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Intraoperative Diaphragmatic Neuromodulation

Not Applicable
Recruiting
Conditions
Postoperative Delirium
Neurosurgery
Phrenic Nerve Stimulation
Interventions
Other: Phrenic nerve stimulation
Registration Number
NCT06518707
Lead Sponsor
Beijing Sanbo Brain Hospital
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
120
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PNS + TOF 1-2Phrenic nerve stimulationPatients 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.
PNS + TOF 0Phrenic nerve stimulationPatients 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.
Primary Outcome Measures
NameTimeMethod
Incidence of deliriumWithin 3 days after surgery

The incidence of delirium is documented using validated delirium scores, determined by either a positive result from the 3-minute diagnostic interview for the Confusion Assessment Method (3D-CAM) scoring sheet, the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), or both

Secondary Outcome Measures
NameTimeMethod
Postoperative pulmonary complicationsWithin 7 days after surgery

Postoperative pulmonary complications may include respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, acute respiratory distress syndrome, aspiration pneumonia, pulmonary embolism, pulmonary edema, and aggravation of existing lung diseases.

Post operative diaphragm dysfunctionBefore the surgery and within 24 hours and 48 hours after surgery.

The patient is placed in a supine position, with a high-frequency linear array probe positioned between the right axillary midline and the 8th to 10th ribs. The probe is rotated to align parallel to the intercostal space. When two parallel high-echo lines appear, the diaphragm is identified between them. The sampling line is placed in the diaphragm movement area, and once the image stabilizes, it is converted to an M-mode ultrasound. The thickness of the inspiratory and expiratory diaphragmatic muscles is measured separately, and the maximum value is obtained by repeating the measurements three times. Diaphragm dysfunction is defined as a fraction of diaphragm thickening less than 20%.

S100 calcium-binding protein B (S-100B)Before the surgery and within 24 hours and 48 hours after surgery.

Evaluation of serum S-100B protein levels in patients at baseline, immediate postoperative state, and 48 hours after surgery.

Length of stay in Intensive Care Unit (ICU)The time from ICU admission to transfer to the ward or death, whichever occurred first, was assessed for up to 180 days.

The time between the patient's admission to the ICU and the patient's discharge from the ICU is referred to as the length of stay in the ICU.

Length of hospital stayThe period from hospital admission to discharge or death, whichever occurred first, was assessed for up to 180 days.

The time between the patient's admission to the hospital and the patient's discharge from the hospital is referred to as the length of stay in the hospital.

White blood cellBefore the surgery and within 24 hours and 48 hours after surgery.

Collect preoperative and postoperative blood routine and biochemical information from patients, specifically focusing on white blood cell counts before and after surgery.

Neuron-specific enolase (NSE)Before the surgery and within 24 hours and 48 hours after surgery.

Evaluation of serum NSE levels in patients at baseline, immediate postoperative state, and 48 hours after surgery.

Glial Fibrillary acidic protein (GFAP)Before the surgery and within 24 hours and 48 hours after surgery.

Evaluation of serum GFAP levels in patients at baseline, immediate postoperative state, and 48 hours after surgery.

Brain-derived neurotrophic factor (BDNF)Before the surgery and within 24 hours and 48 hours after surgery.

Evaluation of serum BDNF levels in patients at baseline, immediate postoperative state, and 48 hours after surgery.

Trial Locations

Locations (1)

Beijing Sanbo Brain Hospital, Capital Medical University

🇨🇳

Beijing, Beijing, China

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