INTRODUCTION
The management of pain in patients with sickle cell disease remains
incomplete and heavily reliant on opioid therapy. [1] Similarly,
pediatric oncology patients with refractory pain due to severe
mucositis, bone pain due to tumor or metastases and end of life pain
have limited utilized treatment options beyond opioids. [2] For
accredited hospitals, The Joint Commission requires pain management
standards inclusive of assessment of pain interventions with the goal of
improving quality of care and decreasing adverse effects of opioid
usage, especially with increasing dosages. [3] High opioid doses for
intractable cancer pain and chronic sickle cell related pain are often
ineffective and should be avoided due to tachyphylaxis and increasing
side effects including sedation, constipation, respiratory depression,
hyperalgesia, allodynia, myotonia and seizure. [4-6]
Chronic opioid utilization leads to tolerance due to downregulation of
N-methyl-ᴅ-aspartate (NMDA) receptors in the spinal cord. [7] As a
NMDA receptor antagonist, ketamine may have beneficial effect on opioid
tolerance and hyperalgesia and act synergistically with morphine.
[4,7] Ketamine additionally has antidepressive effects through its
NMDA receptor blockade. [8] Ketamine is rapidly metabolized and
highly bioavailable when given intravenous or intramuscular. [8]
Multiple publications have reported utilization of subanesthetic
continuous infusion ketamine (i.e., ≤1 mg/kg/h) in pediatric sickle
cell, oncology and chronic pain patients at doses ranging from 0.02-0.4
mg/kg/h (Table 1). [4, 9-23] These studies while generally
retrospective have shown low dose ketamine infusion to be well tolerated
with subjective benefit in some patients without overall impact on
opioid utilization. Based on this literature, we developed a quality
improvement initiative to introduce low dose ketamine infusion (LDKI) to
our hematology/oncology inpatient unit. We subsequently aimed to
determine if LDKI was safe and tolerable in our population and
hypothesized that LDKI would improve pain scores but not decrease opioid
utilization. Here we review our institutional experience and the
relevant literature to date.