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Nitrous oxide (N 2 O) is one of the oldest drugs still in use in medicine. Despite its superior pharmacokinetic properties, controversy remains over its continued use in clinical practice, reflecting in part significant improvements in the pharmacology of other anaesthetic agents and developing awareness of its shortcomings. This narrative review describes current knowledge regarding the clinical use of N 2 O based on a systematic and critical analysis of the available scientific literature. The pharmacological properties of N 2 O are reviewed in detail along with current evidence for the indications and contraindications of this drug in specific settings, both in perioperative care and in procedural sedation. Novel potential applications for N 2 O for the prevention or treatment of chronic pain and depression are also discussed. In view of the available evidence, we recommend that the supply of N 2 O in hospitals be maintained while encouraging its economic delivery using modern low flow delivery systems. Future research into its potential novel applications in prevention or treatment of chronic conditions should be pursued to better identify its role place in the developing era of precision medicine.

Background. Recent studies showed that hyperglycaemia (HG) blocks anaesthetic-induced preconditioning. The influence of HG on anaesthetic-induced postconditioning (post) has not yet been determined. We investigated whether sevoflurane (Sevo)-induced postconditioning is blocked by HG and whether the blockade could be reversed by inhibiting the mitochondrial permeability transition pore (mPTP) with cyclosporine A (CsA). Methods. Chloralose-anaesthetized rats (n¼7‐11 per group) were subjected to 25 min coronary artery occlusion followed by 120 min reperfusion. Postconditioning was achieved by administration of 1 or 2 MAC sevoflurane for the first 5 min of early reperfusion. HG was induced by infusion of glucose 50% (G 50) for 35 min, starting 5 min before ischaemia up to 5 min of reperfusion. CsA (5 or 10 mg kg 21 ) was administered i.v. 5 min before the onset of reperfusion. At the end of the experiments, hearts were excised for infarct size measurements. Results. Infarct size (% of area at risk) was reduced from 51.4 (5.0)% [mean (SD)] in controls to 32.7 (12.8)% after sevoflurane postconditioning (Sevo-post) (P,0.05). This infarct size reduction was completely abolished by HG [51.1 (13.2)%, P,0.05 vs Sevo-post], but was restored by administration of sevoflurane with CsA [35.2 (5.2)%, P,0.05 vs HGþSevo-post]. Increased concentrations of sevoflurane or CsA alone could not restore cardioprotection in a state of HG [Sevo-post2, 54.1 (12.6)%, P.0.05 vs HGþSevo-post; CsA10, 58.8 (11.3)%, P.0.05 vs HGþCsA]. Conclusions. Sevoflurane-induced postconditioning is blocked by HG. Inhibition of the mPTP with CsA is able to reverse this loss of cardioprotection. Br J Anaesth 2008; 100: 465‐71