The External Diaphragm Pacemaker Assisted Extubation in Premature Infants With Invasive Mechanical Ventilation

NCT ID: NCT06404294

Last Updated: 2024-05-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-31
• Study Completion Date: 2024-12-31

Brief Summary

With the development of perinatal medicine, more and more newborns with respiratory failure can be treated due to the use of respiratory support technology. However, long-term invasive mechanical ventilation treatment can lead to a series of complications such as ventilator-associated pneumonia, atelectasis and air leakage syndrome, and increase the risk of bronchopulmonary dysplasia and neurodevelopmental lag of premature infants. It also leads to longer hospital stays and higher hospital costs. To shorten the invasive mechanical ventilation time and improve the success rate of withdrawal through various ways is the development direction of neonatal mechanical ventilation therapy.

Respiratory muscle atrophy is common and rapid in children receiving invasive mechanical ventilation, and is an important cause of ventilator dependence and withdrawal failure. The diaphragm of newborns is the main respiratory muscle, of which the diaphragm type 1 endurance fiber accounts for only about 30%, far lower than the proportion of about 55% in adults, so the diaphragm of newborns is more prone to fatigue. Previous animal experiments and clinical studies in children and adults have confirmed that diaphragmatic pacing therapy applied to patients with long-term invasive mechanical ventilation can prevent diaphragmatic atrophy, reverse diaphragmatic injury, significantly improve diaphragmatic thickness, improve diaphragmatic anti-fatigue ability, thereby increasing lung ventilation, relieving dyspnea, and achieving the effect of assisted extubation.

The neonatology Department of the Children's Hospital Affiliated to Chongqing Medical University started neonatal external diaphragm pacemaker treatment in 2022, and has completed 1383 cases so far, initially showing the effectiveness and safety of external diaphragm pacemaker treatment in neonatal population. But so far, there is no systematic evaluation of clinical intervention effect of external diaphragm pacemaker treatment on neonatal respiratory failure patients at home and abroad. Based on this, the project team intends to conduct a prospective randomized controlled study to systematically evaluate the safety of external diaphragm pacemaker in preterm infants requiring invasive mechanical ventilation for ≥7 days at 28 to 35 weeks of gestation, and to evaluate the efficacy of external diaphragm pacemaker in adjuvant extubation.

Detailed Description

Neonatal respiratory failure is the central or peripheral respiratory dysfunction caused by various reasons, and is an important clinical critical disease of newborns. With the development of perinatal medicine, more and more newborns with respiratory failure can be treated due to the use of respiratory support technology. However, long-term invasive mechanical ventilation treatment can lead to a series of complications such as ventilator-associated pneumonia, atelectasis and air leakage syndrome, and increase the risk of bronchopulmonary dysplasia and neurodevelopmental lag of premature infants. It also leads to longer hospital stays and higher hospital costs. To shorten the invasive mechanical ventilation time and improve the success rate of withdrawal through various ways is the development direction of neonatal mechanical ventilation therapy.

Respiratory muscle atrophy is common and rapid in children receiving invasive mechanical ventilation, and is an important cause of ventilator dependence and withdrawal failure. The diaphragm of newborns is the main respiratory muscle, of which the diaphragm type 1 endurance fiber accounts for only about 30%, far lower than the proportion of about 55% in adults, so the diaphragm of newborns is more prone to fatigue. Studies have shown that phrenic atrophy usually begins within 18-69 hours of invasive mechanical ventilation and progresses at a rate of 4-7% per day.

Previous animal experiments and clinical studies in children and adults have confirmed that diaphragmatic pacing therapy applied to patients with long-term invasive mechanical ventilation can prevent diaphragmatic atrophy, reverse diaphragmatic injury, significantly improve diaphragmatic thickness, improve diaphragmatic anti-fatigue ability, thereby increasing lung ventilation, relieving dyspnea, and achieving the effect of assisted extubation.

In February 1987, the external diaphragm pacemaker independently developed by Chen et al at Sun Yat-sen University of Medical Science was applied to clinical practice, setting a precedent for external diaphragmatic pacing at home and abroad. The basic principle is to perform low-frequency pulse electrical stimulation of the phrenic nerve through the electrodes on the body surface to make the regular contraction and relaxation of the diaphragm and increase the degree of movement of the diaphragm, so as to improve the ventilation function of the patient. In China, Cai et al observed that external diaphragm pacemaker can increase the degree of immediate diaphragm movement in normal people, and significantly increase the degree of immediate movement in patients with chronic obstructive pulmonary disease and the range of diaphragm movement after continuous treatment for 20-30 days, and significantly improve the symptoms of dyspnea.

The neonatology Department of the Children's Hospital Affiliated to Chongqing Medical University started neonatal external diaphragm pacemaker treatment in 2022, and has completed 1383 cases so far, initially showing the effectiveness and safety of external diaphragm pacemaker treatment in neonatal population. But so far, there is no systematic evaluation of clinical intervention effect of external diaphragm pacemaker treatment on neonatal respiratory failure patients at home and abroad. Based on this, the project team intends to conduct a prospective randomized controlled study to systematically evaluate the safety of external diaphragm pacemaker in preterm infants requiring invasive mechanical ventilation for ≥7 days at 28 to 35 weeks of gestation, and to evaluate the efficacy of external diaphragm pacemaker in adjuvant extubation.

Conditions

Invasive Mechanical Ventilation; Extubation

Study Design

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

Study Groups

External Diaphragm Pacemaker treatment group

On the basis of conventional treatment, the patients in this group were treated with external diaphragm pacemaker for 2 weeks or until extubation.

Group Type: EXPERIMENTAL

External Diaphragm Pacemaker treatment

Intervention Type: DEVICE

On the basis of conventional treatment, the patients in this group were treated with external diaphragm pacemaker for 2 weeks or until extubation.The treatment process of external diaphragm pacemaker is as follows: Set parameters: pacing frequency: 5-9 times /min, generally starting from 5 times /min, and adjusted according to the tolerance of the child; Pulse frequency 30 hertz; The stimulation intensity generally starts from 2-3. If the respiratory waveform of the child on the machine is not disturbed, it indicates that the child can tolerate it and the intensity can be appropriately increased. Treatment time: generally starts from 5 minutes, the longest is not more than 20 minutes, the frequency of treatment: 1 time/day in the first week, 2 times/day in the second week.

No External Diaphragm Pacemaker treatment group

The patients in this group were treated with conventional treatment.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

External Diaphragm Pacemaker treatment

On the basis of conventional treatment, the patients in this group were treated with external diaphragm pacemaker for 2 weeks or until extubation.The treatment process of external diaphragm pacemaker is as follows: Set parameters: pacing frequency: 5-9 times /min, generally starting from 5 times /min, and adjusted according to the tolerance of the child; Pulse frequency 30 hertz; The stimulation intensity generally starts from 2-3. If the respiratory waveform of the child on the machine is not disturbed, it indicates that the child can tolerate it and the intensity can be appropriately increased. Treatment time: generally starts from 5 minutes, the longest is not more than 20 minutes, the frequency of treatment: 1 time/day in the first week, 2 times/day in the second week.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Premature infants at 28 to 35 weeks.

2. The premature infant whose invasive mechanical ventilation time ≥7 days.

3. Parents sign an informed consent form.

Exclusion Criteria

1. The premature infant with congenital airway malformation confirmed by chest CT or bronchofiberscopy.

2. The premature infant with congenital genetic metabolic disease.

3. The premature infant with complex congenital heart disease.

4. The premature infant undergoing surgery.

5. The premature infant with severe brain damage.

6. The premature infant with neuromuscular diseases.

7. The premature infant with congenital skin disease, local skin damage or infection.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 3 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Chongqing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Wang Jianhui

Attending neonatologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yuan Shi, M.D

Role: STUDY_DIRECTOR

Children's Hospital of Chongqing Medical University

Locations

Children's hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jianhui Wang, M.D

Role: CONTACT

wangjh@cqmu.edu.cn

+86-13678428167

Facility Contacts

Jianhui Wang, M.D

Role: primary

wangjh@cqmu.edu.cn

13678428167

References

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Reference Type: RESULT

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Reference Type: RESULT

PMID: 18367735 (View on PubMed)

Grosu HB, Lee YI, Lee J, Eden E, Eikermann M, Rose KM. Diaphragm muscle thinning in patients who are mechanically ventilated. Chest. 2012 Dec;142(6):1455-1460. doi: 10.1378/chest.11-1638.

Reference Type: RESULT

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Reference Type: RESULT

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Zambon M, Beccaria P, Matsuno J, Gemma M, Frati E, Colombo S, Cabrini L, Landoni G, Zangrillo A. Mechanical Ventilation and Diaphragmatic Atrophy in Critically Ill Patients: An Ultrasound Study. Crit Care Med. 2016 Jul;44(7):1347-52. doi: 10.1097/CCM.0000000000001657.

Reference Type: RESULT

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Breuer T, Hatam N, Grabiger B, Marx G, Behnke BJ, Weis J, Kopp R, Gayan-Ramirez G, Zoremba N, Bruells CS. Kinetics of ventilation-induced changes in diaphragmatic metabolism by bilateral phrenic pacing in a piglet model. Sci Rep. 2016 Oct 19;6:35725. doi: 10.1038/srep35725.

Reference Type: RESULT

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Hsin YF, Chen SH, Yu TJ, Huang CC, Chen YH. Effects of transcutaneous electrical diaphragmatic stimulation on respiratory function in patients with prolonged mechanical ventilation. Ann Thorac Med. 2022 Jan-Mar;17(1):14-20. doi: 10.4103/atm.atm_158_21. Epub 2022 Jan 14.

Reference Type: RESULT

PMID: 35198044 (View on PubMed)

Sotak M, Roubik K, Henlin T, Tyll T. Phrenic nerve stimulation prevents diaphragm atrophy in patients with respiratory failure on mechanical ventilation. BMC Pulm Med. 2021 Oct 8;21(1):314. doi: 10.1186/s12890-021-01677-2.

Reference Type: RESULT

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Other Identifiers

20240324

Identifier Type: -

Identifier Source: org_study_id