Safety of ketamine in Australia mechanically ventilated intensive care unit patients by doctor Tom Niccol

Efficacy of ketamine in Australia mechanically ventilated ICU 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. Read additional 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.

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.

It is prudent to briefly review the data available on ketamine as an adjunct to analgesia in the non-ICU setting, which may provide some guidance as to the possible effectiveness when ketamine is used in mechanically ventilated ICU patients. Brinck and colleagues performed a Cochrane review of the use of ketamine for postoperative pain. The review included 130 randomised, double-blind, controlled trials of 8341 patients, of which 4588 received ketamine and 3753 were controls.

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.

A prospective open label trial of 146 patients who had undifferentiated agitation in the pre-hospital environment compared a median dose of 5.2 mg/kg intramuscular ketamine versus 10 mg intramuscular haloperidol in the pre-hospital environment. Hypersalivation occurred in 21/56 ketamine patients (30%) versus none in the haloperidol group, leading to intubation for this reason in four patients. Laryngospasm occurred in 3/55 patients (5%) in the ketamine group and none in the haloperidol group. Another prospective observational study examined the effectiveness of a median dose of 4.9 mg/kg intramuscular ketamine in 49 patients with pre-hospital profound agitation. Hypersalivation occurred in nine patients (18%), of which four received atropine therapy. Pre-medication with glycopyrrolate or atropine has been shown to decrease this adverse effect. 7Umunna and colleagues showed there was no increased hypersalivation when ketamine was used as an infusion at 2.0 mg/kg/h for analgesia and sedation.

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.