Prehospital Care
Prehospital care may include the following:
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Obtain intravenous (IV) access
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Place the patient on a cardiac monitor
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Administer IV fluids if the patient is hypotensive
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Administer activated charcoal if the patient has intact mental status and is able to protect the airway
Emergency Department Care
All patients should be monitored for at least 6 hours. Those that develop symptoms will require further monitoring till they return to baseline. Those that are completely asymptomatic 6 hours from the exposure can be medically cleared. Rapid and thorough evaluation of the patient's status is crucial; pay particular attention to the patient's level of sensorium, the ability to maintain an airway, and the respiratory and hemodynamic status.
For carbamazepine toxicity, the following emergency department care may be indicated [41] :
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Place the patient on a cardiac monitor
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Administer intravenous fluids as needed for hypotension
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Gastric lavage may be helpful if performed within 1 hour of ingestion
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Protect the patient’s airway by placing the patient in left lateral decubitus position or by intubating
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Induction of emesis is not recommended because of the risk of CNS depression and seizures
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Administer activated charcoal if the patient is able to protect his or her airway
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Multiple doses of activated charcoal (1 g/kg) can be administered every 2-4 hours to enhance total body clearance and elimination in the patient with significant toxicity
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A saline cathartic or sorbitol may be given with the first dose of charcoal, although evidence for their effectiveness is lacking. Do not repeat activated charcoal administration if ileus is present
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Perform whole-bowel irrigation (WBI) after ingestion of extended-release drug formulation: Adults and adolescents are treated with 1.5-2 L/h (20-30 mL/min) of polyethylene glycol electrolyte lavage solution (PEG-ELS); small children are given 0.5 L/h (25 mL/kg/h)
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Administer sodium bicarbonate when the QRS complex is wider than 100 msec due to carbamazepine toxicity (sodium channel blockade)
Patients with severe poisoning require admission to the ICU. Examples of such patients include those who are comatose on arrival to the facility and those with a deteriorating mental status, hypotension, seizures, or respiratory irregularities (eg, respiratory depression, apnea).
The clinician should be aware of the marginal clinical effect of extracorporal carbamazepine removal. High-efficiency hemodialysis and venovenous hemodialysis may have a similar effect as charcoal hemoperfusion. Peritoneal dialysis is not useful for carbamazepine removal.
Monitor carbamazepine plasma levels to make sure that they are decreasing and correlating with the clinical picture. Admit the patient to the monitored setting with cardiac telemetry. Transfer the patient if appropriate monitoring facilities or critical care areas are not available.
Discharge patients with carbamazepine toxicity if the following conditions are met [41] :
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The patient is symptom free and the carbamazepine level has decreased to less than 4-8 mg/L. Obviously, patients with significant toxicity should be admitted and patients with life threatening or potentially life-threatening signs and/or symptoms should be admitted to an ICU.
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An exception to decreasing the carbamazepine level to a subtherapeutic level is in the patient who is taking carbamazepine for seizure control. These patients may be discharged with a therapeutic serum level of carbamazepine or another substituted anticonvulsant.
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After being “medically cleared," the patient should not be discharged from the hospital until personnel from social services or child protective services or a psychiatrist agrees, if the case required the notification of these professionals.
Medical Care
Activated charcoal and lavage
After the patient's airway, breathing, and circulation are stabilized, therapy with multiple-dose activated charcoal can be considered and should be directed by a medical toxicologist or poison control center. Multi-dose activated charcoal may be of benefit due to the enterohepatic circulation that occurs with carbamazepine overdose. Carbamazepine is one of several important drugs that have enterohepatic circulation (others are phenobarbital and theophylline), which allows treatment of overdose with multiple doses of charcoal, even after all of the drug has been absorbed. This procedure is often referred to as "gut dialysis" because drug levels may rapidly fall after this treatment.
Multi-dose activated charcoal should only be given in cases where there airway is secure. In patients with an impaired gag reflex, this will require insertion of a nasogastric tube after the airway has been protected by endotracheal intubation. In patients with unsecured airways, multi-dose activated charcoal should not be given. Sorbitol should not be used.
It is important to note that serious carbamazepine poisoning is often complicated by drug-induced gastrointestinal (GI) hypomotility. Severe ileus may interfere with the administration of multiple-dose charcoal and with decontamination of the GI tract. GI hypomotility may result in ongoing drug absorption and prolongation of symptoms.
Whole bowel irrigation
Whole bowel irrigation may be used to treat carbamazepine overdoses with sustained-released preparations or in patients who had a massive ingestion. It can also be used if the formation of concretions or pharmacobezoars is suspected. If the carbamazepine level is not decreasing or is even rising despite repeated doses of activated charcoal, the use of whole bowel irrigation should be strongly considered. The use of whole bowel irrigation should be guided by a medical toxicologist or poison control center.
Whole bowel irrigation uses preparations that contain polyethylene glycol (PEG), such as Colyte or Go-lightly. PEG decreases the amount of the toxin in the digestive tract without causing dehydration or electrolyte depletion. The dose is 20-40 mL/kg/h until the patient has clear diarrhea. It is contraindicated in children younger than 9 months and in patients with an acute abdominal problem. In young children, the PEG solution should not be cooled, as that could result in hypothermia. [42]
Charcoal hemoperfusion
Charcoal hemoperfusion has been used to treat patients with life-threatening carbamazepine poisoning. Activated charcoal imbedded in the hemoperfusion cartridge competes with plasma proteins for binding of the drug.
Hemoperfusion is limited to the removal of substances from the blood compartment; therefore, patients receiving drugs with a large volume of distribution may require prolonged hemoperfusion.
Charcoal hemoperfusion may have a more important role in patients with acute toxicity because of the low intrinsic clearance. Hemoperfusion may effectively remove the parent drug and its epoxide metabolite; thus, charcoal hemoperfusion is an important adjuvant therapy in patients with life-threatening carbamazepine poisoning complicated by drug-induced gastrointestinal hypomotility. Repeat hemoperfusion treatments may by necessary until GI motility returns to its previous level.
To the author's knowledge, no written guidelines address the use of charcoal hemoperfusion in carbamazepine poisoning. Hence, a common-sense approach is to use charcoal hemoperfusion in the following situations:
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Associated GI hypomotility or ileus is present and makes the use of activated charcoal ineffective
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The patient's clinical status is deteriorating despite the administration of enteric activated charcoal
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The patient has a severe life-threatening intoxication that causes deep coma, seizures, arrhythmias, and/or respiratory depression; such patients are at risk for rapid deterioration and death
Dialysis
Peritoneal dialysis is ineffective in eliminating carbamazepine from the serum because of the drug's insolubility in water, high protein binding, and relatively large volume of distribution. It had been thought that hemodialysis is also ineffective in treating carbamazepine toxicity for the same reasons. However, case reports have documented successful management of severe carbamazepine toxicity with hemodialysis.
Harder et al reported a case in an adult with acute carbamazepine overdose who was successfully treated with hemodialysis followed by continuous venovenous hemodialysis. The patient’s clinical status and her levels of carbamazepine and its epoxide metabolite markedly and rapidly improved with this treatment. [43]
Ram Prabahar et al successfully treated an adult with severe carbamazepine toxicity using “simple hemodialysis” because hemoperfusion was not available at their facility. Their report also included a review of the available literature on this subject. They concluded that hemodialysis was an effective and relatively safe way of managing severe carbamazepine toxicity, especially when charcoal hemoperfusion is not available. [44]
A systematic review of extracorporeal treatment of carbemazepine poisoning by Ghannoum et al concluded that intermittent hemodialysis is the preferred extracorporeal treatment, but intermittent hemoperfusion or continuous renal replacement therapies are alternatives if hemodialysis is not available. [45]
Ghannoum et al recommend extracorporeal treatment for patients with multiple seizures refractory to treatment or with life-threatening dysrhythmias. They suggest it for patients with prolonged coma or respiratory depression requiring mechanical ventilation and for those with significant, persistent toxicity, particularly when multiple-dose activated charcoal and supportive measures fail to reduce carbamazepine concentrations. Extracorporeal treatment should be continued until clinical improvement becomes apparent or the serum carbamazepine concentration falls below 10 mg/L. [45]
Successful treatment with continuous renal replacement therapy (CRRT) using continuous venovenous hemofiltration (CVVH) has been reported. [46]
Consultations
Consult a medical toxicologist or a certified poison control center. Nephrology consultation is indicated if charcoal hemoperfusion is being considered.
If the patient's history suggests suicidal intent, consult a psychiatrist. In all cases involving an accidental ingestion in a child, personnel from social services or child protective services should be notified to evaluate the patient's home situation.
Long-Term Monitoring
Patients should follow up with their primary care provider within 24-48 hours after their discharge. The physician should reevaluate the patient's condition and discuss the prevention of future episodes.
