Analgesia, Cardiac Output, Low, Hypovolemia
Conditions
Keywords
Methoxyflurane, Fentanyl
Brief summary
The study is a single-centre, placebo-controlled, crossover study on healthy volunteers aiming to explore non-inferiority of methoxyflurane and fentanyl compared to placebo on the tolerance to hypovolemia.
Detailed description
The study will explore the effects of fentanyl and methoxyflurane versus placebo (NaCl; saline) on the hemodynamic response to hypovolemia in healty volunteers. Hypovolemia will be induced in the lower body negative pressure model. XX healthy volunteers will be exposed to inhaled methoxyflurane, 3 ml or intravenous fentanyl, XX mg or placebo in a randomized order (cross-over) at least 3 days apart.
Interventions
PROCEDURELower body negative pressure (LBNP)
LBNP is a model of experimental hypovolemia, whereby the lower body is exposed to negative pressure leading to sequestering of blood in the lower body and central hypovolemia. LBNP will be induced stepwise with increments of 10 mmHg, each level lasting 1 min. LBNP will be terminated at symptoms or signs of impending hemodynamic collapse.
Sponsors
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Both drug interventions (intravenous fentanyl and inhaled methoxyflurane) will have NaCl placebo comparators. As the methoxyflurane has a characteristic smell, some drops of methoxyflurane will be placed on the exterior of the placebo methoxyflurane inhalation devices. Further, the subjects will rinse the mouth with a mouthwash shortly before inhalation to cover the taste of methoxyflurane.
Intervention model description
Randomized, placebo controlled, crossover study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Must be at least 18 years of age. * Must be below 65 years of age. * Signed informed consent and expected cooperation for the study and follow up must be obtained and documented according to ICH GCP, and national/local regulations.
Exclusion criteria
* Any medical condition limiting physical excertional capacity or requiring regular medication (allergy and oral contraceptives excepted) * Pregnancy * History of syncope (syncope of presumed vasovagal nature with known precipitating factor excepted) * Any known cardiac arrhythmia * History of renal disease * History of liver disease * Previous substance abuse * Allery or known serious side-effects to opioids or methoxyflurane
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac output | Measured continuously during LBNP-exposure. | Cardiac output as measured by suprasternal Doppler and/ or non-invasive (volume clamp) pulse contour analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to hemodynamic decompensation | 15 minutes | Time from start LBNP to symtomps or signs of hemodynamic decompensation (and termination of LBNP); defined by: * Symptoms of pre-syncope (light-headedness, nausea or sweating) * Mean arterial pressure-reduction to less than 75% of baseline for \>3 s * Heart rate-reduction to less than 75% baseline for \>3 s |
| Mean arterial pressure | Measured continuously during LBNP-exposure. | Change in mean arterial blood pressure with increasing LBNP, as measured by the volume-clamp method. |
| Stroke volume | Measured continuously during LBNP-exposure. | Change in cardiac stroke volume with increasing LBNP, as measured by suprasternal Doppler and/ or the volume-clamp method. |
Countries
Norway
Outcome results
None listed