Suspected acute post‐transplant neuropsychosis due to interaction of morphine and cyclosporin after a renal transplant

We should like to report a patient who developed severe neurological symptoms 2 days post-transplant after simultaneous intravenous infusion of morphine and cyclosporin (CsA). There is an increasing incidence of transplant patients developing neurological complications and the precise molecular mechanisms of CsA neurotoxicity are yet unknown [1]. We believe this observation may highlight psychiatric manifestation induced by drug interaction between CsA and morphine. A 45-year-old man underwent renal transplantation in January 1999. Pre-operatively, continuous infusion CsA (6 mg.kg−1.day−1) for 2 h was given. Induction of anaesthesia with fentanyl 150 µg, thiopental 4 mg.kg−1 and succinylcholine 1.5 mg.kg−1 was performed. Anaesthesia was maintained with 0.5–2.0% isoflurane in an oxygen/nitrous oxide mixture. Atracurium was administered for additional muscle relaxation. Postoperatively, he was immunosuppressed with CsA (6 mg.kg−1.day−1 continuous infusion for 2 h) combined with methyl prednisolone 120 mg.day−1 intravenously. At the same time, PCA via a Baxter infuser provided a morphine 0.5-mg bolus with a 6-min lockout interval. A total dose of 13 mg and 11 mg was demanded, respectively, for the 1st and 2nd postoperative day. On the 3rd day, he presented with insomnia, anxiety, amnesia, aphasia and severe confusion. All laboratory data were within normal ranges. ICU syndrome was suspected and the PCA was discontinued. Medications including propofol, diazepam and haloperidol were given for 24 h and the symptoms subsided. On the 4th day, oral CsA replaced intravenous administration. The serum creatinine level and CsA level was maintained at 1.3 mg.dl−1 and 300–400 ng.dl−1, respectively. There was no recurrence of neurological manifestations. After transplantation, the immune response signalling pathways can release calcium stored in the endoplasmic reticulum. The sustained high calcium concentration in the cytosol helps to commit the T cell to activation by activating calcium-regulated enzyme such as calcineurin [2]. CsA antagonises Ca2+/calcinurin protein kinase activity, which inhibits gene transcription associated with the brain's dopaminergic and opiate pathways [3]. This may cause symptoms similar to CsA neurotoxicity manifested in clinical practice. On the other hand, during the early post-transplant period, the postischaemic graft kidney may have impaired morphine clearance [4], which may lead to elevated serum morphine level and prolonged opioid action. We hypothesise that the intracellular hypercalcaemic effect of CsA may cause a decreased excitation threshold of the neuronal cell, thereby potentiating or amplifying the dysphoric effect of morphine or causing the neuropsychiatric manifestation during the early post-transplant period in our patient.