Category: Toxicology
Keywords: Lactic acidosis (PubMed Search)
Posted: 1/5/2017 by Kathy Prybys, MD
(Updated: 1/6/2017)
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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.
Category: Toxicology
Keywords: cyanide toxicity, lactic acid (PubMed Search)
Posted: 12/29/2016 by Hong Kim, MD
(Updated: 12/30/2016)
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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.
Bottom line:
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.
Category: Toxicology
Keywords: Acetaminophen, Liver Failure (PubMed Search)
Posted: 12/16/2016 by Kathy Prybys, MD
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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.
Category: Toxicology
Keywords: acetaminophen overdose, APAP levels (PubMed Search)
Posted: 12/8/2016 by Hong Kim, MD
(Updated: 12/9/2016)
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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).
Bottom line:
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 | < 150 ug/mL |
<10 | 0 | 89 |
10-20 | 2 | 79 |
20-50 | 6 | 209 |
50-100 | 19 | 249 |
100-150 | 46 | 253 |
150-200 | 161 | 195 |
200-300 | 276 | 46 |
300-450 | 148 | 5 |
>450 | 38 | 0 |
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
Category: Toxicology
Keywords: Drug Allergy, ADR, ADE (PubMed Search)
Posted: 12/1/2016 by Kathy Prybys, MD
(Updated: 12/2/2016)
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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) | Sedative-hypnotics | 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.
Category: Toxicology
Keywords: heroin overdose, observation period, bystander naloxone (PubMed Search)
Posted: 11/16/2016 by Hong Kim, MD
(Updated: 11/17/2016)
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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).
Clin Toxicol (Phila). 2016 Nov 16:1-7. [Epub ahead of print]
Do heroin overdose patients require observation after receiving naloxone?
Willman MW1, Liss DB1, Schwarz ES1, Mullins ME1.
Category: Toxicology
Keywords: buprenorphine exposure, pediatrics, retrospective study (PubMed Search)
Posted: 10/26/2016 by Hong Kim, MD
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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.
Bottom line
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
Clinical effects
Naloxone
The median hospital stay was 22 hours (7 - 248 hours).
Category: Toxicology
Keywords: CCB poisoning (PubMed Search)
Posted: 10/13/2016 by Hong Kim, MD
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US, Canadian and European critical care and toxicology societies recently published a consensus recommendation is the management of CCB poisoning.
Bottom line:
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.
Briefly:
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)
Category: Toxicology
Keywords: Poison Ivy, Toxicodendron, Urushiol (PubMed Search)
Posted: 10/6/2016 by Kathy Prybys, MD
(Updated: 10/7/2016)
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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.
Fast Facts:
Treatment Tips:
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
Category: Toxicology
Keywords: naloxone, opioid intoxication (PubMed Search)
Posted: 9/15/2016 by Hong Kim, MD
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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)
Findings:
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.
Bottom line:
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.
Category: Toxicology
Keywords: atypical antipsychotic toxicity (PubMed Search)
Posted: 9/8/2016 by Hong Kim, MD
(Updated: 12/13/2024)
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Antipsychotic as a class has diverse range of toxicity. The atypical (2nd generation) antipsychotics are considered to possess less toxicologic manifestation compared to the typical (1st generation) antipsychotics - lower K channel blockade and minimum Na channel blockade properties. However, select atypical antipsychotics overdose can results in significant morbidity in addition to sedation.
Alpha-1 blockade (hypotension)
Antimuscarinic effect (anticholinergic toxicity)
Delayed rectifier K channel blockade (QT prolongation)
Bottom line: Although lethal overdose from atypical antipsychotics are rare, they can result in significant clinical toxicity when ingested alone or in combintation with other classes of medications.
Category: Toxicology
Keywords: One pill killers, pediatric (PubMed Search)
Posted: 8/17/2016 by Hong Kim, MD
(Updated: 8/18/2016)
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In pediatric population, small dose or single pill ingestion can potential result in severe or lethal toxicity.
Clinicians should be mindful of potential toxicity following xenobiotic exposure (below) in pediatric population, especially under the age of 5 years old, even if the patient may initially appear asymptomatic.
Suspected ingestion of above medications/xenobiotics may warrent observation up to 24 hours in asymptomatic pediatric population.
Category: Toxicology
Keywords: Hypoglycemia, Sulfonylureas (PubMed Search)
Posted: 8/4/2016 by Kathy Prybys, MD
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Drug-induced hypoglycemia is an often severe and symptomatic. It is a potentially preventable cause of significant morbidity. In one large study, it accounted for 23% for hospital admissions due to adverse drug events and 4.4% of overall admissions. The majority of hypoglycemic events occur with insulin and sulfonylureas. However, multiple drugs can affect glucose homeostasis and have been cited to cause hypoglycemia in therapeutic dose alone or in combination with other medications or illness. Factors that predispose to low blood sugar include reduced food intake, age, hepatic and renal disease, and severe infection. Beware of the possibility of inducing hypoglycemia in patients taking the following:
Agents with lesser quality evidence as predisposing medications or illnesses were present:
Drugs induced hypoglycemia should always be considered in the differential diagnosis of every patient presenting with low blood glucose. Octreotide antagonizes pancreatic insulin secretion and should be considered for first-line therapy in the treatment of sulfonylurea-induced hypoglycemia particularly when glucose levels cannot be maintained by dextrose infusions. Octreotide is administered 50 mcg subcutaneously (1-10 mcg in children) every 12 hours.
Category: Toxicology
Keywords: novel synthetic opioid, U-47700 (PubMed Search)
Posted: 8/1/2016 by Hong Kim, MD
(Updated: 12/13/2024)
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Recently, there have been several news reports regarding the emergence of synthetic opioids in the U.S. and Canada. There are multiple synthetic opioids that have been identified as potential agents of abuse including W-18, U-47700, fentanyl derivatives, AH-7921 and MT-45. These compounds share a similar story with synthetic cannabinoid where they were synthesized for research purpose or by pharmaceutical companies but were not marketed. They are often sold as “research chemicals” over the internet.
In July 2016, three case reports have been published regarding several cases of U-47700 intoxication in San Diego, CA and Dallas, TX.
It is unknown if currently available heroin is cut with above mentioned synthetic opioids. Like other opioid receptor agonists, administration of naloxone will likely reverse the opioid toxidrome. But clinical experience in reversing synthetic opioids intoxication with naloxone is limited.
Bottom line:
Irrespective of whether an ED patient is exposed to synthetic opioids or "traditional" opioids of abuse (prescription opioid pain medication or heroin), the management of opioid intoxication management remains unchanged for respiratory depression.
Category: Toxicology
Keywords: Pediatric exposure, laundry detergent pods (PubMed Search)
Posted: 6/23/2016 by Hong Kim, MD
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Laundry detergent pods were introduced in 2012 to make washing clothes more "convenient." Since then, pediatric exposures to laundry detergent pods have increased as the use of these detergent pods have become more common in homes. Like other household chemical exposure, small, colorful candy like appearances of laundry detergent pods can attract the attention of < 3 years old children resulting in unintentional exposure due to curiosity or taste.
Most frequent clinical effects (2013 - 2014 national poison center data) from exposure to detergents in general (laundry detergent pods and nonpods & dishwasher detergent):
Laundry detergent pod vs. nonpods:
Laundry detergent pods (only) also resulted in following:
Cases of caustic exposure-like injuries have also been reported (corneal abrasion and esophageal injury)
Bottom line:
Pediatric laundry detergent (nonpods) exposures usually have self-limited symptoms. However, laundry detergent pod exposure can cause more serious clinical effects that may require hospitalization.
Category: Toxicology
Keywords: loperamide, opioid alternative, cardiac toxicity (PubMed Search)
Posted: 6/15/2016 by Hong Kim, MD
(Updated: 12/13/2024)
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Loperamide is a peripheral mu-opioid receptor agonist that is found in over the counter anti-diarrheal medication. Following the trend of opioid abuse epidemic, loperamide has been promoted on online drug-use forum as a treatment for opioid withdrawal and as a possible alternative to methadone. At the same time, recreational use of loperamide has been increasing as an opioid alternative. Unlike therapeutic use of loparamide (2 – 4 mg), loraparmide abusers take supratherapeutic doses (e.g. 50 – 100 mg) to penetrate the CNS to produce opioid effects.
In published case reports, loperamide caused cardiac Na channel blockade (similar to TCA and bupropion) and K channel blockade, resulting in EKG changes including QRS interval > 100 msec with terminal R wave in aVR and QTc prolongation, respectively. Loperamide associated death has also been reported (autopsy finding), although the exact cause of death was not determined.
It is unclear if administration of NaHCO3 can reverse the cardiac Na channel blockade as in TCA and bupropion as the clinical experiences have been limited.
Bottom line:
Category: Toxicology
Keywords: ketamine, agitation, prehospital, haloperidol (PubMed Search)
Posted: 6/7/2016 by Bryan Hayes, PharmD
(Updated: 6/27/2016)
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Ketamine is gaining traction as a prehospital option for managing severe agitation or excited delirium syndrome. Previous reports have mostly been case series, but a new prospective study adds some important information that may help delineate ketamine's role in this setting. [1] The study and an accompanying commentary are both open access. [2]
What They Did
Open-label before-and-after prospective comparison of haloperidol (10 mg IM) versus ketamine (5 mg/kg IM) for the treatment of acute undifferentiated agitation.
What They Found
Appliation to Clinical Practice
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Category: Toxicology
Keywords: Bupropion, Seizure, Cardivascular instability (PubMed Search)
Posted: 6/2/2016 by Kathy Prybys, MD
(Updated: 6/3/2016)
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Bupropion (Wellbutrin, Zyban) is one of the most frequently prescribed antidepressants and smoking cessation agents. A lesser incidence of undesirable side effects such as weight gain and sexual dysfunction when compared to other antidepressants lends to its popularity. Bupropion's mechanism of action is only partially understood but it is known to be a norepinephine dopamine reuptake inhibitor and anticholinergic receptor blocker at certain nicotinic receptors. Bupropion has a monocyclic structure similar to amphetamines. Seizures are a major concern in overdose. When first released, Bupropion was initially withdrawn from the market due to its narrow therapeutic window with seizures occurring at doses as low as 450 mg.
Life threatening Bupropion ingestion, Is there a role for intravenous fat emulsion? Livshits Z, Feng L, et al. Basic & Clinical Toxicology & Pharmacology, 2011, 109. 418-22.
Incidence and onset of delayed seizures after overdoses of extended release Bupropion. Starr P, Klein-Schwartw W, et al. Am Journal EM, 2009 Oct(27)8: 911-15.
Category: Toxicology
Keywords: digoxin, chronic, poisoning, immune Fab (PubMed Search)
Posted: 5/9/2016 by Bryan Hayes, PharmD
(Updated: 5/12/2016)
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Patients with chronic digoxin toxicity generally have multiple co-morbidities such as renal failure, dehydration, and cardiac failure. Sick patients with chronically high digoxin levels may have more than just digoxin toxicity as the cause of illness.
A New Study
Prospective observational study with the primary objective to investigate changes in free digoxin concentrations and clinical effects on heart rate and potassium concentrations in chronic digoxin poisoning when digoxin immune Fab are given.
What They Found
One to two vials of digoxin immune Fab initially bound all free digoxin confirming Fab efficacy. However, this was associated with only a moderate improvement in HR (49 to 57 bpm) and potassium (5.3 to 5.0 mmol/L).
Application to Clinical Practice
Chan BS, et al. Efficacy and effectiveness of anti-digoxin antibodies in chronic digoxin poisonings from the DORA study (ATOM-1). Clin Toxicol. 2016 Apr 27. Epub ahead of print. [PMID 27118413]
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Category: Toxicology
Keywords: Extracorporeal Membrane Oxygenation, ECMO, toxicology, poison (PubMed Search)
Posted: 4/13/2016 by Bryan Hayes, PharmD
(Updated: 4/14/2016)
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The American College of Medical Toxicology's ToxIC Registry is a self-reporting database completed by medical toxicologists across 69 insitutions in the US.
Application to Clinical Practice
In settings where ECMO is available, it may be a potential treatment option in severely poisoned patients. From the limited data, ECMO was generally administered prior to cardiovascular failure and might be of benefit particularly during the time the drug is being metabolized.
Table from the Case Series
Wang GS, et al. Extracorporeal Membrane Oxygenation (ECMO) for Severe Toxicological Exposures: Review of the Toxicology Investigators Consortium (ToxIC). J Med Toxicol 2016;12(1):95-9. [PMID 26013746]
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