Safety of ketamine in Australia mechanically ventilated intensive care unit spitalized patients by Tom Niccol: In Australian and New Zealand, mechanically ventilated patients account for about 35% of all adult patients admitted to the intensive care unit (ICU). In addition to treating the primary illness, international clinical practice guidelines emphasise five critical domains in the management of ventilated patients. These are pain assessment and management, sedation and agitation prevention, delirium assessment and treatment, rehabilitation and mobilisation, and minimising sleep disruption. Find more information on https://www.facebook.com/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.
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.
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.
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.
