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SPA Newsletter.
A case of propofol toxicity: further evidence for a causal mechanismDavinia E Withington, Mary K. Decell, Tareq Al Ayed. Pediatric Anesthesia 2004;14: 505 Death after re-exposure to propofol in a 3-year-old child: a case reportJosef Holzki, Christoph Aring, Alex Gillor. Pediatric Anesthesia 2004;14: 265 In the first article, the authors describe a fascinating case of apparent propofol toxicity in a five month-old male who underwent his third operation for cleft lip repair. His previous two surgeries were complicated by wound dehiscence caused by postoperative agitation. Therefore, the surgeon requested 48 hours of postoperative sedation to allow the start of wound healing. The anesthetic consisted of propofol, fentanyl, and vecuronium. Postoperatively, the patient was sedated with a continuous propofol infusion. On the second postoperative day, brown urine was noted and a blood gas showed pH 7.21 with bicarbonate of 18 mmol/L. Propofol was discontinued. The total propofol infused was 4339 mg over 62 hours (mean infusion rate 192 mcg/kg/min). On the third postoperative day the child developed several cardiac dysrrhythmias, including bradycardia, unresponsive to pressors, chronotropes, and trancutaneous pacing. The patient developed multisystem organ failure including lactic acidosis, hepatic dysfunction, coagulopathy, renal failure, and rhabdomyolysis. The child received two sessions of charcoal hemoperfusion which resulted in an immediate improvement in hemodynamics and normalization of acid-base status. He received hemodialysis for five days, inotropic support until day seven, was extubated on day 12, and discharged three weeks after surgery. Subsequently, an acute serum specimen, which was stored frozen, was sent for acylcarnitine profile analysis at Duke University. This revealed a disturbance of fatty acid oxidation with elevated levels of acylcarnitine intermediates. The profile of a follow-up specimen was normal and the child has done well since discharge. In the second report, a three-year-old boy was sedated with propofol to aid mechanical ventilation following massive aspiration. For the first 15 hours the child received an infusion of 20 mg/kg/hr (333 mcg/kg/min) instead of 20 mg/hr because of a drug administration error. The child developed bronchospasm with combined respiratory and metabolic acidosis. The propofol infusion was discontinued and the acidosis resolved. Thirteen hours later, with the child awake and fighting the ventilator again, the propofol infusion was restarted, averaging 4.2 mg/kg/hr for the next eight hours. After eight hours of this infusion, bradydysrrythmias and metabolic acidosis appeared. The patient was noted to be hypotensive despite high doses of inotropes, had a palpably enlarged liver, elevated transaminases, and grossly lipemic serum. Despite stabilization of the circulation with a pacemaker and inotropic support, the patient had refractory metabolic acidosis. He suffered a cardiac arrest 16 hours after termination of the second infusion and could not be resuscitated. Comment: The first case is very similar to one previously described in Toronto.1 Notably, in this case charcoal hemoperfusion was chosen because it clears propofol from the body more efficiently than venovenous hemofiltration. At least 18 pediatric cases of propofol toxicity have now been published. This case report, along with others, provides further evidence of the association of propofol infusion with metabolic acidosis and multisystem organ failure. The clinical features of propofol infusion syndrome are: 1. Sudden onset marked bradycardia According to Bray, the diagnosis is made when feature 1 + any one of the subsequent findings are present.2 The current theory is that prolonged infusion of propofol can impair entry of acylcarnitine esters into mitochondria, interfering with fatty acid oxidation. This phenomenon, combined with insufficient carbohydrate intake necessary to suppress fatty acid catabolism, leads to the propofol infusion syndrome.3 In the same issue as the first case, an electronic questionnaire of pediatric intensive care units having fellowship training programs, revealed that propofol was still being used for sedation in 47% of UK units and 61% of North American units. The time has come to condemn ICU sedation with propofol in children, particularly young children with inadequate carbohydrate intake. It also seems fair to ask whether prolonged intraoperative propofol infusions should be used in young infants. Lastly, it would be interesting to know if infusion of the lipid vehicle alone, in the setting of inadequate carbohydrate intake, would yield similarly abnormal acylcarnitine profiles. References
Reviewed by: Samuel Golden, MD, FAAP Table of Contents
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