Effect of physical rehabilitation using oromotor stimulation, manual airway clearance technique, positioning, tactile and kinaesthetic stimulation (PROMPT) protocol on respiratory and neuromuscular function in neonatal respiratory distress syndrome (NRDS)- a protocol for randomized controlled trial

Introduction

Hyaline membrane disease, also referred to as Neonatal Respiratory Distress Syndrome (NRDS), is a serious respiratory illness that primarily affects premature babies. The hallmark of this disease is decreased lung function based on by an absence of pulmonary surfactant, which is essential for preserving alveolar stability and averting collapse during expiration. Being the primary cause of respiratory distress in infants, non-respiratory distress syndrome (NRDS) presents a complicated range of difficulties for medical practitioners, demanding early diagnosis and treatment to maximize results. Premature babies, particularly those born before 28 weeks of gestation, have a higher prevalence of (NRDS), which has an inverse relationship with gestational age. The significance of surfactant, a lipid-protein complex generated by type II alveolar cells in the lungs, is shown by this association. Premature babies frequently don’t have enough surfactant, which causes surface tension to rise and alveolar collapse, which prevents enough oxygen exchange. RDS, also known as neonatal respiratory distress syndrome, is a common cause of respiratory distress in infants. It often manifests itself a few hours after birth, usually right after delivery. RDS mostly affects preterm newborns, with term infants affected sporadically as well. The incidence of RDS is negatively correlated with the infant’s gestational age, with smaller and more preterm neonates experiencing more severe illness. RDS remains the primary cause of morbidity and mortality in preterm infants, despite the fact that treatment techniques such as prenatal corticosteroids, surfactants, and sophisticated respiratory care of the newborn have improved the results for patients affected by the condition.¹

Surfactant deficit is the cause of neonatal respiratory distress syndrome, particularly when the lungs are still developing. A lack of surfactant causes the surface tension in the alveoli and tiny airways to rise, which lowers the juvenile lung’s compliance. To stop the alveolus from collapsing or from filling with fluid, the pressures at the air-fluid interface must be carefully balanced.²

The clinical course of neonatal respiratory distress syndrome (RDS) and the long-term outcomes of the neonates are the primary factors associated with complications of RDS. Even though the morbidity linked to RDS has decreased with surfactant therapy, many individuals still experience problems both during and after the acute phase of the disease. Acute side effects from invasive mechanical ventilation or positive pressure ventilation include pneumothorax, pneumomediastinum, and pulmonary interstitial emphysema, which are air-leak syndromes. In very low birth weight newborns with RDS, there is also an increased risk of cerebral bleeding and patent ductus arteriosus, however these conditions are not directly related to preterm.³

One long-term RDS consequence is BPD. The etiology of BPD includes inflammation and lung damage in addition to stunted lung growth. In addition to lacking surfactant, the premature infant’s immature lung also has reduced compliance, impaired fluid clearance, and immature vascular development, all of which put the lung at risk for damage and inflammation and further interfered with the alveolar and pulmonary vasculature’s normal development.^4–6 Additionally, reduced antioxidant capacities of the premature lung and oxidative stress from hyperoxia brought on by mechanical breathing both cause the lung to deteriorate further by increasing the production of pro-inflammatory cytokines such TGF-β1.

Another complication of RDS is neurodevelopmental delay, which is more common in infants who have had prolonged mechanical breathing. In addition, newborns with RDS had a higher incidence of cerebral palsy, which decreased with increasing gestational age.⁷ There is a correlation between the duration of artificial ventilation and higher incidence of cerebral palsy and neurodevelopmental delay.⁸

Oro motor stimulation, positioning, tactile, and kinesthetic stimulation (PROMPT) is one physical rehabilitation strategy that has shown promise in treating preterm newborns’ respiratory, pulmonary, and neuromuscular problems. But there is still a dearth of empirical data demonstrating the effectiveness of these kinds of therapies, especially when used in randomized controlled trials (RCTs).⁹

By examining the complete effects of PROMPT on respiratory, pulmonary, and neuromuscular outcomes in preterm newborns with NRDS, this study aims to close this information gap. The application of a randomized controlled trial design facilitates a thorough analysis of the intervention’s effects, offering important new information to the developing field of newborn care.

By carefully examining these aspects, this research hopes to improve neonatal care practices and lay the groundwork for future developments aimed at enhancing the well-being and results of this susceptible group.

Objective of the study

Exclusion criteria

• • Significant Congenital Abnormalities.

• • Profound Hemodynamic Instability.

• • Life-Threatening Situations: Neonates with urgent and critical medical conditions other than NRDS, necessitating immediate interventions, may be ineligible.

• • Serious Neurological Complications: Neonates with severe neurological issues that could independently affect neuromuscular function, apart from NRDS, may be excluded.

• • Parental Denial or Incapacity to Participate: Parents or guardians who decline to provide consent for their neonate to participate in the study or are unable to adhere to study requirements may be excluded.

• • Unstable Respiratory Condition: Neonates with an unstable respiratory status hindering the initiation or continuation of the rehabilitation intervention may be excluded.

• • Severe Coagulation Disorders: Neonates with significant coagulation disorders that may pose risks to the safety of rehabilitation interventions may be excluded.

Group A will receive the PROMPT protocol as an adjunct to medical treatment by paediatric physiotherapist. for 6 weeks daily, for 30 minutes, or until the neonate/infant is successfully weaned off the mechanical ventilator, based on their medical condition, or until the intervention concludes on the last day of the neonate’s transfer from the NICU to the ward.

Group B will receive standardized medical treatment protocols + Conventional Physiotherapy (Chest percussion, vibration and suctioning) administered by neonatal specialists and paediatric physiotherapist. Both groups will continue treatment until the neonate/infant is successfully weaned off the mechanical ventilator, based on their medical condition, or until the intervention concludes on the last day of the neonate’s transfer from the NICU to the ward. Assessments will be conducted at baseline, 2nd week, 4th week, 6th week, and after a 3-month follow-up, infant will be evaluated in high-risk clinic, where both primary and secondary variables will be evaluated (Figure 1).

Figure 1. CONSORT flow chart.

PROMPT Treatment Protocol:

Physical

Rehabilitation

Oro motor stimulation (Table 1)

Table 1. ORO motor stimulation (O).

Treatment	Descriprtion	Intensity
Cheek stretch	Apply light pressure to compress the tissue by placing the index finger at the base of the nose. Forming a C shape, move the finger first toward the ear and then downhill to the lip corner. On the other side, repeat the identical process.	2 minutes
Upper lip stimulation	Press the index finger gently against the top lip's corner to compress the tissue. Take a circular motion with the finger, moving it from one corner to the center and back again to the other corner. Proceed in reverse to change the direction.	2 minutes
Lower lip stimulation	Press down on the lower lip's corner with your index finger to compress the skin. Move the finger in a circular manner, starting from the corner and going all the way to the centre and back again to the other corner.	2 minutes
Upper gum stimulation	Applying firm pressure gradually, place the finger in the middle of the gum and slide it toward the rear of the mouth, then back towards the center.	2 minutes
Lower gum stimulation	Place the finger in the middle of the gum, press firmly and consistently, and then work your way slowly towards the back of the mouth.	2 minutes
Tongue stimulation	Position the finger between the lower gum and the lateral aspect of the tongue at the level of the molars. Press down to move the tongue in the other direction as you move the finger in the direction of the midline. Quickly press the finger into the cheek to produce a squeezing feeling, and then press firmly on the hard palate for three seconds. After that, press the finger down until it touches the middle of the tongue.	2 minutes
TMJ stroke	To incorporate Temporomandibular Joint (TMJ) strokes into oro motor stimulation, methods that target the muscles surrounding the jaw joint must be used. These techniques include kneading the jaw joint gently, moving in circles, and applying pressure with concentration to the surrounding muscles. Improving blood flow, relieving tense muscles, and enhancing orofacial muscular coordination are the goals.	2 minutes

Manual airway clearance technique (Table 2)

Table 2. Manual airway clearance technique (M).¹⁰

Treatment	Descriprtion	Intensity
Percussion	Chest percussion involves tapping the chest using percussor cups, resembling suction cups, to create vibrations in the airways of the lungs. These vibrations aid in loosening mucus, facilitating its removal through coughing.	30 percussion for 5 sets
Active gentle vibration	A rapid, sensitive trill-type movement was used to actively deliver gentle vibrations while exhaling. Mild vibrations were applied after percussion to help shift secretions in the direction of the bigger airways. Each newborn's chest vibrations were manually applied by covering the targeted region with one hand's fingers on the chest wall. A faint vibrating motion was produced by the isometric contraction of the hand and forearm muscles. Concurrently, the other hand supported the head of the infant, keeping the palm cupped to cradle the head for the length of the treatment.	30 vibration for 5 sets
Postural drainage	The newborn was kept in a flat supine position during the anterior segment drainage of the left and right upper lobes. To address the right and left lateral basal segments of the lower lobes, drainage was performed as the neonate leaned forward at a 90-degree angle, followed by percussion over the uppermost sections of the lower ribs. Percussion was applied over the side of the chest beneath the clavicles, extending towards the nipple area, with caution to avoid direct pressure on the sternum.	Each drainage position was applied for a duration of 5 minutes per position.
Reflex stimulation for respiratory facilitation	The neonate is positioned in the supine decubitus, and gentle digital pressure is applied to a specific point on the hemithorax, precisely between the 7th and 8th ribs (corresponding to the diaphragm muscle insertion) along the mammillary line. This designated area is referred to as a “trigger point.” Activation of the trigger point induces respiratory activity by causing compression on the stimulated side, leading to an increase in ipsilateral pulmonary ventilation per minute and facilitating contralateral pulmonary expansion (3 minutes and repeated 4 to 6 times consecutively, involving the 7th right hemitoracic space for 3 minutes, followed by the 7th left hemithorax space for 3 minutes, and repeating this sequence for both the 7th right and left spaces. If secretions are present, the respiratory facilitation technique is combined with a prolonged slow expired technique tailored for preterm infants.)	This program is implemented three times a day until the neonate achieves complete respiratory autonomy.
Suctioning	The goal of nasotracheal suctioning (NTS) for tracheal aspiration was to remove accumulated sputum, blood, pulmonary secretions, saliva, and other foreign materials from the nasopharyngeal and trachea. The process was carried out by the nurse, who used sub-atmospheric pressure to extract a sterile, flexible, multi-eyed catheter. The neonate's sub-atmospheric pressure to between 80 and 100 mm Hg in order to remove secretions. Active mild vibrations were applied first, and then suctioning was done.	Suctioning was performed after the use of active gentle vibrations.

Positioning (Table 3)

Table 3. Positioning.^11,12

Treatment	Descriprtion	Intensity
Swaddling Positing	Swaddling is a traditional practice of wrapping infants snugly in a blanket or cloth to restrict their movement. It is often done to help babies sleep better and feel more secure. However, it's important to note that swaddling should be done safely to avoid potential risks. Here are some general guidelines on the swaddling position: Back Position Loose at the Hips: Hands Up or Hands-to-Face Flexed Legs.	3 hours per day
Hammock handling	The approach known as "hammock positioning," which is thought to be easy and inexpensive, entails placing the PTNB (Premature new born) in a rectangular-shaped hammock that is secured at the ends of the incubators and is usually made of fabric. This approach's therapeutic position minimizes postural irregularities and asymmetries linked to preterm and NICU stay while theoretically simulating the intrauterine environment. It also promotes relaxation and the development of spontaneous and functional motor abilities.	3 hours per day

Tactile and Kinesthetic stimulation (Table 4)

• i. APGAR: The APGAR score was created in 1952 by Columbia University anaesthesiologist Dr. Virginia Apgar. Coincidentally, APGAR serves as a helpful acronym to represent the elements of the score: appearance, respiration, activity, pulse, and grimace. Neonatal can be quickly assessed using the score both at the time of delivery and during resuscitation. The Apgar score is based on several factors, such as colour, breathing, muscular tone, heart rate, and reflexes. In order to detect hemodynamic compromise symptoms such cyanosis, hypoperfusion, bradycardia, hypotonia, respiratory depression, or apnoea, Apgar score is used. Each component receives a score of either 1 or 2. All new-borns have their scores recorded at one minute and five minutes, with extended recordings made at five-minute intervals for those who score seven or lower at that point. In people who need resuscitation as a way to track their reaction. 7 to 10 is considered a reassuring score.¹³

• ii. ABG Analysis: Arterial blood gas (ABG) analysis is a crucial tool for assessing a newborn’s respiratory and metabolic status, especially if they are in the NICU. An ABG assay provides information on acid-base balance, ventilation, oxygenation, and electrolyte status. The specific physiology and normal values for this particular group must be taken into consideration when interpreting the results of the newborn ABG.

Table 4. Tactile and kinesthetic stimulation [T].

Treatment	Descriprtion	Intensity
Tactile stimulation	For tactile stimulation, the neonate was stroked with moderate pressure, a procedure that required the use of both hands. While getting tactile stimulation, the newborn was placed in the prone (face-down) position.	Each stimulation session involved a 10-minute duration of gentle Stimulation sessions were conducted twice daily, with a minimum interval of 30 minutes after feeding and at least 2 hours after the preceding session.
Kinaesthetic stimulation	Kinesthetic stimulation was applied to the infant's hip, knee, ankle, shoulder, elbow, and wrist through passive movements. During this phase, the infant was placed face-up in a crib or on the parent's lap.	Each stimulation session involved a 10-minute duration of gentle Stimulation sessions were conducted twice daily, with a minimum interval of 30 minutes after feeding and at least 2 hours after the preceding session.

Secondary outcome measure:

• i. Silverman-Anderson Respiratory Severity Score (RSS): Silverman-Anderson Respiratory Severity Score (RSS): The Silverman-Anderson Respiratory Severity Score (RSS), created by doctors Sidney Silverman and Stuart L. Anderson, is a clinical instrument used to evaluate the level of respiratory distress in neonates, especially those with respiratory distress syndrome (RDS). This tool, which is frequently used in neonatal intensive care units (NICUs), helps medical personnel determine whether a patient needs breathing support or interventions by helping them measure the patient’s level of respiratory distress^14,15

IICC: 62.5% sensitivity, 61.9% specificity, 24.7% PPV, 89.2% NPV, and an overall diagnostic accuracy of 61.9%.

• ii. Ballard Score: A clinical method for estimating a new-born’s gestational age, the Ballard Score is also referred to as the Ballard Maturational Assessment. This scoring system was created in 1979 by Dr. Jeanne L. Ballard to assist medical professionals in assessing a variety of physical and developmental features in order to determine the level of physical and neuromuscular maturation.¹⁶

Ethics and dissemination

RESEARCH ETHICS APPROVAL:

The study has been presented in the IEC and got approval from Datta Meghe Institute of Higher Education and research (DU), Sawangi (Meghe), Wardha, on 30th January 2024 with Ref No. DMIHER/IEC/2024/65.

CONSENT AND ASSENT: All neonates before giving the intervention, the informed assent and consent will be taken from the parents.

CONFIDENTIALITY: Any information pertaining to the subjects participating in the study shall be maintained confidential. Any patient-related information will only be used with due permission from the subjects.

DECLARATION OF INTERESTS: There are no financial or competing interests to mention.

ACCESS TO DATA: All the data collected during or after the study shall be stored and maintained by the study’s Principal Investigator. The PI will have access to the final trial dataset, and it will be shared with de-identification after receiving a formal request for research and publication purposes only.

ANCILLARY AND POST-TRIAL CARE: Care shall be provided to the study subjects in case of events leading to harm from trial participation by the PI in accordance with the policy of Ravi Nair Physiotherapy College and DMIHER.

DISSEMINATION POLICY: Any data collected during or after the study will only be used for academic and research-related purposes culminating in a publication in a reputed journal.

Discussion

The proposed study has significant implications for neonatal care by exploring the potential benefits of physical rehabilitation, specifically the PROMPT protocol, in managing neonatal respiratory distress syndrome (NRDS). If the results demonstrate positive effects on respiratory and neuromuscular function, it could lead to the development of new therapeutic interventions to improve outcomes for neonates with NRDS. Additionally, the study may contribute to the growing body of evidence supporting the role of physical rehabilitation in neonatal care, potentially influencing clinical practice guidelines and standards of care. NRDS is a common and life-threatening condition in neonates, often requiring intensive medical management. Investigating non-pharmacological interventions like physical rehabilitation is clinically relevant, especially considering the potential long-term respiratory and neurodevelopmental consequences of NRDS. Addressing respiratory and neuromuscular function early in neonates with NRDS may lead to improved short- and long-term outcomes, including reduced respiratory complications, shorter hospital stays, and improved neurodevelopmental outcomes.

The PROMPT protocol focuses on enhancing motor function and coordination through tactile-kinesthetic stimulation, potentially promoting the development of respiratory and neuromuscular control in neonates with NRDS. By incorporating gentle, hands-on techniques, the PROMPT protocol may facilitate respiratory muscle activation, improve chest wall compliance, and enhance overall respiratory mechanics in neonates with NRDS. Successful completion of this trial may warrant further research to optimize the implementation of physical rehabilitation interventions in neonatal care settings. Future studies could explore the feasibility and efficacy of integrating the PROMPT protocol into multidisciplinary neonatal care protocols or early intervention programs for infants at risk of respiratory and neuromuscular dysfunction. In conclusion, the proposed randomized controlled trial investigating the effect of physical rehabilitation with the PROMPT protocol on respiratory and neuromuscular function in neonates with NRDS holds promise for improving clinical outcomes and advancing our understanding of non-pharmacological interventions in neonatal care. Addressing the study’s implications, clinical relevance, potential mechanisms of action, limitations, and future directions is essential for informing researchers, clinicians, and policymakers about the potential benefits and challenges associated with this innovative approach.