From the Guidelines
Ketamine doses that typically cause postoperative delirium range from 0.5 to 1.0 mg/kg when given intravenously as a bolus, as supported by the most recent and highest quality study 1.
Key Points to Consider
- Lower doses of 0.1 to 0.5 mg/kg are less likely to cause delirium while still providing analgesic effects.
- The risk of delirium increases with higher doses, particularly above 1 mg/kg, and is more common in elderly patients, those with pre-existing cognitive impairment, or patients with psychiatric disorders.
- To minimize the risk of postoperative delirium while still benefiting from ketamine's analgesic properties, clinicians often use sub-anesthetic doses (0.1-0.3 mg/kg) or continuous infusions at 0.05-0.2 mg/kg/hr rather than larger bolus doses.
- Ketamine causes these psychomimetic effects through its antagonism of NMDA receptors in the brain, particularly affecting areas involved in perception and cognition, as noted in 1.
- The emergence phenomena typically manifest as vivid dreams, hallucinations, confusion, or a sense of dissociation from one's body, usually occurring within the first few hours after administration.
Factors Influencing Delirium Risk
- Patient age: Elderly patients are at higher risk of delirium, as indicated by 1.
- Pre-existing cognitive impairment: Patients with pre-existing cognitive impairment are at higher risk of delirium.
- Psychiatric disorders: Patients with psychiatric disorders are at higher risk of delirium.
- Dose and administration: Higher doses and bolus administration increase the risk of delirium, while sub-anesthetic doses and continuous infusions may reduce this risk, as suggested by 1 and 1.
From the Research
Dose of Ketamine and Delirium
- The dose of ketamine that typically causes delirium postoperatively is not clearly established, as studies have shown varying results 2, 3, 4, 5, 6.
- A study published in 2017 found that high-dose ketamine (1.0 mg/kg) was associated with more postoperative hallucinations and nightmares compared to placebo, but did not decrease delirium in older adults after major surgery 2.
- Another study published in 2016 found that low-dose S-ketamine (0.25 mg/kg bolus and 0.125 mg/kg/h infusion) was associated with higher delirium scores compared to minimal-dose S-ketamine (0.015 mg/kg/h infusion) 3.
- A 2021 study found that ketamine, alone or in combination with haloperidol, was not significantly superior to placebo for prevention of postoperative brain dysfunction and delirium 4.
- A protocol for a randomized controlled trial published in 2022 aims to evaluate the effect of intraoperative prophylactic S-ketamine on the incidence of postoperative delirium in elderly patients undergoing non-cardiac thoracic surgery 5.
- A systematic review and meta-analysis published in 2018 found that the incidence of postoperative delirium did not differ between groups receiving intraoperative ketamine administration and those receiving no intervention, but patients receiving ketamine seemed at lower risk of postoperative cognitive dysfunction 6.