Successful Treatment of Acute Phenobarbital Intoxication by Hemodiafiltration

To the Editor:

A 47-year-old woman was admitted to the ICU in a coma. Twelve hours before admission, the patient had taken pills and had gone to sleep. Because of family problems, a suicide attempt was considered a possible cause of the unconsciousness. The woman worked as a pharmacy technician. She had a noncontributory medical history and did not use drugs or alcohol.

Shortly after admission the patient was intubated because of respiratory insufficiency. Physical examination and laboratory results were normal. The patient was hemodynamically stable with a normal blood pressure and heart rate. A CT scan of the cerebrum did not reveal any abnormalities. The patient did not respond to repeated doses of flumazenil. The patient was given two doses of activated charcoal (40 g) combined with sodium sulphate (30 g) at 11 and 15 hours after admission.

Drug screening was negative for benzodiazepines, amphetamines, cannabinoids, cocaine, methadone, opiates, and acetaminophen. The screening was positive for barbiturates. By a specific immunoassay (FPIA) a phenobarbital serum concentration of 106 mg/L (toxic level >40 mg/L)¹ was measured, explaining the patient's clinical state.

Due to phenobarbital's long half-life (t1/2= 1.5–4.9 days) (1) and the high serum level, the patient was anticipated to remain comatose for days, without extracorporeal elimination. The benefits of hemoperfusion (2[#x02013]5) and hemodialysis (6[#x02013]8 in phenobarbital intoxication have been described. Hemoperfusion is generally considered more efficient than hemodialysis because of the high protein binding of phenobarbital. However, hemoperfusion is associated with a larger number of complications compared to hemodialysis (9). In order to overcome back filtration associated with hemodialysis with high-flux membranes, hemodiafiltration was chosen as the treatment modality in this patient. To our knowledge no data are available about the effectiveness of hemodiafiltration in phenobarbital overdose.

Sixteen hours after admission, the patient was treated with 4 hours of hemodiafiltration using a high-flux, high-efficiency membrane (Polyflux 24S, Gambro®; Lund Sweden; surface area 2.4 m²). Dialysate flow rate was 500 mL/min, blood flow rate was 400 mL/min, filtration rate was 2 L/h. Within 30 minutes, the patient regained consciousness and became restless. Peripheral serum concentrations of phenobarbital as well as serum levels immediately after hemodiafiltration were measured. In Fig. 1, peripheral phenobarbital serum levels vs. time after admission are depicted. The calculated half-life time during hemodiafiltration was 2.4 h [derived from t = 16 h (94.4 mg/L) and t = 20 h (30.3 mg/L)] compared to 64 h [derived from t = 0 h (121.9 mg/L) and t = 13 h (106 mg/L)] before and 26 h [derived from t = 38.4 h (23.8 mg/L) and t = 56 h (15 mg/L)] after hemodiafiltration. No rebound effect was seen after cessation of the treatment. The patient fully recovered and was discharged 72 h after admission. We estimate the contribution to the enhanced clearance of the two doses of charcoal, administered before hemodiafiltration, to be modest².

Figure 1. Phenobarbital serum concentration vs. time after admission. The arrows indicate the time at which hemodiafiltration was started and stopped (t = 16 h and t = 20 h).

This case illustrates that hemodiafiltration with a high-efficiency dialyser gives excellent clearance of phenobarbital. The half-life of phenobarbital during hemodiafiltration (2.4 h) is comparable or shorter compared to reports in literature during hemoperfusion (4.5–16.4 h) (2,3,4,5) and hemodialysis (3.2–8.3 h) (6,7,8). Hemodiafiltration appears to be an effective treatment of phenobarbital intoxication.