Efficacy of ketamine in Australia mechanically ventilated intensive care unit patients by Dr. 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. Find more details at 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.
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.
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.
High dose. There are four studies that examine the effect of ketamine infusion on ICPs. Kolenda et al, Bourgoin et al and Schmittner et al are described in Table 2. The fourth study, also by Bourgoin and colleagues, was a single-centre randomised controlled trial of 30 patients with severe traumatic brain injury which compared ketamine with sufentanil as target-controlled infusions for sedation. Both groups also received midazolam. Target plasma concentrations of ketamine and sufentanil were set and efficacy of sedation assessed. The patients had a mean age of 29 ± 11 years and 29 ± 12 years for ketamine and sufentanil respectively. Plasma concentrations were targeted and doses were not reported.
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.