Keywords: activated charcoal, large acetaminophen overdose, NAC dose (PubMed Search)
Acetaminophen (APAP) overdose is the leading cause of liver failure in the U.S. and Europe. Large APAP ingestion can result in hepatotoxicity despite the early initiation of n-acetylcysteine (NAC).
A recently published study from Austrialia investigated the effect of activate charcoal and increasing the NAC dose for large APAP overdose patients (3rd bag: 100 to 200 mg/kg over 16 hours) during first 21 hours of NAC therapy
acetaminophen ratio (first APAP level taken between 4 to 16 hour post ingestion / APAP level on the Rumack nomogram line at that time point) was determined to compare APAP levels at different time points among study sample
first APAP level at 4 hour post ingestion = 400
APAP level on the Rumack APAP nomogram at 4 hour post ingestion = 150
APAP ratio = 400/150 = 2.67
Note: Any increase in NAC dosing from the standard 21 hour therapy should be performed after consulting your regional poison center.
Chiew AL et al. Massive paracetamol overdose: an obsevational study of the effect of activated charcoal and increased acetylcysteine dose (ATOM-2). Clin Toxicol 2017;55:1055-1065. PMID: 28644687.
Keywords: green urine (PubMed Search)
Different chemical, food or pharmaceutical agent exposure can change the color of the urine.
What could cause this patient's urine to turn green?
Green or greenish-blue color urine can result from exposure to follow substances:
The picture came from a patient who received methylene blue after being diagnosed with methemoglobinemia (65%).
Keywords: cardioactive steroids, cardioactive glycoside (PubMed Search)
Many medications are discovered from plants (quinine – cinchona trees) or organisms (penicillin – mold [penicillicum]).
Digoxin was isolated from foxglove (Digitalis lanata), a colorful floral plant often found in many gardens. There are other sources of cardioactive steroids (aka cardiac glycosides) that have similar effect as digoxin.
Non-digoxin cardioactive steroid exposure can result in a positive digoxin level due to cross reactivity. This confirms exposure; however, the “digoxin level” does not represent the true extent of the ingested dose or toxicity.
Non-digoxin cardioactive steroid toxicity
Keywords: strychnine (PubMed Search)
Her first book “The mysterious affair at Styles,” Agatha Christie introduced her lead detective in her novels, Hercule Poirot - the Belgian detective. She also described the death of Mrs. Emily Inglethorp by strychnine.
Strychnine is found in a disc-like seed of strychnos nux-vomica, a tree native to tropical Asia and North Australia.
It is currently used as rodenticide (moles and gophers), in Chinese herbal medicine and a traditional remedy in Cambodia.
Strychnine inhibits binding of glycine (a major inhibitory neurotransmitter in spinal cord) to Cl-channel resulting in identical clinical syndrome – seizure-like generalized muscle contraction with normal mental status – as tetanus toxin. Tetanus toxin inhibits the release of presynaptic glycine in the spinal cord.
Goal: decrease muscle hyperactivity
Keywords: Arsenic poisoning (PubMed Search)
Agatha Christie is an English crime novelist who frequently used poisons in her books to murder the victims. In her book, Murder is Easy, Ms. Christie uses arsenic/arsenic trioxide to kill several characters.
Primary source of arsenic in general population is contaminated food, water and soil. Arsenic exists in several forms: elemental, gaseous (arsine), organic and inorganic (trivalent or pentavalent).
Arsenic trioxide has also been used to treat acute promyelocytic leukemia in China; it’s use in other leukemia, lymphoma, and other solid tumors are currently being investigated.
Arsenic primarily inhibits the pyruvate dehydrogenase complex and multiple other enzymes involved in the citric cycle/oxidative phosphorylation, resulting in mitochondrial dysfunction.
Acute toxicity of arsenic after ingestion
Keywords: SGLT2 inhibitors, diabetes (PubMed Search)
During the past several years, several new classes of diabetic medications were introduced for clinical use, including SGLT2 inhibitors (canagliflozin, dapagliflozin and empagliflozin).
SGLT2 inhibitors prevent reabsorption of glucose in the proximal convoluted tubules in the kidney and does not alter insulin release.
A recent retrospective study (n=88) of 13 poison center data from January 2013 to December 2016 showed
49 patients were evaluated in a health care facility (HCF) with 18 admissions. Referral to HCF was more common in pediatric patients. This was likely due to unfamiliarity with a new mediation and lack of toxicity data.
Other case reports have shown higher incidence of DKA with the therapeutic use of SGLT2 vs. other classes of DM medications.
Limit data is available regarding the toxicologic profile of SGLT2 inhibitors.
Based upon this small retrospective study, hypoglycemia may not occur and majority of the patient experience minimal symptoms.
Schaeffer SE et al. Retrospective review of SGLT2 inhibitor exposures reported to 13 poison center. Clin Toxicol (Phila).2017 Aug 16:1-5 PMID: 28812381
Burke KR et al. SGLT2 inhibitors: a systematic review of diabetic ketoacidosis and related risk factors in the primary literature. Pharmacothearpy. 2017;37:187-194
Keywords: fentanyl, first responder exposure (PubMed Search)
There have been reports of “intoxication” or adverse effects among first responders and law enforcement due to exposure to a “powder” suspected to be fentanyl or its analog.
This has led to a significant concern among first responders and law enforcement when investigating or handling “powder” at the scene of overdose or drug enforcement related raids. (http://www.foxnews.com/health/2017/08/15/police-department-gets-hazmat-like-protective-gear-for-overdose-calls.html)
American College of Medical Toxicology and American Association of Clinical Toxicology recently published a position statement to help clarify the potential health risk associated with exposure to fentanyl and its analogs.
Keywords: dabigatran reversal, Idarucizumab (PubMed Search)
Full cohort analysis idarucizumab for dabigatran associated bleeding was recently published in NEJM.
This study evaluated the laboratory correction of elevated ecarin clotting time or diluted thrombin time induced by dabigatran and time to either cessation of bleeding (Group A: patients with GI bleeding, traumatic bleeding, or ICH) or time to surgery (Group B: patients requiring surgical intervention within 8 hours).
Group A (n=301): Median time to the cessation of bleeding was 2.5 hours in 134 patients.
Group B (n=202): Median time to intended surgery after infusion of idarucizumab was 1.6 hours.
100% reversal of abnormal ecarin clotting time or diluted thrombin time within 4 hours after the administration
Authors concluded thate idaurcizumab is an "effective" reversal agent for dabigatran.
Overall, the findings are more promising compared to the interim analysis that was published in 2015.
Infusion of idarucizumab decreased the dabigatran level from 110 ng/mL (Group A) and 73.6 ng/mL (Group B) to < 20 ng/mL.
Rebound levels of > 20 ng/mL were noted in 191 patients after 12 – 24 hours after idarucizumab adminiatration
Thrombotic events occured in 24 patients (14 in Group A and 10 in Group B) within 30 days after treatment
Serious adverse events occured in 23.3% of the patients within 5 days.
Most frequent events were:
Pollack CV et al. Idarucizumab for dabigatran reversal - full cohort analysis. N Eng J Med 2017;377:431-41.
Keywords: salicylate poisoning, endotracheal intubation, hemodialysis (PubMed Search)
Patients with severe salicylate poisoning may require endotracheal intubation due to fatigue from hyperventilation or mental status change.
A previously published study (Stolbach et al. 2008) showed that mechanical ventilation increases the risk of acidemia and clinical deterioration.
A small retrospective study investigated the impact of hemodialysis (HD) in intubated patients with salicylate poisoning.
53 cases with overall survival rate of 73.2%
In patients with salicylate level > 50 mg/dL
If salicylate level > 80 mg/dL
There is moratality benefit of HD in intubated salicylate-poisoned patient.
McCabe DJ, Lu JJ. The association of hemodialysis and survival in intuated salicylate-poisoned patients. Amer J Emerg Med 2017;35:899-903.
Stolbach QI, Hoffman RS, Nelson LS. Mechanical ventilation was associated with acidemia in a case series of salicylate-poisoned patients. Acad Emerge Med 2008;15;866-869.
Keywords: hydrogen peroxide (PubMed Search)
Hydrogen peroxide (H2O2) is a common household liquid that is used for wound irrigation/antiseptic and cosmetic purposes. The concentration of household product is 3% to 5% and is considered to be relatively safe except in large volume ingestion.
High-concentration H2O2 (>10%) is commercially available as “food grade” (35%) that is diluted for household use or for alternative medicine therapy (i.e. hyperoxygenation).
Ingestion of high-concentration of H2O2 can result in caustic injury as well as ischemic injury from gas embolism.
Ingestion of 1 mL of 3% H2O2 produces 10 mL of O2 gas while 1 mL of 35% H2O2 produces 115 mL of O2 gas.
Common symptoms/findings of H2O2 ingestions includes:
A retrospective review of >10% H2O2 ingestion from National Poison Data System showed:
Hatten BW et al. Outcomes after high-concentration peroxide ingestions. Ann Emerg Med. 2017;69:726-736.
Keywords: drugs of abuse, street name (PubMed Search)
Street names for illicit substance are diverse and unique. Knowing what your patient used prior to ED presentation can help with the management of their intoxication.
DEA recently released 7 page list of common street names for drugs of abuse.
But keep in mind that what our patients purchase and use may not actually contain the drug that they intended to purchase (e.g. fentanyl being sold as heroin).
Keywords: foodborne botulism (PubMed Search)
Botulism is a rare neurologic condition characterized by GI symptoms that progressed to cranial nerve dysfunction and symmetric descending paralysis. Foodborne botulism is due to ingestion of botulinum toxin that is produced by clostridium botulinum, an ubiquitous bacterium in our environment.
Maryland Department of Health and Mental Hygiene
CDC Emergency Operations Center: 770-488-7100
Foodborne botulism is characterized by
Keywords: lactic acidosis (PubMed Search)
Lactic acids are often elevated in critical care patients (e.g. septic shock). It can be also elevated in setting of drug overdose or less frequently in therapeutic use due to interference of oxidative phosphorylation. Some of the agents include:
Kraut JA, Madias NE. Lactic acidosis, N Engl J Med 2014;371:2309-19.
Keywords: sodium bicarbonate, sodium acetate (PubMed Search)
FDA announced a shortage of sodium bicarbonate on 3/01/17. Sodium bicarbonate is frequently used in acid-base disorder as well as in poisoning (cardiac toxicity from Na-channel blockade, e.g. TCA & bupropion, and salicylate poisoning).
Acetate is a conjugate base of acetic acid where acetate anion forms acetyl CoA and enters Kreb cycle after IV administration. Final metabolic products of acetate are CO2 and H2O, which are in equilibrium with bicarbonate via carbonic anhydrase activity.
Administration of sodium acetate increases the strong ion difference by net increase in cations, as acetate is metabolize, and leads to alkalemia.
Adverse events from sodium acetate infusion have been associated with its use as dialysate buffer: myocardial depression, hypotension, hypopnea leading to hypoxemia and hyperpyrexia. However, such adverse events have not been reported in toxicologic application.
Sodium acetate can be administered safely in place of sodium bicarbonate if sodium bicarbonate is not available due to shortage.
Sodium acetate dose:
Neavyn MJ, Boyer EW, Bird SB, et al. Sodium acetate as a replacement for sodium bicarbonate in medical toxicology: a review. J Med Toxicol 2013;9:250-254.
Keywords: adult clonidine overdose (PubMed Search)
Clinical signs and symptoms of clonidine overdose include CNS depression, bradycardia, and miosis. Other effects include early hypertension, followed by hypotension and respiratory depression, especially in children.
Although clonidine overdose in children is well described, frequency of clinical signs/symptoms in adults is not well characterized.
Recently, a retrospective study was performed in a hospital in Australia looking at clonidine overdose in adults.
Among isolated clonidine overdose, patients experienced:
Isbister GK et al. Adult clonidine overdose: prolonged bradycarida and central nervous system depression, but not severe toxicity. Clin Toxicol 2017;55:187-192.
Keywords: methadone overdose, hypoglycemia (PubMed Search)
Methadone overdose produces classic signs and symptoms of opioid intoxication - CNS and respiratory depression with pinpoint pupils. However, methadone overdose has also been associated with hypoglycemia – a relatively uncommon adverse effect.
Several case reports have been published over the past years. Recently, a case of refractory hypoglycemia was reported in a woman, without a history of diabetes, after ingesting 250 mL of methadone (18.2 mg/kg).
She required, in additional to naloxone infusion for respiratory depression, dextrose infusion (initially D10 then D20) for 54 hours.
Incidence of hypoglycemia has also been observed in patient with rapid methadone dose escalation as well as in cancer patient who were started on methadone for pain control with dose-depedent association.
In a mice study, methadone induced a dose dependent hypoglycemia - 20 mg/kg methadone resulted in decrease in average glucose level of 172 +/- 7 mg/dL to 55 +/- 6 mg/dL. This effect was reversed by naloxone administration. morphine, fentanyl, oxycodone and levorphanol did not produce hypoglycemia.
However, in the case report published in Clinical Toxicology Nov 2016, naloxone infusion did not effect the hypoglycemia.
Keywords: salicylate poisoning (PubMed Search)
A small retrospective study of an acute poisoning cohort attempted to identify risk factors for severe outcome in salicylate poisoning.
Severe outcomes were defined as
A multivariate analysis of 48 patients showed that older age and increased respiratory rate were independent predictors of severe outcomes when adjusted for salicylate level.
Initial salicylate acid level was not predictive of severe outcome.
Elevated lactic acid level was also a good predictor of severe outcome in univariate analysis but not in multivariate analysis.
Shively RM et al. Acute salicylate poisoning: risk factors for sever outcome. Clin Toxicol 2017 Jan 9:1-6. doi: 10.1080/15563650.2016.1271127. [Epub ahead of print]
Keywords: cyanide toxicity, lactic acid (PubMed Search)
Smoke inhalation victims (house fires) are at risk of carbon monoxide (CO) and cyanide poisoning (CN). CO exposure/poisoning can be readily evaluated by CO - Oximetry but CN level can be obtained in majority of the hospital.
Lactic acid level is often sent to evaluate for CN poisoning.
In a manuscript published in 1991, N Engl J Med by Dr. FJ Baud is the source of this data.
CN blood levels were measured in 109 residetial fire victims in France prior to any treatment was initiated.
Baud FJ et al. Elevated blood cyanide concentrations in victims of smoke inhalation. N Engl J Med 1991;325:1761-6.
Keywords: acetaminophen overdose, APAP levels (PubMed Search)
Recent study evaluated whether an acetaminophen (APAP) level obtained less than 4-hour post acute ingestion can predict which patient would not require n-acetylcysteine (NAC). APAP cutoff level of 100 ug/mL was used for analysis. This was a secondary analysis of the Canadian Acetaminophen Overdose Study database (retrospective study).
Table 2. Diagnostic accuracy of acetaminophen concentration obtained 2 to 4 hours post-ingestion to identify subsequent potentially toxic concentration measured 4 to 20 hours pos-ingestion.
Subsequent 4-hour equivalent [APAP]
[APAP] obtained 2 to 4 hours post-ingestion
< 150 ug/mL
Yarema MC, et al. Can a serum acetaminophen concentration obtained less than 4 hours post-ingestion determine which patients do not rquire treatment with acetylcysteine? Clin Toxicol 2016; online early: doi: 10.1080/15563650.2016.1247959
Keywords: heroin overdose, observation period, bystander naloxone (PubMed Search)
Recently a review paper was published regarding the duration of observation in heroin overdose patients who received naloxone.
It made several conclusions regarding heroin overdose:
It should be pointed out that this is a review paper of limited number of articles with variable quality. Additionally, the clinical history of “heroin use” may be unreliable as fentanyl and novel synthetic opioids are also sold as “heroin.” Providers should exercise appropriate clinical judgement when caring for these patients.
The paper attempted to answer following questions
Review conclusion (8 articles): Patients were safe to release if they had normal mentation and vital signs. Mortality from recurrent heroin toxicity was 0.13% - 0.49% within 24 to 48 hours after naloxone administration.
Review conclusion (5 articles): Wide range of observation period is reported. One study showed that 1-hour observation is sufficient when patients have normal ambulation, normal vital signs and GCS of 15 after 1-hour observation.
Review conclusion (15 articles): Rate of successful reversal ranged from 83% to 100% in the literature. Bystander and first responder naloxone administration is associated with minimum risk outside of mild opioid withdrawal symptoms.
The conclusion of this review paper only applies to heroin intoxication, a short-acting opioid. However, it can be difficult to discern clinically what type of opioid is causing the clinical toxicity as “heroin” may actually be other opioids such as fentanyl or other novel synthetic opioids (e.g. U-47700).