In the midst of an unprecedented opioid epidemic, there have been considerable efforts to expand access to naloxone (Doyon S, et al. J Med Toxicol 2014;10:431-4). If the situation arises when you need to write a prescription for it, here's how:
Option 1: Naloxone vial and needle traditional IM/SQ using 0.4 mg/mL injection vial and needles (least expensive $40, FDA approved)
Naloxone 0.4 mg/mL single dose vial and 3 cc, 23 g, 1 inch syringes, #2 each
SIG: Inject 1 mL intramuscularly upon signs of opioid overdose. May repeat X 1. Call 911.
Option 2: IMS/Amphastar 2 mg/2 mL prefilled syringe and mucosal atomization device ($95/kit, products FDA approved but intranasal administration is off-label)
Naloxone 2 mg/2 mL prefilled syringe and intranasal atomizer device, #2 each
SIG: Spray one-half of syringe (1 mL) into each nostril upon signs of opioid overdose. May repeat X 1. Call 911.
Option 3: Evzio Autoinjector ($200-700 per Rx though many insurances cover it and the company has vouchers available, FDA approved in 2014, evzio.com/hcp)
Evzio 0.4 mg, #1 two-pack
SIG: Use as directed upon signs of opioid overdose. May repeat X 1. Call 911.
Patient has the following Head CT, what is your differential diagnosis? There are only a few characteristic toxins that can cause this type of finding on CT.
A new review summarized published adverse effects when IV lipid emulsion is used along with venous-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiotoxic drug poisoning.
Not surprisingly, running fat through the ECMO circuit can cause some issues. Here's what's been published:
It's unclear how these findings should change management if using both treatment modalities, but at the very least, be aware that fat depostion in the VA-ECMO circuits and increased blood clot formation can occur.
| Performance Characteristics of Common Drug Abuse Screening Immunoassays | ||
| Drug/Class | Detection Interval (***) | Comments |
| Amphetamines | 1-2 days (2-4 days) | Decongestants, ephedrine,l-methamphetamine, selegilene & bupropion metabolites may give False (+) results; MDA & MDMA are variably detected |
| Barbiturates | 2-4 days | Phenobarbital may be detected for up to 4 weeks |
| Benzodiazepines | 1-30 days | Benzos vary in reactivityand potency; False (+) results may be seen with oxaprozin |
| Cannabinoids | 1-3 days (>1 month) | Screening assays detect inactive and active cannabinoids; Confirmatory assays detects inactive metabolite THCA (tetrahydrocannabinoic acid) |
| Cocaine | 2 days (1 week) | Screening & confirmatory assays detect inactive metabolite BE (benzoylecgonine); False (+) results are unlikely |
| Opiates | 1-2 days; 2-4 days (<1 week) | Semisynthetic opiates derived from morphine show variable cross-reactivity; Fully synthetic opioids (e.g., fentanyl, meperidine, methadone, propoxyphene, tramadol) have minimal cross reactivity; Quinolone may cross-react |
| Methadone | 1-4 days | Doxylamine may cross-react |
| Phencyclidine | 4-7 days (>1 month) | Dextromethorphan, diphenhydramine, ketamine, & venlafaxine may cross react |
| Propoxyphene | 3-10 days | Duration of positivity depends on cross reactivity of metabolite norpropoxyphene |
(***)Values are after typical use; values in parentheses are after heavy or prolonged use.
Tetrodotoxin is lethal poison that blocks sodium channels. A famous sushi called "Fugu" is cut from a puffer fish that contains this poison. The idea is to get just enough of the toxin to cause peri-oral paresthesia but not too much to get seizures, paralysis and cardiac dysrrhythmias. A recent outbreak in Minneapolis, Minnesota was just reported in the MMWR so it can really happen anywhere, its a great read - dried puffer was bought from a market in NYC.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6351a2.htm
2-3 mg of the toxin is lethal to an adult human. No antidote exists though I would try hypertonic sodium bicarbonate for the cardiac dysrrhythmias and appropraite supportive. If the patient survives 24 hrs, the patient will do well without sequelae if appropriately supported.
Hydroxocobalamin is an effective cyanide antidote when administered intravenously. Although intraosseous (IO) access is often used in critically ill patients with difficult or delayed IV access, the efficacy of IO administration has not been investigated until recently.
In a recent randomized animal study, acute cyanide toxicity was induced in two groups of swine where 150 mg/kg Hydroxocobalamin was administered via IV vs. IO. The survival rate, reversal of hypotension, and laboratory results were similar between the IV and IO group.
The finding of this study suggest that IO administration of Hydroxocobalamin is as efficacious as IV administration and its administration in acute cyanide toxicity should not be delayed due to lack of IV access when IO access is available.
Application to Clinical Practice
WBI can facilitate removal of select toxicants from the gastrointestinal tract in some patients, but there is no convincing evidence from clinical studies that it improves the outcome of poisoned patients.
It is believed that administration of beta-blocker administration in patients with cocaine chest pain will produced increased vasoconstriction due to “unopposed alpha effect.”
Several retrospective studies on the use of beta-blocker in patients with cocaine-induced chest pain concluded the use of beta-blocker to be safe.
So is the unopposed alpha effect just a theory?
Lange RA et al. 1990 Ann Internal Med
Design: randomized, double-blind, placebo controlled trial.
30 (38- 68 years old) patients undergoing cardiac catherization for chest pain evaluation were studied.
Cocaine (intranasal administration) resulted in:
Administration of propranolol (intracoronary infusion) resulted in additional:
Complete coronary occlusion observed in 1 patient with ST elevation
Epicardial coronary arterial segment constriction >10% in 5 patients.
Bottom Line: Lange RA et al. 1990 demonstrates that the “unopposed alpha effect” does occur in coronary artery when beta-blocker is administered in a setting of acute cocaine exposure. Overall, the use of beta-blocker in the ED management of cocaine-induce acute chest pain is not a prudent option. It is unknown if the cocaine dose, last use of cocaine (days), or CAD history influence the “safety” of beta-blocker initiation/use during inpatient hospitalization.
Should beta blockers be withheld in cocaine-chest pain patients?
A new study retrospectively compared patients who received beta blockers as an inpatient to those who did not. Even though the beta blocker group had higher risk clinical characteristics, there was no difference in the composite primary end point of myocardial infarction, stroke, ventricular arrhythmia, or all-cause mortality within 24 hours of beta blocker use.
Important Limitations
The potentially dangerous interaction between beta blockers and cocaine is likely a much larger issue in patients with very recent cocaine use in the setting of a catecholamine surge. A retrospective analysis likely doesn't include those patients.
Application to Clinical Practice
While this study doesn't answer the question about beta blocker use in acute cocaine toxicity, it does provide some reassurance about the safety of beta blockers given for cocaine-related chest pain.
Sympathomimetic toxicity is a known toxidrome that is complicated by the development of rhabdomyolysis. There are multiple stimulant agents that induce sympathomimetic toxicity including, synthetic cathinones, cocaine, amphetamines, and methamphetamines.
A recent retrospective, single-center, chart review in the age range of 14-65 years sought to determine the prevalence of rhabdomyolysis in patients with sympathomimetic toxicity and compare rates among patients using specific agents. Rhabdomyolysis and severe rhabdomyolysis were defined as CK>1000 and 10,000 IU/L, respectively.
Rhabdomyolysis occurred in 42% of study subjects (43/102)
Prevalence in 89 subjects due to a single-stimulant exposure:
Rhabdomyolysis
1) Synthetic cathinone (MDPV, alpha-PVP) 63% (12/19)
2) Methamphetamine 40% (22/55)
3) Cocaine 33% (3/9)
4) Other single agents (methylphenidate, pseudoephedrine, phentermine) 0% (0/6)
Severe Rhabdomyolysis
1) Synthetic cathinone 26% (5/19)
2) Methamphetamine 3.6% (2/55)
3) Cocaine 11% (1/9)
4) Other single agents (methylphenidate, pseudoephedrine, phentermine) 0% (0/6)
In this study, patients exposed to synthetic cathinones were more likely to develop rhabdomyolysis and severe rhabdomyolysis compared to the non-cathinone-exposed group.
Bottom Line:
Be aware of this increased risk from synthetic cathinones along with other stimulants. Treat aggressively with IV fluids, rapid correction of hyperthermia, benzodiazepines to control manifestations of sympathomimetic toxicity to reduce muscle activity and metabolic demand.
Cyanide poisoning is rare but highly lethal. Cyanide exposure can occur during residential fire (most common source of exposure) where combustion of synthetic materials (i.e. plastic and polyurethane) releases cyanide gas as well as other toxic gases, including carbon monoxide. Although carbon monoxide poisoning can be readily identified by CO-Hb level using CO-oximetry, serum/blood cyanide level is not readily available for acute management.
However, elevated lactate level (> 10 mmol/L ) has shown to be highly correlated with toxic level of cyanide (40 micromol/L or 1 mg/L) in smoke inhalation victims (Baude FJ et al. N Engl J Med 1991;325:1761-6).
Bottom line: when managing smoke inhalation victims, think about cyanide poisoning in addition to carbon monoxide poisoning and check the lactate level. Lactate > 10 mmol/L is suggestive of cyanide poisoning and should be treated with hydroxocobalamin.
The pattern of prescription drug abuse continues to center around semisynthetic opioids like oxycodone and hydrocodone. Federal regulations have now raised hydrocodone to a schedule II drug like oxycodone. Despite efforts, the slope for natural and semisynthetic opioids remains steep. The ED measures of education, limit prescriptions for acute pain, minimize number of days/pills prescribed and utlize the prescription drug monitoring program are some basics that can assist you in better prescribing habits.
A new population-based case-control study in older adults has linked the administration of trimethoprim-sulfamethoxazole (Bactrim, TMP-SMX) to increased risk of sudden death in patients also receiving angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB). [1]
Hyperkalemia is the suspected cause. [2] Compared to amoxicillin, TMP-SMX was associated with an increased risk of sudden death (adjusted odds ratio 1.38, 95% confidence interval 1.09 to 1.76) within 7 days of exposure to the antibiotic.
Practice Change
In older patients receiving ACE-Is or ARBs, TMP-SMX is associated with an increased risk of sudden death. When appropriate, alternative antibiotics should be considered.
Digoxin-specific antibodies are produced in immunized sheep and have high binding affinity for digoxin and, to a lesser extent, digitoxin and other cardiac glycosides. The Fab fragment binds free digoxin and once the digoxin-Fab complex is formed, the digoxin molecule is no longer pharmacologically active. The complex is renally eliminated and has a half-life of 14-20 hours (may increase 10-fold with renal impairment). Reversal of signs of digoxin/digitalis intoxication usually occurs within 30-60 minutes, with complete reversal varying up to 24 hours.
Contraindication: None known. Caution is warranted in patients with known sensitivity ot ovine (sheep) products. Product may contain traces of papain and caution advised in patients with allergies to papain, papaya extracts, chymopapain.
Adverse effects:
1) Monitor for potential hypersensitivity reactions and serum sickness
2) In patients with renal insufficiency and impaired renal clearance of dig-Fab complex, a delayed rebound of free serum digoxin levels may occur
3) Removal of the effect of digoxin/digitalis may exacerbate preexisting heart failure
4) Removal of digoxin/digitalis effect may cause hypokalemia
Laboratory interaction: Digoxin-Fab complex cross-reacts with the antibody commonly utilized in quantitative immunoassay techniques. This results in falsely high serum concentrations of digoxin due to measurement of the inactive Fab complex. Therefore, measure free digoxin levels, which may be useful for patients with renal impairment.
Dosing: Each vial of Fab product binds 0.5 mg of digoxin.
Digoxin-specific Fab (round up vial calculation)
# of vials = Digoxin concentration (ng/mL) x Pt Wt (kg)
100
Valproic acid (VPA) is often used to treat seizure disorder and mania as a mood stabilizer. The mechanism of action involves enhancing GABA effect by preventing its degradation and slows the recovery from inactivation of neuronal Na+ channels (blockade effect).
VPA normally undergoes beta-oxidation (same as fatty acid metabolism) in the liver mitochondria, where VPA is transported into the mitochondria by carnitine shuttle pathway.
In setting of an overdose, carnitine is depleted and VPA undergoes omega-oxidation in the cytosol, resulting in a toxic metabolite.
Elevation NH3 occurs as the toxic metabolite inhibits the carbomyl phosphate synthase I, preventing the incorporation of NH3 into the urea cycle.
Signs and symptoms of acute toxicity include:
Laboratory abnormalities
Treatment: L-carnitine
In a precursor to a forthcoming international guideline on the management of calcium channel blocker poisoning, a new systematic review has been published assessing the available evidence.
A few findings from the systematic review:
Stay tuned for the international guideline coming out soon. One treatment recommendation from the new guideline, reported at the 8th European Congress on Emergency Medicine last month, is not to use glucagon.
Cardioactive steroids are among the many treatments used for CHF, and for the control of ventricular response rate in atrial tachydysrhythmias. There are many sources of cardioactive steroids:
Pharmaceutial: Digoxin, Digitoxin
Plants: Oleander, Yellow Oleander, Foxglove, Lily of the Valley, Dogbane, Red Squill
Animal: Bufo marinus toad
It is a potent Na+-K+-ATPase inhibitor and can lead to hyperkalemia in acute ingestion with associated signs and symptoms of N/V, abdominal pain, bradycardia and possibly, hypotension.
Toxicity should be suspected with bidirectional ventricular tachycardia or atrial tachycardia with high-degree AV block
Therapeutic range of digoxin of 0.5 - 2.0 ng/mL is helpful but not a sole indicator of toxicity
Indication for antidote (Digoxin-specific Antibody Fragments) include:
1) Digoxin-related life-threatening dysrhythma
2) Serum K+ > 5.0 mEq/L in acute ingestion
3) Serum digoxin concentration >15ng/mL at any time, or >10 ng/mL 6 hours postingestion
4) Ingestion of 10 mg in adult; 4 mg in pediatric
5) Poisoning by non-digoxin cardioactive steroid
When you prescribe certain medications, it may require some further instructions to avoid ethanol or a disulfiram like reaction (nausea, vomiting, flushing) may occur. Keep this short list in your brain:
1) Particular cephalosporins: cefotetan is a the one more likely
2) Nitrofurantoin
3) Sulfonylureas: chlorpropamide and tolbutamide
4) Metronidazole
5) Trimethoprim-sulfamethoxazole
Food poisoning can occur with many different food groups/items, as well as how the food is prepared, handled or stored.
There are three specific “food poisonings” associated with fish consumption can cause serious toxicity/illness beyond GI symptoms: Ciguatera, Scrombroid, tetrodotoxin (puffer fish)
Ciguatera
Symptoms:
May progress to develop…
Treatment: supportive care and mannitol in presence of severe neurologic symptoms (limited evidence).
Scrombroid
Symptoms:
Tx: H1/H2 blockers and supportive care
Serious reactions: treat like allergic/anaphylactic reaction
Tetrodotoxin
Symptoms:
Treatment: supportive care and intubated if needed.
