Pentobarbital suicide attempt in a young pregnant veterinary assistant

Abstract

We describe a case of pentobarbital (Dolethal®) acute intoxication in a 20 weeks pregnant woman and discuss the intoxication consequences in the mother and in the foetus. We report the case of a 24-year-old pregnant veterinary assistant who attempt to kill herself by ingestion of 9 g of pentobarbital. At the EMS arrival, the patient is in cardio respiratory arrest and an external cardiac massage is undertaken. It permits to restore the cardio respiratory activity without the use of adrenaline or external electrical shock. The patient is then intubated and transferred directly to medical intensive care unit for further management. At the admission, a hypotension and a deep hypothermia at 33.3 °C are observed. The neurological examination also reveals reactive miosis, hypotonia and a Glasgow Coma Scale (GCS) score of 3. A complete blood biological investigation including a screening by LC-MS-MS of pharmaceuticals and drugs of abuse has been performed at the admission. It has been completed by a regular measurement of pentobarbital concentrations by HPLC-DAD in sera samples taken respectively at 3, 11, 30, 50 and 70 ho after the supposed ingestion of pentobarbital. As there are few data in the literature regarding the pentobarbital toxicokinetics in pregnant women, we have conducted a non-compartmental analysis using the PKSolver software to determine the toxicokinetics parameters including elimination half-life (t 1/2 ), total plasma clearance (Cl), volume of distribution (V D ) and area under the curve (AUC). Para clinical exams (an electroencephalogram [EEG]) (on day 1) and multiple foetal ultrasounds (at the admission and on day 2) have also been performed to evaluate the gravity of the intoxication in the mother and in the foetus. At the beginning of her care, the patient shows no alteration of her biological parameters except of hypercapnic acidosis (pH: 7.28, pCO2: 50 mmHg). The toxicological analyses don’t reveal the presence of any drug apart from pentobarbital. The pentobarbital serum concentration measured 3 h after pentobarbital ingestion is very high (68.3 mg/L) and a 6 h continuous veinoveinous haemodiafiltration (CCVHDF) has been quickly set up. The serum pentobarbital concentration measured at the end of the CCVHDF (i.e. 11 h after the pentobarbital ingestion) has been determined at 33.6 mg/L (t 1/2 = 8 h). After the haemodialysis stopping, pentobarbital sera concentrations then slowly decrease and are respectively equal to 28.9, 15.9 and 6.7 mg/L at 30, 50 and 70 h after the overdose (t 1/2 = 19.2 h). The non-compartmental analyse has permit to estimate the pentobarbital toxicokinetics parameters in our pregnant patient. Thus V D , Cl and AUC have been respectively calculated at 126.5 L, 76.7 mL/min and 1782.5 mg/L*h. The decrease in pentobarbital concentrations has been correlated with a progressive improvement of the patient consciousness state (evaluated at the admission by an EEG and by the GCS score and then regularly monitored by the GCS score) and with a recovery of spontaneous foetal movements on day 2. As pentobarbital is exclusively reserved for veterinary use in France, few cases of voluntary acute intoxication have been described in recent years and, to our knowledge, no case has been reported in pregnant woman. In our patient, the initial pentobarbital concentration is very high. The rapid setting up of CVVHDF has allowed the pentobarbital elimination half-life to be divided by 2 and to decrease the intoxication duration. Thus foetal movements, that were absent at admission, have been recovered on day 2. During the end course of the pregnancy, no malformation or any development problem have been observed in the foetus. However, as barbiturates cross the placental barrier and distribute in foetal tissues and especially in the brain, close post-natal monitoring is recommended to evaluate the possible later consequences of this in utero exposure.