Keywords: clonidine toxicity, high-dose naloxone (PubMed Search)
Clonidine, (central alpha-2 receptor agonist) can produce opioid-like toxidrome in addition to its cardiac effects (bradycardia and hypotension). Previous studies have shown that naloxone has variable (~40%) success in reversing CNS/respiratory depression and cardiac effect.
A recent retrospective study (n=51) of pediatric poisoning showed that administration of 5 to 10 mg had improved reversal of clonidine toxicity.
Total of 51 somnolent patients: 5- 10 mg of naloxone reversed 40 patients
There was no adverse effect from naloxone administration.
Repeat administration of naloxone was required in some patients.
Seger DL, Loden JK. Naloxone resersal of clonidine toxicity: dose, dose, dose. Clin Toxicol (Phila) 2018 Mar 16:1-7. doi: 10.1080/15563650.2018.1450986. [Epub ahead of print]
Keywords: adulterated synthetic cannabinoid, elevated INR, brodifacoum (PubMed Search)
In the past couple of weeks, there have been reports from Illinois about patients using adulterated synthetic cannabinoids, resulting in elevated INR and bleeding. To date, there are approximately 70 cases including 3 fatalities. Brodifacoum, a long-acting vitamin K mediated anticoagulant (similar to warfarin) has been identified in 10 cases. Brodifacoum is frequently used as rodenticide.
This week, Maryland Poison Center received our first notification of a patient with bleeding and elevated INR due to suspected adulterated synthetic cannabinoid use.
When evaluating our patient population:
Patient management of suspected cases:
Patient can be discharged when INR < 2 is achieved with oral vitamine K regimen only (without recent FFP infusion).
Review of published cases highlights that most patients are started on a median doses of 100 mg/day (range: 15 - 600 mg) and stabilize on a PO regimen of 50-100 mg/day. Prolonged PO vitamin K course of 2 – 3 months or longer should be anticipated.
Pease call the Maryland Poison Center at 1-800-222-1222 as we are working with the Maryland Department of Health and CDC to track these cases.
Gunja N, Coggins A, Bidny S. Management of intentional superwarfarin poisoning with long-term vitamin K and brodifacoum levels. Clinical Toxicology. 2011;49(5):385-390. doi:10.3109/15563650.2011.587126.
Keywords: nerve agents, organophosphate compounds (PubMed Search)
Recently, an ex-Russian spy and his daughter were poisoned in Salisbury, England using a Soviet nerve agent called Novichok. He joins a list of defectors and ex-spies who's poisoning have been connected to Russia.
Nerve agents are organophosphate compounds, similar to the commercially available pesticides, but significantly more potent. Nerve agents such as VX take seconds to minutes to irreversibly inhibit acetylcholinesterase by “aging” and result in clinical toxicity.
Signs and symptoms
Keywords: cyanide, signs and symptoms (PubMed Search)
Signs and symptoms of acute cyanide poisoning are not well characterized due to its rare occurrence. Commonly mentioned characteristics of bitter almond odor and cherry red skin have poor clinical utility.
Recently published review of 65 articles (102 patients) showed that most patients experienced following signs and symptoms:
There is no clear toxidrome for cyanide poisoning.
In a poisoned patient, health care providers should consider cyanide in their differential diagnosis in the presence of severe metabolic and lactic acidosis (lactic acid > 8 in isolated cyanide poisoning or > 10 in smoke/fire victim).
Parker-Cote JL et al. Challenges in the diagnosis of acute cyanide poisoning. Clin Toxicol 2018 Feb 8:1-9. doi: 10.1080/15563650.2018.1435886. [Epub ahead of print]
Keywords: nystagmus, toxic (PubMed Search)
Abnormal ocular movement (e.g. nystagmus) can often be observed in select CNS pathology.
Certain drugs/toxin overdose can also induce nystagmus.
In an "unknown" intoxication, physical exam findings such as nystagmus may help narrow the identity of the suspected ingestion/overdose.
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.