Remifentanil
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Apnoea: case report A girl [age not stated] developed apnoea following administration of remifentanil during induction of anaesthesia. An early school-age girl was scheduled for a surgery of protruding ear. After investigation, she was assumed to have minimal risk with anaesthesia (ASA I). She was pre-medicated with paracetamol and midazolam. For local infiltration anaesthesia, she started receiving IV remifentanil 0.3 µg/kg/minute infusion through pump. Due to anxiety/ distress, the propofol infusion was started at the same time with a pre-programmed propofol bolus. She went under anaesthesia quickly. She developed a short-term apnoea, which was suspected to be due to remifentanil. The girl quickly began to breathe spontaneously again. She had a RR of 20–26 breaths/minute and a tidal volume of 120–140mL (almost normal for her age in a calm, awake patient). Therefore, the remifentanil infusion was increased up to 1 µg/kg/minute (high dose). The infusion pump, connections and peripheral venous catheter were checked to rule out possibility of disconnection, an error in programming or paravenous infusion. Even after the administration of remifentanil at 4 µg/kg, she showed no expected signs of opioid efficacy. Therefore, another anaesthesiologist was consulted. At that time, she was sleeping but was breathing on her own and with pupils of normal size. A new check was conducted to rule out the most common sources of faulty effect. A new syringe of remifentanil was requested to rule out the possibility of something wrong with the contents of the previous syringe. Meanwhile, she received rapidly repeated doses of the IV fentanyl of up to 100µg i.e. 4.8 µg/kg. Fentanyl also showed no effect. The previous remifentanil syringe was then replaced with a new syringe. Even with a total dose of remifentanil 8 µg/kg (170µg; overdose) over 15–20 minutes she still had RR of around 20 breaths/minutes and unchanged tidal volume. Then she received IV morphine 2mg but had no effect. Therefore, anaesthesia was changed to combined anaesthesia with sevoflurane, and the propofol infusion was stopped. Propofol bolus was then administered along with cisatracurium besilate. She was intubated. Her HR increased to 140 bpm and BP increased to 118/67mm Hg. Subsequently, she received ketamine and bupivacaine with adrenaline. The anaesthesia was further maintained using ketamine and sevoflurane. Thereafter, the surgery was completed. Prior to waking up, she received dexamethasone as adjuvant pain relief and nausea prophylaxis and ketorolac. Post-operatively, her pain was controlled with paracetamol and ibuprofen. Later, it was found out that she had a homozygous Arg181Cys gene defect in the OPRM1 gene. This gene defect was determined to be responsible for the lack of response to opioids (remifentanil, fentanyl and morphine). Author comment: "It is well known that there is large interindividual variability in opioid response, but a dose of 4 µg/kg remifentanil over 7–8 minutes is 2–4 times that which would induce apnoea in the vast majority of
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