Viewpoint
Less invasive surfactant administration: a word of caution

https://doi.org/10.1016/S2352-4642(19)30405-5Get rights and content

Summary

Surfactant is a cornerstone of neonatal critical care, and the presumed less (or minimally) invasive techniques for its administration have been proposed to reduce invasiveness of neonatal critical care interventions. These techniques are generally known as less invasive surfactant administration (LISA) and have quickly gained popularity in some neonatal intensive care units. Despite the increase in the use of LISA, we believe that the pathobiological background supporting its possible clinical benefits is unclear. Similarly, it is unclear whether there are any ignored drawbacks, as LISA has been tested in only a few trials and some physiopathological issues seem to have gone unnoticed. Active research is warranted to fill these knowledge gaps before LISA can be firmly recommended. In this Viewpoint, we provide an in-depth analysis of LISA techniques, based on physiological and pathobiological factors, followed by a critical appraisal of available clinical data, and highlight some possible future research directions.

Section snippets

Background

Surfactant is a cornerstone of neonatal critical care and has drastically improved the care of preterm babies with respiratory distress syndrome due to primary surfactant deficiency.1, 2 Surfactant is usually administered via an endotracheal tube followed by mechanical ventilation. Duration of mechanical ventilation has been shortened as much as possible, given its deleterious effect on the developing lung. Thus, the intubation, surfactant, and extubation (INSURE) technique has been diffused on

The importance of pathobiological and physiopathological background

The US Food and Drug Administration recommends that the development of a medical procedure or device should follow a pathway similar to that of pharmacological research. Therefore, although the process can vary among different countries, procedures and devices should be preliminarily tested in laboratory settings, animal models, or both, then assessed in clinical trials of increasing complexity, provided that there is a solid pathobiological background that leads the researcher to hypothesise a

Benefits of less invasive techniques

It is difficult to find solid pathobiological reasons justifying clinical benefits linked to these new surfactant administration techniques. Essentially, it is important to understand how the reduction in tube diameter may have clinical advantages, if it is uncoupled with other changes in the procedure itself, such as different sedation or ventilation policies. The following physiopathological hypotheses associated with LISA have been formulated and deserve to be discussed: improved CPAP

Detrimental effects of less invasive techniques

A 2017 European survey reported short-term adverse effects of LISA, which seem similar to those of INSURE, although whether these effects are worse with one technique than the other is unclear.75 Given the shared need for laryngoscopy and the similarities of the two techniques, most of these side-effects should be transient and evenly distributed between the two techniques.

However, some points should be highlighted. We have previously shown that the use of thin feeding catheters leads to

Critical appraisal of randomised controlled trials

Two meta-analyses have shown the benefits of LISA techniques.84, 85 Meanwhile, the number of published trials has risen to eight;6, 86, 87, 88, 89, 90, 91, 92 only two of them have a multicentre design.6, 86 Five of them have been done in low-income or middle-income countries,88, 89, 90, 91, 92 and the three larger studies in well established neonatal units.6, 86, 87 These trials have methodological biases, like any other, and only some of them are well described in the original manuscripts and

Future research and development

A practical guide about LISA was published during the revision of this manuscript, by colleagues with expertise in LISA techniques.94 The questions about the transmission of CPAP, the need for sedation, and the unlikely risk of INSURE-related lung injury remain unanswered. Conversely, the described flaws in the physiopathological background of LISA trials and their ambiguous message are echoed. In particular, reliable comparisons of LISA versus well performed INSURE are lacking and, in fact, a

Acknowledgments

We are grateful to Lucilla Pezza for her kind help to create the artwork.

References (95)

  • JD Kaplan et al.

    Physiologic consequences of tracheal intubation

    Clin Chest Med

    (1991)
  • R Carbajal et al.

    Premedication for tracheal intubation in neonates: confusion or controversy?

    Semin Perinatol

    (2007)
  • A Higgs et al.

    Guidelines for the management of tracheal intubation in critically ill adults

    Br J Anaesth

    (2018)
  • XF Li et al.

    Effects of different surfactant administrations on cerebral autoregulation in preterm infants with respiratory distress syndrome

    J Huazhong Univ Sci Technolog Med Sci

    (2016)
  • MK Ball et al.

    Body temperature effects on lung injury in ventilated preterm lambs

    Resuscitation

    (2010)
  • MC Walsh et al.

    Extremely low birthweight neonates with protracted ventilation: mortality and 18-month neurodevelopmental outcomes

    J Pediatr

    (2005)
  • PS van der Burg et al.

    Effect of minimally invasive surfactant therapy on lung volume and ventilation in preterm infants

    J Pediatr

    (2016)
  • DG Sweet et al.

    European consensus guidelines on the management of respiratory distress syndrome—2019 update

    Neonatology

    (2019)
  • RA Polin et al.

    Surfactant replacement therapy for preterm and term neonates with respiratory distress

    Pediatrics

    (2014)
  • E Herting et al.

    Less invasive surfactant administration (LISA): chances and limitations

    Arch Dis Child Fetal Neonatal Ed

    (2019)
  • PA Dargaville

    Innovation in surfactant therapy I: surfactant lavage and surfactant administration by fluid bolus using minimally invasive techniques

    Neonatology

    (2012)
  • H Verder et al.

    Surfactant treatment of newborn infants with respiratory distress syndrome primarily treated with nasal continuous positive air pressure. A pilot study

    Ugeskr Laeger

    (1992)
  • General considerations for animal studies for medical devices: draft guidance for industry food and drug administration staff

  • AG De Paoli et al.

    Pharyngeal pressure in preterm infants receiving nasal continuous positive airway pressure

    Arch Dis Child Fetal Neonatal Ed

    (2005)
  • M Colnaghi et al.

    Pharyngeal pressure value using two continuous positive airway pressure devices

    Arch Dis Child Fetal Neonatal Ed

    (2007)
  • G Jourdain et al.

    Continuous positive airway pressure delivery during less invasive surfactant administration: a physiologic study

    J Perinatol

    (2018)
  • R Centorrino et al.

    Mechanics of nasal mask-delivered HFOV in neonates: a physiologic study

    Pediatr Pulmonol

    (2019)
  • N Singh et al.

    Does the RAM cannula provide continuous positive airway pressure as effectively as the Hudson prongs in preterm neonates?

    Am J Perinatol

    (2019)
  • JS Gerdes et al.

    Factors influencing delivered mean airway pressure during nasal CPAP with the RAM cannula

    Pediatr Pulmonol

    (2016)
  • SE Courtney et al.

    Lung recruitment and breathing pattern during variable versus continuous flow nasal continuous positive airway pressure in premature infants: an evaluation of three devices

    Pediatrics

    (2001)
  • BC King et al.

    Mask versus prongs for nasal continuous positive airway pressure in preterm infants: a systematic review and meta-analysis

    Neonatology

    (2019)
  • IA Du Rand et al.

    British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE

    Thorax

    (2013)
  • B Ergan et al.

    The use of bronchoscopy in critically ill patients: considerations and complications

    Expert Rev Respir Med

    (2018)
  • J Carlens et al.

    Complications and risk factors in pediatric bronchoscopy in a tertiary pediatric respiratory center

    Pediatr Pulmonol

    (2018)
  • Harjeet et al.

    Anatomical dimensions of trachea, main bronchi, subcarinal and bronchial angles in fetuses measured ex vivo

    Pediatr Anesth

    (2008)
  • H Jit et al.

    Dimensions & shape of the trachea in the neonates, children & adults in northwest India

    Indian J Med Res

    (2000)
  • P Fayoux et al.

    Determination of endotracheal tube size in a perinatal population: an anatomical and experimental study

    Anesthesiology

    (2006)
  • TM Wani et al.

    Upper airway in infants—a computed tomography-based analysis

    Paediatr Anaesth

    (2017)
  • K Mehler et al.

    Use of analgesic and sedative drugs in VLBW infants in German NICUs from 2003–2010

    Eur J Pediatr

    (2013)
  • MY Oncel et al.

    Nasal continuous positive airway pressure versus nasal intermittent positive-pressure ventilation within the minimally invasive surfactant therapy approach in preterm infants: a randomised controlled trial

    Arch Dis Child Fetal Neonatal Ed

    (2016)
  • C Jackson

    The technique of insertion of intratracheal insufflation tubes

    Paediatr Anaesth

    (1996)
  • BD King et al.

    Reflex circulatory responses to direct laryngoscopy and tracheal intubation performed during general anesthesia

    Anesthesiology

    (1951)
  • L Reid et al.

    Irritation of respiratory tract and its reflex effect on heart surgery

    Surg Gynecol Obstet

    (1940)
  • CC Wycoff

    Endotracheal intubation: effects on blood pressure and pulse rate

    Anesthesiology

    (1960)
  • J Siedlecki

    Disturbances in the function of cardiovascular system in patients following endotracheal intubation and attempts of their prevention by pharmacological blockade of sympathetic system

    Anaesth Resusc Intensive Ther

    (1975)
  • EJ Fox et al.

    Complications related to the pressor response to endotracheal intubation

    Anesthesiology

    (1977)
  • J Henderson

    Airway management in the adult

    (2010)
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