Comparison Of Surfactant Lung Lavage With Standard Care In The Treatment Of Meconium Aspiration Syndrome (Sur-Lu-Lav)

Surfactant Lung Lavage Versus Standard Care In The Treatment Of Meconium Aspiration Syndrome- A Randomized Controlled Study

The purpose of this study is to evaluate the role of surfactant lung lavage in the treatment of meconium aspiration syndrome. Aspiration of meconium into the tracheo-bronchial tree with the onset of respiration results in meconium aspiration syndrome (MAS). Aspirated meconium inhibits surfactant function directly and also decreases its synthesis by its toxic effects on type 2 pneumocytes. There is no specific treatment recommended for meconium aspiration syndrome. Numerous studies have shown that exogenous surfactant improves outcome in babies with meconium aspiration. Surfactant replacement alone does not remove meconium from airways and multiple doses may be required .Therefore an effective therapy to improve outcome is crucial in treating infants with meconium aspiration. Surfactant Lung lavage has been shown to be alternative to bolus therapy in treating neonates with meconium aspiration as shown by many pilot studies. So the investigators have decided to study the role surfactant lung lavage in the treatment of meconium aspiration syndrome.

Study Overview

• Status: Completed
• Conditions: Meconium Aspiration Syndrome
• Intervention / Treatment: Drug: Bovine surfactant

Detailed Description

Meconium is an odourless, thick, blackish green material first demonstrable in the foetal intestinal tract during the third month of gestation. Approximately 10-15% of deliveries are complicated by the passage of meconium around the time of delivery. The risk of meconium stained amniotic fluid (MSAF) is strongly correlated with gestational age. An adverse intrauterine environment with resultant foetal asphyxia is proposed as the most common explanation for MSAF.

Aspiration of meconium into the tracheo-bronchial tree with the onset of respiration results in meconium aspiration syndrome (MAS). MAS is defined as respiratory distress with compatible chest x-ray finding in an infant born through MSAF whose symptoms cannot be otherwise explained. Despite current interventions such as intubation with tracheal suction, it is estimated that 5-20 % of infants born through MSAF develop MAS. It represents a leading cause of perinatal morbidity. Approximately 50% of the infants with MAS require mechanical ventilation; 15%-30% develop pulmonary air leaks and 5%-12% die.

The pathophysiology of meconium aspiration syndrome includes airway obstruction, surfactant inactivation, inflammation and pulmonary hypertension. Meconium itself inactivates the surfactant in the alveoli and its presence also causes secondary surfactant deficiency as meconium is toxic to type 2 alveolar cells which secrete surfactant. There is no specific treatment recommended for meconium aspiration syndrome .Treatment for MAS is generally supportive and includes supplemental oxygen as needed, assisted ventilation to maintain lung volume and improve gas exchange, and circulatory support with volume resuscitation and vasopressor infusions to maintain adequate perfusion. Successful treatment of meconium aspiration relies on effective meconium removal without inactivating or washing out surfactant, followed by appropriate ventilator care.

Surfactant replacement in neonates with severe meconium aspiration syndrome has been shown to improve oxygenation and reduce the severity of respiratory failure, air leaks and need for extracorporeal membrane oxygenation.

Surfactant replacement alone does not remove the meconium present in the airways and hence multiple doses may be required. Therefore an effective strategy to improve outcome in neonates with MAS needs to not only remove meconium but also retain the surfactant for adequate lung expansion and function.

Lung lavage using diluted surfactant has recently been shown to be an alternative to bolus therapy in treating MAS. This has advantage of removing surfactant inhibitors from alveolar space, in addition to augmenting surfactant concentration in alveolar space. Initial pilot case series using surfactant lung lavage have shown promise and there is a need to systematically study this in a RCT. The same has also been expressed in the literature on this subject. Hence the purpose of this prospective randomized controlled trial is to compare the efficacy of surfactant lung lavage over standard therapy in the treatment of meconium aspiration syndrome.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110001
      • Kalawati Saran children's Hospital, Lady Hardinge Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Gestation age ≥ 37 week
• Cephalic presentation
• Singleton pregnancy
• Presence of meconium stained amniotic fluid or staining of meconium in skin,umbilical cord or nails.
• Non vigorous babies
• Presence of respiratory distress(Downes score ≥4)
• Presence of meconium below vocal cords or chest x ray suggestive of meconium aspiration
• Age < 2 hours

Exclusion Criteria:

• Major congenital malformations
• Congenital heart disease
• Hydrops fetalis
• Air leaks
• Pulmonary hemorrhage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No Lavage; Neonate randomized to this group will be managed as per the standard protocol in the neonatal ward. The evaluation of respiratory distress will be done using Downe's score at hourly intervals till 24 hrs, followed by 2 hourly intervals till 72 hrs and finally 4 hourly intervals till resolution of clinical distress.
Experimental: Surfactant Lavage; The diluted surfactant is instilled into endotracheal tube over a period of 15 to 20 seconds. Once the instillation is complete, 5 manual breaths will be provided and infant will be repositioned supine. The suction catheter will be inserted and advanced to a position approximately 5mm past the end of endotracheal tube. Suction will be activated for no more than 10 seconds and would be temporarily halted earlier if the oxygen saturation value falls by > 5% of the prelavage value. The same shall be resumed once prelavage oxygen saturation has been restored. The infant's bed will now be moved back to horizontal position. Once the neonate is STABLE, suctioning will be again repeated. The total retrieved volume is measured and recorded.This procedure will be done in both right and left lateral decubitus position	Drug: Bovine surfactant; Dose of diluted surfactant : 20ml/kg; Type :Bovine surfactant; Phospholipid concentration: 5 mg/ml; Number of lavages to be given: 2 (10ml/kg each)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
duration of oxygen therapy in hours	The duration of oxygen therapy, mode of delivery, FiO2 and flow rate will be documented hourly within first 2 hours before lavage and in post lavage- hourly up to first 24 hours, 2 hourly up to 72 hours and 4 hourly thereafter till the cessation of oxygen therapy	till discharge or death
Severity of respiratory distress	The severity of respiratory distress will be assessed using Downe's Score. These parameters will be documented hourly within first 2 hours before lavage and in post lavage hourly up to first 24 hours, 2 hourly up to 72 hours and 4 hourly thereafter till the cessation of respiratory distress	till discharge or death
need for mechanical ventilation	The babies will be assessed for the need for mechanical ventilation as per standard unit protocols.	till discharge or death

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of mechanical ventilation	Total duration of mechanical ventilation, mode and ventilator parameters are noted till the baby is on mechanical ventilation.	till discharge or death
Complications	Incidence of PPHN by Echocardiography and Pneumothorax by transillumination confirmed by chest x-ray.	till discharge
Incidence of sepsis	Incidence of sepsis defined as -; SUSPECTED SEPSIS - Sepsis Screen > 2 parameters positive and/or; CONFIRMED SEPSIS - Sepsis Screen positive + Blood or CSF culture positive for bacteria. Sepsis Screen; Total leukocyte count < 5000/mm3; Absolute neutrophil count < 1800/cu.mm.(Low counts as per Manroe chart for term neonates); Immature/total neutrophil ratio > 0.2; Micro-ESR > 15mm in 1st hour; C Reactive Protein (CRP) > 1 mg/dl	till discharge
Mortality		till discharge
Duration of Hospital stay		till discharge

Collaborators and Investigators

• Sponsor: Lady Hardinge Medical College
• Investigators: Study Chair: Sushma Nangia, MBBS, MD, DM, Lady Hardinge Medical College, New Delhi, India

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: March 7, 2011
• First Submitted That Met QC Criteria: March 7, 2011
• First Posted (Estimate): March 8, 2011

Study Record Updates

• Last Update Posted (Estimate): July 15, 2014
• Last Update Submitted That Met QC Criteria: July 14, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Neonate; Meconium aspiration syndrome; surfactant lung lavage
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Fetal Diseases; Pregnancy Complications; Lung Injury; Syndrome; Meconium Aspiration Syndrome; Respiratory System Agents; Pulmonary Surfactants
• Other Study ID Numbers: LHMC/2011/Sur-Lu-Lav