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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sushma Nangia, M.D., Lady Hardinge Medical College
ClinicalTrials.gov Identifier:
NCT01310621
First received: March 7, 2011
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention
Meconium Aspiration Syndrome
Drug: Bovine surfactant

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Surfactant Lung Lavage Versus Standard Care In The Treatment Of Meconium Aspiration Syndrome- A Randomized Controlled Study

Resource links provided by NLM:


Further study details as provided by Lady Hardinge Medical College:

Primary Outcome Measures:
  • duration of oxygen therapy in hours [ Time Frame: till discharge or death ] [ Designated as safety issue: No ]
    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

  • Severity of respiratory distress [ Time Frame: till discharge or death ] [ Designated as safety issue: No ]
    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

  • need for mechanical ventilation [ Time Frame: till discharge or death ] [ Designated as safety issue: No ]
    The babies will be assessed for the need for mechanical ventilation as per standard unit protocols.


Secondary Outcome Measures:
  • Duration of mechanical ventilation [ Time Frame: till discharge or death ] [ Designated as safety issue: No ]
    Total duration of mechanical ventilation, mode and ventilator parameters are noted till the baby is on mechanical ventilation.

  • Complications [ Time Frame: till discharge ] [ Designated as safety issue: No ]
    Incidence of PPHN by Echocardiography and Pneumothorax by transillumination confirmed by chest x-ray.

  • Incidence of sepsis [ Time Frame: till discharge ] [ Designated as safety issue: No ]

    Incidence of sepsis defined as -

    1. SUSPECTED SEPSIS - Sepsis Screen > 2 parameters positive and/or
    2. CONFIRMED SEPSIS - Sepsis Screen positive + Blood or CSF culture positive for bacteria.

    Sepsis Screen

    1. Total leukocyte count < 5000/mm3
    2. Absolute neutrophil count < 1800/cu.mm.(Low counts as per Manroe chart for term neonates)
    3. Immature/total neutrophil ratio > 0.2
    4. Micro-ESR > 15mm in 1st hour
    5. C Reactive Protein (CRP) > 1 mg/dl

  • Mortality [ Time Frame: till discharge ] [ Designated as safety issue: No ]
  • Duration of Hospital stay [ Time Frame: till discharge ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: January 2011
Study Completion Date: April 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.

  Eligibility

Ages Eligible for Study:   up to 2 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01310621

Locations
India
Kalawati Saran children's Hospital, Lady Hardinge Medical College
New Delhi, Delhi, India, 110001
Sponsors and Collaborators
Lady Hardinge Medical College
Investigators
Study Chair: Sushma Nangia, MBBS, MD, DM Lady Hardinge Medical College, New Delhi, India
  More Information

No publications provided

Responsible Party: Sushma Nangia, M.D., Professor of Pediatrics, Lady Hardinge Medical College
ClinicalTrials.gov Identifier: NCT01310621     History of Changes
Other Study ID Numbers: LHMC/2011/Sur-Lu-Lav
Study First Received: March 7, 2011
Last Updated: July 14, 2014
Health Authority: India: Indian Council of Medical Research

Keywords provided by Lady Hardinge Medical College:
Neonate
Meconium aspiration syndrome
surfactant lung lavage

Additional relevant MeSH terms:
Meconium Aspiration Syndrome
Syndrome
Disease
Fetal Diseases
Infant, Newborn, Diseases
Lung Diseases
Lung Injury
Pathologic Processes
Pregnancy Complications
Respiration Disorders
Respiratory Tract Diseases
Pulmonary Surfactants
Pharmacologic Actions
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014