New guidelines for the use of IV ketamine infusions for acute pain management have been published as a special article in Regional Anesthesia and Pain Medicine (2018;43:456-466).
The guidelines were jointly developed by the American Society of Regional Anesthesia and Pain Medicine (ASRA), the American Academy of Pain Medicine and the American Society of Anesthesiologists.
“We have vast experience with the use of ketamine treating severe acute pain, usually in the context of chronic opioid use, chronic pain or with substance use disorder,” said Eugene R. Viscusi, MD, a co-author of the guidelines and the president-elect of ASRA. “We have found ketamine to be an incredibly useful tool with a very acceptable side effect profile, typically less than those from opioids. There is a common misconception, based on the side effects observed with ketamine as an anesthetic, that it is dangerous or that severe side effects should be expected. Because the typical dose for acute pain is in the subanesthetic range, the side effects are usually minimal and generally well tolerated,” explained Dr. Viscusi, who also is a professor of anesthesiology, the chief of pain medicine and the director of acute pain management at Sidney Kimmel Medical College at Thomas Jefferson University, in Philadelphia.
“We hope that the development of the guidelines undertaken by the ASRA will help clinicians understand both the utility and general tolerability of ketamine as an adjunctive agent in managing the most challenging acute pain situations.”
Question and Answer Guidelines
The guidelines pose six key questions and present evidence-supported conclusions, based on a review of articles from MEDLINE, Embase, Google Scholar and Cochrane Database of Systematic Reviews, among other search engines, and manual examination of the bibliographic sections of all manuscripts.
These guidelines are intended for institutions, regulatory bodies, third-party payors and practitioners. The goals are to develop protocols, guide decision making, and improve patient outcomes and safety. The guidelines also define levels of evidence that are based on certainty of benefit and outline what the levels of certainty mean.
Question 1: Which patients and acute pain conditions should be considered for ketamine treatment?
Conclusion: For patients undergoing painful surgery, subanesthetic ketamine infusions should be considered. Ketamine also may be warranted for opioid-dependent or opioid-tolerant patients undergoing surgery, or with acute or chronic sickle cell pain. For patients with sleep apnea, ketamine may be appropriate as an adjunct to limit opioid use.
Question 2: What dose range is considered subanesthetic, and does the evidence support dosing in this range for acute pain?
Conclusion: Ketamine bolus doses should not exceed 0.35 mg/kg, whereas infusions for acute pain generally should not exceed 1 mg/kg per hour in settings lacking intensive monitoring. However, dosing outside this range may be indicated because of an individual patient’s pharmacokinetic and pharmacodynamic factors and other considerations, such as prior ketamine exposure. However, ketamine’s adverse effects prevent some patients from tolerating higher doses for acute pain; therefore, unlike for chronic pain management, lower doses in the range of 0.1 to 0.5 mg/kg per hour may be necessary to achieve an acceptable balance between analgesia and adverse events.
Question 3: What is the evidence to support ketamine infusions as an adjunct to opioids and other analgesic therapies for perioperative analgesia?
Conclusion: There is moderate evidence to support using subanesthetic IV 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.
Question 4: What are the contraindications to ketamine infusions in the setting of acute pain management, and do they differ from chronic pain settings?
Conclusion: Patients with poorly controlled cardiovascular disease or who are pregnant or have active psychosis should avoid ketamine. Similarly, for hepatic dysfunction, patients with severe disease, such as cirrhosis, should not take the medicine; however, ketamine can be given with caution for moderate disease by monitoring liver function tests before infusion and during infusions in surveillance of elevations. On the other hand, ketamine should not be given to patients with elevated intracranial pressure or elevated intraocular pressure.
Question 5: What is the evidence to support nonparenteral ketamine for acute pain management?
Conclusion: Intranasal ketamine is beneficial for acute pain management by achieving effective analgesia and amnesia/procedural sedation. Patients for whom IV access is difficult and in children undergoing procedures are likely candidates. But for oral ketamine, the evidence is less convincing, although anecdotal reports suggest this route may provide short-term advantages in some patients with acute pain.
Question 6: Does any evidence support IV ketamine patient-controlled analgesia (PCA) for acute pain?
Conclusion: The evidence is limited to support IV ketamine PCA as the sole analgesic for acute or periprocedural pain. There is moderate evidence, however, to support the addition of ketamine to an opioid-based IV PCA regimen for acute and perioperative pain therapy.
Despite ketamine’s drawbacks, including the potential for adverse psychotomimetic and cardiovascular effects, the sedative remains a powerful and inexpensive tool for managing acute pain. There is also renewed interest in ketamine as a viable alternative to opioids.