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Efficacy of ketamine in Australia ventilated ICU admissions by Tom Niccol

Nov
30

Safety of ketamine in Australia mechanically ventilated intensive care unit admissions with doctor 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 additional information at https://www.instagram.com/tomniccol/.

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.

In addition, a meta-analysis of six studies with a total of 331 patients reviewed the evidence for the anti-inflammatory effects of ketamine, as evidenced by interleukin (IL)-6 levels, when given during surgery. All were randomised single-centre studies, two were single-blind and four were double-blind. Four studies included patients undergoing cardiac surgery and two included patients undergoing abdominal surgery. Most used ketamine as an adjunct to induction of anaesthesia or just before incision and the dose range was an intravenous bolus of 0.15–0.5 mg/kg.

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.

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.

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