2.3 Routes of administration
The most common route of administration is intravenous. Other routes often employed include intramuscular and oral routes. Increasingly, several other routes are being explored such as subcutaneous, intranasal, epidural, rectal, topical, nebulization, and transdermal.34,35,36 Studies to evaluate the plasma levels of ketamine after nasal and rectal administration as compared to intravenous administration in children have found acceptable levels for analgesia.37 The transdermal route has also been shown to be effective for postoperative analgesia.38Pharmacokinetic details of major routes of administration have been depicted in table 1. The bioavailability of oral ketamine is low because of the extensive first-pass metabolism.39 There is a paucity of data on the pharmacological aspects of the lesser-known routes.
Uses
The primary purpose for the development of ketamine was anesthesia, due to its aforementioned unique advantages over opioids. Its safety profile also allowed its use in non-OT settings including wars and mass casualties.43 However, with the advent of newer anesthetic agents and the propensity for neurocognitive effects of ketamine, its use declined significantly, especially in the developed world. Nevertheless, its utility continued to be evaluated, and lately, it is gaining renewed interest as an adjunct to opioid-based anesthesia, to overcome issues like post-anesthesia delirium.44Ketamine is also considered a particularly useful agent for pediatric anesthesia because of its safety profile. Ketamine has been adjudged as an excellent drug for short-term medical procedures, due to its potent analgesic and sedative effect, favorable hemodynamic profile, and short duration of action.
The excellent analgesic effect of ketamine has been known for almost five decades, with the added benefit of much lesser neuropsychiatric adverse effects noted with the doses sufficient for analgesia. Although several reports have found it to be remarkably effective for neuropathic pain, including chronic cancer-related pain, systematic evidence for the same from large-scale randomized controlled trials is lacking.45,46,47,48 The analgesic efficacy of ketamine has also been replicated in children of various ages and disease profiles.49,50,51
Systemic ketamine has been used in acute severe asthma owing to its bronchodilatory effect, although clear evidence of benefit is lacking.52,53,54 Similarly, the role of ketamine in refractory and super-refractory status epilepticus is being increasingly recognized wherein it acts chiefly through its antagonistic effect on excitatory glutaminergic action.55 However, no standard protocols are available for either of these uses. Another well-described use of ketamine is in treatment-resistant depression in adults, wherein it has been thoroughly investigated. A recent systematic review of the efficacy of ketamine for treatment-resistant mood disorders in children found an overall beneficial effect in terms of depressive symptoms, suicidality and mood lability, but emphasized on the need for further systematic evaluation in children.56 Intranasal ketamine is useful in migraine by reducing the severity of aura.57
Scope in Pediatric Oncology