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.
Bottom line:
Sodium acetate can be administered safely in place of sodium bicarbonate if sodium bicarbonate is not available due to shortage.
Sodium acetate dose:
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.
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:
Bottom line:
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 | Usually none |
| 10-20 | Occasional mild nystagmus |
| 20-30 | Nystagmus |
| 30-40 | Ataxia, slurred speech, extrapyramindal effects |
| 40-50 | Lethargy, confusion |
| >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.
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.
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:
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.
Bottom line:
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:
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.
Limitations
Bottom line
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:
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:
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.
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:
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.
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.
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
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.
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:
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:
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.
