Efficacy of ketamine in Australia ventilated intensive care unit admissions from 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. See even more information 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.
One study compared an S-ketamine anaesthesia of a bolus of 1–3 mg/kg followed by infusion of 2–4 mg/kg/h versus sufentanil infusion. Five of the studies reported that racemic or S-ketamine reduced the inflammatory response after surgery as measured by plasma/serum IL-6 concentrations. This response was most pronounced in the early (within 6 hours) postoperative period. It is possible that this anti-inflammatory effect of ketamine may provide some benefit to mechanically ventilated ICU patients.
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.
A wide range of surgeries were included. Ten studies used only S-ketamine and one study used only R-ketamine. The rest of the studies used racemic ketamine at predominantly bolus doses of 0.25–1 mg/kg and infusions of 2–5 μg/kg/min (0.12–0.3 mg/kg/h). Most studies had less than 50 patients in each arm. Ketamine infusion reduced morphine equivalents by 8 mg at 24 hours and by 13 mg at 48 hours with associated decreased pain scores. Pooled CNS adverse events included hallucinations, dizziness, confusion, drowsiness, sedation, nightmares, and visual disturbances. There was no statistical difference in pooled events when ketamine was compared with placebo (5.2% v 4.2%; risk ratio, 1.17; 95% CI, 0.95–1.43). The authors concluded that “perioperative intravenous ketamine probably reduces postoperative analgesic consumption and pain intensity. CNS adverse events were little different with ketamine or control”.
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.