Setting Of Overdose Research Articles

Perioperative Hypoxia Secondary to Phenazopyridine-induced Methemoglobinemia in an Adolescent Patient Without Renal Insufficiency or Overdose: An Unusual Case

Phenazopyridine is a common, well-tolerated medication with minimal side effects. Severe side effects are rare and include methemoglobinemia in setting of overdose, elderly patients, renal insufficiency, and chronic use. Here, we report a case of methemoglobinemia-induced perioperative hypoxia in an adolescent patient without renal insufficiency or overdose which has not been reported previously. This case underscores the importance of judicious use of this medication in all patients but notably in pediatric patients and those with chronic lung disease.

Antidotes in Poisoning.

ABSTRACTIntroductionAntidotes are agents that negate the effect of a poison or toxin. Antidotes mediate its effect either by preventing the absorption of the toxin, by binding and neutralizing the poison, antagonizing its end-organ effect, or by inhibition of conversion of the toxin to more toxic metabolites. Antidote administration may not only result in the reduction of free or active toxin level, but also in the mitigation of end-organ effects of the toxin by mechanisms that include competitive inhibition, receptor blockade or direct antagonism of the toxin.Mechanism of action of antidotesReduction in free toxin level can be achieved by specific and non-specific agents that bind to the toxin. The most commonly used non-specific binding agent is activated charcoal. Specific binders include chelating agents, bioscavenger therapy and immunotherapy. In some situations, enhanced elimination can be achieved by urinary alkalization or hemadsorption. Competitive inhibition of enzymes (e.g. ethanol for methanol poisoning), enhancement of enzyme function (e.g. oximes for organophosphorus poisoning) and competitive receptor blockade (e.g. naloxone, flumazenil) are other mechanisms by which antidotes act. Drugs such as N-acetyl cysteine and sodium thiocyanate reduce the formation of toxic metabolites in paracetamol and cyanide poisoning respectively. Drugs such as atropine and magnesium are used to counteract the end-organ effects in organophosphorus poisoning. Vitamins such as vitamin K, folic acid and pyridoxine are used to antagonise the effects of warfarin, methotrexate and INH respectively in the setting of toxicity or overdose. This review provides an overview of the role of antidotes in poisoning.How to cite this articleChacko B, Peter JV. Antidotes in Poisoning. Indian J Crit Care Med 2019;23(Suppl 4):S241–S249.

A randomized usability assessment of simulated naloxone administration by community members.

Expanded access to naloxone has been identified as a key intervention for reducing opioid-related morbidity and mortality. It is not known which naloxone device will result in rapid, successful administration when administered by community members. The aims of this study were to estimate and compare (1) the rate of successful administration and (2) time to successful administration for single-step nasal spray, multi-step atomized nasal spray and intramuscular simulated naloxone by community members. A prospective, single-site, open-label, randomized usability assessment of simulated naloxone administration in a convenience sample of community members. Participants were randomized to single-step nasal spray (SP), multi-step atomized nasal spray (AT) or intramuscular simulated (IM) naloxone and asked to administer the simulated medication to a mannequin after completing a 2-minute training video. New York, USA at a state fair that attracts between 60 000 and 120 000 individuals daily. A total of 138 participants completed the study over a 2-day period in September 2016. All participants were at least 18years of age and had no prior naloxone training. The rate of successful administration and time to successful administration were recorded for each device. The SP device (100%; P<0.001) had a higher rate of success compared with the IM device (69.6%). Although success differed between the AT (89.1%) device and IM device, as well as the AT device and SP device, these differences were not significant. The SP device also had a shorter median time to successful administration (34.3sec) compared with the IM (99.9sec; P<0.001) and AT (110.3; P<0.001) devices. After video training, community members are able to (1) administer single-step nasal spray naloxone with a higher rate of success than intramuscular naloxone in a simulated overdose setting and (2) administer single-step nasal spray naloxone more rapidly than both intramuscular and multi-step atomized nasal spray naloxone.

Review of Biguanide (Metformin) Toxicity.

In the 1920s, guanidine, the active component of Galega officinalis, was shown to lower glucose levels and used to synthesize several antidiabetic compounds. Metformin (1,1 dimethylbiguanide) is the most well-known and currently the only marketed biguanide in the United States, United Kingdom, Canada, and Australia for the treatment of non-insulin-dependent diabetes mellitus. Although phenformin was removed from the US market in the 1970s, it is still available around the world and can be found in unregulated herbal supplements. Adverse events associated with therapeutic use of biguanides include gastrointestinal upset, vitamin B12 deficiency, and hemolytic anemia. Although the incidence is low, metformin toxicity can lead to hyperlactatemia and metabolic acidosis. Since metformin is predominantly eliminated from the body by the kidneys, toxicity can occur when metformin accumulates due to poor clearance from renal insufficiency or in the overdose setting. The dominant source of metabolic acidosis associated with hyperlactatemia in metformin toxicity is the rapid cytosolic adenosine triphosphate (ATP) turnover when complex I is inhibited and oxidative phosphorylation cannot adequately recycle the vast quantity of H+ from ATP hydrolysis. Although metabolic acidosis and hyperlactatemia are markers of metformin toxicity, the degree of hyperlactatemia and severity of acidemia have not been shown to be of prognostic value. Regardless of the etiology of toxicity, treatment should include supportive care and consideration for adjunct therapies such as gastrointestinal decontamination, glucose and insulin, alkalinization, extracorporeal techniques to reduce metformin body burden, and metabolic rescue.

Knowledge of the 911 Good Samaritan Law and 911-calling behavior of overdose witnesses

ABSTRACTBackground: Overdose deaths tripled between 1999 and 2014. Most fatal overdoses are witnessed, offering an opportunity for bystanders to call 911. However, fear of arrest may prevent them from calling authorities. Many states have passed 911 Good Samaritan laws that protects the 911 caller and overdose victim from prosecution for drug possession. Little is known, however, about whether the law affects 911-calling behavior of overdose witnesses. We investigated the relationship between knowledge of a 911 Good Samaritan Law (GSL) and 911-calling behavior of study participants trained in opioid overdose rescue. Methods: We enrolled 351 individuals (n = 351) trained in overdose rescue and educated about the New York State GSL in a prospective longitudinal study. Trained researchers conducted baseline, three, six and 12-month follow-up surveys with study participants to assess participant knowledge of the GSL and responses to witnessed overdoses. Results: At the twelve-month follow-up, participants had witnessed 326 overdoses. In the overdose events where the participant had correct knowledge of the GSL at the time of the event, the odds of a bystander calling 911 were over three times greater than when the witness had incorrect knowledge of the GSL (OR = 3.3, 95% CI, 1.4–7.5). This association remained significant after adjusting for age, gender, race of the witness and overdose setting (AOR = 3.6, 95% CI, 1.4–9.4). Conclusions: To our knowledge, this is the first study to show an association between knowledge of the GSL and 911-calling behavior. Legislation that protects overdose responders along with public awareness of the law may be an effective strategy to increase rates of 911-calling in response to overdose events and decrease overdose-related mortality.

Editors' Note

Editors' Note: In “Clinical Reasoning: A young woman with respiratory failure, hearing loss, and paraplegia,” Ntranos et al. discussed the case of a patient with lesions in the globus pallidi, spinal cord, and cochleae in the setting of opioid overdose and respiratory failure. They concluded that the patient's neurologic syndrome was related to hypoxia. Commenting on this article, Dr. Berg asks the authors whether they considered the possibility of methylmalonic acidemia (MMA) as a potential underlying susceptibility factor because the lesions on the patient's MRI in the globus pallidi are characteristic of MMA. He suggests testing the patient's urine for MMA and blood for B12 level. Dr. Ntranos confirms that they checked the methylmalonic acid serum level, which was undetectable. Commenting on the same article, Drs. Bhatt and Adams propose that the patient's cochlear injury is related directly to opiate toxicity rather than hypoxia. Ntranos et al. stand by their hypothesis, explaining that the patient referenced by Bhatt and Adams was using multiple toxic substances for which the composition is unknown and that the presence of opiate receptors in cochlear cells does not mean that their stimulation will cause neurotoxicity. They suggest that additional research is needed to determine the direct effect of opiate use in cochlear cells. —Chafic Karam, MD, and Robert C. Griggs, MD Editors' Note: In “Clinical Reasoning: A young woman with respiratory failure, hearing loss, and paraplegia,” Ntranos et al. discussed the case of a patient with lesions in the globus pallidi, spinal cord, and cochleae in the setting of opioid overdose and respiratory failure. They concluded that the patient's neurologic syndrome was related to hypoxia.

Bilateral blindness secondary to optic nerve ischemia from severe amlodipine overdose: a case report

BackgroundCalcium channel blockers are commonly prescribed medications; calcium channel blocker overdose is becoming increasingly prevalent. The typical presentation of a calcium channel blocker overdose is hypotension and decreased level of consciousness. We describe a case of a calcium channel blocker overdose that led to bilateral cortical blindness, a presentation that has not previously been reported.Case presentationA 49-year-old white woman with known bilateral early optic atrophy presented to our hospital with hypotension and obtundation following a known ingestion of 150 mg of amlodipine. She was transferred to our intensive care unit where she was intubated, mechanically ventilated, and required maximal vasopressor support (norepinephrine 40 mcg/minute, epinephrine 40 mcg/minute, and vasopressin 2.4 units/hour) along with intravenously administered crystalloid boluses. Despite these measures, she continued to deteriorate with persistent hypotension and tachycardia, as well as anuria.Intralipid emulsion therapy was subsequently administered to which no initial response was observed. A chest X-ray revealed diffuse pulmonary edema; intravenous diuresis as well as continuous renal replacement therapy was initiated.Following the initiation of continuous renal replacement therapy, her oxygen requirements as well as urine output began to improve, and 3 days later she was liberated from mechanical ventilation. Following extubation, she complained of new onset visual impairment, specifically seeing only red-green colors, but no objects. An ophthalmologic examination revealed that this was due to bilateral optic atrophy from prolonged hypotension during the first 24 hours after the overdose.ConclusionPersistent hypotension in the setting of a calcium channel blocker overdose can lead to worsening optic atrophy resulting in bilateral cortical blindness.

Survival Despite Severe Hyperthermia and Multi-Organ System Dysfunction Following Week-Long Use of an MDPV Containing "Stain Remover"

Synthetic amphetamine and cathinone analogs are sympathomimetic hallucinogens that can cause significant toxicity. Hyperthermia in the setting of sympathomimetic overdose is typically associated with a high mortality. We report a case of neurologically intact survival after extreme hyperthermia in the setting of a sympathomimetic overdose. A 29 year-old male ingested a methylenedioxypyrovalerone "stain remover" and exhibited excited delirium and severe sympathomimetic effects. Multi-organ system toxicity included severe hyperthermia, acidosis, hypoglycemia, intracranial hemorrhage, status epilepticus, myocardial infarction, hypotension, rhabdomyolysis, acute renal failure, acute hepatic injury, and coagulopathy. With aggressive cooling, intravenous fluids, benzodiazepine use, peripheral vasopressors, and hemodialysis, he had a good neurologic outcome at the time of discharge after a 17-day hospital course. Despite a high mortality rate with severe hyperthermia, this case suggests that patients with toxin-induced multi-system organ dysfunctionand associated hyperthermia may recover with early aggressive supportive care.

Wait a minute: Not all cases of paracetamol overdose need N-acetylcysteine, quality improvement project in Hamad General Hospital Emergency Department

Background: Management of serious paracetamol overdose with N-acetylcysteine (NAC) is an effective strategy. Early treatment with NAC prevents the formation of a toxic metabolite that leads to hepatic injury. However, inappropriate treatment with NAC and overtreatment with NAC can lead to potential adverse side effects and unnecessary hospital admission. The aim of the study was to assess the administration of NAC in the setting of paracetamol overdose and determine whether the institutional use of this antidote is consistent with the international standards. We hypothesize that some patients receive antidotal NAC unnecessarily after paracetamol exposure, and that a simple quality improvement intervention in educational activity may improve the administration of this antidote. Methods: A retrospective quality improvement chart review evaluated charts of patients who were treated with NAC for paracetamol exposure over a 2-month period in the Emergency Department of Hamad General Hospital. The quality improvement intervention consisted of establishing a paracetamol clinical practice guideline, providing access to a treatment nomogram for NAC use, enhancing educational activities to improve the clinician's understanding of appropriate NAC use, and establishing a clinical toxicology service for all paracetamol exposures. Results: NAC administration to 67% of the cases after paracetamol exposure were found to be medically unnecessary according to the established international guidelines for management of paracetamol overdose. Post-intervention measurement showed significant improvement by decreasing unnecessary NAC administration to only 33%. Conclusion: In our institution, NAC treatment after paracetamol exposure is usually administered unnecessarily. Inappropriate administration of this antidote results in a significant waste of resources and unnecessarily prolonged hospital stay. Adherence to the clinical practice guidelines may lead to a significant improvement in this antidote use after paracetamol exposure. Given that this antidote is used inappropriately despite widespread knowledge that guidelines for paracetamol exposure exist, we believe that continuous education on the topic, chart audits and feedback, and use of a clinical toxicology service may improve the knowledge and appropriate use of this antidote and will improve patient care.

Use and knowledge of single dose activated charcoal: A survey of Australian doctors.

The use of single dose activated charcoal (SDAC) as a means of gastric decontamination is declining. The present study examined the potential use of SDAC in common overdose scenarios by Australian emergency doctors, compared with clinical toxicologists and current guidelines. We conducted a cross-sectional survey of emergency doctors and toxicologists on the use of SDAC. The survey covered demographic data, education and previous use of SDAC and six clinical scenarios. The scenarios selected included agents not bound to SDAC, sustained-release preparations and ingestions at varying time points. Statistical calculations were performed using Fisher's exact test. There were 397 emergency doctors and 20 toxicologists who responded to the survey. Seventy-one per cent (n=280/397) of emergency doctors indicated they had received some education on decontamination. Eighty-three per cent (n=331/397) had administered SDAC during their medical career, 29% (n=117/397) within the past year. There was a significant difference in responses between emergency doctors and toxicologists in two scenarios; a toxic paracetamol ingestion presenting within 1 h (P=0.009) and verapamil ingestion in a 3 year old boy (P=0.001). Toxicologists were more likely to administer SDAC in these scenarios, 89% (n=16/18) and 88% (n=15/17), respectively, compared with 52% (n=197/381) and 43% (n=158/371) of emergency doctors. Our study showed that there is a significant variation in the use of SDAC between toxicologists and emergency doctors in some scenarios. Clinical toxicologists are more likely to administer SDAC in certain overdose settings. It is essential to provide education on the benefits versus actual risks of SDAC in acute poisoning so that doctors will understand when to administer SDAC or seek further advice.

Factors influencing naproxen metabolite interference in total bilirubin assays

BackgroundThe factors influencing naproxen metabolite O-desmethylnaproxen (ODMN) positive interference in diazo-based Jendrassik and Grof (JG) total bilirubin (Tbil) assays and lack of interference in direct bilirubin (Dbil) assays have not been resolved. The objective of this study was to understand the conditions causing this interference pattern. MethodsPooled normal and ultra-filtered plasma samples spiked with ODMN and naproxen were measured on the Beckman Coulter DxC and AU instruments. Absorbance spectra were obtained for ODMN mixed with Dbil reagent at original and adjusted pH. Absorbance spectra were also obtained for ODMN and bilirubin samples mixed with Tbil assay reagents. ResultsODMN produces a positive interference in the DxC JG Tbil assays, but not the AU Tbil or Dbil assays or the DxC Dbil assay. Neutralizing the acidic pH of AU and DxC Dbil reagents allows ODMN to react with diazo salts. ODMN samples mixed with DxC and AU Tbil reagents produce broad peaks from 450 to 560nm and 400 to 540nm, respectively. The DxC JG Tbil assay monitors a change in absorbance at 520nm close to peak absorbance wavelength of diazo-reacted ODMN, whereas the AU Tbil assay monitors a change in absorbance at 570/660nm, beyond the peak absorbance wavelengths of diazo-reacted ODMN. ConclusionThe acidic pH of diazo-based Dbil assay reagents inhibits the reaction of ODMN with diazo salts. The AU JG Tbil assay is a reliable method to measure Tbil in the setting of naproxen overdose.

Outcomes of patients resuscitated from cardiac arrest in the setting of drug overdose

ObjectivesTo compare the attributes and clinical outcomes of patients with cardiac arrest in the setting of drug overdose (OD) to patients with cardiac arrest from non-drug related etiologies. MethodsWe utilized a US inpatient cardiac arrest registry used to study targeted temperature management (TTM) to identify patients with cardiac arrest in the setting of drug overdose between 2005 and 2013. Data regarding the cardiac arrest, resuscitation interventions, use of post-arrest TTM, urine drug screen, survival, and neurologic outcome were examined. These results were compared to patients suffering cardiac arrest from other causes during the same time period using Wilcoxon rank-sum tests for continuous variables and chi-square tests on categorical variables. ResultsApproximately 2.5% (64/2584) of cardiac arrests occurred in the setting of drug overdose. Patients in the OD cohort were younger, more likely to be male, and more likely to have an out-of-hospital cardiac arrest that was unwitnessed with no bystander CPR and from a non-shockable rhythm. However, the patients in the OD cohort had similar rates of survival and good neurologic outcomes (Cerebral Performance Category 1–2) compared to non-OD patients. A fraction of initially resuscitated patients in each group (8% in OD cohort vs. 15% in non-OD cohort, p=ns) did not receive post-arrest TTM due to prompt awakening following resuscitation. ConclusionsPatients resuscitated from cardiac arrest in the setting of drug OD have neurologic and survival outcomes comparable to non-OD patients despite lower rates of bystander CPR, shockable rhythms, and witnessed arrest.

Extracorporeal treatment for valproic acid poisoning: Systematic review and recommendations from the EXTRIP workgroup

Background. The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup presents its systematic review and clinical recommendations on the use of extracorporeal treatment (ECTR) in valproic acid (VPA) poisoning. Methods. The lead authors reviewed all of the articles from a systematic literature search, extracted the data, summarized the key findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote was conducted to determine the final workgroup recommendations. Results. The latest literature search conducted in November 2014 retrieved a total of 79 articles for final qualitative analysis, including one observational study, one uncontrolled cohort study with aggregate analysis, 70 case reports and case series, and 7 pharmacokinetic studies, yielding a very low quality of evidence for all recommendations. Clinical data were reported for 82 overdose patients while pharmaco/toxicokinetic grading was performed in 55 patients. The workgroup concluded that VPA is moderately dialyzable (level of evidence = B) and made the following recommendations: ECTR is recommended in severe VPA poisoning (1D); recommendations for ECTR include a VPA concentration > 1300 mg/L (9000 μmol/L)(1D), the presence of cerebral edema (1D) or shock (1D); suggestions for ECTR include a VPA concentration > 900 mg/L (6250 μmol/L)(2D), coma or respiratory depression requiring mechanical ventilation (2D), acute hyperammonemia (2D), or pH ≤ 7.10 (2D). Cessation of ECTR is indicated when clinical improvement is apparent (1D) or the serum VPA concentration is between 50 and 100 mg/L (350–700 μmol/L)(2D). Intermittent hemodialysis is the preferred ECTR in VPA poisoning (1D). If hemodialysis is not available, then intermittent hemoperfusion (1D) or continuous renal replacement therapy (2D) is an acceptable alternative. Conclusions. VPA is moderately dialyzable in the setting of overdose. ECTR is indicated for VPA poisoning if at least one of the above criteria is present. Intermittent hemodialysis is the preferred ECTR modality in VPA poisoning.

A Child With Acute Liver and Kidney Failure Ongoing Encephalopathy: Effectiveness of Plasmapheresis on Acetaminophen Overdose, A Case Report

Acetaminophen (APAP) is a commonly used analgesic and antypiretic medication. APAP -induced liver necrosis has been studied extensively, but extrahepatic manifestations of APAP toxicity are not described well in the literature. Adolescents and young adults may be more prone to renal insufficiency in the setting of APAP overdose; however, the reason for this finding is unclear. Here we report therapeutic misadventure of APAP-associated acute renal and liver failure and effectiveness of plasmapheresis on hepatic encephalopathy. Int J Clin Pediatr. 2014;3(2):63-65 doi: http://dx.doi.org/10.14740/ijcp143w

Unintentional opioid overdose deaths in New York City, 2005–2010: A place-based approach to reduce risk

BackgroundDrug poisoning is the leading cause of death from injuries in the United States. In New York City (NYC), unintentional drug poisoning death is the third leading cause of premature death, and opioids are the most commonly occurring class of drugs. Opioid overdose prevention efforts aim to decrease the number of people at risk for overdose and to decrease fatality rates among those using opioids by improving overdose response. These strategies can be enhanced with a comprehensive understanding of the settings in which overdoses occur. MethodsA cross-sectional analysis of unintentional opioid poisoning deaths in NYC from 2005 to 2010 (n=2649). Bivariate and multivariate analyses were performed to identify factors associated with settings of fatal opioid overdose. ResultsThree-quarters of the sample overdosed in a home; one-tenth in an institution, and the remaining in a public indoor setting, the outdoors or another non-home setting. Factors associated with overdosing at home include female gender, college degree, residence in the borough of Staten Island, and combined use of opioid analgesics and benzodiazepines. Factors associated with overdosing outside of the home include ages 35–64, residence in Manhattan, and use of heroin. ConclusionThe sample represents a near census of unintentional opioid overdose deaths in NYC during the study period, and allows for the identification of demographic and drug-using patterns by setting of overdose. Because most opioid overdoses occur inside the home, opioid overdose response programs can most efficiently address the epidemic by both reducing the risk of overdose in the home and targeting those who may be in the home at the time of an overdose for overdose response training. Approaches include minimizing risk of misuse and diversion through safe storage and safe disposal programs, physician education on prescribing of opioid analgesics and benzodiazepines, prescription of take-home naloxone, and Good Samaritan laws.

Escitalopram and QTc prolongation

One should not conclude from the discussion by Lam1 that escitalopram is free of cardiac risks. Citalopram and escitalopram differ marginally in terms of their risk of prolonging the QTc interval sufficient to link to torsade de pointes (TdP). Citalopram and escitalopram each demonstrate a dose-dependent QTc prolongation.1 Although the magnitude of QTc prolongation appears to be greater for citalopram than escitalopram, the dose–QTc correlation is similar for both drugs. While the U.S. Food and Drug Administration and Health Canada issued warnings only for citalopram, the Medicines and Healthcare Products Regulatory Agency in the United Kingdom issued safety warnings for both citalopram and escitalopram.2 The threshold for clinical significance of the QTc interval is an absolute duration of 500 ms or longer or a change from baseline of 60 ms or more.3 The warnings did not specify whether any participants enrolled in the thorough QTc studies exceeded these thresholds for either drug. About 500 escitalopram overdoses and nearly 600 citalopram overdoses have been described, without serious cardiac sequelae or deaths due to either drug.4 Less than one-third of patients with citalopram overdoses presented with QTc interval prolongation. In 1 study, 14% of patients with escitalopram overdoses presented with QTc interval prolongation. In another study, the proportion of prolonged QTc intervals associated with escitalopram overdoses (1.7%) was not significantly different from that associated with citalopram overdoses (3.7%). These studies preclude a definitive assessment of the relative cardiotoxicity of citalopram versus escitalopram, but they do not demonstrate clinically meaningful differences in cardiotoxic effects. The mechanisms underlying drug-associated QTc interval prolongation are not well understood. Drug dosage is only 1 of several factors that increase the risk of QTc interval prolongation. In this regard it is notable that fewer than one-third of overdoses with citalopram or escitalopram are associated with QTc prolongation. If dose were a major factor with these drugs, you might expect that most overdoses would be associated with QTc prolongation. In our review,5 QTc interval prolongation or TdP due to citalopram occurred in the setting of citalopram overdose and/or in the presence of well-established risk factors, including advanced age, existing cardiac illness, multiple medical illnesses, electrolyte disturbances (hypokalemia, hypomagnesaemia) and concomitant use of QTc-prolonging drugs. These and other risk factors (baseline prolonged QTc, metabolic inhibition from other drugs, and hepatic impairment) have been emphasized in the regulatory warnings and would be particularly important for drugs like citalopram and escitalopram that prolong QTc interval marginally. Physicians should be mindful of these risk factors when prescribing these medications.

Lipid Rescue 911: Are Poison Centers Recommending Intravenous Fat Emulsion Therapy for Severe Poisoning?

Intravenous fat emulsion (IFE) therapy is a novel treatment that has been used to reverse the acute toxicity of some xenobiotics with varied success. We sought to determine how US Poison Control Centers (PCCs) have incorporated IFE as a treatment strategy for poisoning. A closed-format multiple-choice survey instrument was developed, piloted, revised, and then sent electronically to every medical director of an accredited US PCC in March 2011. Addresses were obtained from the American Association of Poison Control Centers listserv, and participation was voluntary and remained anonymous. Data were analyzed using descriptive statistics. The majority of PCC medical directors completed the survey (45 out of 57; 79 %). Of the 45 respondents, all felt that IFE therapy played a role in the acute overdose setting. Most PCCs (30 out of 45; 67 %) have a protocol for IFE therapy. In a scenario with "cardiac arrest" due to a single xenobiotic, directors stated that their center would "always" or "often" recommend IFE after overdose of bupivacaine (43 out of 45; 96 %), verapamil (36 out of 45; 80 %), amitriptyline (31 out of 45; 69 %), or an unknown xenobiotic (12 out of 45; 27 %). In a scenario with "shock" due to a single xenobiotic, directors stated that their PCC would "always" or "often" recommend IFE after overdose of bupivacaine (40 out of 45; 89 %), verapamil (28 out of 45; 62 %), amitriptyline (25 out of 45; 56 %), or an unknown xenobiotic (8 out of 45; 18 %). IFE therapy is being recommended by US PCCs; protocols and dosing regimens are nearly uniform. Most directors feel that IFE is safe but are more likely to recommend IFE in patients with cardiac arrest than in patients with severe hemodynamic compromise.

Treatment of Bleeding Complications When Using Oral Anticoagulants for Prevention of Strokes

Major bleeding in patients taking oral anticoagulants for stroke prevention can progress to catastrophic bleeding if it is not controlled. This is especially of concern if the bleeding is related to the use of a novel oral anticoagulant (NOAC) such as dabigatran or rivaroxaban, given the dearth of literature addressing the reversal of their anticoagulant effects. The goal of treatment is to prevent progression to catastrophic hemorrhage or exsanguination, and decrease bleeding-related morbidity and mortality. Clinical decisions in such instances should be made in a timely fashion to address the necessity for intervention. Animal models have shown potential for the use of 'fresh frozen plasma (FFP) or prothrombin complex concentrate (PCC) in reversing bleeding related to novel oral anticoagulants. However, there is paucity of clinical trials assessing the efficacy of these agents in humans in such clinical scenarios. Hence, there are no guidelines or ideal agents to use in such a scenario. We do not recommend the use of FFP for bleeding related to NOACs. In the setting of early overdose of dabigatran (within 3-4hours), activated charcoal may be given, and hemodialysis may be used if there is evidence of critical organ bleeding. In our opinion, 4-factor PCC or 3-factor PCC at a dose of about 50U/kg may be given in an emergency setting to manage bleeding related to factor Xa inhibitors such as rivaroxaban or apixaban, but not direct thrombin inhibitors such as dabigatran. We are also of the opinion that aPCC (FEIBA®) would not be helpful for management of direct thrombin inhibitor (dabigatran)-related bleeding, based on current available efficacy data in humans. We reserve the use of Novoseven® as a last resort, given the lack of pre-clinical or clinical data supporting its ability to reverse the anticoagulant effects of NOACs, except in one case report where it was used in combination with hemodialysis.

An Acute Ibuprofen Overdose Masking a SevereStaphylococcus aureusMeningitis: A Case Report

Acute bacterial meningitis has a low incidence (3/100,000 in the United States) and yet high fatality rate (approximately 14–16%) and classically presents as a triad of fever, neck stiffness, and altered mental status. However, less than half of patients with meningitis present with this classic triad. We present the clinical course of a patient who initially presented to the emergency department after overdosing on ibuprofen for what he described as back pain secondary to mechanical injury. However, the patient's condition quickly deteriorated: he developed tachycardia, mental status changes, was intubated due to respiratory distress, and then suffered an 8-minute PEA arrest before return of spontaneous circulation was achieved. After the patient was stabilized, in addition to the nonsteroidal anti-inflammatory drug (NSAID) overdose Staphylococcus aureus meningitis, bacteremia, and pneumonia were diagnosed. We report this case to illustrate that the initial presentation of meningitis may be extremely unusual especially in the setting of NSAID overdose and the acutely decompensating patient. As the risk of adverse clinical outcomes increases with delays in appropriate antibiotic therapy, it is therefore crucial to recognize the many signs and symptoms of meningitis, typical and atypical, and quickly begin appropriate treatment.

Adverse Effects of Dabigatran

Letters18 December 2012Adverse Effects of DabigatranRyan P. Radecki, MDRyan P. Radecki, MDFrom The University of Texas Health Science Center at Houston, Houston, TX 77030.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-12-201212180-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:I thank Dr. Pazmiño for his insightful perspective about the contribution of renal insufficiency to the enhanced anticoagulant effect of dabigatran. Despite the favorable safety profile of dabigatran compared with that of warfarin shown in the RE-LY trial (1), exclusion of patients with impaired glomerular filtration rates reduces the external validity of the findings of the RE-LY investigators. This demonstrates a familiar principle in medical practice about observed discrepancies between efficacy in controlled trials and effectiveness in clinical practice.Although I agree with the theoretical utility of hemodialysis in the setting of dabigatran overdose, this reversal strategy will ...