Safety of ketamine in Australia mechanically ventilated intensive care unit admissions from doctor 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. Discover extra 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.
Ketamine used in anaesthetic doses (1–4.5 mg/kg intravenous) leads to dissociative anaesthesia: the patient appears conscious (eyes open, able to swallow) with preserved respiratory function and pharyngeal and laryngeal reflexes, but is unaware, unable to process or respond to sensory input. In addition, analgesia may also be mediated through serotonin and noradrenaline receptor activation and reuptake inhibition, as well as effects on δ, ϰ and μ opioid receptors. Unlike opioid medications, ketamine is thought to have little effect on gastrointestinal μ receptors, minimising the risk of constipation.
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.
Although the intravenous dose required for induction of anaesthesia has been reported to be 1–4.5 mg/kg, a commonly recommended dose regime is 1.0 mg/kg followed by repeated boluses of 0.5–1.0 mg/kg if initial sedation is inadequate. A recommended dose for analgesia is an intravenous infusion of 0.27–0.75 mg/kg/h. Low dose ketamine when given as an intravenous bolus for acute postoperative pain has been defined as a subanaesthetic dose or < 1 mg/kg. Low dose ketamine, when given as an infusion, is less well defined. One review defined low dose infusion as ≤ 0.2 mg/kg/h. Alternatively, subdissociative dosing of 0.1–0.4 mg/kg/h has also been described as low dose.
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.
