Evidence supports the use of intravenous (IV) ketamine for acute pain in a variety of contexts, including as a stand-alone treatment, as an adjunct to opioids, and, to a lesser extent, as an intranasal formulation, according to the first guidelines on the use of ketamine for acute pain management.
Ketamine has captured headlines recently for its potential role in treating severe depression and posttraumatic stress syndrome. Ketamine is also increasingly being used in inpatient and outpatient settings to manage acute pain.
One driving force behind this is the growing effort to reduce the risk for long-term opioid use after acute exposure and its subsequent complications, including addiction. Yet, to date, few recommendations have been available to guide this emerging acute pain therapy.
"The goal of this document is to provide a framework for doctors, for institutions and for payers on use of ketamine for acute pain, who should get it and who should not get it," guideline author Steven Cohen, MD, from Johns Hopkins School of Medicine in Baltimore, Maryland, told Medscape Medical News.
The guidelines were published online June 7 in Regional Anesthesia and Pain Medicine.
Reduced Need for Opioids
Development of the guidelines on use of ketamine for acute pain was a joint effort spearheaded by the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine, which approved the document, as did the American Society of Anesthesiologists' Committees on Pain Medicine and Standards and Practice Parameters.
The guidelines state that subanesthetic ketamine infusions should be considered for patients undergoing painful surgery and may be considered for opioid-dependent or opioid-tolerant patients undergoing surgery.
Ketamine may be considered for opioid-dependent or opioid-tolerant patients with acute or chronic sickle cell pain. For patients with sleep apnea, ketamine may be considered as an adjunct to limit opioids, the guidelines note.
The use of ketamine in subanesthetic doses has "exploded and there definitely seems to be a strong signal that ketamine is effective for acute pain, and a lot of patients don't have other options," Cohen commented.
On dosing, the guidelines recommend that ketamine bolus doses do not exceed 0.35 mg/kg and that infusions for acute pain generally do not exceed 1 mg/kg per hour in settings without intensive monitoring. The authors acknowledge that individual pharmacokinetic and pharmacodynamic differences, as well as other factors, such as prior ketamine exposure, may warrant dosing outside this range.
The guidelines also state that moderate evidence supports use of subanesthetic intravenous ketamine bolus doses (up to 0.35 mg/kg) and infusions (up to 1 mg/kg per hour) as adjuncts to opioids for perioperative analgesia.
Ketamine should be avoided in people with poorly controlled cardiovascular disease, those with active psychosis, and pregnant women.
For hepatic dysfunction, evidence supports that ketamine infusions should be avoided in individuals with severe disease and used with caution, with monitoring of liver function test results before infusion and during infusions in surveillance of elevations in individuals with moderate disease. Ketamine should be avoided in individuals with elevated intracranial pressure and elevated intraocular pressure.
"Powerful, Inexpensive" Tool
The guidelines state that intranasal ketamine is beneficial for acute pain management; it provides not only effective analgesia but also amnesia and procedural sedation.
Scenarios in which this should be considered include individuals for whom IV access is difficult and children undergoing procedures.
For oral ketamine, the evidence is "less robust, but small studies and anecdotal reports suggest it may provide short-term benefit in some individuals with acute pain," the authors say.
They found only "limited" evidence to support patient-controlled IV ketamine analgesia as the sole analgesic for acute or periprocedural pain. However, there is moderate evidence of benefit of the addition of ketamine to opioid-based IV patient-controlled analgesia for acute and perioperative pain management, the authors note.
They conclude that "despite its drawbacks, ketamine remains a powerful and inexpensive tool for practitioners who manage acute pain. We believe its use will continue to expand as more institutions treat increasingly challenging patients in the perioperative period as well as those with painful disease exacerbations while trying to combat the opioid epidemic."
They say more research is needed to "refine selection criteria for the treatment of acute pain and possible prevention of chronic pain, to determine the ideal dosing and treatment regimen to include coadministration of ketamine with opioids and adjuvants, and to better understand the long-term risks of ketamine in patients who receive serial treatments for frequent acute pain exacerbations."
This research had no commercial funding. The authors have disclosed no relevant financial relationships.
Reg Anesth Pain Med. Published online June 7, 2018. Abstract