INTRAVENOUS KETAMINE INFUSIONS FOR ACUTE PAIN MANAGEMENT
Regional Anesthesia and Pain Medicine: July 2018 – Volume 43 – Issue 5 – p 456–466.
Subanesthetic ketamine, a phencyclidine analog and dissociative anesthetic agent, was first used as a general anesthetic in the 1960s. The use of ketamine in subanesthetic concentrations for analgesia and other indications has exploded recently. The rationale for using ketamine in chronic compared with acute pain is different. For chronic pain, ketamine is purported to reverse central sensitization and enhance descending modulatory pathways; hence, the use of higher cumulative dosages and serial infusions is often advocated. Ketamine’s analgesic properties in acute pain likely derive from its reversible antagonism of the N-methyl-D-aspartate receptor, although it exerts effects on μ-opioid receptors, muscarinic receptors, monoaminergic receptors, γ-aminobutyric acid receptors, and several others.
To date, few recommendations are available to guide this emerging acute pain therapy. In Regional Anesthesia and Pain Medicine: July 2018, a “Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists” was published.
DISCUSSION on Key Questions
I. Which Patients and Acute Pain Conditions Should Be Considered for Ketamine Treatment?
In the case of subanesthetic ketamine in the acute pain setting, patients who benefit most fall into several broad categories.
- The first group of patients are those undergoing surgery in which the expected postoperative pain will be severe. This includes upper abdominal and thoracic surgery, where the greatest benefit in opioid reduction has been reported, as well as lower abdominal, intra-abdominal, and orthopedic (limb and spine) procedures. (grade B recommendation, moderate level of certainty)
Patients undergoing procedures with expected mild levels of pain, such as tonsillectomy and head and neck surgery, have not been shown to benefit from perioperative ketamine.
- Another group of patients who may be considered for acute ketamine therapy are those who are opioid tolerant or opioid dependent and presenting for surgery or those with an acute exacerbation of a chronic condition. (grade B recommendation, low level of certainty)
- Opioid-dependent nonsurgical patients might benefit from ketamine during acute exacerbations of chronic pain conditions. In patients with sickle cell disease. (grade C recommendation, low level of certainty)
- The last subset of patients for whom ketamine may be beneficial is those who are at increased risk for opioid-related respiratory depression, such as those with obstructive sleep apnea (OSA). (grade C recommendation, low level of certainty).
II. What Dose Range Is Considered Subanesthetic, and Does the Evidence Support Dosing in This Range for Acute Pain?
The common subanesthetic dose of ketamine used in clinical practice is intravenous (IV) 0.3- to 0.5-mg/kg bolus, with or without an infusion (usually started at 0.1–0.2 mg/kg per hour) depending on the duration of analgesic response required for a patient. The majority of acute pain studies used bolus doses of less than 0.5 mg/kg and infusion rates of less than 0.5 mg/kg per hour (8 μg/kg per minute).
Therefore, we recommend that ketamine bolus doses do not exceed 0.35 mg/kg, and infusions for acute pain generally do not exceed 1 mg/kg per hour in settings without intensive monitoring, but we also acknowledge that individual pharmacokinetic and pharmacodynamic differences, as well as other factors (eg, prior ketamine exposure), may warrant dosing outside this range. Ketamine’s adverse effects will prevent some patients from tolerating higher doses in acute pain settings, and unlike for chronic pain therapy, lower doses (ie, 0.1–0.5 mg/kg per hour) may be needed to achieve an adequate balance of analgesia and adverse effects (grade C recommendation, moderate level of certainty).
III. What Are the Contraindications to Ketamine Infusions in the Setting of Acute Pain Management, and Do They Differ From Chronic Pain Settings?
- Evidence indicates that ketamine should be avoided in individuals with poorly controlled cardiovascular disease (grade C evidence, moderate level of certainty)
- Pregnancy or active psychosis (grade B evidence, moderate level of certainty).
- For hepatic dysfunction, evidence supports that ketamine infusions should be avoided in individuals with severe disease (eg, cirrhosis) and used with caution (ie, with monitoring of liver function tests before infusion and during infusions in surveillance of elevations) in individuals with moderate disease (grade C evidence, low level of certainty)
- Evidence indicates that ketamine should be avoided in individuals with elevated intracranial pressure and elevated intraocular pressure (grade C evidence, low level of certainty)
IV. What Is the Evidence to Support Nonparenteral Ketamine for Acute Pain Management?
Ketamine is currently approved only for parenteral administration as an anesthetic agent. At present, no FDA-approved nonparenteral formulations exist for oral or intranasal (IN) administration.
in a systematic review evaluating IN ketamine (dose range, 2–10 mg/kg) for procedural sedation and analgesia in children.
We conclude that the use of IN ketamine is beneficial for acute pain management, providing not only effective analgesia but also amnesia and procedural sedation. Particular scenarios in which this should be considered include individuals for whom IV access is difficult and children undergoing procedures (grade C recommendation, low-to-moderate level of certainty). 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 (grade C recommendation, low level of certainty)
V. Does Any Evidence Support Patient-Controlled IV Ketamine Analgesia for Acute Pain?
We conclude that evidence is limited for the benefit of IV-PCA–delivered ketamine as the sole analgesic for acute or periprocedural pain (grade C recommendation, low level of certainty). We conclude that moderate evidence supports the benefit of the addition of ketamine to an opioid-based IV-PCA for acute and perioperative pain management (grade B recommendation, moderate level of certainty)
Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Regional Anesthesia and Pain Medicine: July 2018 – Volume 43 – Issue 5 – p 456–466.