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: Pediatric poisoning, household , fatalities (PubMed Search)
Children less than 5 years of age account for the majority of poisoning exposures in the United States. As expected, accessible household items are the most frequently reported exposures and include cosmetics and personal care products, household cleaning substances, medications, and foreign bodies. Opioids are responsible for the highest incidence of hospitalizations followed by benzodiazepines, sulfonylureas, and cardiovascular drugs (beta & calcium channel blockers, and centrally acting antiadrenergic agents). Rise in buprenorphine use has led to significant increases in pediatric exposures. The most common sources of prescription medications were pills found on the ground, in a purse or bag, night stand, or pillbox. The 2015 American Association of Poison Centers Annual report lists 28 fatalities in children less than 5 year of age. Fatalities occurred from exposures to the following: narcotics (9), disc and button batteries (5), carbon monoxide (4), and other substances (10).
Highlighted AAPC cases include:
Poison prevention education of patients prescribed opioids or other highly toxic "one pill killers" who have young children in their household is recommended and could be potentially life saving.
2015 Annual Report of the American Association of Poison Centers' National Poison Data System: 33rd Annual Report. Mowrey JB, et al. Clinical Toxicology, 54:10.924-1109.
Emergency Hospitalizations for Unsupervised Prescription Medication Ingestions by Young Children, Lovegrove MC, et al. Pediatrics. 2014,134 (4) e1009-e1016 .
The Underrecognized Toll of Prescription Opioid Abuse on Young Children. Bailey JE, et al. Ann of Emerg Med. April 2009:53(4): 419-24. doi:10.1016/j.annemergmed.2008.07.015.Epub 2008 Sep 6.
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: Dilantin, Ataxia (PubMed Search)
Phenytoin is a first line anticonvulsant agent for most seizure disorders with the exception of absence and toxin-induced seizures. It has erratic gastrointestinal absorption with peak serum levels occurring anywhere from 3-12 hours following a single oral dose. 90% of circulating phenytoin is bound to albumin but only the unbound free fraction is active to cross cell membranes and exert pharmacological effect. Measured serum phenytoin levels reflect the total serum concentration of both the free and protein bound portions. Therapeutic range is between 10-20 mg/L. Free phenytoin levels are not often measured but are normally between 1-2 mg/L. Individuals with decreased protein binding (elderly, malnourished, hypoalbuminemia, uremia, and competing drugs) may have clincial toxicity despite a normal total phenytoin level. Toxicity consists of predominantly ocular and neurologic manifestations involving the vestibular and cerebellar systems:
|Plasma level, µg/mL||Clinical manifestations|
|10-20||Occasional mild nystagmus|
|30-40||Ataxia, slurred speech, extrapyramindal effects|
|>50||Coma, rare seizures|
Treatment of overdose is primarily supportive with serial drug level testing and neurologic exams. There is no evidence that gastrointestinal decontamination improves outcome. Routine cardiac monitoring is not necessary for overdose following oral ingestions. Cardiac toxicity is rarely seen and only with parenteral administration.
Phenytoin posisoning. Craig S. Neurocrit Care. 2005;3(2): 161-70.
Severe oral phenytoin overdose does not cause cardiovascular morbidity. Wyte CD, et al. Annals of EM. 1997; 20(5). 508-512.
Cardiac Monitoring after phenytoin overdose. Evers M, et al. Heart & Lung. 1997; 26:325-328.
Keywords: EDS, Excited Delirium (PubMed Search)
Excited delirium syndrome (EDS) is a life-threatening condition caused by a variety of factors including drug intoxication. EDS is defined as altered mental status, hyperadrenergic state, and combativeness or aggressiveness. It is characterized by tolerance to significant pain, tachypnea, diaphoresis, severe agitation, hyperthermia, non-compliance or poor awareness to direction from police or medical personnel, lack of fatigue, superhuman strength, and inappropriate clothing for the current environment. These patients are at high risk for sudden death. Toxins associated with this syndrome include:
Ketamine at 4mg/kg dose can be given by intramuscular route and has been demonstrated to be safe and effective treatment for EDS.
Top 10 Facts You Need to Know About Synthetic Cannabinoids: Not So Nice Spice Kemp, Ann M. et al. The American Journal of Medicine , Volume 129 , Issue 3 , 240 - 244.
Synthetic cannabinoid drug use as a cause or contributory cause of death. Labay, LM. et al. Forensic Science International , Volume 260 , 31 - 39.
Sudden Death Due To Acute Cocaine Toxicity—Excited Delirium in a Body Packer. Sheilds, LB, Rolf CM, et al. J Forensic Sci, 2015. 60: 1647–1651.
Excited Delirium and Sudden Death: A Syndromal Disorder at the Extreme End of the Neuropsychiatric Continuum. Mash, DC.Frontiers in Physiology. 2016; 7:435.
Prehospital Ketamine is a Safe and Effective Treatment for Excited Delirium in a Community Hospital Based EMS System, Scaggs, TR, Glass, DM, et al. Prehospital and Disaster Medicine. 2016 31(5), 563–569.
Keywords: Buprenorphine, Suboxone (PubMed Search)
The current opioid epidemic is considered the worst drug crisis in American history responsible for 50,000 deaths per year in the US from overdose of heroin and opioid prescription drugs. A 200% increase in the rate of overdose deaths involving opioids occurred between 2000 and 2014. The continued rise in opioid related deaths calls for an urgent need for treatment. Three types of medication-assisted therapies (MATs) are available for treating patients with opioid addiction:methadone, buprenorphine, and naltrexone. Suboxone a combination of buprenorphine and naloxone, is emerging as one of the best choices for the following reasons:
Rudd RA, Seth P, David F, Scholl L. Increase in Drug and Opioid-involved Overose Deaths -Unted States, 2010-2015. MMWR Morb Mortal Wkly Rep. ePub: 16 December 2016.
Jones HE. Practical Considerations for the Clinical Use of Buprenorphine. Science & Practice Perspectives. 2004;2(2):4-20.
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: Urine Drug Sreen (PubMed Search)
Urine drug screens are most commonly performed by immunoassay technology utilizing monoclonal antibodies that recognizes a structural feature of a drug or its metabolites. They are simple to perform. provide rapid screening, and qualitative results on up to 10 distinct drug classes with good sensitivity but imperfect specificity. This can lead to false positive results and the need for confirmatory testing. UDS does not detect synthetic opiates or cannabinoids, bath salts (synthetic cathinones), and gamma-hydroybutyrate. Most common drug classes detected are the following:
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: Lactic acidosis (PubMed Search)
Lactic acidosis is the most common cause of anion gap metabolic acidosis in all hospitalized patients. An elevated lactate level is an important marker of inadequate tissue perfusion causing subsequent shift to anaerobic metabolism and occuring in a variety of disease states such as sepsis. In patients with unexplained lactic acidosis without systemic hyoperfusion or seizure suspect the following toxins:
Understanding lactic acidosis in paracetamol (acetaminophen) poisoning. Shah, AD, Wood DM, et al. British Journal of Clinical Pharmacology 2011.71: 20–28.
Value of lactic acidosis in the assessment of the severity of acute cyanide poisoning. Baud FJ, et al. Crit Care Med. 2002;30(9):2044-50.
The Importance of the osmolality gap in ethylene glycol intoxication. Oostvogels R, et al. BMJ 2013 Dec 7;347:31-33.
Can Acute overdose metformin lead to lactic acidosis? Wilis BK, et al. Amer J Emerg Med. 2010;28:857.
Bench to bedside review: Severe lactic acidosis in HIV patients treated with nucleoside analogue reverse transcriptase inhibitors. Classens Y-E, et al. Critical Care. 2003;7(3):226-232.
A case of Kombucha Teas Toxicity. Kole A SH, Jones HD, et al. J Intensive care Med.2009:24(3) 205-7.
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, Liver Failure (PubMed Search)
Acetaminophen is one of the most common pharmaceutical ingestions in overdose and a leading cause of acute of liver failure in the U.S. Early recognition and treatment is critical for prevention of morbidity.
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: Drug Allergy, ADR, ADE (PubMed Search)
Misclassification of adverse drug effects as allergy is commonly encountered in clinical practice and can lead to use of suboptimal alternate medications which are often less effective.
DRUGS FREQUENTLY IMPLICATED IN ALLERGIC DRUG REACTIONS
Aspirin (other analgesics-antipyretics)
Iodinated contrast media
Understanding adverse drug reactions and drug allergies: principles, diagnosis and treatment aspects. Pourpak Z, et al. Recent Pat Inflamm Allergy Drug Discov. 2008 Jan;2(1):24-46.
Drug Allergy: An Updated Practice Parameter. Joint Task Force. Annals of Allergy, Asthma, & Immunology. Vol 105 ctober , 2010.
Antibiotic allergies in the medical record: effect on drug selection and assessment of validity. Lutomski,DM. Pharmacotherapy. 2008 Nov;28(11) 1348-53.
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).
Keywords: buprenorphine exposure, pediatrics, retrospective study (PubMed Search)
Recently, a retrospective study of unintentional buprenorphine/naloxone exposure among pediatric population was published. All patients were evaluated by toxicologists at the time of initial hospital presentation (or transfer) at the study center.
A retrospective study of single center/referral center’s toxicology consultation service.
88 patients were included. (median age: 24 months [range: 10 to 77 months]). Majority were transferred from other hospitals.
Sources of the medication were
The median hospital stay was 22 hours (7 - 248 hours).
Keywords: CCB poisoning (PubMed Search)
US, Canadian and European critical care and toxicology societies recently published a consensus recommendation is the management of CCB poisoning.
1. First line therapy remains unchanged: IV calcium, atropin, high-dose insulin (HIE) therapy, vasopressor support (norepinephrine and/or epinephrine).
2. Refractory to first line therapy: increase HIE, lipid-emulsion, transvenous pacemaker
3. Refractory shock, periarrest or cardiac arrest: Above (#1 & #2) plus ECMO if available.
Overall, there has not been a signficant changes to the current management of CCB poisoning. However, there is a nice flow chart of the algorithm/recommendation in the article. The authors note that the "level of evidenc was very low" for all intervention.
A. asymptomatic patients
B. First line therapy
C. Refractory to first line therapy
D. Refratory shock or periarrest
E. Cardiac arrest
St-Onge, M et al. Experts consensus recommendations for the management of calcium channel blocker poisoning in adults. Crit Care Med 2016 (http://journals.lww.com/ccmjournal/Abstract/publishahead/Experts_Consensus_Recommendations_for_the.96757.aspx)
Keywords: Poison Ivy, Toxicodendron, Urushiol (PubMed Search)
Fall clean up = Poison Ivy, oak, sumac (Toxicodendron species) which is ubiquitous in North America but it can also be found in British Columbia, Mexico and in parts of Asia. These plants are truly the scourge of outdoor enthusiasts and agricultural workers responsible for up to 40 million cases of miserable often temporarily incapacitating rashes annually.
Toxicodendron dermatitis:poison ivy,oak, sumac. Gladman AC. Wilderness Environ Med. 2006. Summer ;17(2):120-8.
Compositions and methods for removing urushiol and treating resulting skin condition.
US 7858570 B2
Keywords: naloxone, opioid intoxication (PubMed Search)
Naloxone has been used to reverse opioid-induced respiratory depression for decades. The “standard” dose of opioid intoxication has been 0.4 mg. However, over the past decade, initial naloxone dose for opioid intoxication has evolved to recommend a lower initial dose (0.04 – 0.05 mg).
A recent article by Connors et al. reviewed 25 medical resources (internet, medical texts and study guides) of different medical specialties (internal medicine, medical toxicology, emergency medicine, pediatrics, anesthesiology, pain medicine and general medicine)
Recent editions of emergency medicine text (Rosen’s and Tinitinalli) recommend using 0.04 – 0.05 mg IV in ED patients with history of opioid dependence. Higher doses of naloxone are recommended for non-opioid dependent/apneic patients.
However, history of opioid dependence is difficult to obtain in patients with opioid induced CNS/respiratory depression.
Administering 0.4 mg or higher dose may/can acute agitation or opioid withdrawal symptoms that can utilize more ED resources to calm agitated patient/management of withdrawal. Thus it may be prudent to use low-dose strategy (0.04 mg IV with titration) to minimize the risk of precipitating naloxone-induced opioid withdrawal/agitation.
In opioid-induced respiratory depression/apneic patients:
To make 0.04 mg naloxone solution:
Connors NJ, Nelson LS. The evolution of recommneded naloxone dosing for opioid overdose by medical specialty. J Med Toxicol 2016;12:276-281.