Clinical trial NCT03132519: Optimal Remifentanil Ce for Preventing Severe Cough and Hyperdynamic Response During Tracheal Extubation
Official title: Optimal Remifentanil Site-effect Concentration for Preventing Severe Cough and Hyperdynamic Response During Tracheal Extubation After Sevoflurane vs. Desflurane. A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cough
Hypertension
Keywords: Cough
Hypertension
Remifentanil
Sevoflurane
Desflurane
Lead sponsor: Fundacion Clinica Valle del Lili
Sponsor class: OTHER
First posted: 2017-04-28
Enrollment: 364
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pain, cough, hypertension and tachycardia are frequent events during extubation due to a secondary stimulation of mechanoreceptors located in the airway. The mechanical effect of the endotracheal tube activates autonomic reflexes, a situation that could potentially impair the clinical condition of patients. Previous studies have used remifentanil during emergence and extubation showing good results to control this reflex response. However, it is unknown so far, the optimal effect site concentration (Ce) of remifentanil to allow a better control of these events with a low incidence of adverse effects after have received inhaled anesthesia plus remifentanil for anesthetic maintenance. This study will determine the Ce of remifentanil associated with a lower proportion of cough and hyperdynamic circulatory response during extubation for emergency after exposure to sevoflurane or desflurane.

Detailed description: Single-center, randomized, double-blind protocol. The investigators aim to include 368 patients under balanced anesthesia with sevoflurane or desflurane to be randomly allocated into 6 different remifentanil Ce groups \[77 individuals in each of interventional groups (2.0 vs. 2.5 ng/ml) and 30 in each of the control groups (1.0 ng/ml) administrated by a target-controlled infusion (TCI) system during emergence and tracheal extubation .

Once informed consent is obtained and inclusion/exclusion criteria are met, subjects will be randomized before starting of the surgical procedure. This information will remain blinded to the attendant anesthesiologist and the independent evaluator during the process of extubation, except for type of inhaled anesthetic for maintenance .

The intervention will start when the anesthesiologist decide to suspend the sevorane or desflurane dial. At this moment, the fresh flow gas of the anesthesia machine will be adjusted to 7-8 liters per minute and the infusion of remifentanil will be set up to establish a Ce of 2.0 ng/ml or 2.5 ng/ml. All patients will be extubated only when all of these three parameters exist: response to name by eyes opening, response to orders of breathing and mouth opening.

The evaluation and outcomes measurement will include: Presence and intensity of cough and changes in heart rate and blood pressure during eyes opening in response to calling by name, tracheal extubation and 2.5 min after, time to get to be extubated after inhaled anesthetic discontinuation, episodes of hypoxemia and sedation state during the first 25 minutes after extubation, requirements of rescue analgesia and postoperative nausea and vomit during this period.

Close monitoring of patients will take place and data will be collected during the preoperative, intraoperative and postoperative stages until discharge from the post anesthesia care unit. Lost to follow and adverse events will be assessed. An interim committee will evaluate partial results of the study when it reaches 25 and 50% of recruitment, so the investigators can continue building thereof according to analysis obtained.

Statistical analysis will be performed by a independent statistician based on "intention to treat" principle. In addition, excluded data and its reasons for exclusion will be evaluated. For the descriptive exploratory analysis, continuous variables will be presented as means (standard deviation) or medians (interquartile ranges). The degree of dispersion, shape and position as the fulfillment of normality will be analyzed using the t of Student or Mann-Whitney tests as appropriate. Categorical variables will be presented as proportions and compared using the chi-square or Fisher 's exact tests as appropriate. Time-varying measures analysis of variance for repeated measures will be used to make comparisons between groups.

Eligibility criteria: Study Population:

Patients undergoing planned surgery who want to avoid coughing during emergence and extubation (Head and Neck Surgery, abdominal, neurosurgery and intraocular)

Inclusion Criteria:

* American Society of Anesthesia status I and II
* Age between 18 to 60 years.
* Elective surgery.

Exclusion Criteria:

* Uncontrolled hypertension. (SBP\> 180 mmHg) at pre anesthesia area.
* Active or uncontrolled pulmonary disease.
* Signs or history of difficult airway.
* Recent respiratory infection.
* Train-of-four (TOF) index \<90% at the end of surgery.
* Patients who have received some form of pre oral medication.
* Body mass Index above 30 kg/m2.
* Concomitant use of epidural catheter.
* Urgent surgery.

Primary outcomes:
measure: Cough during emergency from anesthesia
timeFrame: From eye opening up to 2.5 minutes after tracheal extubation
Secondary outcomes:
measure: Cardiac response during emergence from anesthesia
timeFrame: From discontinuation of inhalational anesthetics up to 2.5 minutes after tracheal extubation
measure: Pressor response during emergence from anesthesia
timeFrame: From discontinuation of inhalational anesthetics up to 2.5 minutes post-extubation
measure: Time to eye opening
timeFrame: From inhaled anesthetic discontinuation until the moment of eye opening response to verbal command (calling by name), assessed up to 20 minutes.
measure: Time to tracheal extubation
timeFrame: From inhaled anesthetic discontinuation until the event of tracheal extubation, assessed up to 20 minutes.
measure: Halogenated end tidal concentration at tracheal extubation
timeFrame: From eyes opening until the event of tracheal extubation, assessed up to 20 minutes.
measure: Respiratory rate during post-extubation
timeFrame: From tracheal extubation to 25 minutes later
measure: Post-extubation hypoxemia
timeFrame: From tracheal extubation to 25 minutes
measure: Rescue analgesia requirement in the immediate postoperative time
timeFrame: From tracheal extubation up to first postoperative hour
measure: Postoperative nausea and vomiting
timeFrame: From tracheal extubation to first postoperative hour
Other outcomes:
Locations:
city: Cali
country: Colombia
facility: Fundacion Valle del Lili
state: Valle
Study officials:
affiliation: Fundacion Clinica Valle del Lili
name: Fredy G Ariza, MD., MSc.
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion Clinica Valle del Lili
name: Ivan F Quintero, MD
role: STUDY_CHAIR
References: