The Critically Ill “Tox Patient”

The Case

34 year-old woman with past medical history of postpartum cardiomyopathy (EF 15%) with AICD, mechanical mitral valve replacement, and depression was brought in by EMS for non-accidental ingestion of bupropion, furosemide, and warfarin. The dosage, number of tablets, and timing of ingestion was unknown. The patient was lethargic and mildly confused but protecting her airway. During the evaluation, the patient had a tonic-clonic seizure which resolved with 2mg lorazepam IV. ECG showed sinus tachycardia with HR 105, QRS 126ms, QTc 513ms. The patient was given 2 ampules of sodium bicarbonate for the prolonged QRS. Shortly afterwards, the blood pressure dropped to 90s/60s and  was refractory to IV fluid bolus. This was followed by a 2^nd seizure. A second dose of 2mg lorazepam was administered. The patient was then intubated for airway protection and started on propofol and norepinephrine infusions. (Editor’s note: Patients with low EF are often “fluid under-resuscitated”. Bedside lung/IVC sonography may be used to establish fluid tolerance and allow for the appropriate amount of fluid in small, serial boluses. Furthermore, after intubation and mechanical ventilation, one may be more aggressive with fluid resuscitation.)

The local poison control center was contacted and recommended whole bowel irrigation given a possible ingestion of sustained-release bupropion preparation. Chest X-ray and CT head were unremarkable. Significant laboratory results showed Na⁺ 121, K⁺ 2.9, and INR 2.2. Potassium was repleted, and the patient was admitted to the MICU where whole bowel irrigation was started (Editor’s note: Patients with hypokalemia are often magnesium-depleted; magnesium should always be supplemented along with potassium. Magnesium is also has both anti-epileptic and antidysrythmIc function. GI decontamination was not initiated until the next morning in the MICU; for any possible benefit in toxic ingestions to occur, it should be started as soon as possible). Norepinephrine was discontinued later on the same day. Whole bowel irrigation was continued for 24 hours. The patient was extubated on hospital day #2 with no recurrent seizure activity and transferred to medicine on hospital day #3.

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Evaluation of the Tox Patient

For every patient in the ED, the priority is always stabilization. After the primary survey (ABCs) is complete in the tox patient, we continue with the acronym ‘DEFGHI’.

D – Dextrose: not necessary to give everyone dextrose, but just a reminder to get a fingerstick

E – ECG

F – Physical exam (or Foley for anticholinergic toxidrome)

G – GI decontamination

H – Help: call your local poison control center

I – Ant-I-dote: a specific agent may be indicated, however most cases will only require good supportive care

The Tox ECG

Manini et al (2010) looked at ECG characteristics in a small group of poisoned patients who were associated with a composite endpoint of adverse cardiovascular events (ACVE). These consisted of:

• Hypotension requiring vasopressors
• Myocardial injury defined as elevated troponin
• Dysrhythmia defined as ventricular tachycardia or fibrillation
• Cardiac arrest

The study group (n=34) included poisoned patients who went on to develop ACVE and the control group (n=101) was made up of poisoned patients who did not develop ACVE. All cases were called in to New York Poison Control Center.

• They found that a prolonged QTc at the upper limit of normal was highly associated with their composite endpoint of ACVE (p = 0.02) and even more when the QTc was greater that 500ms (p < 0.01).
• There was no difference in mean QRS duration between groups.
• When they narrowed the endpoints to include only dysrhythmia (VT or VF) and cardiac arrest, additional ECG characteristics were identified which included:
  • QRS > 120ms (p < 0.05, OR = 4.0)
  • QTc > 500ms (p < 0.01, OR = 5.5)
  • Presence of ectopy (p <0.01, OR = 7.5)
  • Any non-sinus rhythm (p < 0.01, OR = 10.5)

GI  Decontamination

The goal is to limit the harm from the ingested agents.

Activated charcoal (or other binding agent)

• Inconsistent evidence. If administering activated charcoal (AC), it is recommended to start within an hour of ingestion.
• Works by adsorption. Binds to agents to prevent GI absorption but also draws toxins out of serum (“gut dialysis”).
• If ingested agent is a sustained release/long-acting preparation (our patient ingested bupropion XL), consider multi-dose activated charcoal (AC). It is extremely important that you make sure your AC is NOT combined with a cathartic (most combined preps use sorbitol). If AC-cathartic combination is used, the multi-dose regimen is contraindicated due to risk of volume depletion with electrolyte shifts. Giving one dose of a combined AC-cathartic preparation is acceptable in adults, but cathartics should be avoided altogether in children.

Whole bowel irrigation

• Inconsistent evidence for benefit; however, it is often recommended for ingestion of sustained-release preparations.
• Works by decreasing GI transit time to decrease absorption of toxin.
• Performed by administering 1-2L per hour of polyethylene glycol via NG or OG tube, running until rectal effluent becomes clear. This can get messy, and a rectal tube may make things easier for your patient and nurse.

Other forms of GI decontamination: ipecac, gastric lavage, cathartics

• Evidence for their use is also inconsistent.
• If a cathartic is given, do not use more than one dose. Cathartics should NOT be used in children.
• See the joint position statements on the above from the American Association of Clinical Toxicology (AACT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT).

Management

When possible, toxin-specific management is best. However, good supportive care is all that is needed in most cases. There are cases where a nonspecific antidote may be given. Intravenous lipid emulsion (ILE) appears to be a promising agent with limited FDA-approved uses at the moment, but this may be changing in the future. ILE is a combination of triglycerides and phospholipids that is thought to work by some combination of two mechanisms:

1) The Lipid Sink Theory – removes fat-soluble toxins from their bindings sites and deposits them in adipose tissue

2) The Enhanced Metabolism Theory – the combination of phospholipids & triglycerides gives the myocardium an abundance of free fatty acid substrate to enhance its metabolic activity

• Cao et al (2015) performed a systematic review of 103 case reports of ILE use.
  • Only 16 of 103 (15.5%) were associated with treatment “failure”.
  • There were case reports showing benefit in both lipid-soluble AND water-soluble xenobiotics.
  • Adverse events were rare and included pancreatitis and distortion of lab values due to ‘extreme lipemia’ (for up to 36 hours in one case).
• Sirianni et al (2008) published a case report of a patient in cardiac arrest after overdose of buproprion and lamotrigine. Advanced cardiac life support was performed for 70 minutes with no improvement. ILE was then given as a last resort, and ROSC was achieved within 1 minute (not bad eh?). The patient went on to be discharged from the hospital with normal cardiac activity and only slight neurologic deficits.

Take Home Points

• Have a systematic way of evaluating patients with toxic ingestions and always include a fingerstick and ECG.
• Know the concerning ECG features to look out for after a toxic ingestion.
• There is no clear evidence showing benefit of GI decontamination, but it may limit the harm in toxic ingestions and should be considered if a patient arrives within 1 hour of ingestion or if a sustained-release preparation was ingested.
• If you are going to give multiple doses of activated charcoal, make sure that your preparation is NOT combined with sorbitol (or another cathartic).
• Contact your local poison control center for assistance with toxic ingestions/exposures. They are extremely helpful.
• For patients who are in cardiac arrest or hemodynamically unstable, ­­consider administering intravenous lipid emulsion. It is an emerging antidote and has been shown to have a wider range of clinical applications than previously thought.

References

– Manini AF, Nelson L, Skolnick AH, Slater W, Hoffman RS. Electrocardiographic predictors of adverse cardiovascular events in suspected poisoning. J Med Toxicol. 2010. 6:106-115.

– Albertson TE, et al. Gastrointestinal decontamination in the acutely poisoned patient. Int J of Emerg Med. 2011;4:65.

– McNamara RM, Aaron CK, Gemborys M, Davidheiser S. Efficacy of charcoal cathartic versus ipecac in reducing serum acetaminophen in a simulated overdose. Ann Emerg Med. 1989. 18(9):934-8.

– Curtis RA, Barone J, Giacona N. Efficacy of ipecac and activated charcoal/cathartic. Prevention of salicylate absorption in a simulated overdose. Arch Intern Med. 1984. 144(1):48-52.

– Goldfrank’s Toxicologic Emergencies, ninth edition,2011, McGraw-Hill Companies, Inc. Chapter 72 Serotonin Reuptake Inhibitors and Atypical Antidepressants, pgs 1043-1044.

– Cao, D, et al. Intravenous lipid emulsion in the emergency department: a systematic review of recent literature. J Emerg Med. 2015. 48;3:387-397.

– Sirianni AJ, Osterhoudt KC, Calello DP, et al. Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine. Ann Emerg Med. 2008;51:412.

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