Controlled Ventilation During Anesthetic Emergence

Introduction

Emergence from general anesthesia is the transition from the anesthetized state to recovery of consciousness, spontaneous ventilation, protective airway reflexes, and physiologic stability. An ideal emergence is timely and smooth, with minimal coughing, bucking, agitation, airway obstruction, hypoxemia, and excessive sympathetic stimulation.

Coughing around tracheal extubation is common and may increase arterial and intracranial pressure, disrupt surgical repairs, increase bleeding, and worsen patient discomfort. Several pharmacologic strategies, including dexmedetomidine, remifentanil, fentanyl, and lidocaine, have been investigated to reduce emergence coughing. However, these agents may be associated with adverse effects such as bradycardia, hypotension, sedation, or respiratory depression.

Ventilatory management during emergence has received less attention. Pressure-support ventilation can facilitate the transition to spontaneous breathing, and previous peri-extubation studies have reported effects on cough severity, emergence time, and postoperative atelectasis. However, the optimal degree of ventilatory assistance during awake emergence with an endotracheal tube is not well established. Maintaining controlled or full-support ventilation until predefined recovery criteria are reached has not been fully evaluated in routine adult operating-room practice.

This study was designed as a prospective, randomized, open-label, parallel-group clinical trial comparing conventional supported weaning with continuation of controlled or full-support mechanical ventilation during emergence from sevoflurane anesthesia. The hypothesis was that the controlled or full-support ventilation strategy would reduce peri-extubation airway responses, particularly coughing and agitation, without delaying extubation or impairing hemodynamic or respiratory stability.

Study Design and Setting

This prospective, randomized, open-label, parallel-group clinical trial was conducted at King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia. Recruitment occurred from May 2024 through November 2024.

The study was approved by the Institutional Review Board at King Abdullah International Medical Research Center, IRB approval number ICT22R/009/10, dated 11 November 2022. Written informed consent was obtained from all participants.

Participants

Eligible participants were adults aged 18 to 65 years undergoing elective surgery with sevoflurane-based general anesthesia and endotracheal intubation.

Eligibility criteria included American Society of Anesthesiologists physical status I or II, body mass index below 35 kg/m2, and no history of obstructive sleep apnea.

Exclusion criteria included pregnancy, psychiatric illness, obstructive sleep apnea, and anticipated difficult airway.

Randomization and Masking

Eligible patients were screened by the study investigators on the day before surgery to confirm eligibility. A group of anesthesiologists was prospectively trained in the standardized anesthetic technique, emergence criteria, assigned ventilation strategies, extubation procedure, and completion of the study data collection form.

On the day of surgery, written informed consent was obtained by one of the study investigators before randomization. Participants were then randomly allocated in a 1:1 ratio to either the standard emergence group or the controlled-ventilation intervention group using a simple coin-flip method. Heads were assigned to the intervention group and tails were assigned to the standard group.

The coin flip was performed by the operating-room circulating nurse only after written informed consent and enrollment had been completed. Therefore, treatment allocation was not known before enrollment.

Following randomization, a study progress note documenting enrollment and group allocation was entered and secured in the patient's electronic medical record by a sub-investigator. The anesthesiologist assigned to the case was then informed of the treatment allocation and performed emergence and extubation according to the protocol specified for the assigned study group. The attending anesthesiologist also completed the study data collection sheet.

Because the anesthesiologist delivering the intervention needed to know the allocated ventilation strategy, blinding of the treating anesthesiologist was not feasible. Blinding of outcome assessors was not prospectively documented.

During recruitment, an interim study progress meeting was held with a representative of the Institutional Review Board to review trial conduct and protocol adherence. The study was audited in accordance with the institutional research oversight process.

Standardized Anesthetic Management

Standard monitoring included pulse oximetry, noninvasive blood pressure, electrocardiography, and temperature monitoring. Processed electroencephalographic depth monitoring using the bispectral index or Entropy was applied. Train-of-four monitoring was used when neuromuscular blocking agents were administered.

Premedication consisted of midazolam 0.05 mg/kg intravenously. Anesthesia was induced with fentanyl 1.5 micrograms/kg intravenously, propofol 2 mg/kg intravenously, and rocuronium 0.6 mg/kg intravenously.

Anesthesia was maintained with sevoflurane in an oxygen and air mixture at a fraction of inspired oxygen of approximately 0.5, targeting a bispectral index value of 40 to 60.

Intraoperative ventilation was standardized using a tidal volume of approximately 8 mL/kg and positive end-expiratory pressure of 6 cmH2O. Respiratory rate was adjusted to maintain arterial partial pressure of carbon dioxide between 35 and 45 mmHg.

Rocuronium 0.1 to 0.2 mg/kg was administered in supplemental boluses as clinically required, with the final dose given at least 45 minutes before the anticipated end of anesthesia.

Analgesia consisted of intraoperative fentanyl and intravenous paracetamol 15 mg/kg. Granisetron 1 mg, with or without dexamethasone 8 mg, was administered for prophylaxis against postoperative nausea and vomiting. Active warming measures were used throughout the procedure.

When neuromuscular blockade reversal was required, neostigmine 50 micrograms/kg was administered with glycopyrrolate 0.2 mg for each 1 mg of neostigmine. Extubation was performed only after recovery of the train-of-four ratio to at least 0.9.

Emergence Interventions

At the end of surgery, sevoflurane was discontinued, the fraction of inspired oxygen was increased to 1.0, and oropharyngeal suctioning was performed.

In the standard group, patients transitioned to conventional supported or spontaneous weaning using continuous positive airway pressure plus pressure support ventilation, pressure support ventilation alone, or synchronized intermittent mandatory ventilation, according to routine anesthesiologist practice.

In the intervention group, ventilatory assistance was maintained using a controlled or full-support strategy. Recorded modes included pressure-controlled ventilation, pressure-controlled ventilation-volume guaranteed, synchronized intermittent mandatory ventilation, and volume-controlled ventilation, with a target respiratory rate of 12 to 16 breaths per minute.

Fresh gas flow was maintained at 10 to 15 L/min until the end-tidal sevoflurane concentration reached approximately 0.2 percent.

When the end-tidal sevoflurane concentration was approximately 0.2 percent, the train-of-four ratio was at least 0.9, and the bispectral index or Entropy value was between 80 and 100, the patient was called by name.

Tracheal extubation was performed when the patient opened the eyes and the attending anesthesiologist judged awake extubation to be appropriate.

Outcome Measures

Hemodynamic and respiratory observations included systolic blood pressure, diastolic blood pressure, heart rate, and peripheral oxygen saturation measured at 5-minute intervals through 45 minutes.

Emergence outcomes included the number and duration of coughing or bucking episodes while the endotracheal tube remained in place; agitation, defined as involuntary movement such as pushing or kicking or failure to follow commands; laryngospasm; bronchospasm; hypoxia; need for continuous positive airway pressure; and time from discontinuation of sevoflurane to removal of the endotracheal tube.

Recovery responses included eye opening, mouth opening, head lift, and hand grip. Patients were reassessed in the post-anesthesia care unit.

Sample Size

The sample-size calculation assumed that the proportion of uncomplicated extubations would increase from 60 percent with standard emergence to 90 percent with the intervention. With a two-sided 95 percent confidence level, 80 percent power, and 1:1 allocation, the calculated sample size was 38 participants per group, for a total of 76 participants. Planned enrollment was increased to 41 participants per group to allow for attrition.

Statistical Analysis

Continuous variables were assessed for normality using the Shapiro-Wilk test. Normally distributed variables were summarized using the mean and standard deviation and compared using the independent-samples t test. Non-normally distributed variables were summarized using the median and interquartile range and compared using the Mann-Whitney U test.

Categorical variables were summarized as number and percentage and compared using Fisher's exact test.

Repeated systolic blood pressure, diastolic blood pressure, heart rate, and peripheral oxygen saturation measurements were additionally analyzed using generalized estimating equations with a Gaussian family, identity link, exchangeable working correlation structure, participant-level clustering, categorical time, study group, and a group-by-time interaction. Robust standard errors and omnibus Wald tests were used for inference.

A two-sided P value below 0.05 was considered statistically significant. Exploratory bivariate analyses assessed whether age, body mass index category, or American Society of Anesthesiologists physical status was associated with outcomes that differed between groups.