Ziad N. Kazzi

Acute Metformin Overdose: Examining Serum pH, Lactate Level, and Metformin Concentrations in Survivors Versus Nonsurvivors: A Systematic Review of the Literature

STUDY OBJECTIVE Metformin is known to cause potentially fatal metabolic acidosis with an increased lactate level in both overdose and therapeutic use. No association between mortality and serum pH, lactate level, or metformin concentrations, though intuitive, has yet been described. This systematic literature review is designed to evaluate the association between mortality and serum pH, lactate level, and metformin concentrations in acute metformin overdose. METHODS We reviewed the literature by using the MEDLINE, EMBASE, CINAHL, and TOXNET databases for cases of metformin overdose with documented mortality data and values of serum pH, lactate level, and metformin concentrations. When available, patient age, patient sex, and whether patients received intravenous sodium bicarbonate therapy or hemodialysis were also analyzed. Cases meeting inclusion criteria were analyzed to determine whether a difference in distribution of nadir serum pH, peak serum lactate level, or peak serum metformin concentrations existed between overdose survivors and nonsurvivors. RESULTS We identified 10 articles that had 1 or more cases meeting our inclusion criteria. In total, there were 22 cases of metformin overdose (5/22 died) that met inclusion criteria. No intentional overdose patients died whose serum pH nadir was greater than 6.9, maximum lactate concentration less than 25 mol/L, or maximum metformin concentration less than 50 microg/mL (therapeutic range 1 to 2 microg/mL). Intentional overdose patients with a nadir serum pH less than 6.9 had 83% mortality (5/6), those with lactate concentration greater than 25 mmol/L had 83% mortality (5/6), and those with metformin concentration greater than 50 microg/mL had 38% mortality (5/12). Nadir serum pH and peak serum lactate and metformin concentration distributions in survivors and nonsurvivors revealed that survivors had a median nadir pH of 7.30, interquartile range (IQR) 7.22, 7.36; nonsurvivors, a median nadir pH of 6.71, IQR 6.71, 6.73; survivors, a median peak lactate level of 10.8 mmol/L, IQR 4.2, 12.9; nonsurvivors, a median peak lactate level of 35.0 mmol/L, IQR 33.3, 39.0; survivors, a median peak metformin level of 42 microg/mL, IQR 6.6, 67.6; and nonsurvivors, a median peak metformin level of 110 microg/mL, IQR 110, 110. CONCLUSION No cases of acute metformin overdose meeting the studys inclusion criteria were found in which patients with a nadir serum pH greater than 6.9, peak serum lactate concentrations less than 25 mmol/L, or peak serum metformin concentrations less than 50 microg/mL died. Patients with acute metformin overdose who died had much lower serum pH nadirs and much higher peak serum lactate and metformin concentrations than those who survived.

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.

Abstract 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 Bazetts (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.

Radiological preparedness-awareness and attitudes: A cross–sectional survey of emergency medicine residents and physicians at three academic institutions in the United States

Context. Emergency preparedness has been increasingly recognized as important. Research shows many medical personnel feel unprepared to respond to radiation incidents. Knowledge and attitudes of emergency medicine residents and faculty are largely unstudied, regarding their abilities to provide care for radiation disaster victims. It is unknown whether receiving training in radiological emergency preparedness improves knowledge and attitudes. Objectives. (1) Assess the attitudes of emergency medicine residents and faculty toward a radiological disaster; (2) Assess knowledge gaps of emergency medicine residents and faculty regarding radiological emergency preparedness; (3) Assess the attitudes of emergency medicine residents and faculty toward different educational strategies. Methods. An electronic survey was sent to 309 emergency medicine residents and faculty at three U.S. academic institutions. Analyses were performed using SAS 9.0 software. Results. The survey response rate was 36.6%. Only 37% and 28% of respondents had attended radiological preparedness training in the preceding 5 years or any training in radiation detection, respectively. Higher proportions of trained physicians were: (1) more familiar with DTPA and Prussian blue; (2) more comfortable assessing, decontaminating, and managing victims of radiation incidents; and (3) more comfortable using radiation detectors than their untrained counterparts. Many respondents were unable to differentiate between contamination with and exposure to radiological material. Classroom teaching at the workplace and prepackaged educational materials were most frequently rated as the preferred educational method for radiation preparedness training. Discussion and conclusion. Our results suggest a need for additional radiological-nuclear preparedness training for emergency medicine residents and faculty. Training should include radiation detection, decontamination, explaining differences between radiation exposure and contamination, and teaching patient management, including DTPA and Prussian blue.

Exotic venomous snakebite drill

Background. There were 900 exotic venomous snakebites reported from 2000 to 2009. The Association of Zoos and Aquariums’ recommends institutions housing venomous reptiles have protocols for appropriate and timely transport of envenomed individuals to hospitals. The study objective was to evaluate functional aspects and potential problems of our emergency operation procedure designed for handling the response to an exotic venomous snakebite during implementation via a simulated drill. The emergency operation procedure consists of two protocols, the protocol for zoo personnel and exotic snakebite protocol for hospital personnel. Methods. Before the exercise the poison center (PC), zoo, Emergency Medical Services (EMS), receiving hospital emergency department (ED), and pharmacy were contacted. The emergency operation procedure was reviewed to determine areas of deficiency. A checklist of all required actions for each participating institution was created for use during the exercise. The exercise was divided into four phases: zoo, EMS, PC, and ED. Each phase was evaluated by an independent observer. Results. Review of the emergency operation procedure revealed sufficient and easy to follow information for zoo personnel. However, the exotic snakebite protocol for hospital personnel lacked details regarding signs and symptoms expected from each exotic venomous species in the zoo; and indications, dosing, and instructions on reconstitution for each of the antivenom carried by the zoo. Zoo, EMS, ED, and PC personnel completed 95%, 90%, 83%, and 25% of the required tasks, respectively. The PC encountered problems communicating the exotic snakebite protocol for hospital personnel to the ED due to phone and fax equipment failures. Creative solutions to the PC system issues were not identified in a timely manner. Despite the shortcomings, the time from simulated envenomation to antivenom (AV) administration was under an hour. Conclusions. This drill identified several issues leading to revision of our exotic snakebite protocol for hospital personnel. We also identified suboptimal PC response in the application of the emergency operation procedure. We encourage every poison center in cooperation with local zoos to perform a similar exercise.

Radiological Emergency Preparedness: A Survey of Nuclear Medicine Technologists in the United States

Because of the increasing risk of radiological emergencies, public health agencies and first-response organizations are working to increase their capability of responding. Nuclear medicine technologists (NMTs) have expertise in certain areas, such as radiation safety, radiobiology, decontamination, and the use of radiation detection and monitoring equipment, that could be useful during the response to events that involve radiological materials. Methods. To better understand the potential role that NMTs may have in response efforts, a cross-sectional survey was conducted. The survey was sent electronically to the 7,000 members of the Technology Section of the Society of Nuclear Medicine and Molecular Imaging. Eight hundred fifty NMTs responded to the survey, for a response rate of 12.14%. The study queried NMTs across the United States on their knowledge of using radiation detection and monitoring equipment, such as a scintillation γ-cameras, Geiger counters, thyroid probes, well counters, and portal monitors; willingness to participate in response efforts during a nuclear reactor accident, nuclear weapon detonation, or dirty bomb detonation; access to radiation detection and monitoring equipment within their work setting; familiarity with current preparedness guidance and tools provided by the Centers for Disease Control and Prevention and U.S. Department of Health and Human Services; and registration in volunteer initiatives such as the Emergency System for Advance Registration of Volunteer Health Professionals, Metropolitan Medical Response System, and Medical Reserve Corps. Results. Survey results suggest that NMTs are knowledgeable and willing to respond to radiological emergencies, regardless of number of years of work experience. Radiological preparedness training within the last 5 y significantly increases NMTs’ willingness to respond and familiarity with current guidance and tools provided by the Centers for Disease Control and Prevention and Department of Health and Human Services. Respondents reported a low participation level in volunteer programs, and most agreed that continuing education should include radiological emergency preparedness. Conclusion. NMTs should be considered an untapped resource and should be strategically recruited for involvement in radiological emergency preparedness planning and training. NMTs should also consider becoming involved in local volunteer initiatives because they have the knowledge and willingness to provide assistance during a radiological emergency.

Pandemic influenza preparedness: bridging public health academia and practice.

In 2006, the Alabama Department of Public Health, through the University of Alabama at Birmingham’s South Central Center for Public Health Preparedness, sponsored a series of infectious disease outbreak exercises in Alabama’s six hospital planning regions. The six exercises were conducted in rural and metropolitan areas and were designed to be full-scale assessments of multiagency and multijurisdictional responses to an infectious disease outbreak. This article details the lessons learned from the exercises and collaborations of academia with the public health practice and emergency response communities. We provide the results for our qualitative assessment with the hope that this information can identify trends and potential issues applicable to regions and future disasters outside of Alabama. Thus, while these exercises took place in one state, the trends we observed may be generalizable to other locales as well.

Opportunity for Collaboration Between Radiation Injury Treatment Network Centers and Medical Toxicology Specialists

Objectives The Radiation Injury Treatment Network (RITN) comprises >50 centers across the United States that are poised to care for victims of a radiation emergency. The network is organized around bone marrow transplant centers because these facilities excel in both radiation medicine and the care of patients with severe bone marrow depression. A radiation emergency may cause not only irradiation from an external source but also internal contamination with radioactive material. Because medical toxicologists are trained in radiation injury management and have expertise in the management of internal contamination, RITN centers may benefit from partnerships with medical toxicology resources, which may be located at academic medical centers, hospital inpatient clinical services, outpatient clinics, or poison control centers. Methods We determined the locations of existing RITN centers and assessed their proximity to various medical toxicology resources, including medical toxicology fellowship programs, inpatient toxicology services, outpatient toxicology clinics, and poison control centers. Data were derived from publicly available Internet sources in March 2015. Results The majority of RITN centers do not have a medical toxicology fellowship, an inpatient toxicology service, or an outpatient toxicology clinic within the same institution. Fifty-seven percent of RITN centers have at least one of these resources located in the same city, however, and 73% of centers have at least one of these resources or a poison control center within the same city. Ninety-five percent of RITN centers have at least one medical toxicology resource within the state. Conclusions Most RITN centers are located in the same city as at least one medical toxicology resource. Establishing relationships between RITN centers and medical toxicologists needs to be explored further.

Articles You Might Have Missed

Detoxification and counseling-only aftercare have been treatment mainstays for patients with opioid use disorder. Since long-term abstinence is rarely achieved, additional treatment with medication has been increasing. In the USA, buprenorphine-naloxone (BUP-NX) is the most commonly prescribed agent for medication-assisted opioid treatment. Naltrexone is similarly employed in patients diagnosed with an opioid use disorder. It is available in a long-acting, injectable form (XR-NTX); however, concerns surrounding induction limit its use to well selected individuals. A concurrent Norwegian study concluded that XR-NTX is noninferior to BUP-NX for preventing short-term relapse to opioid use.

Utility of QT interval corrected by Rautaharju method to predict drug-induced torsade de pointes

Abstract Introduction: New QT correction formulae derived from large populations are available such as Rautaharju’s [QTcRTH = QT * (120 + HR)/180] and Dmitrienko’s [QTcDMT = QT/RR0.413]. These formulae were derived from 57,595 and 13,039 cases, respectively. Recently, a study has shown that they did not experience errors across a wide range of heart rates compared to others. Objectives: (1) To determine the best cut-off value of QTcRTH and QTcDMT as a predictor of torsade de pointes (TdP) and (2) to compare the sensitivity and specificity using the cut-off value of QTcRTH with those of the QTcBazett (QTcBZT), QTcFridericia (QTcFRD), and QT nomogram. Methods: Data were derived from two data sets. All cases aged over 18 years with an exposure to QT-prolonging drugs. Group-1, all cases developed TdP. Data in Group-1 were obtained from systematic review of reported cases from Medline since its establishment until 10 December 2015. Group-2 is composed of those who overdosed on QT prolonging drugs but did not develop TdP. This data set was previously extracted from a chart review of three medical centers from January 2008 to December 2010. Data from both groups were used to calculate QTcRTH and QTcDMT. The cut-off values from QTcRTH and QTcDMT that provided the best sensitivity and specificity to predict TdP were then selected. The same method was applied to find those values from QTcBZT, QTcFRD, and QT nomogram. The receiver operating characteristic curve (ROC) was applied where appropriate. Results: Group-1, 230 cases of drug-induced TdP were included from the systematic review of Medline. Group-2 (control group), which did not develop TdP, consisted of 292 cases. After applying all of the correction methods to the two datasets, the best cut-off values that provided the best accuracy (Ac) with the best sensitivity (Sn) and specificity (Sp) for each formula were as follows: QTcRTH at 477 milliseconds (ms), Ac = 89.08%, Sn = 91.30% (95%CI = 86.89–94.61), Sp = 87.33%(95%CI = 82.96–90.92); QTcDMT at 475 ms, Ac = 88.31%, Sn =91.30% (95%CI = 86.89–94.61), Sp = 85.96%(95%CI = 81.44–89.73); QTcBZT at 490 ms, Ac = 86.97%, Sn = 88.26% (95%CI = 83.38–92.12), Sp = 85.96% (95%CI = 81.44–89.73); QTcFRD at 473 ms, Ac = 88.89%, Sn = 89.13% (95%CI = 84.37–92.84), Sp =88.70% (95%CI = 84.50–92.09). We found a significant difference (p-value = 0.0020) between area under the ROC of the QTcRTH (0.9433) and QTcBZT (0.9225) but not QTcFRD (0.9338). The Ac, Sn, and Sp of the QT nomogram were 89.08%, 91.30% (95%CI = 86.89–94.61), and 87.33% (95%CI = 82.96–90.92), respectively, and they were all equal to those of QTcRTH. Conclusion: Rautaharju method not only produced minimal errors for QT interval correction but also at QTcRTH 477 ms, it could predict TdP as accurately as QT nomogram and was better than the QTcBZT.

Elderly Man With Dyspnea

A 65-year-old man with no cardiac history presented to the emergency department with dyspnea. Vitals signs were unstable and chest radiograph showed multifocal pneumonia. He was intubated and a left subclavian central line was placed for initiation of vasopressors. On chest radiograph to evaluate line placement, the catheter was noted to be coursing in the left chest without crossing to the right mediastinum (Figure 1). The ultrasonographic bubble test aided in identifying the location of the central line and allowing its immediate use (Figure 2; Video E1, available online at http://www. annemergmed.com).