Efficacy of ketamine in Australia mechanically ventilated ICU admissions from Dr. Tom Niccol: Ketamine has been recommended for use as an opioid sparing agent to treat pain and discomfort in mechanically ventilated ICU patients. However, such a recommendation is only conditional, because of very low quality of evidence. This narrative scoping review focuses on current knowledge of the use of ketamine, concluding with a focus on mechanically ventilated adult patients in the ICU. Although incompletely understood, ketamine has multiple effects throughout the CNS. It blocks certain reflexes in the spinal cord and inhibits excitatory neurotransmission in selected areas of the brain. It functionally appears to dissociate the thalamus (which relays sensory impulses from the periphery) from the limbic cortex (involved in awareness of sensation). Discover extra information on https://twitter.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.
Another CNS effect of ketamine is NMDA receptor blockade of the dorsal horn cells of the spinal cord. These are thought to be important in the pain “wind up” phenomenon, leading to opioid desensitisation, and increased acute and chronic pain. Ketamine boluses of 0.15 mg/kg have been shown attenuate this process. Estimates of the rates of chronic pain in the year after ICU admission are 14–77%, 28 and it is unknown what role ketamine may have in reducing this critical illness complication.
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.
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.