Sickle cell disease and nitrous oxide-induced neuropathy

We report three cases of peripheral neuropathy in patients with sickle cell disease. All had a history of frequent painful crises and regular attendance at our Accident and Emergency department where nitrous oxide analgesia was administered for prolonged periods. All three patients (one male and two females) presented with difficulty in walking associated with paraesthesiae, and neurological examination revealed signs compatible with a peripheral sensorimotor neuropathy, later confirmed by nerve conduction studies. Serum vitamin B12 levels were mildly reduced in two patients and very low in one patient (< 10 ng/l). Haemoglobin levels in all the patients were unchanged compared with their steady-state levels but one had developed a macrocytosis (103 fl). Schilling tests were normal in two patients, and two patients had negative gastric parietal antibodies. All three patients were given intramuscular vitamin B12 in addition to avoiding further exposure to nitrous oxide, and their neurological symptoms improved completely. As nitrous oxide is known to cause a neuropathy similar to that seen in pernicious anaemia, we postulate that nitrous oxide analgesia combined with low B12 levels was the cause of the marked neuropathy in these patients. As a result of our observations and the probable association, we now do not use nitrous oxide analgesia in the management of patients with sickle cell disease.