicologists for evaluation and management recommendations. We searched MEDLINE, EMBASE, and unpublished abstracts from toxicology scientific meetings for references relevant to PHACT. Authors independently screened publications for inclusion criteria: publication in English, human study population, subject(s) are symptomatic (except for isolated hip pain), and cobalt values in any matrix (blood, serum, urine, CSF, synovial fluid) available for review. Data from 10 cases are reviewed. Patients with suspected PHACT had findings consistent with cobalt toxicity, including thyroid, cardiac, and neurologic dysfunction. Signs and symptoms appeared between 3 and 72 months after arthroplasty (median 19 months). Neurologic symptoms were most common. Ancillary testing varied considerably. All patients had elevated cobalt levels in one or more matrices. Enhanced elimination was attempted in 27 % of patients. At this time, the information currently available regarding patients with suspected PHACT is inadequate to guide clinical decision making. No consensus has been reached regarding the management of Co-HP patients with systemic symptoms. Indications for chelation have not been established and require further study. Improved case definitions, improved surveillance, and controlled studies are needed to elucidate the scope of this problem and guide future investigations.

Terlipressin with limited fluid resuscitation in a swine model of hemorrhage.

BACKGROUND: Principles of damage control resuscitation include minimizing intravenous fluid (IVF) administration while correcting perfusion pressure as quickly as possible. Recent studies have identified a potential advantage of vasopressin over catecholamines in traumatic shock. Terlipressin (TP) is a vasopressin analogue used to reverse certain shock etiologies in some European countries. STUDY OBJECTIVE: We evaluated three dosages of TP when combined with a limited colloid resuscitation strategy on mean arterial pressure (MAP) and lactatemia in a swine model of isolated hemorrhage. METHODS: Sixty anesthetized swine underwent intubation and severe hemorrhage. Subjects were randomized to one of four resuscitation groups: 4 mL/kg Hextend(®) (Hospira Inc, Lake Forest, IL) only, 3.75 µg/kg TP + Hextend, 7.5 µg/kg TP + Hextend, or 15 µg/kg TP + Hextend. MAP and heart rate were recorded every 5 min. Baseline and serial lactate values at 30-min intervals were recorded and compared. RESULTS: Subjects receiving 7.5 µg/kg TP had significantly higher MAPs at times t15 (p = 0.012), t20 (p = 0.004), t25 (p = 0.018), t30 (p = 0.032), t35 (p = 0.030), and t40 (p = 0.021). No statistically significant differences in lactate values between TP groups and controls were observed. CONCLUSION: Subjects receiving 7.5 µg/kg of TP demonstrated improved MAP within 10 min of administration. When combined with minimal IVF resuscitation, TP doses between 3.75 and 15 µg/kg do not elevate lactate levels in hemorrhaged swine.

Development of a ballistic model of combat groin injury.

BACKGROUND: The current leading cause of death to troops in Operations Enduring Freedom results from improvised explosive devices. The need for accurate models of combat trauma in research is an ever present challenge and crucial to our efforts to save the lives of our injured troops. Current swine models of groin injury use a scalpel to create the wound, which provides for a controlled environment but limits the resemblance to real combat injuries. We sought to develop a reliable ballistic model of fragmentation injury that will allow for new research and training opportunities in the field of combat casualty care. METHODS: A jet remote opening device was developed to inflict a fragmentation injury to the groin of 20 anesthetized swine. Laser positioning ensured alignment. After hemorrhage, subjects were treated with standard resuscitative measures and monitored for 180 minutes to determine survival. RESULTS: Subject survival was 95% at 3 minutes postinjury and 75% at 180 minutes. Survival rates were similar to actual survival data collected from Operations Enduring Freedom (p = 0.993). Blood loss during initial hemorrhage averaged 15.4 (±6.0) mL/kg. No instances of peritoneal violation by the shrapnel fragments were revealed on necropsy. CONCLUSIONS: We developed a ballistic mechanism of injury in a model that replicates improvised explosive device-created wounds. The injury was reliably reproduced in each subject, with survival rates equating those of real casualties. We think that this model represents a true effectiveness model of injury that opens the doors for advanced research endeavors in combat casualty care.

Comparison of Celox-A, ChitoFlex, WoundStat, and combat gauze hemostatic agents versus standard gauze dressing in control of hemorrhage in a swine model of penetrating trauma.

OBJECTIVES: Uncontrolled hemorrhage remains one of the leading causes of trauma deaths and one of the most challenging problems facing emergency medical professionals. Several hemostatic agents have emerged as effective adjuncts in controlling extremity hemorrhage. However, a review of the current literature indicates that none of these agents have proven superior under all conditions and in all wound types. This study compared several hemostatic agents in a lethal penetrating groin wound model where the bleeding site could not be visualized. METHODS: A complex groin injury with a small penetrating wound, followed by transection of the femoral vessels and 45 seconds of uncontrolled hemorrhage, was created in 80 swine. The animals were then randomized to five treatment groups (16 animals each). Group 1 was Celox-A (CA), group 2 was combat gauze (CG), group 3 was Chitoflex (CF), group 4 was WoundStat (WS), and group 5 was standard gauze (SG) dressing. Each agent was applied with 5 minutes of manual pressure. Hetastarch (500 mL) was infused over 30 minutes. Hemodynamic parameters were recorded over 180 minutes. Primary endpoints were attainment of initial hemostasis and incidence of rebleeding. RESULTS: Overall, no difference was found among the agents with respect to initial hemostasis, rebleeding, and survival. Localizing effects among the granular agents, with and without delivery mechanisms, revealed that WS performed more poorly in initial hemostasis and survival when compared to CA. CONCLUSIONS: In this swine model of uncontrolled penetrating hemorrhage, SG dressing performed similarly to the hemostatic agents tested. This supports the concept that proper wound packing and pressure may be more important than the use of a hemostatic agent in small penetrating wounds with severe vascular trauma.

Comparison of ChitoFlex®, CELOX™, and QuikClot® in control of hemorrhage.

BACKGROUND: Exsanguinating extremity wounds remain the primary source of battlefield mortality. Operating forces employ three agents in Iraq: HemCon® (HemCon Medical Technologies, Inc., Portland, OR), QuikClot® (Z-Medica Corporation, Wallingford, CT), and CELOX™ (SAM Medical, Tualatin, OR). Anecdotal reports suggest that these agents are less useful on small entrance, linear-tract injuries. ChitoFlex® (HemCon Medical Technologies, Inc., Portland, OR) has been introduced but is untested. STUDY OBJECTIVES: To compare the equivalency of the ChitoFlex® dressing, QuikClot® ACS+™ dressing, CELOX™, and standard gauze in their effectiveness to control bleeding from non-cavitary groin wounds. METHODS: Forty-eight swine were randomly assigned to one of four treatment groups: standard gauze dressing (SD), ChitoFlex® dressing (CF), QuikClot® ACS+™ dressing (QC), and CELOX™ dressing (CX). A groin injury with limited vessel access was created in each animal. Subjects were resuscitated with 500 mL of hetastarch. The primary endpoint was 180-min survival. Secondary endpoints included total blood loss in mL/kg, incidence of re-bleeding, survival times among the animals that did not survive for 180 min, failure to achieve initial hemostasis, incidence of recurrent bleeding, time to initial re-bleeding, amount of re-bleeding, and mass of residual hematoma. RESULTS: Survival occurred in 10 of 12 SD animals, 10 of 12 CF animals, 10 of 12 QC animals, and 9 of 12 CX animals. No statistically significant difference was found. CONCLUSION: In our study of limited-access extremity bleeding, ChitoFlex® performed equally well in mitigating blood loss and promoting survival. The ChitoFlex® dressing is an equally effective alternative to currently available hemostatic agents. However, no agents were superior to standard gauze in our model of limited access.