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Comparative pharmacokinetics (PK) of nebulised and intravenous ketamine and dexmedetomidine in ventilated patients

Grant Title
Comparative pharmacokinetics (PK) of nebulised and intravenous ketamine and dexmedetomidine in ventilated patients
Chief Investigator/s
ANZCA Area of Research
Project Summary
Sub-optimal analgesia and sedation in the intensive care setting causes adverse patient outcomes, including impaired sleep in 46 per cent, reduced quality of life, impaired mobility, high economic costs for patient readmission into hospital/intensive care due to pain, besides a 30 per cent incidence of neurological side-effects and respiratory events in 3 per cent. Dexmedetomidine and ketamine have sedative-analgesic properties. Intravenous administration is commonly used for both but is associated with side-effects (low blood pressure, low heart rate and excessive sedation).

Nebulised dexmedetomidine and ketamine have been previously used safely. Due to the unique advantages of administration via the lung, nebulisation of sedative-analgesic medications may result in more favourable blood concentrations for safety and clinical effectiveness. Side effects are likely to be minimised because the high peak concentrations that follow intravenous administration are avoided.

Currently, there are no clinical data on nebulised ketamine and dexmedetomidine which limits our ability to select appropriate doses for appropriate clinical effects. Mechanical ventilation in the intensive care unit provides the ideal setting to evaluate the drug delivery systems in a safe manner. Defining the lung dose prior to clinical studies is essential. A comparative plasma study of nebulised versus intravenous ketamine and dexmedetomidine will allow us to derive the dose equivalency for the two different administration routes (intravenous and nebulised). The data could then be used to generate dosing guidelines for clinical trials in diverse patient groups.

The study results will provide important data to guide dosing for the clinical application of nebulised ketamine and dexmedetomidine. This will be used to provide analgesia and comfort in a non-invasive form in pre-hospital trauma, palliative care, post-operative care, and emergency medicine patients. Thus, this study fulfils an important and urgent requirement for investigation into a novel and non-invasive route of analgesic and sedative administration leading to a positive impact in the field of clinical medicine, health service and research.
Grant Type
Robin Smallwood Bequest
Funding Year
Funding Amount