Diederik Van Sassenbroeck

Abrupt awakening phenomenon associated with gamma-hydroxybutyrate use : A case series

Case reports mention a sudden awakening from GHB-associated coma but do not specify its time course. The aim of the present case series was to investigate the time course of the awakening from GHB intoxication and the relationship to plasma concentrations of GHB and the presence of other drugs. Unconscious (GCS ≤8) participants at six large rave parties who were treated at medical stations were included. Serial blood samples were taken every 10 to 30 minutes for toxicological analysis. At the same time-points, the depth of coma was scored with the Glasgow Coma Score (GCS). Fifteen out of 21 unconscious patients proved to be positive for GHB. Fourteen of these had ingested one or more other drugs. The median GHB plasma concentration upon arrival in the medical station was 212 μg/ml (range 112 to 430 μg/ml). In 10 patients the GCS was scored more than twice, allowing study of the time course. The GCS of these patients remained ≤8 for a median time of 90 minutes (range 30 to 105 minutes). The duration of the transition between GCS of ≤8 and ≥12 was 30 minutes (range 10 to 50 minutes). A subgroup of five patients had a GCS of 3 upon arrival and remained at 3 for a median time of 60 minutes (range 30 to 110 minutes), while the median time for the transition between the last point with GCS 3 and the first with GCS 15 was 30 minutes (range 20 to 60 minutes). This case series illustrates that patients with GHB intoxications remain in a deep coma for a relatively long period of time, after which they awaken over about 30 minutes. This awakening is accompanied by a small change in GHB concentrations. A confounding factor in these observations is co-ingested illicit drugs.

Three Cases of Substitution Errors Leading to Hyoscine Hydrobromide Overdose

We report three patients with anticholinergic poisoning caused by the substitution of hyoscine hydrobromide for hyoscine butylbromide in preparations compounded by two different pharmacists. The patients took the preparations for gastrointestinal discomfort and presented with altered mental status, tachycardia, facial flushing, dilated pupils, and dry skin shortly after the ingestion. In one patient the intoxication was initially not recognized and he was treated as suffering from an acute cerebrovascular accident. Two patients experienced long-lasting effects such as decreased ability to concentrate, memory disturbances, tremor, and photo- and phonophobia. It was obviously impossible to elucidate the exact nature of the relationship between the intoxication and these long-lasting complaints. Information from the Belgian poison control center revealed that cases of substitution error with hyoscine hydrobromide are not unique. The Belgian authorities issued a warning to all pharmacists.

Influence of Hypovolemia on the Pharmacokinetics and Electroencephalographic Effect of γ-Hydroxybutyrate in the Rat

Background Hypovolemia alters the effect of propofol in the rat by influencing the pharmacokinetics and the end organ sensitivity. We now studied the effect of hypovolemia on the anesthetic &ggr;-hydroxybutyrate (GHB) because in contrast with propofol it increases blood pressure. Methods Thirty-two rats were randomly assigned to undergo moderate hypovolemia or a control procedure. Each rat received either an infusion of sodium–GHB (390 mg · kg−1 · 5 min−1) or the same volume of an equimolar solution of sodium chloride (6.9%). Plasma samples were taken for GHB assay (high-performance liquid chromatography) and the electroencephalography and blood pressure values were recorded. A two-compartment model with Michaelis–Menten elimination was fitted to the concentration-time data and a sigmoid Emax model to the electroencephalographic effect versus effect site concentration curve allowing the study of the end organ sensitivity. Results Plasma concentration–time curves and the total volume of distribution in hypovolemic and normovolemic rats were comparable with only small but significant differences in central volume of distribution and the intercompartmental clearance. There was no significant difference either in the distribution from the plasma to the brain (ke0) or in the end organ sensitivity (EC50 = 335 ± 76 &mgr;g/ml in control vs. 341 ± 89 &mgr;g/ml in hypovolemic rats). GHB temporarily increased mean arterial pressure in both groups, which cannot be explained by the sodium salt alone. Conclusions Hypovolemia does not influence the overall concentration–time curve of GHB and induces no changes in the electroencephalographic effect of GHB in the rat. This difference with propofol may be due to the fact that it increases blood pressure but also due to its different pharmacokinetic properties.

Influence of naloxone on the increased sensitivity to propofol during hypovolemia in the rat.

ObjectiveHypovolemia has been shown to decrease the dose requirement for propofol. This increased effect has been explained partially by an increased end organ sensitivity to the anesthetic effect of propofol. We used the opioid blocking agent naloxone to test the hypothesis that endogenous opioids may be involved in this increased sensitivity. SubjectsThirty-two chronically instrumented rats were assigned randomly to either the hypovolemia (n = 16) or the control (n = 16) group. InterventionsAfter pretreatment of each rat in the two groups with either intravenous saline (n = 8) or naloxone (3 mg/kg; n = 8), an intravenous infusion of propofol (150 mg·kg−1·hr−1) was given until 5 secs of electrical suppression of the electroencephalographic signal was observed. Return of righting reflex was used to assess depth of anesthesia, and the propofol blood concentration was determined simultaneously with high-performance liquid chromatography. Measurements and Main Results The mean propofol blood concentrations at the return of righting reflex were significantly lower in the hypovolemic animals compared with the controls within both naloxone-treated (2.1 ± 0.2 &mgr;g/mL vs. 2.9 ± 0.2 &mgr;g/mL;p < .01) and saline-treated (2.2 ± 0.1 vs. 3.0 ± 0.2 &mgr;g/mL;p < .01) rats. The mean concentrations were not different between the saline- and naloxone-treated rats either within the hypovolemic group or within the control group. ConclusionsThe results of our study indicate that it is unlikely that the increased end organ sensitivity to propofol during hypovolemia is mediated by endogenous opioids, because it was not reversed by naloxone.