Page 38 - Delaware Medical Journal - July/August 2020

Table 3: AAPT Diagnostic Criteria for Chronic Pain Associated With SCD7
Core Diagnostic Criteria for Chronic Pain Associated With SCD:
1) Lab test-confirmed diagnosis of SCD
2) Reports persistent pain for most days over past 6 months in single/multiple locations
3) At least 1 in the region of reported pain:
• Palpation elicits focal pain or tenderness.
• Movement elicits focal pain.
• Decreased range of motion or weakness.
• Evidence of skin ulcer.
• Evidence of hepatobiliary or splenic imaging abnormalities (e.g. splenic infarct chronic
pancreatitis) in the region.
• Evidence of imaging abnormalities consistent with bone infarction or avascular
necrosis in the region.
4) No other diagnosis that better explains the signs and symptoms.
the original pain or be uniquely distinct. Although the exact pathophysiology is unknown, it is hypothesized that there is sensitization of nociceptors and neuroplastic alterations in both the central and peripheral nervous systems. Multiple research studies support the involvement of CNS excitatory amino acid receptors, such as N-methyl- D-aspartate aka NMDA, which is in part
a direct effect of the opioids.8 Therefore, current mainstays of management include reducing opioid dosages with optional adjunctive NMDA receptor modulators (e.g. ketamine). Ketamine is primarily used for
its anesthetic properties; however, sub- anesthetic dosing supports additional roles in treating pain, depression, agitation, and status epilepticus.9 Ketamine’s primary mechanism of action is through antagonism of NMDA receptors in the CNS. It also has additional activity with opioid receptors and inhibits
the re-uptake of serotonin, dopamine, and norepinephrine.10 In vivo and in vitro studies have shown analgesic equivalence between ketamine and opioids.11–13 The PICHFORK trial showed that intranasal ketamine (1 mg/kg) provided equivalent analgesia
for moderate-to-severe pain as intranasal fentanyl (1.5 mcg/kg), with a mild side-effect 13
The use of ketamine in managing SCD pain is widely reported with promising results. In one large, single-site study, Sheehy et
al. reported on ketamine use for analgesia among n=181 patients with SCD pain in the
outpatient setting. Dosing was dependent on whether the patient was opioid naive (0.05- 0.4 mg/kg/hr), opioid tolerant (0.05-1 mg/ kg/hr), or had opioid-induced hyperalgesia (1 mg/kg/hr). Ketamine reduced pain scores by a mean of 2 points (out of 10), MME use by 1 mg/kg, with an average pain reduction of1pointbyday2and3pointsbyday5of therapy. Overall, 60% of patients with SCD had greater than 20% pain reduction from continuous ketamine infusion. Fifty-two percent had a greater than 20% reduction
in MME intake, suggesting ketamine
may also be used safely to reduce opioid
use in the outpatient setting.3 reported similar success using a combination ketamine-midazolam regimen to reduce ketamine side effects, and found that after one day, morphine requirements decreased by a mean of 30 mg/day and pain score from a mean of 9.1 to 5.7.14 Lubega et al., in a direct comparison of IV ketamine 1 mg/kg to IV morphine 0.1 mg/kg for acute severe VOC pain in children 7-18 years old (n=240), found that ketamine had less treatment failure (28.3% vs. 40%) and faster onset of pain relief; however, patients receiving ketamine were 11.3 times more likely to experience medication side effects.2 Similar experiences have been reported in pediatrics in the setting of high-dose opioid use among mechanically ventilated children.15
Despite the growing body of literature supporting concomitant use of ketamine with opioids as an opioid-sparing approach
to pain management, the use of ketamine as a mechanism to wean patients off high-dose opioids is a less reported but important, Quinlan et al. report on a cohort of eight patients with chronic pain, with opioid- related tolerance and suspected hyperalgesia, anesthetic ketamine infusion to allow withdrawal from their opioids. All patients tolerated the protocol without hemodynamic instability (blood pressure), over-sedation,
or poorly controlled pain.16 Both Uprety et al and Jennings et al report cases of SCD pain uncontrolled by escalating doses of opioids and non-ketamine adjuvant therapy that
were ultimately controlled after initiating ketamine.17,18 Similar reports have also emerged among adults.19–21 However, despite these positive experiences, the data to support this practice is still limited and consensus guidelines have yet to be established.1,22 This case is amongst the earliest to describe the use of ketamine to wean a pediatric patient with SCD off high-dose opioids and further illustrates the potential role ketamine holds for managing pain related to SCD.
CONCLUSION
Ketamine provides a safe and effective method to rapidly wean patients off high doses of opioids, especially in the setting
of OIH. In some cases, it may even help control pain in patients where opioids fail. Concomitant use of ketamine with opioids may prove useful for managing patients with recurrent pain. This is particularly
true for patients with SCD who represent a population where pain episodes are almost guaranteed, begin in childhood, and have
a high baseline risk of requiring frequent opioids and of developing chronic pain. This case is amongst the earliest to describe the use of ketamine to wean a pediatric patient with SCD off high-dose opioids and further illustrates the potential role ketamine holds for managing SCD pain.
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Del Med J | July/August 2020 | Vol. 92 | No. 4