We hypothesize that ketamine stimulates breathing and reverses opioid-induced respiratory depression. We will perform a placebo-controlled randomized and double blind study on the effect of increasing doses of S-ketamine on remifentanil-induced…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
opioid-geinduceerde ademdepressie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Ventilation
Secondary outcome
-
Background summary
Modern medicine relies heavily on opioids for suppression of nociception.
Consequently opioids are used during anesthesia to suppress autonomic
responses, during procedural sedation to reduce nociception, and given for
treatment of acute (postoperative) pain and chronic pain. However, the use of
opioids comes with serious side effects of which opioid-induced respiratory
depression (OIRD) is most dangerous. OIRD may be related to sedation, loss of
upper airway patency and central depression of rhythm generation.
There are various options to prevent or treat OIRD. We previously showed that
the K+-channel blocker GAL021 effectively reverses OIRD. GAL021 is still
experimental and will require many years of additional research before it may
be used in clinical practice. Alternatives to GAL021 that may be used
clinically are scarce. One possibility is ketamine, which is a non-competitive
N-methyl-D-aspartate (NMDA) receptor antagonist but interacts with many more
receptor system. It is our clinical experience that ketamine is without serious
respiratory events, in fact various experimental and human studies associate
ketamine with respiratory stimulation. For example, in mice with a RETT
syndrome phenotype, ketamine improved respiration with a reduction of the
number of RETT-syndrome related apneas, which is due to either NMDA receptor or
nicotinergic acetylcholine receptor antagonism. In rats, Eikermann et al.
showed that ketamine stimulates breathing and activates upper airway tone. Also
human studies indicate that ketamine stimulates breathing activity. Mortero et
al. showed that co-administration of ketamine with propofol significantly
improved ventilation in sedated patients compared with propofol sedation only.
While these data indicate that ketamine stimulates breathing there are no
studies on ketamine*s effect on opioid-induced respiratory depression. Our
study proposal is to investigate the effect of ketamine on respiration in
healthy volunteers with suppressed breathing caused by an opioid.
Study objective
We hypothesize that ketamine stimulates breathing and reverses opioid-induced
respiratory depression. We will perform a placebo-controlled randomized and
double blind study on the effect of increasing doses of S-ketamine on
remifentanil-induced respiratory depression in healthy male and female
volunteers.
Study design
Double-Blind, randomized, placebo controlled
Intervention
Infusion of ketamine on top of a remifentanil infusion.
Study burden and risks
The burden and risk of the study are limited. The investigators have ample
experience in the use of the chosen treatments and the experimental setup.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Healthy male and female volunteers, aged 18 and older
Exclusion criteria
- Known or suspected neuromuscular or a (family) history of any neuromuscular disease;
- A history of allergic reaction to food or medication including study medication;
- Any current or previous medical (including high blood pressure), neurological or psychiatric illness (including a history of anxiety);
- Alcohol abuse (> 21 units/week);
- Illicit drug use in the past 30 days before inclusion;
- Pregnancy or lactation;
- Participation in any medical or drug trial in the month prior to the current study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-002148-17-NL |
| CCMO | NL57918.058.16 |