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

Extubation Clinical Trial

Official title:

A Randomized Controlled Study of the External Diaphragm Pacemaker Assisted Extubation in Premature Infants With Invasive Mechanical Ventilation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06404294
• Other study ID #: 20240324
• Status: Recruiting
• Phase: N/A
• Start date: March 31, 2024
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: Children's Hospital of Chongqing Medical University
• Contact: Jianhui Wang, M.D
• Phone: +86-13678428167
• Email: wangjh[@]cqmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 3 Months

Eligibility

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.

Related Conditions & MeSH terms

• Extubation
• Invasive Mechanical Ventilation

Intervention

Device:
• 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.

Locations

Country	Name	City	State
China	Children's hospital of Chongqing Medical University	Chongqing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Chongqing Medical University

Country where clinical trial is conducted

China, 

References & Publications (10)

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: — View Citation

Dassios T, Vervenioti A, Dimitriou G. Respiratory muscle function in the newborn: a narrative review. Pediatr Res. 2022 Mar;91(4):795-803. doi: 10.1038/s41390-021-01529-z. Epub 2021 Apr 19. — View Citation

Francis CA, Hoffer JA, Reynolds S. Ultrasonographic Evaluation of Diaphragm Thickness During Mechanical Ventilation in Intensive Care Patients. Am J Crit Care. 2016 Jan;25(1):e1-8. doi: 10.4037/ajcc2016563. — View Citation

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. — View Citation

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. Ep — View Citation

Johnson RW, Ng KWP, Dietz AR, Hartman ME, Baty JD, Hasan N, Zaidman CM, Shoykhet M. Muscle atrophy in mechanically-ventilated critically ill children. PLoS One. 2018 Dec 19;13(12):e0207720. doi: 10.1371/journal.pone.0207720. eCollection 2018. — View Citation

Levine S, Nguyen T, Taylor N, Friscia ME, Budak MT, Rothenberg P, Zhu J, Sachdeva R, Sonnad S, Kaiser LR, Rubinstein NA, Powers SK, Shrager JB. Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med. 2008 Mar 27;358(13):1 — View Citation

Sieck GC, Fournier M, Blanco CE. Diaphragm muscle fatigue resistance during postnatal development. J Appl Physiol (1985). 1991 Aug;71(2):458-64. doi: 10.1152/jappl.1991.71.2.458. — View Citation

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. — View Citation

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.0000 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Invasive mechanical ventilation time	Time from invasive mechanical ventilation to extubation	through study completion, up to 100 days of life
Secondary	Diaphragm geometry and function	Diaphragm ultrasound	through study completion, up to 100 days of life
Secondary	Duration of oxygen use	Duration of oxygen use	through study completion, up to 100 days of life
Secondary	Incidence of bronchopulmonary dysplasia	Incidence of bronchopulmonary dysplasia	through study completion, up to 100 days of life
Secondary	Mortality	Mortality	through study completion, up to 100 days of life