Optimal Remifentanil Ce for Preventing Severe Cough and Hyperdynamic Response During Tracheal Extubation (REX)

Optimal Remifentanil Site-effect Concentration for Preventing Severe Cough and Hyperdynamic Response During Tracheal Extubation After Sevoflurane vs. Desflurane. A Randomized Clinical Trial

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Cough
• Intervention / Treatment: Drug: Remifentanil

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.

• Study Type: Interventional
• Enrollment (Actual): 364
• Phase: Phase 4

Contacts and Locations

Study Locations

• Colombia
  • Valle
    • Cali, Valle, Colombia, 76001000
      • Fundacion Valle del Lili

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sevo-2.0; This group will maintain remifentanil infusion by TCI to 2 ng/ml during emergence and extubation after have received sevoflurane during procedure.	Drug: Remifentanil; To maintain remifentanil Ce at 1.0 (control) vs. 2.0 vs. 2.5 ng/ml by a TCI system during anesthesia emergence until tracheal extubation; Other Names: Ultiva
EXPERIMENTAL: Sevo-2.5; This group will maintain the remifentanil infusion by TCI to 2.5 ng/ml during emergence and tracheal extubation after have received sevoflurane during surgical procedure.	Drug: Remifentanil; To maintain remifentanil Ce at 1.0 (control) vs. 2.0 vs. 2.5 ng/ml by a TCI system during anesthesia emergence until tracheal extubation; Other Names: Ultiva
EXPERIMENTAL: Des-2.0; This group will maintain the remifentanil infusion by TCI to 2.0 ng/ml during emergence and tracheal extubation after have received desflurane during surgical procedure.	Drug: Remifentanil; To maintain remifentanil Ce at 1.0 (control) vs. 2.0 vs. 2.5 ng/ml by a TCI system during anesthesia emergence until tracheal extubation; Other Names: Ultiva
EXPERIMENTAL: Des-2.5; This group will maintain the remifentanil infusion by TCI to 2.5 ng/ml during emergence and tracheal extubation after have received desflurane during surgical procedure.	Drug: Remifentanil; To maintain remifentanil Ce at 1.0 (control) vs. 2.0 vs. 2.5 ng/ml by a TCI system during anesthesia emergence until tracheal extubation; Other Names: Ultiva
ACTIVE_COMPARATOR: Sevo-Control; This group will maintain the remifentanil infusion by TCI to 1.0 ng/ml during emergence and tracheal extubation after have received sevoflurane during surgical procedure.	Drug: Remifentanil; To maintain remifentanil Ce at 1.0 (control) vs. 2.0 vs. 2.5 ng/ml by a TCI system during anesthesia emergence until tracheal extubation; Other Names: Ultiva
ACTIVE_COMPARATOR: Des-Control; This group will maintain the remifentanil infusion by TCI to 1.0 ng/ml during emergence and tracheal extubation after have received desflurane during surgical procedure.	Drug: Remifentanil; To maintain remifentanil Ce at 1.0 (control) vs. 2.0 vs. 2.5 ng/ml by a TCI system during anesthesia emergence until tracheal extubation; Other Names: Ultiva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cough during emergency from anesthesia	Assess the presence and intensity of cough : 0) No cough, 1) A single episode of cough, 2) More than one episode of nonsustained cough, 3) sustained and repetitive cough with head elevation.	From eye opening up to 2.5 minutes after tracheal extubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac response during emergence from anesthesia	Assessment of heart rate (bpm) during awakening and tracheal extubation: Measurements of systolic blood pressure will be obtained at the time of suspending of the halogenated (Basal 2) , eye opening, tracheal extubation and 2.5 minutes after extubation	From discontinuation of inhalational anesthetics up to 2.5 minutes after tracheal extubation
Pressor response during emergence from anesthesia	Assessment of systolic blog pressure (mmHg) during awakening and tracheal extubation: Measurements of systolic blood pressure will be obtained at the time of suspending of the halogenated (Basal 2) , eye opening, tracheal extubation and 2.5 minutes after extubation	From discontinuation of inhalational anesthetics up to 2.5 minutes post-extubation
Time to eye opening	Time in seconds from inhaled anesthetic discontinuation to eye opening response to call by name and touch stimuli.	From inhaled anesthetic discontinuation until the moment of eye opening response to verbal command (calling by name), assessed up to 20 minutes.
Time to tracheal extubation	Time in seconds from inhaled anesthetic discontinuation to safety conditions for tracheal extubation (patients must respond positively to three different commands: "open your eyes " , "breath deep " and "open your mouth ")	From inhaled anesthetic discontinuation until the event of tracheal extubation, assessed up to 20 minutes.
Halogenated end tidal concentration at tracheal extubation	Inhaled gas concentration measured in vol % by the gas analyzer at tracheal extubation	From eyes opening until the event of tracheal extubation, assessed up to 20 minutes.
Respiratory rate during post-extubation	Number of breaths per minute during spontaneous ventilation.	From tracheal extubation to 25 minutes later
Post-extubation hypoxemia	Continuous non-invasive measurement of the percentage of hemoglobin that is attached to oxygen through a pulse oximeter . Episodes of arterial oxygen saturation less than 92% , which is present in the next 10 minutes to extubation were recorded and encourage the patient to breathe through call and tactile stimulation as necessary during this time. If you arrived 10 minutes after extubation the patient continues to present desaturation because bradypnea / intermittent apnea the same process will continue until the patient has spontaneous ventilation ( breathing without any verbal or tactile stimulation ) .	From tracheal extubation to 25 minutes
Rescue analgesia requirement in the immediate postoperative time	Amount of opioid requirements for rescue analgesia during first postoperative hour (other opioids dose will be converted to equipotent milligrams of morphine.	From tracheal extubation up to first postoperative hour
Postoperative nausea and vomiting	Rated on a scale of 0-3, representing presence and intensity of nausea and / or vomiting within the first postoperative hour 0 = no nausea; = mild nausea without vomiting episodes; = nausea and a single episode of vomiting; = more than one episode of vomiting during the first hour	From tracheal extubation to first postoperative hour

Collaborators and Investigators

• Sponsor: Fundacion Clinica Valle del Lili
• Investigators: Principal Investigator: Fredy G Ariza, MD., MSc., Fundacion Clinica Valle del Lili; Study Chair: Ivan F Quintero, MD, Fundacion Clinica Valle del Lili

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (ACTUAL): November 1, 2015
• Study Completion (ACTUAL): February 1, 2016

Study Registration Dates

• First Submitted: April 25, 2014
• First Submitted That Met QC Criteria: April 24, 2017
• First Posted (ACTUAL): April 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 2, 2017
• Last Update Submitted That Met QC Criteria: April 28, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Remifentanil; Hypertension; Desflurane; Cough; Sevoflurane
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Hypertension; Cough; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil
• Other Study ID Numbers: REX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data available for future validations at institutional database system from Clinical Research Center, Fundación Valle del Lili of