None listed
Conditions
Brief summary
This project intends to investigate the respiratory effects of a low dose ketamine infusion in patients suffering from obstructive sleep apnoea (OSA). Recent studies have shown that over 25% of patients undergoing surgery may be suffering from Obstructive sleep apnoea (OSA). An estimated 80% of patients with OSA would undergo surgery without a diagnosis. Due to the epidemic of obesity on the rise, the prevalence of OSA, which is common among overweight people, is expected to increase over time. Ketamine is a medication different from the morphine family of medications (opioids), that is used as an adjunct to opioids in pain management following surgery. Low-dose ketamine infusion results in reduced opioid requirements, less sedation, a lower rate of postoperative nausea and vomiting with no change in breathing patterns. Previous trials, both in volunteers and postoperative patients not suffering from OSA, has shown improved oxygen saturation and a lower carbon dioxide level in the blood when ketamine was used with opioid medications. Hypothesis: Based on results from previous trials involving ketamine, we anticipate this medication to have a beneficial effect on breathing during sleep in patients suffering from OSA. The results of this study will enable us to identify whether ketamine is a suitable medication for use in patients suffering from OSA. This will help create accurate guidelines on the management of patients with OSA undergoing surgery. Design: We will administer either low-dose ketamine or a placebo (normal saline) as an infusion to volunteers suffering from severe OSA and conduct a standard in-lab sleep study to assess the blood oxygen level, breathing pattern and sleep pattern. Each patient will receive both a ketamine infusion and the placebo infusion in a random order with a period of one week between the two sleep studies. This will be a single centre, double-blind, randomised, crossover study. Patients with severe OSA will be randomly assigned to receive either ketamine or a placebo in the sequence given below, during an in-lab, overnight polysomnogram (PSG). Sequence A – infusion of ketamine during PSG 1 and a placebo infusion during PSG 2. Sequence B – placebo infusion during PSG 1 and ketamine infusion during PSG 2. Sample size: 22 patients Study duration: 12 months Aim: To identify whether a ketamine infusion significantly affects the ventilation of OSA patients during sleep, when given in doses used for pain relief following surgery. Primary endpoint: ‘Oxygen desaturation index’ of the patients will be compared between the PSG with a ketamine infusion and the PSG with a placebo infusion.
Interventions
This will be a single centre, double-blind, randomised, crossover study. Patients with severe OSA will be randomly assigned to receive an intravenous ketamine or a placebo infusion in the sequence given below, during an in-lab, overnight polysomnogram (PSG).
Sequence A – infusion of ketamine during PSG 1 and a placebo infusion during PSG 2.
Sequence B – placebo infusion during PSG 1 and ketamine infusion during PSG 2.
A ketamine dose of 100micrograms per kilogram per hour as an
This will be a single centre, double-blind, randomised, crossover study. Patients with severe OSA will be randomly assigned to receive an intravenous ketamine or a placebo infusion in the sequence given below, during an in-lab, overnight polysomnogram (PSG). Sequence A – infusion of ketamine during PSG 1 and a placebo infusion during PSG 2. Sequence B – placebo infusion during PSG 1 and ketamine infusion during PSG 2. A ketamine dose of 100micrograms per kilogram per hour as an infusion with a maximum dose of 12mg per hour for patients weighing over 120kg will be administered to the study participants. Target duration for the infusion is 8hrs. The infusion will be stopped at 8 hours, excluding times the infusion was interrupted for any reason. Infusion duration will be less if the patient wakes up earlier than expected or cessation of infusion due to side effects. The total volume of trial infusion administered and the duration of the infusion will be recorded by the investigators. Minimum of a 7 day washout period will be included between the two infusions for every participant.
Sponsors
Prof. John R Wheatley
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
20 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Patients diagnosed with severe obstructive sleep apnoea with an AHI >30/hour on a polysomnogram (PSG) done in the Westmead Sleep Disorders Laboratory
Exclusion criteria
1. Hypersensitivity to ketamine 2. Severe COPD (FEV1/FVC < 70%; FEV1 < 50% predicted) 3. Diagnosis of moderate to severe pulmonary hypertension (mean PAP >40mmHg) as per WHO criteria. 4. Neuromuscular disorder causing muscle weakness 5. Patients with a previous diagnosis of OSA who are already receiving CPAP therapy 6. Pre-menopausal women 7. Patients with neurotic traits or psychiatric illness (e.g., schizophrenia and acute psychosis) 8. Severe cardiovascular disease (i.e. heart failure, severe or poorly controlled hypertension, recent myocardial infarction) 9. History of stroke, cerebral trauma, intracerebral mass or haemorrhage 10. Participants who are required to operating machinery or engaging in other hazardous activities within 24 hrs after the infusion. 11. History of chronic opioid, benzodiazepine or other sedative medication use/abuse Regular use of more than one standard drink of alcohol before sleep
Outcome results
None listed