Ketamine: Reinventing Chronic Pain Management | Page...
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Login | Register | Subscription PRACTICE SETTING Ketamine: Reinventing Chronic Pain Management | Page 2 Jeannette Y. Wick, RPh, MBA, FASCP Published Online: Friday, August 8, 2014 What Route? To minimize adverse events associated with ketamine use, researchers are examining the use of administration routes other than intravenous. Oral ketamine, as an injectable liquid or a compounded product, is subject to hepatic first-pass metabolism and is less effective than parenteral doses. It also lacks a clear dose-response relationship. 22,35 Some study results suggest that the oral route leads to few side effects. 36 Topical formulations of ketamine or ketamine with other potential analgesics has been used for managing several painful conditions (eg, pelvic pain, pruritus) with mixed results. 22,37-39 Managing Pain Ketamine use in pain management evolved from its perioperative use. Perioperative pain is expected, but may have physical or psychological consequences that delay rehabilitation and prolong hospitalization. 1 Most surgeons use opioids to treat postoperative pain and supplement with regional anesthesia, other analgesics, and adjuvant agents as needed. 1,23,40 Some patients respond poorly or incompletely to opioids; ketamine may help these patients. 26,27,41 In low doses, NMDA-receptor antagonists can provide analgesia and circumvent opioid-related tolerance, hyperalgesia, and allodynia. 10,23,40 Randomized, placebo-controlled, double-blind clinical trials (RCTs) have found that perioperative subanesthetic doses of ketamine added to opioid analgesia improved pain scores and reduced opioid consumption by approximately 30% to 50%. Ketamine was given as an intermittent low-dose intravenous bolus or a continuous infusion. It reduced opioid-related nausea and vomiting and added no additional significant adverse effects. 42,43 Ketamine can also be given with morphine patient-controlled analgesia, contributing a morphine-sparing effect. Patients with chronic neuropathic pain, opioid dependence or tolerance, and acute hyperalgesia seem to benefit more. 42,43 Low-dose ketamine administered before the surgical incision can lead to better analgesia for 24 hours after surgery. 1 Most studies report no significant increase in psychomimetic adverse effects when ketamine is added to morphine. 42,43 Sickle Cell Crisis and Chronic Noncancer Pain Acute sickle cell disease creates severe pain with a neuropathic element. Several published guidelines recommend using opioids as first-line treatment, but some patients are unresponsive to even high opioid doses. Rapidly escalating opioid doses may induce acute tolerance and opioid-induced hyperalgesia. 29,44 Case studies (but no RCTs) indicate that adding a low-dose ketamine infusion to opioids can improve pain in sickle cell disease. 44 Usually, NMDA receptors activate continually only after a severe, sustained painful stimulus allows sufficient glutamate release. This is why ketamine may be useful as an adjuvant in several types of chronic central and peripheral neuropathic pain (Table 2 23,45,46 ). Several of ketamine’s properties may prevent chronic pain from developing: Dampening of nociception Prevention or attenuation of hyperalgesia, allodynia, and tolerance Attenuating central sensitization and windup phenomenon from repeated noxious stimuli when previously nonpainful stimuli become exaggerated and painful 23,40 Clinicians have used short-term subanesthetic doses of ketamine to treat neuropathic pain. 45 Scheduled infusions over several days can improve pain scores in patients with chronic pain; a few MORE ARTICLES >> Pharmacist Threatened with Explosives During Robbery A Delaware man warned a Walgreens pharmacist that he would blow himself up with explosives if she did not comply with his demands for prescription pills. Graft Device Now Approved for Diabetic Foot Ulcers Patients with certain diabetic foot ulcers now have a new treatment option. Pharmacy Week in Review: January 8, 2016 This weekly video program highlights the latest in pharmacy news, product news, and more. Retail Pharmacist MTM Roles Supported by US House More than 40 members of the US House of Representatives have expressed support for greater pharmacist roles in improvements made to Medicare Part D’s medication therapy management (MTM) program. News Videos Resource Centers Continuing Education Community Publications Latest Articles Ketamine: Reinventing Chronic Pain Management | Page 2 http://www.pharmacytimes.com/publications/issue/2014/august201... 1 of 4 1/10/16, 3:07 PM
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PRACTICE SETTING
Ketamine: Reinventing Chronic Pain Management | Page 2Jeannette Y. Wick, RPh, MBA, FASCPPublished Online: Friday, August 8, 2014
What Route?To minimize adverse events associated with ketamine use, researchers are examining the use ofadministration routes other than intravenous. Oral ketamine, as an injectable liquid or a compoundedproduct, is subject to hepatic first-pass metabolism and is less effective than parenteral doses. It also lacksa clear dose-response relationship.22,35 Some study results suggest that the oral route leads to few sideeffects.36 Topical formulations of ketamine or ketamine with other potential analgesics has been used formanaging several painful conditions (eg, pelvic pain, pruritus) with mixed results.22,37-39
Managing PainKetamine use in pain management evolved from its perioperative use. Perioperative pain is expected, butmay have physical or psychological consequences that delay rehabilitation and prolong hospitalization.1
Most surgeons use opioids to treat postoperative pain and supplement with regional anesthesia, otheranalgesics, and adjuvant agents as needed.1,23,40 Some patients respond poorly or incompletely to opioids;ketamine may help these patients.26,27,41
In low doses, NMDA-receptor antagonists can provide analgesia and circumvent opioid-related tolerance,hyperalgesia, and allodynia.10,23,40 Randomized, placebo-controlled, double-blind clinical trials (RCTs) havefound that perioperative subanesthetic doses of ketamine added to opioid analgesia improved pain scoresand reduced opioid consumption by approximately 30% to 50%. Ketamine was given as an intermittentlow-dose intravenous bolus or a continuous infusion. It reduced opioid-related nausea and vomiting andadded no additional significant adverse effects.42,43
Ketamine can also be given with morphine patient-controlled analgesia, contributing a morphine-sparingeffect. Patients with chronic neuropathic pain, opioid dependence or tolerance, and acute hyperalgesiaseem to benefit more.42,43 Low-dose ketamine administered before the surgical incision can lead to betteranalgesia for 24 hours after surgery.1 Most studies report no significant increase in psychomimetic adverseeffects when ketamine is added to morphine.42,43
Sickle Cell Crisis and Chronic Noncancer PainAcute sickle cell disease creates severe pain with a neuropathic element. Several published guidelinesrecommend using opioids as first-line treatment, but some patients are unresponsive to even high opioiddoses. Rapidly escalating opioid doses may induce acute tolerance and opioid-induced hyperalgesia.29,44
Case studies (but no RCTs) indicate that adding a low-dose ketamine infusion to opioids can improve painin sickle cell disease.44 Usually, NMDA receptors activate continually only after a severe, sustained painfulstimulus allows sufficient glutamate release. This is why ketamine may be useful as an adjuvant in severaltypes of chronic central and peripheral neuropathic pain (Table 223,45,46).
Several of ketamine’s properties may prevent chronic pain fromdeveloping:
Dampening of nociceptionPrevention or attenuation of hyperalgesia, allodynia, andtoleranceAttenuating central sensitization and windup phenomenonfrom repeated noxious stimuli when previously nonpainfulstimuli become exaggerated and painful23,40
Clinicians have used short-term subanesthetic doses of ketamineto treat neuropathic pain.45 Scheduled infusions over several dayscan improve pain scores in patients with chronic pain; a few
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Ketamine: Reinventing Chronic Pain Management | Page 2 http://www.pharmacytimes.com/publications/issue/2014/august201...
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studies report pain relief persisting for weeks following treatment,indicating that ketamine may be disease modifying.46
Cancer PainLimited but increasing data support ketamine use in refractory cancer pain. Adding a small dose of ketamineto opioid therapy in a patient with opioid tolerance, called burst therapy, can improve pain management.12,47
Patients on highdose opioids whose cancer pain has a neuropathic component may respond to oralketamine.48 Adding a small dose of ketamine to patient-controlled morphine seems to improve painmanagement, and some researchers are testing a ketamine mouthwash for mucositis.49,50
EndnoteLarge, well-designed RCTs are needed to confirm the analgesic role of ketamine. Most studies suggest, andexperts believe, that ketamine use should be reserved for patients in whom opioids, anticonvulsants, orantidepressants have failed.3,36 Because pain management is an off-label use for ketamine, cliniciansshould consult with field experts for dosing recommendations.
Ms. Wick is a visiting professor at the University of Connecticut.
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