Clinical trial NCT06518707: Intraoperative Diaphragmatic Neuromodulation
Official title: Impact of Intraoperative Diaphragmatic Neuromodulation on Postoperative Complications in Neurosurgical Patients: A Prospective, Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Neurosurgery
Phrenic Nerve Stimulation
Postoperative Delirium
Keywords: Phrenic nerve stimulation
Postoperative delirium
Postoperative pulmonary complications
Lead sponsor: Beijing Sanbo Brain Hospital
Sponsor class: OTHER
First posted: 2024-07-24
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The intervention groups include two groups: each group will receive phrenic nerve stimulation under different degrees of neuromuscular blockade, i.e., the TOF 0 group and the TOF 1-2 group.
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Incidence of delirium
timeFrame: Within 3 days after surgery
Secondary outcomes:
measure: Postoperative pulmonary complications
timeFrame: Within 7 days after surgery
measure: Post operative diaphragm dysfunction
timeFrame: Before the surgery and within 24 hours and 48 hours after surgery.
measure: Length of stay in Intensive Care Unit (ICU)
timeFrame: The time from ICU admission to transfer to the ward or death, whichever occurred first, was assessed for up to 180 days.
measure: Length of hospital stay
timeFrame: The period from hospital admission to discharge or death, whichever occurred first, was assessed for up to 180 days.
measure: White blood cell
timeFrame: Before the surgery and within 24 hours and 48 hours after surgery.
measure: S100 calcium-binding protein B (S-100B)
timeFrame: Before the surgery and within 24 hours and 48 hours after surgery.
measure: Glial Fibrillary acidic protein (GFAP)
timeFrame: Before the surgery and within 24 hours and 48 hours after surgery.
measure: Brain-derived neurotrophic factor (BDNF)
timeFrame: Before the surgery and within 24 hours and 48 hours after surgery.
measure: Neuron-specific enolase (NSE)
timeFrame: Before the surgery and within 24 hours and 48 hours after surgery.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Sanbo Brain Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Sanbo Brain Hospital
name: Zhonghua Shi, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: