Misdiagnosis of Malignant Hyperpyrexia

One report concerned a post-operative death which the expert for the coroner thought was probably due to serotonin syndrome and iatrogenic pulmonary oedema. The coroner raised concerns about the apparent lack of knowledge regarding recognition and treatment of neuroleptic malignant syndrome versus serotonin syndrome.

In this case the combination of fentanyl and ondansetron was thought to have caused serotonin syndrome. The use of Dantrolene and poor fluid management were also highlighted.  We pointed out that this drug combination is extremely common in analgesia and sedation, and the incidence of either of these two complications is vanishingly rare. However, we would recommend the following articles about these conditions.1,2,3 We would also recommend as long a delay as practical between the administration of ondansetron and fentanyl during anaesthesia.

Since SALG’s response was submitted, the manufacturer of Dantrium 20mg vials has withdrawn these from the UK market. The use of Dantrium (Dantrolene Sodium) 20mg vials was thought to contribute to fluid overload as each vial requires 60ml of sterile water to reconstitute, and in addition contains 3000 mg of mannitol. The initial treatment dose is 2.5 mg/kg so an 80 kg patient required 10 vials containing 600 ml of water and 30 g of mannitol.

Dantrium has now been discontinued and is being replaced by Dantrolene sodium hemiheptahydrate, produced by Agilus. This comes in 120 mg vials and has the same 2.5 mg/kg dose. A 200 mg dose of Agilus is dissolved in 33 ml of water and does not contain mannitol, reducing the risk of fluid overload.

References

1. Bartakke, A. et al, Serotonin syndrome in the perioperative period, BJA Education, 20(1): 10e17 (2020) https://doi.org/10.1016/j.bjae.2019.10.003

2. Adnet, P. et al, Neuroleptic malignant syndrome, British Journal of Anaesthesia 85 (1): 129-35 (2000) https://doi.org/10.1093/bja/85.1.129

3. Baldo, B. and Rose, M., The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review. British Journal of Anaesthesia, 124 (1): 44e62 (2020) https://doi.org/10.1016/j.bja.2019.08.010