4.1 Cancer-related pain
Cancer-related pain can be severely debilitating. Opioids have traditionally been the mainstay of pain management in such patients. However, the somnolence induced by these drugs may sometimes be unacceptable, with impairment in the child’s quality of life and ability to communicate. Moreover, tolerance to opioids is a common concern, with requirements of increasingly higher doses. Ketamine, due to its low sedation potential and safe hemodynamic profile, has been used as an adjunct to opioids and is often regarded as second-line therapy after opioids for intractable neuropathic pain in pediatric oncology practice, with usual doses ranging from 0.025-0.3 mg/kg/hour.58In pediatric end-of-life care, the role of ketamine patient-controlled analgesia (PCA) has also been mentioned.59 Low dose ketamine infusion for refractory pain in children with cancer has been shown to significantly reduce pain as well as the requirement of opioid dose.60,61,62 In this regard, the anti-hyperalgesic and anti-allodynic effect of ketamine has been well-described.63,64 However, a recent systematic review found no post-operative opioid-sparing effect of ketamine in children.65 Epidural ketamine in combination with morphine has been found to increase the duration of analgesia.66 Oral ketamine doses ranging from 0.25-1 mg/kg/dose are safe and effective in children with chronic pain.67 Oral ketamine offers the distinct advantage of the ease of administration combined with potent analgesic, something which has so far been achieved satisfactorily only with a handful of agents. Despite the emerging evidence for ketamine for cancer pain, its use currently remains largely off-label. World Health Organization (WHO) has discontinued its guidelines on the pharmacological treatment of persisting pain in children with medical illnesses (2012) in light of new evidence and is revising it, but perhaps it would be premature to list ketamine as an upfront analgesic after opioids for children with cancer.68 Moreover, ketamine doesn’t find a mention in WHO guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents (2018), in the absence of concrete evidence from high-quality studies.69Table 2 provides a summary of the prospective studies of ketamine for cancer pain in children.