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.
Digoxin-specific antibody fragments (Fab) are safe and indicated in all patients with life-threatening dysrhythmias and an elevated digoxin concentration. However, full neutralizing doses of digoxin-Fab are expensive and may not be required (not to mention cumbersome to calculate).
Based on pharmacokinetic modeling and published data, a new review suggests a simpler, more stream-lined dosing scheme as follows:
In imminent cardiac arrest, it may be justified to give a full neutralizing dose of digoxin-Fab.
In acute poisoning, a bolus of 80 mg (2 vials), repeat if necessary, titrated against clinical effect, is likely to achieve equivalent benefits with much lower total doses.
With chronic poisoning, it may be simplest to give 40 mg (1 vial) at a time and repeat after 60 min if there is no response.
Dysrhythmia-induced sudden death, termed "sudden sniffing death syndrome," is well described phenomena due to inhalant (chlorinated and aromatic hydrocarbon) abuse.
Common inhalants include:
Chlorinated hydrocarbons: Degreasers, spot removers, dry-cleaning agents
Fluorocarbons: Freon gas, deodarants
Toluene: Paint thinners, spray paint, airplane glue
Butane: Lighter fluid, fuel
Acetone: Nail polish remover
The common theory behind the syndrome is cardiac sensitization that increases susceptibility of the heart to systemic catecholamines (epinephrine, norepinephrine, etc). Usually, it occurs after an episode of exertion in that any excess catecholamine exposure causes irritability of the myocardium, resulting in dysrhythmias (V. fib, V. tach) and cardiac arrest.
If acute dysrhythmias is due to myocardial sensitization, sympathomimectis should be avoided. Beta-adrenergic antagonist can be used for the catecholamine-sensitized heart.
E-cigarette popularity has increased and with that another possible source of toxicity. The most recent MMWR shows how e-cigarette use has increased over the past 5 years. The general toxicity involves nicotine toxicity with nausea, vomiting, eye irritation as the major sources of toxicity. Only one reported death where the nicotine reservoir was accessed and then injected IV in a suicide attempt.
There are some reports of asthma exacerbations but is more likely due to the vapor flavor and not the nicotine.
Since synthetic cannabinoids arrived on the scene, we have become familiar with their sympathomimetic effects such as emesis, tachycardia, hypertension, agitation, hallucinations, and seizures.
Acute kidney injury is also being linked to synthetic cannabinoid use. Several clusters have been described in a handful of states, the most recent coming from Oregon with 9 patients.
AKI seems to be one more adverse effect to be on the lookout for when evaluating patients after synthetic cannabinoid use.
Bath salts (synthetic cathinones) commonly contain multipe synthetic drugs and can be ingested, smoked, or administered intravenously. The designer stimulant mephedrone (4-methylcathinone) is among the most popular of the derivatives of the naturally occurring psychostimulant cathinone. Bath salt use is on the rise and is responsible for a large number of ED visits.
In spite of their ban, bath salts are still available over the counter in specialty shops and through the Internet with common product names such as: "Ivory Wave," "Cloud 9," "Purple Wars," "Vanilla Sky," "Bliss," etc. They are commonly marketed with the disclaimer, "not for human consumption."
Their presentation mimics other sympathetic drugs through pathways similar to amphetamines. The primary psychological effects have a duration of roughly 3-4 hours, with physiologic effects lasting from 6-8 hours.
| Physical Effects | Behavioral & Mental Status Effects |
| Tachycardia | Agitation |
| Hypertension | Paranoia |
| Dysrhythmias | Hallucinations |
| Hyperthermia | Psychosis |
| Seizures | Violent behavior |
| Sweating | Delusions |
Management is largely supportive and includes IV hydration, benzodiazepines, and close monitoring in the ICU setting.
Ondansetron is a highly effective anti-emetic that, since it has gone generic, is also quite inexpensive. There have been some reports of QT prolongation and cardiac arrhythmias especially with the high-dose 32mg IV dose for chemotherapy patients.
Is still safe in our ED population? A large systematic review was done in this month's Ann Emerg Med July 2014,p19-31.
Take Home Points:
1) No reports of arrhythmia associated with single dose administration identified
2) 80% of 60 unique reports were IV
3) 83% had significant PMH or already on a QT prolonging drug
Conclusion: Ondansetron doesn't warrant routine EKG or electrolyt screening in oral administration.High dose IV and High Risk patients do require more vigilance with EKG and electrolyte screening.
Metformin is the first line medication for the treatment of type II diabetes. A rare complication of chronic metformin use is MALA.
The association between metformin accumulation and development of lactic acidosis is controversial as patients with suspected MALA experience concurrent illnesses such as sepsis/septic shock, tissue hypoxia, and/or organ dysfunction (especially renal failure).
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