Page 131 Acute Pain Management
P. 131
The following tick boxes represent conclusions based on clinical experience and expert
opinion.
Neuropathy and bone marrow suppression are rare but potentially serious complications
of nitrous oxide use, particularly in at‐risk patients (U).
The information about the complications of nitrous oxide is from case reports only. There
are no controlled studies that evaluate the safety of repeated intermittent exposure to
nitrous oxide in humans and no data to guide the appropriate maximum duration or
number of times a patient can safely be exposed to nitrous oxide. The suggestions for the
use of nitrous oxide are extrapolations only from the information above. Consideration
should be given to duration of exposure and supplementation with vitamin B12,
methionine, and folic or folinic acid (U).
If nitrous oxide is used with other sedative or analgesic agents, appropriate clinical
monitoring should be used (U).
4.3.2 NMDA-receptor antagonists
NMDA receptor/ion channel complexes are sited peripherally and centrally within the nervous
system (De Kock & Lavand'homme, 2007). Activation of NMDA receptors via glutamate release
from excitatory synapses augments the propagation of nociceptive information and is linked
to learning and memory, neural development and neuroplasticity, as well as acute and chronic
pain states and opioid‐induced tolerance. At the spinal level, NMDA receptor activation results CHAPTER 4
in the development of central sensitisation manifested clinically as hyperalgesia and allodynia
(De Kock & Lavand'homme, 2007; Hocking et al, 2007).
The NMDA‐receptor antagonists ketamine, dextromethorphan, amantadine, memantine and
magnesium have been investigated for the management of acute pain.
Ketamine
In low (sub‐anaesthetic) doses, ketamine acts primarily as a non‐competitive antagonist of the
NMDA receptor, although it also binds to many other sites in the peripheral and central
nervous systems (Visser & Schug, 2006; Hocking et al, 2007). The principal effect of ketamine at
these doses is as an ‘antihyperalgesic’, ‘antiallodynic’ and ‘antitolerance’ agent and not as a
primary analgesic per se (Hocking et al, 2007). Consequently, ketamine’s main role is as an
adjuvant in the treatment of pain associated with central sensitisation such as in severe acute
pain, neuropathic pain and ‘opioid‐resistant’ pain. It may also reduce the incidence of chronic
postsurgical pain (CPSP) (see Section 9.1) and attenuate opioid‐induced tolerance and
hyperalgesia (see Section 11.7).
Ketamine may also be useful for the treatment of opioid‐resistant or ‘breakthrough’ cancer
pain and, in higher doses or combined with agents such as midazolam, it can provide effective
and safe analgesia for painful procedures (see below).
Elia and Tramer (Elia & Tramer, 2005 Level I) reviewed a heterogenous group of studies, with
varying routes of ketamine administration (parenteral and non‐parenteral) and dosing
regimens. They found no clinically significant effect on pain scores for up to 48 hours after
surgery (although the difference was significant up to 24 hours, pain scores were reduced, on
average, by less than 1 cm on a 10 cm VAS). Despite demonstrating a significant (30%) opioid‐
sparing effect, there was no reduction in opioid‐related adverse effects, including PONV.
Bell et al (Bell et al, 2006 Level I) also reviewed studies of ketamine given by a variety of routes
at a variety of times relative to the surgery, but concentrated their meta‐analysis on ketamine
infusions used in conjunction with morphine PCA. They also reported opioid‐sparing but, in
Acute pain management: scientific evidence 83
