WHY A SEPARATE CLINICAL PRACTICE GUIDELINE FOR KETAMINE?

WHY A SEPARATE CLINICAL PRACTICE
GUIDELINE FOR KETAMINE?
Emergency physicians already have access to various
standards,6 policies,7 guidelines,8,9 and review articles10,11
dealing with the general practice of procedural sedation and
analgesia. However, ketamine displays unique features that
warrant considering it separately from other sedatives.
The underlying pharmacology of ketamine is fundamentally
different from that of other procedural sedation and analgesia
agents. This drug exerts its effect by “disconnecting” the
thalamocortical and limbic systems, effectively dissociating the
central nervous system from outside stimuli (eg, pain, sight,
sound). The resulting trancelike cataleptic state of “sensory
isolation”12 is characterized by potent analgesia, sedation, and
amnesia while maintaining cardiovascular stability and
preserving spontaneous respirations and protective airway
reflexes.4,12-16 Complete analgesia permits performance of
extremely painful procedures.
Rather than displaying the dose-response continuum
observed with all other procedural sedation and analgesia agents,
ketamine dissociation appears at a dosing threshold of
approximately 1.0 to 1.5 mg/kg intravenously (IV) or 3 to 4
mg/kg intramuscularly (IM). In smaller doses, ketamine exhibits
analgesia and disorientation. Once the dissociative threshold is
reached, administration of additional ketamine does not
enhance or deepen sedation, as would be the case with opioids,
sedative-hypnotics, or inhalational agents.4,17 For these other
agents, the more drug administered, the more the patient
progresses along the sedation continuum, with increasing
probability of ventilatory depression. In contrast, the quantity of
ketamine administered has no clinically important effect on
airway integrity and respirations within the range of clinically
administered doses and using standard administration
methods.2-4,14,17-20 Accordingly, dissociative sedation can be
readily achieved by administration of a single IV or IM loading
dose, and the only need for titration, in contrast to other
sedatives, is to maintain the dissociative state over time.
This unique mechanism of action has made it challenging to
reconcile ketamine with the traditional stages of the sedation
continuum.17 Dissociated patients are unable to respond to
external stimuli (including repeated or painful stimulation), and

thus this sedated state is inconsistent with traditional definitions
of “moderate sedation” or “deep sedation.”6,8,9 This
nonresponsiveness has led some to label it “general anesthesia”;
however, this definition is also incompatible with ketamine
because it specifies that “the ability to independently maintain
ventilatory function is often impaired” and that “patients often
require assistance in maintaining a patent airway.”6,8,9
Ketamine-related airway and respiratory adverse events are rare
rather than “often,” and thus lumping the drug into this
category unfairly suggests an exaggerated level of risk.
The optimal resolution to such confusion is the application
of a separate definition altogether, as has been advocated by the
American College of Emergency Physicians: “A trancelike
cataleptic state characterized by profound analgesia and
amnesia, with retention of protective airway reflexes,
spontaneous respirations, and cardiopulmonary stability,” ie,
dissociative sedation.1,7,10,17 When others attempt to fit ketamine
into one of the traditional sedation continuum states, they should
recognize its technical incompatibility with that definition.
Ultimately, semantic debates over what to call ketamine serve little
purpose. It is more important to appreciate that ketamine is
fundamentally distinct pharmacologically from general anesthetic
agents and other procedural sedation and analgesia agents.4,17