Intraoperative Diaphragmatic Neuromodulation

NCT ID: NCT06518707

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-26
• Study Completion Date: 2025-02-01

Brief Summary

This prospective, single-center, randomized controlled clinical trial aims to investigate the impact of intraoperative phrenic nerve stimulation (i.e., diaphragmatic neuromodulation) on postoperative complications in neurosurgical patients. The primary objective is to assess the effect on postoperative brain injury, including the development of delirium and changes in biomarkers. Additionally, the incidence of postoperative pulmonary complications will be investigated.

Detailed Description

【Background】Postoperative complications, such as delirium and pulmonary complications, commonly occur in patients undergoing craniotomy. In preclinical studies, phrenic nerve stimulation (i.e., diaphragmatic neuromodulation) has been reported to effectively mitigate brain injury and pulmonary complications. However, its intraoperative administration and its impact on postoperative complications in this population are largely unknown.

【Method】In this prospective, single-center, randomized controlled clinical trial, patients receiving elective craniotomy will be screened. Eligible patients will be randomly divided into three groups: 1) Control group (without any interventions); 2) Intraoperative phrenic nerve stimulation (PNS) without total neuromuscular blockade (Train-of-Four (TOF) = 0); 3) Intraoperative PNS with partial neuromuscular blockade (TOF in the range of 1-2). Diaphragm ultrasound will be performed to assess diaphragm function before surgery and at 24 hours and 48 hours after surgery, respectively. Postoperative delirium will be assessed daily using the 3D-CAM and CAM-ICU within 3 days. Plasma biomarkers of brain injury will also be tested at baseline, 24 hours, and 48 hours after surgery. Pulmonary complications will be diagnosed by three independent clinicians based on laboratory tests, imaging, and clinical signs.

【Aims and Hypothesis】The primary aims are to investigate the impact of intraoperative diaphragmatic neuromodulation on brain injury, including the occurrence of delirium and changes in biomarkers. The secondary aims are the incidence of postoperative pulmonary complications and other clinical outcomes. We hypothesize that intraoperative diaphragmatic neuromodulation could reduce brain injury induced by craniotomy, as well as the incidence of postoperative delirium and pulmonary complications.

Conditions

Neurosurgery; Phrenic Nerve Stimulation; Postoperative Delirium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Control group

No intervention will be performed; all protocols during surgery will follow the clinical routine.

Group Type: NO_INTERVENTION

No interventions assigned to this group

PNS + TOF 0

Patients in this group will receive PNS during surgery, with the train-of-four (TOF) maintained at a level of 0. Additionally, to ensure complete blockade of the neuromuscular system, the Post-Tetanic Count (PTC) will be monitored and maintained at less than or equal to 3 simultaneously.

Group Type: EXPERIMENTAL

Phrenic nerve stimulation

Intervention Type: OTHER

A commercial phrenic nerve stimulation equipment will be used during surgery. Phrenic nerve stimulation intensity will be determined before surgery, ensuring significant diaphragm contraction under stimulation. The use of an electric knife will be avoided during surgery. Tidal volume, airway pressure, and vital signs will be monitored continuously.

PNS + TOF 1-2

Patients in this group will receive PNS during surgery, and the TOF will be maintained at levels 1-2. In this group, the neuromuscular junction will not be fully blocked.

Group Type: EXPERIMENTAL

Phrenic nerve stimulation

Intervention Type: OTHER

A commercial phrenic nerve stimulation equipment will be used during surgery. Phrenic nerve stimulation intensity will be determined before surgery, ensuring significant diaphragm contraction under stimulation. The use of an electric knife will be avoided during surgery. Tidal volume, airway pressure, and vital signs will be monitored continuously.

Interventions

Phrenic nerve stimulation

A commercial phrenic nerve stimulation equipment will be used during surgery. Phrenic nerve stimulation intensity will be determined before surgery, ensuring significant diaphragm contraction under stimulation. The use of an electric knife will be avoided during surgery. Tidal volume, airway pressure, and vital signs will be monitored continuously.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years old;
• Body mass index ≤ 30 kg/㎡;
• American Society of Anesthesiologists Classification: I-II level;
• Patients who undergo elective supratentorial tumor resection surgery;
• Mechanical ventilation during operation ≥ 4h;
• Signed informed consent form;

Exclusion Criteria

• With known respiratory diseases, such as chronic obstructive pulmonary disease, obstructive sleep apnea, asthma, etc.;
• History of respiratory infection within 6 months before surgery;
• Received invasive or non-invasive mechanical ventilation within 6 months;
• Contraindications to extracorporeal diaphragmatic pacemakers, such as pneumothorax, active pulmonary tuberculosis, and wearing a cardiac pacemaker;
• Diagnosis with neuromuscular dysfunction diseases such as Guillain-Barre syndrome, myasthenia gravis, muscle atrophy, etc.;
• Pregnant or lactating patients;
• Preoperative cognitive impairment, consciousness disorders.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Sanbo Brain Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhonghua Shi, MD, PhD

Deputy president of the department ICU

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhonghua Shi, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Beijing Sanbo Brain Hospital

Locations

Beijing Sanbo Brain Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

Dia-the-Brain

Identifier Type: -

Identifier Source: org_study_id