Clinical pharmacology : other adjuvants

Nitrous oxide is a useful short-acting adjunct, which provides some analgesia in labor and is effective for procedural analgesia in adults and children in a wide variety of settings. Its adverse effects on vitamin B12, in particular with repeat exposure, require consideration and supplementation to avoid rare, but serious toxicity leading to bone marrow suppression and neuropathy. Continuous infusions of low doses of the N-methyl-Daspartate (NMDA) receptor antagonist ketamine have opioid-sparing effects and reduce adverse effects of opioids in the acute pain setting. This approach also has a preventive analgesic effect, provides analgesia in pain poorly responsive to opioids, and may be particularly useful in settings of hyperalgesia, allodynia, and opioid tolerance. The alpha-2 adrenoreceptor agonists clonidine and dexmedetomidine have an opioid-sparing effect in the acute pain setting; however, they can lead to sedation and hypotension. Anticonvulsants, in particular the gabapentinoids gabapentin and pregabalin, are not only effective in acute neuropathic pain states, but also in reducing postoperative pain and opioid requirements. They may become an important component of multimodal analgesia. Antidepressants play no role as adjuvants in the treatment of acute pain, but have shown a preventive effect on the development of subsequent chronic pain states. Corticosteroids, in particular dexamethasone, are not only a very effective prophylaxis for postoperative nausea and vomiting, but also reduce pain and swelling in certain postoperative settings. Calcitonin is an effective treatment for the pain of vertebral crush fractures and for postamputation phantom limb pain. Systemic administration of lidocaine is an effective treatment of acute neuropathic pain of peripheral and central origin; due to its anti-inflammatory effect it might also be a useful adjuvant for perioperative pain treatment with benefits for analgesia and outcome.