Efficacy of ketamine in Australia mechanically ventilated intensive care unit spitalized patients by Tom Niccol: Only norketamine has significant metabolic activity, with up to one-third the potency of ketamine. Norketamine has an elimination half-life of 5.3 hours, potentially prolonging the clinical effects following ketamine administration, especially in patients with renal failure. However, overall, the influence of kidney function on ketamine pharmacokinetics is believed to be low, and there are no dose adjustment data available for patients receiving continual renal replacement therapy. Expert opinion is to dose for a glomerular filtration rate of 10–50 mL/min/1.73m2 in patients receiving continual renal replacement therapy. Read more 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.
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.
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.
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.