She was noted to have blue lips and oxygen saturations were recorded at 80%. A signaling pathway Guedel airway was inserted (to which Miss Z did not respond) and oxygen was administered via a facemask. This resulted in an improvement in her oxygen saturations. She was again taken by ambulance to the accident and emergency department. On arrival at the accident and emergency department intravenous flumazenil was administered, and it was noted that she almost immediately regained consciousness. Inhibitors,research,lifescience,medical She remained in hospital for a period of observation for 4 hours but no further deterioration was noted. Following these reactions Miss Z has not received any further benzodiazepines.

Discussion This case demonstrates the potential hazard of using a drug with a long half-life for rapid tranquillization, particularly if multiple doses are needed over a short period of time. Figure 1 illustrates an estimation of plasma levels in our patient assuming a half-life of 39 hours to generate the gradient of Inhibitors,research,lifescience,medical the line and assuming that plasma level rise is directly proportional to the dose given. It can be seen that as the next dose of medication is given before the first half-life has been reached, the maximum plasma drug level

is continuing to rise. The last dose of clonazepam was only 0.5 mg, but as indicated in Figure 1 it is likely that the plasma level increased to the same level as the previous night. Inhibitors,research,lifescience,medical If Miss Inhibitors,research,lifescience,medical Z’s metabolism of clonazepam resulted in an increased half-life of the medication longer than 39 hours, then the rise in plasma levels would have been more dramatic. Figure 1. Estimated clonazepam

plasma level with repeated doses. As well as the long half-life, a further factor which may have Inhibitors,research,lifescience,medical contributed to Miss Z’s delay in onset of severe respiratory depression/respiratory arrest is the enterohepatic recycling associated with clonazepam. This can result in multiple peaks in plasma concentration [Davies et al. 2010]. The other possible cause of the symptoms in this case which was considered was the possibility of an allergic reaction in view of the reported lip swelling and blistering. However, in view of the fact that the symptoms occurred several hours after the medication was given and the patient recovered without any treatment for allergy makes this unlikely. No swelling or blistering was reported by Mephenoxalone the accident and emergency staff. The other fact that points against it being an allergic cause was the rapid response and recovery after intravenous flumazenil was administered. An additional issue raised by this case is the fact that there is an effective reversing agent for the effects of benzodiazepines, i.e. flumazenil [Thompson et al. 2006; Heard et al. 2009]. However, it is only licensed for intravenous use, which is not a route available to nursing staff in most mental health hospitals.