Enhanced elimination of phenobarbital using charcoal haemoperfusion in a patient with severe poisoning

Abstract

Editor'We present data from a patient with severe phenobarbital poisoning who we treated with charcoal haemoperfusion and multiple-dose activated charcoal (MDAC). A 66-yr-old male naive to phenobarbital therapy was brought to hospital by ambulance, intubated, and manually ventilated, after intentional ingestion of 6 g of phenobarbital. He had a background of unremitting chronic abdominal pain, ischaemic heart disease, hypertension, and congenital partial atonic bowel. Time of ingestion was unclear but <5 h before. Signs at presentation were ventilatory frequency 12 bpm, pulse oximetry 100% (FIO2 100%), hypotension (88/58 mm Hg), heart rate 64 beats min−1, Glasgow coma score 3/15, miosis (2 mm bilaterally), areflexia, and hypothermia (33.1°C). An arterial blood gas (FIO2 100%) demonstrated pH 7.29, Po2 72 kPa, Pco2 7 kPa, and lactate 1.8 mmol litre−1. I.V. normal saline and epinephrine infusions were commenced and a warming blanket was applied. A nasogastric tube was inserted and normal bowel sounds were heard, allowing for the commencement of MDAC 25 g every 2 h. The patient was transferred to the intensive care unit (ICU). Initial phenobarbital concentration was 409 µmol litre−1 (reference range 65–170 µmol litre−1) and with serial measurements over the following 7 h, it did not decrease (Fig. 1). In anticipation of a prolonged ICU admission, concern over use of an epinephrine infusion in a patient with coronary artery disease, and potential suboptimal response to MDAC, given the history of partial atonic bowel, charcoal haemoperfusion was commenced. This was performed using a PrismaFlex machine with a Gambro Adsorba 30C cartridge and blood flow 300 ml min−1 for 5 h. Approximately 1 h after starting haemoperfusion, the patient became hypertensive, so epinephrine was stopped and a glyceryl trinitrate infusion commenced. Over the next hour, spontaneous respiratory effort returned. At the conclusion of the 5 h treatment, the serum phenobarbital concentration was 214 µmol litre−1. Metabolic disequilibria complicating the treatment included hypomagnesaemia 0.55 mmol litre−1, hypocalcaemia 1.55 mmol litre−1, hypophosphataemia <0.3 mmol litre−1, and thrombocytopaenia 68×109 litre−1, which were readily corrected. A rebound increase in serum phenobarbital concentration did not occur. Treatment with MDAC continued overnight and the apparent elimination half-life of phenobarbital was 19.1 h. Progressive clinical recovery was observed, including opening his eyes and spontaneous movement of four limbs. The patient was alert 24 h after stopping haemoperfusion, allowing for weaning of MDAC the following day. Extubation and cessation of mechanical ventilation followed, 59 h after admission. He continued to make rapid improvement thereafter and was discharged from ICU after 77 h. Using multiple paired blood samples, the initial extracorporeal phenobarbital clearance was calculated to be 163 ml min−1, a potentially 40-fold increase in endogenous clearance,1Roberts DM Buckley NA Enhanced elimination in acute barbiturate poisoning'a systematic review.Clin Toxicol. 2011; 49: 2-12Crossref PubMed Scopus (50) Google Scholar but this decreased progressively with saturation of the charcoal cartridge, amounting to only 64 ml min−1 at the conclusion of the treatment. The total amount of phenobarbital removed by haemoperfusion was calculated to be 2.3 g, more than 30% of the reported exposure. This case documents apparent clinical and pharmacokinetic benefits from enhanced elimination in the treatment of severe acute phenobarbital poisoning. Improvements in respiratory and haemodynamic status were apparent within hours of treatment. In contrast, intoxication may persist for many days in patients with phenobarbital poisoning who do not receive these treatments.1Roberts DM Buckley NA Enhanced elimination in acute barbiturate poisoning'a systematic review.Clin Toxicol. 2011; 49: 2-12Crossref PubMed Scopus (50) Google Scholar These clinical benefits most likely relate to the marked increase in phenobarbital clearance by haemoperfusion and MDAC. This is possible because phenobarbital has a small volume of distribution, minimal protein binding, and low endogenous clearance.1Roberts DM Buckley NA Enhanced elimination in acute barbiturate poisoning'a systematic review.Clin Toxicol. 2011; 49: 2-12Crossref PubMed Scopus (50) Google Scholar On the basis of the limited literature available, it is not possible to confirm that charcoal haemoperfusion improves clinical outcomes in all patients with severe poisoning.2Chau AMT Roberts DM More data on the effect of haemoperfusion for acute poisoning is required.Blood Purif. 2011; 31: 41Crossref PubMed Scopus (3) Google Scholar While this technique is less commonly used in recent times, our case demonstrates that with appropriate monitoring, it can be a safe and effective treatment. None declared.