Safety of ketamine in Australia mechanically ventilated intensive care unit spitalized patients with Tom Niccol: Following intravenous bolus administration, ketamine’s rapid onset of action within 30 seconds for “dissociative anaesthesia” (see below) is due to its high lipid solubility and low protein binding, allowing it to cross the blood–brain barrier readily. Its elimination half-life is 3.1 hours in healthy volunteers and 5.0 hours in critically unwell patients. Ketamine is hepatically metabolised to norketamine and dehydronorketamine which are then renally excreted. Read extra info on Tom Niccol Australia.

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.

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.

Raised intracranial pressure: Early observational studies suggested ketamine was associated with raised ICP in patients with space-occupying lesions 71, 72 and there were concerns with its use in traumatic and non-traumatic brain injury. However, to address these concerns, there have been several small randomised controlled trials of ketamine combined with midazolam versus narcotic combined with midazolam. Low dose. There are no studies using low dose ketamine to study its effects on raised ICP.

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.