Optimal Remifentanil Ce for Preventing Severe Cough and Hyperdynamic Response During Tracheal Extubation
Condition: Cough; Hypertension
MeSH terms: Cough; Hypertension
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Remifentanil
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): Ultiva
Intervention MeSH terms: Remifentanil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Cough; Hypertension; Remifentanil; Sevoflurane; Desflurane