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.