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