Induction of Anaesthesia Clinical Trial
Official title:
A Phase IV Study to Investigate the Effects of Varied Remifentanil Concentrations on Propofol Requirements for Loss of Consciousness, Response to Painful Stimuli, Bispectral Index and Associated Haemodynamic Changes
A prospective, randomised, phase IV trial including 150 patients.
To evaluate the effects of varied concentrations of remifentanil on the proposal
requirements for the loss of consciousness and response to pain and to evaluate the
haemodynamic changes and processed EEG (BIS) during induction of anaesthesia.
BackGround
The combination of remifentanil and propofol infusions is a widely used method of total
intravenous anaesthesia. (1) Target controlled infusion (TCI) is a pharmacokinetic (PK)
infusion system using data from a large population of patients to calculate and deliver
stable concentrations of a drug based on a three compartment PK model. Both propofol and
remifentanil are ideal drugs for delivery in this way because of their quick distribution,
metabolism and excretion. (2) Remifentanil is a potent synthetic opioid receptor (MOR)
agonist with a short recovery irrespective of the duration of its administration. This is
due to it being quickly broken down by non-specific esterases in blood and tissues. (3)
Remifentanil like all opioids is not very hypnotic in clinically relevant concentrations.
(4)
Remifentanil has been shown to reduce propofol requirements during induction and maintenance
of anaesthesia. (5)(6) Also modest doses of remifentanil markedly reduce the amount of
propofol required to ablate response to painful stimuli. The relationship between propofol
and remifentanil has been reported as synergistic but additive when using propofol
concentrations within the clinical range. (7)(8) However in other studies, BIS has shown no
interaction between propofol and remifentanil (9)(10) A correlation between BIS, painful
stimuli and other opioids has been demonstrated. (11) It has been suggested that BIS values
can change with propofol and painful stimuli and this can aid administration of remifentanil
in a dose dependent manner. (12) Since propofol and remifentanil are ubiquitously used
together, the interaction between these drugs and EEG needs to be defined in more detail.
Trial Objectives To see whether remifentanil affects the dose of proposal required for loss
of consciousness and loss of response to painful stimuli and whether this is reflected in
changes in brain EEG (bispectral index BIS)
Hypothesis That the effect site concentration of proposal at loss of consciousness will only
be moderately affected by concurrently remifentanil infusion but BIS will not change. That
the clinical response to painful stimuli will markedly decrease when there is concurrent
infusion of remifentanil. With painful stimuli there will be an increase in BIS but this
will be blocked by remifentanil.
Methodology From the start date of the study, the first 100 patients eligible will be
included. Patients will be allocated into one of two groups, group A or group B by a
computer generated randomization table.
For each patient, after receiving written consent, the patient will enter the theatre where
they are going to have their elective operation. Standard anaesthetic monitoring will be
applied, plus a BIS monitor. External peripheral nerve stimuli electrodes will be placed
over the ulner nerve on the dominant arm. IV access will be gained by the anaesthetist. All
infusions will run through the same IV cannula using standardized one way valves.
One anaesthetist will look after the air way while the second anesthetist or a research
assistant will fill in the data collection sheet and determine point of loss of
consciousness and point of loss of response to painful stimuli. The air way anesthetist will
know by a sealed envelope whether the patient is on group A or B. For the patients in group
A, the remifentanil infusion, using the minto effect site concentration model, will be set
at 0ng/ml. For the patients in group B the remifentanil infusion will be set at 3ng/ml.
After 5 minutes the propofol infusion will commence, using the Marsh effect site
concerntration TCI model, at 1mcg/ml and will be increased by 0.2mcg/ml every one minute.
Heart Rate, blood pressure and BIS number will be recorded every minute. Every 30 seconds
the anaesthetist will prompt the patient with the vocal stimuli "say your name" in a
constant tone and volume. Loss of consciousness will be defined as the point at which the
patient fails to respond to the vocal stimuli and light tactite stilulation. At this point
BIS, heart rate, blood pressure and propofol effect site concentration will be recorded.
After loss of consciousness, a tetanic stimuli will be applied using the peripheral nerve
stimulator and repeated every thirty seconds. The propofol infusion will continue to be
increased every one minutes by 0.2mcg/ml. Loss of response to painful stimuli will be
defined as the point at which the patient fails to make a withdrawal motion from the tetanic
stimulation. Here, heart rate, blood pressure BIS number and propofol effect site
concentration will be recorded.
After loss of response to painful stimuli the study is complete, no further date will be
collected, the peripheral nerve stimulator will be removed, the anaesthesia will continue
and surgery will commence as usual.
;
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00965107 -
Onset Time of Thiopental Versus Propofol in the Elderly
|
Phase 4 | |
| Completed |
NCT02186990 -
Comparison of Etomidate, Propofol and Etomidate-propofol Combination in Terms of Effects on Haemodynamic Response to Intubation
|
Phase 4 | |
| Completed |
NCT00506246 -
Efficacy and Safety Study of Two Propofol Formulations
|
Phase 3 | |
| Completed |
NCT05294679 -
Explore the Clinical Application Value of Ciprofol in Painless Colonoscopy
|
N/A |