Effects of Small-dose S-ketamine on Anesthesia-induced Atelectasis in Anesthetized Patients Accessed by Pulmonary Ultrasound

Effects of Small-dose S-ketamine on Anesthesia-induced Atelectasis in Patients Undergoing General Anesthesia Accessed by Pulmonary Ultrasound：Study Protocol for a Randomized, Double-blinded Controlled Trial

Background: Atelectasis occurs in the majority of patients with general anesthesia, which can lead to postoperative pulmonary complications (PPCs) and affect the postoperative outcome. However, there is still no exact method to prevent it though agents. S-ketamine may prevent atelectasis due to its airway smooth muscle relaxation and anti-inflammatory effects. Lung ultrasound is a portable and reliable bedside imaging technology for diagnosing anesthesia-induced atelectasis. Here, we intend to assess whether small-dose of S-ketamine can reduce the incidence of atelectasis after intubation under general anesthesia using lung ultrasound, in order to prevent the early formation of perioperative atelectasis and perioperative pulmonary complications.

Methods: The trial is a single institution, prospective, randomized controlled, parallel grouping, double-blind study. From October 2021 to March 2022, 100 patients (18-60 years old) scheduled for elective surgery will be recruited from Beijing Tiantan Hospital, Capital Medical University, and randomly assigned to the S-ketamine group (Group S) and the normal saline group (Group N) at a ratio of 1:1. The label-masked agents will be given 5 minutes before induction and all patients will undergo a standardized general anesthesia protocol. Related data will be collected at three time point: after radial artery puncture (T1), 15 minutes after tracheal intubation (T2) and before extubation (T3). The primary outcome will be the total LUS scores at T2. Secondary outcomes include LUS scores in 6 chest regions at T2; total LUS scores at T3; arterial blood-gas analysis results (PaCO2, PaO2) and PaO2/FiO2 at T2 and T3, plateau pressure(Pplat) and dynamic lung compliance (Cdyn) at T2 and T3; the incidence of postoperative complications associated with S-ketamine and postoperative pulmonary complications (PPCs) 2 and 24 hours after surgery；.

Discussion: This trial aims to explore whether a simple and feasible application of S-ketamine before the induction of general anesthesia can prevent atelectasis. The results of this study may provide new ideas and direct clinical evidence for the prevention and treatment of perioperative pulmonary complications during anesthesia.

Key words: atelectasis, S-ketamine, ultrasound, RCT, protocol

Study Overview

• Status: Unknown
• Conditions: Atelectasis
• Intervention / Treatment: Drug: S-ketamine; Drug: normal saline group

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age of 18 - 60 years;
2. American Society of Anesthesiologists (ASA) physical status of I - II;
3. Patients scheduled for urinary, obstetrics and gynecology surgery in supine position or lithotomy position under general anesthesia, and the expected operation time is more than 1 hour;
4. Patients and their authorized surrogates have signed the informed consent form.

Exclusion Criteria:

1. Patients who have difficulty in applying pulmonary ultrasound, such as chest fractures, surgical history, etc;
2. Patients who have a history of upper respiratory tract infection one month before surgery, or a history of smoking more than 6 packs/year;
3. Preoperative chest X-ray or CT abnormalities, including atelectasis, pneumothorax, pleural effusion or pneumonia;
4. BMI>30kg/㎡;
5. Expected difficulty in intubation or mask ventilation;
6. Patients with significant increase in intraocular pressure and intracranial pressure before surgery;
7. Patients allergic to S-ketamine, propofol and opioids.
8. Patients with a positive history of psychiatric disorders.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: S-ketamine group	Drug: S-ketamine; Patients will receive the label-covered trial agent covered by the label after premedication 5 min before induction. Agent preparation method of S-ketamine group (Group S): Draw the dosage of S-ketamine 0.25mg ·kg -1 and dilute it with normal saline to 5ml in opaque 5-ml syringes.
PLACEBO_COMPARATOR: saline group	Drug: normal saline group; Patients will receive the label-covered trial agent covered by the label after premedication 5 min before induction. Normal saline group (Group N): 5ml of normal saline, labeled as "study agents".

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
total lung sonography scores(LUS) scores at T2	Using SonoSite M-Turbo with a 5-12 MHz linear transducer,patients will be scanned and scored in the supine position following the lung ultrasound method described by Sun L and colleagues. Briefly, six regions will be scanned on in each hemithorax. Scans 1 and 2 will be performed at the midline of the clavicle, scans 3 and 4 will be performed in the axilla midline. The intercostal scans (Scans 5-6) will be performed in the fifth and sixth intercostal spaces of the posterior axillary line. Place a linear probe parallel to the ribs and scan the intercostal space of each region using a two-dimensional view sequentially from right to left, cranial to caudal, and anterior to posterior within 2 minutes.Each region will be categorised and assigned into four scores(0-3) based on B-lines.Add the scores in all twelve regions to get total lung sonography scores(LUS). Finally get a score between 0 (no atelectasis) and 36 (complete atelectasis).	T2：at the time of tracheal intubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LUS scores in 6 chest regions(scans 1-6) at T2	Using SonoSite M-Turbo with a 5-12 MHz linear transducer,patients will be scanned and scored in the supine position following the lung ultrasound method described by Sun L and colleagues. Briefly, six regions will be scanned on in each hemithorax. Scans 1 and 2 will be performed at the midline of the clavicle, scans 3 and 4 will be performed in the axilla midline. The intercostal scans (Scans 5-6) will be performed in the fifth and sixth intercostal spaces of the posterior axillary line. Place a linear probe parallel to the ribs and scan the intercostal space of each region using a two-dimensional view sequentially from right to left, cranial to caudal, and anterior to posterior within 2 minutes.Each region will be categorised and assigned into four scores(0-3) based on B-lines. Finally get six sets of data betweem 0(no atelectasis) and 6 (complete atelectasis).	T2：at the time of tracheal intubation
total LUS scores at T3	Using SonoSite M-Turbo with a 5-12 MHz linear transducer,patients will be scanned and scored in the supine position following the lung ultrasound method described by Sun L and colleagues. Briefly, six regions will be scanned on in each hemithorax. Scans 1 and 2 will be performed at the midline of the clavicle, scans 3 and 4 will be performed in the axilla midline. The intercostal scans (Scans 5-6) will be performed in the fifth and sixth intercostal spaces of the posterior axillary line. Place a linear probe parallel to the ribs and scan the intercostal space of each region using a two-dimensional view sequentially from right to left, cranial to caudal, and anterior to posterior within 2 minutes.Each region will be categorised and assigned into four scores(0-3) based on B-lines. Finally get a score between 0 (no atelectasis) and 36 (complete atelectasis).	T3：5min before extubation
arterial blood-gas analysis results (PaCO2, PaO2) and PaO2/FiO2 at T2 and T3	arterial blood samples will be obtained through radial artery puncture and blood-gas measurements will be performed immediately using a standard technique (ABL800) to get arterial blood-gas analysis results (PaCO2, PaO2) and PaO2/FiO2 at T2 and T3	after tracheal intubation (T2) and 5min before extubation (T3)
plateau pressure and dynamic lung compliance (Cdyn) at T2 and T3	[Cdyn = tidal volume/(PIP-PEEP)]	after tracheal intubation (T2) and 5min before extubation (T3)
the incidence of postoperative complications associated with S-ketamine 2 and 24 hours after surgery	visual impairment, dizziness, pathological irritability, nightmares and hallucinations	2 and 24 hours after surgery
the incidence of postoperative pulmonary complications (PPCs)	the clinical outcome defifinitions of PPCs will adopt European joint taskforce guidelines published in 2015 which include respiratory infection; respiratory failure; atelectasis; pleural effusion; pneumothorax; bronchospasm, aspiration pneumonia; pulmonary edema; ARDS; tracheobronchitis; pulmonary oedema; exacerbation of pre-existing lung disease; pulmonary embolism	2 and 24 hours after surgery

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2021
• Primary Completion (ANTICIPATED): October 1, 2021
• Study Completion (ANTICIPATED): March 1, 2022

Study Registration Dates

• First Submitted: February 2, 2021
• First Submitted That Met QC Criteria: February 7, 2021
• First Posted (ACTUAL): February 9, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 9, 2021
• Last Update Submitted That Met QC Criteria: February 7, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: atelectasis; ultrasound; RCT; S-ketamine; protocol
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Pulmonary Atelectasis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Psychotropic Drugs; Antidepressive Agents; Ketamine; Esketamine
• Other Study ID Numbers: 20210106

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No