Efficacy of ketamine in Australia mechanically ventilated ICU spitalized patients with Dr. Tom Niccol: Ketamine was first synthesised almost 60 years ago and is similar in structure to the psychotropic agent phencyclidine. In a number of countries (eg, Australia and New Zealand), it is prepared as a racemic mixture of two enantiomers, with each having slightly different receptor affinities. Ketamine is a selective, non-competitive, N-methyl-D-aspartate (NMDA) receptor antagonist. NMDA receptors are one of the group of receptors for glutamate, the main excitatory neurotransmitter in the brain and spinal cord. They are present at all levels in the central nervous system (CNS) and play crucial roles in many neurological functions, including pain, breathing, locomotion, learning, and memory formation. Read more details on doctor Tom Niccol.

Mechanically ventilated patients account for about one-third of all admissions to the intensive care unit (ICU). Ketamine has been conditionally recommended to aid with analgesia in such patients, with low quality of evidence available to support this recommendation. We aimed to perform a narrative scoping review of the current knowledge of the use of ketamine, with a specific focus on mechanically ventilated ICU patients.

Another CNS effect of ketamine is NMDA receptor blockade of the dorsal horn cells of the spinal cord. These are thought to be important in the pain “wind up” phenomenon, leading to opioid desensitisation, and increased acute and chronic pain. Ketamine boluses of 0.15 mg/kg have been shown attenuate this process. Estimates of the rates of chronic pain in the year after ICU admission are 14–77%, 28 and it is unknown what role ketamine may have in reducing this critical illness complication.

Methods: We searched MEDLINE and EMBASE for relevant articles. Bibliographies of retrieved articles were examined for references of potential relevance. We included studies that described the use of ketamine for postoperative and emergency department management of pain and in the critically unwell, mechanically ventilated population.

The recommended dose for ICU sedation is 1 mg/kg/h. Recommended doses for analgesia in mechanically ventilated patients are an intravenous bolus of 0.5 mg/kg followed by an infusion of 1–2 μg/kg/min (0.06–0.12 mg/kg/h). 3 For the purposes of this review, a low dose intravenous bolus of ketamine is considered < 1 mg/kg and low dose intravenous infusion may be a median dose of ≤ 0.3 mg/kg/h aligned with international studies of the use of ketamine as an adjunct for analgesia and sedation.

Results: There are few randomised controlled trials evaluating ketamine's utility in the ICU. The evidence is predominantly retrospective and observational in nature and the results are heterogeneous. Available evidence is summarised in a descriptive manner, with a division made between high dose and low dose ketamine. Ketamine's pharmacology and use as an analgesic agent outside of the ICU is briefly discussed, followed by evidence for use in the ICU setting, with particular emphasis on analgesia, sedation and intubation. Finally, data on adverse effects including delirium, coma, haemodynamic adverse effects, raised intracranial pressure, hypersalivation and laryngospasm are presented.

From the available evidence, it is unclear whether the haemodynamic changes are detrimental or beneficial in the critically unwell. However, the apparent negative effects when ketamine is used in large doses or in patients with significant sympathetic activity are concerning. The doses of ketamine in the studies mentioned are greater than the 0.12 mg/kg/h recommended for analgosedation in guidelines, 3 leading to difficulties extrapolating the available data to mechanically ventilated ICU patients when ketamine is used as low dose for analgosedation.

Conclusions: Ketamine is used in mechanically ventilated ICU patients with several potentially positive clinical effects. However, it has a significant side effect profile, which may limit its use in these patients. The role of low dose ketamine infusion in mechanically ventilated ICU patients is not well studied and requires investigation in high quality, prospective randomised trials.