Editing Meconium aspiration syndrome (section)

== Treatment ==
Most infants born through MSAF do not require any treatments (other than routine postnatal care) as they show no signs of respiratory distress, as only approximately 5% of infants born through MSAF develop MAS.<ref name=":0" /> However, infants which do develop MAS need to be admitted to a neonatal unit where they will be closely observed and provided any treatments needed. Observations include monitoring [[heart rate]], [[respiratory rate]], [[oxygen saturation]] and [[Blood glucose monitoring|blood glucose]] (to detect worsening [[respiratory acidosis]] or the development of [[hypoglycemia]]).<ref name=":8">{{Cite journal|last1=Stenson|first1=BJ|last2=Smith|first2=CL|date=2012|title=Management of Meconium Aspiration Syndrome|journal=Paediatrics and Child Health|volume=22|issue=12|pages=532–535|doi=10.1016/j.paed.2012.08.015}}</ref> In general, treatment of MAS is more supportive in nature.

=== Assisted ventilation techniques ===
To clear the airways of meconium, [[trachea]]l suctioning can be used however, the efficacy of this method is in question and it can cause harm.<ref name=":9">{{Cite journal|last1=Aguilar|first1=AM|last2=Vain|first2=NE|date=2011|title=The Suctioning in the Delivery Room Debate|journal=Early Human Development|volume=87S|pages=S13–S15|doi=10.1016/j.earlhumdev.2011.01.003|pmid=21277716 }}</ref>

In cases of MAS, there is a need for supplemental oxygen for at least 12 hours in order to maintain oxygen saturation of haemoglobin at 92% or more. The severity of respiratory distress can vary significantly between newborns with MAS, as some require minimal or no supplemental oxygen requirement and, in severe cases, mechanical ventilation may be needed.<ref>{{Cite journal|last1=Vain|first1=NE|last2=Szyld|first2=EG|last3=Prudent|first3=LM|last4=Wiswell|first4=TE|last5=Aguilar|first5=AM|last6=Vivas|first6=NI|date=2004|title=Oropharyngeal and Nasopharyngeal Suctioning of Meconium-Stained Neonates Before Delivery of their Shoulders: Multicentre, Randomised Controlled Trial|journal=Lancet|volume=364|issue=9434 |pages=597–602|doi=10.1016/S0140-6736(04)16852-9|pmid=15313360 |s2cid=29268118 }}</ref><ref name=":1" /> The desired oxygen saturation is between 90 and 95% and [[PaO2|PaO<sub>2</sub>]] may be as high as 90mmHg.<ref name=":10">{{Cite journal|last1=Chettri|first1=S|last2=Bhat|first2=BV|last3=Adhisivam|first3=B|date=2016|title=Current Concepts in the Management of Meconium Aspiration Syndrome|journal=Indian J Paediatr|volume=83|issue=10|pages=1125–1130|doi=10.1007/s12098-016-2128-9|pmid=27206687|s2cid=4723566}}</ref> In cases where there is thick meconium deep within the lungs, [[mechanical ventilation]] may be required. In extreme cases, [[extracorporeal membrane oxygenation]] (ECMO) may be utilised in infants who fail to respond to ventilation therapy.<ref name=":1" /> While on ECMO, the body can have time to absorb the meconium and for all the associated disorders to resolve. There has been an excellent response to this treatment, as the survival rate of MAS while on ECMO is more than 94%.<ref>{{Cite journal|last=Short|first=BL|date=2008|title=Extracorporeal Membrane Oxygenation: Use in Meconium Aspiration Syndrome|journal=Journal of Perinatology|volume=28|pages=S79–S83|doi=10.1038/jp.2008.152|pmid=19057615|doi-access=free}}</ref>

Ventilation of infants with MAS can be challenging and, as MAS can affect each individual differently, ventilation administration may need to be customised. Some newborns with MAS can have homogenous lung changes and others can have inconsistent and patchy changes to their lungs. It is common for sedation and muscle relaxants to be used to optimise ventilation and minimise the risk of [[pneumothorax]] associated with dyssynchronous breathing.<ref name=":8" />

=== Inhaled nitric oxide ===
Inhaled [[nitric oxide]] (iNO) acts on [[vascular smooth muscle]] causing selective pulmonary [[vasodilation]]. This is ideal in the treatment of [[Persistent pulmonary hypertension|PPHN]] as it causes vasodilation within ventilated areas of the lung thus, decreasing the ventilation-perfusion mismatch and thereby, improves oxygenation. Treatment utilising iNO decreases the need for [[Extracorporeal membrane oxygenation|ECMO]] and mortality in newborns with hypoxic respiratory failure and PPHN as a result of MAS. However, approximately 30-50% of infants with PPHN do not respond to iNO therapy.<ref name=":10" />

=== Antiinflammatories ===
As inflammation is such a huge issue in MAS, treatment has consisted of anti-inflammatories.

==== Glucocorticoids ====
[[Glucocorticoid]]s have a strong anti-inflammatory activity and works to reduce the migration and activation of [[neutrophil]]s, [[eosinophil]]s, [[Monocyte|mononuclear]] cells, and other cells. They reduce the migration of neutrophils into the lungs ergo, decreasing their adherence to the [[endothelium]]. Thus, there is a reduction in the action of mediators released from these cells and therefore, a reduced inflammatory response.<ref name=":11">{{Cite journal|last1=Mokra|first1=D|last2=Mokry|first2=J|date=2011|title=Glucocorticoids in the Treatment of Neonatal Meconium Aspiration Syndrome|journal=Eur J Pediatr|volume=170|issue=12|pages=1495–1505|doi=10.1007/s00431-011-1453-2|pmc=3221844|pmid=21465122}}</ref><ref name=":7" />

Glucocorticoids also possess a genomic mechanism of action in which, once bound to a [[glucocorticoid receptor]], the activated complex moves into the [[Cell nucleus|nucleus]] and inhibits [[Transcription (biology)|transcription]] of [[Messenger RNA|mRNA]]. Ultimately, effecting whether various proteins get produced or not. Inhibiting the transcription of nuclear factor ([[NF-κB]]) and protein activator ([[AP-1 transcription factor|AP-1]]) attenuates the expression of pro-inflammatory cytokines ([[Interleukin-1 family|IL-1]], [[Interleukin 6|IL-6]], [[Interleukin 8|IL-8]] and [[Tumor necrosis factor superfamily|TNF]] etc.), enzymes ([[Phospholipase A2|PLA<sub>2</sub>]], [[Cyclooxygenase-2|COX-2]], [[Nitric oxide|iNOs]] etc.) and other biologically active substances.<ref name=":12">{{Cite journal|last1=Czock|first1=D|last2=Keller|first2=F|last3=Rasche|first3=FM|last4=Haussler|first4=U|date=2005|title=Pharmacokinetics and Pharmacodynamics of Systemically Administered Glucocorticoids|journal=Clinical Pharmacokinetics|volume=44|issue=1|pages=61–98|doi=10.2165/00003088-200544010-00003|pmid=15634032|s2cid=24458998}}</ref><ref name=":11" /><ref name=":7" /> The anti-inflammatory effect of glucocorticoids is also demonstrated by enhancing the activity of lipocortines which inhibit the activity of PLA<sub>2</sub> and therefore, decrease the production of [[arachidonic acid]] and mediators of [[lipoxygenase]] and [[cyclooxygenase]] pathways.<ref name=":11" />

[[Anti-inflammatory|Anti-inflammatories]] need to be administered as quickly as possible as the effect of these drugs can diminish even just an hour after meconium aspiration. For example, early administration of [[dexamethasone]] significantly enhanced [[gas exchange]], reduced ventilatory pressures, decreased the number of [[neutrophil]]s in the bronchoalveolar area, reduced [[Edema|oedema]] formation and oxidative lung injury.<ref name=":7" /> However, glucocorticoids may increase the risk of infection and this risk increases with the dose and duration of glucocorticoid treatment. Other issues can arise, such as aggravation of [[diabetes mellitus]], [[osteoporosis]], skin [[atrophy]] and [[growth retardation]] in children.<ref name=":12" />

==== Inhibitors of phosphodiesterase ====
[[Phosphodiesterase]]s (PDE) degrades [[Cyclic adenosine monophosphate|cAMP]] and [[Cyclic guanosine monophosphate|cGMP]] and, within the [[respiratory system]] of a newborn with MAS, various isoforms of PDE may be involved due to their pro-inflammatory and [[Smooth muscle tissue|smooth muscle]] contractile activity. Therefore, non-selective and selective inhibitors of PDE could potentially be used in MAS therapy. However, the use of PDE inhibitors can cause [[cardiovascular]] side effects. Non-selective PDE inhibitors, such as [[methylxanthines]], increase concentrations of cAMP and cGMP in the cells leading to [[Bronchodilator|bronchodilation]] and [[vasodilation]]. Additionally, methylxanthines decreases the concentrations of calcium, [[acetylcholine]] and [[monoamines]], this controls the release of various mediators of inflammation and [[bronchoconstriction]], including [[prostaglandin]]s. Selective PDE inhibitors target one subtype of [[phosphodiesterase]] and in MAS the activities of [[Phosphodiesterase 3|PDE-3]], [[Phosphodiesterase 4|PDE-4]], [[Phosphodiesterase 5|PDE-5]] and PDE-7 may become enhanced.<ref name=":7" /> For example, [[Milrinone]] (a selective PDE3 inhibitor) improved oxygenation and survival of neonates with MAS.<ref>{{Cite journal|last1=Bassler|first1=D|last2=Choong|first2=K|last3=McNamara|first3=P|last4=Kirpalani|first4=H|date=2006|title=Neonatal Persistent Pulmonary Hypertension Treated with Milrinone: Four Case Report|journal=Biology of the Neonate|volume=89|issue=1|pages=1–5|doi=10.1159/000088192|pmid=16155380|s2cid=38587541}}</ref>

==== Inhibitors of cyclooxygenase ====
[[Arachidonic acid]] is metabolised, via [[cyclooxygenase]] (COX) and [[lipoxygenase]], to various substances including [[prostaglandin]]s and [[leukotriene]]s, which exhibit potent pro-inflammatory and [[Vasoactivity|vasoactive]] effects. By inhibiting COX, and more specifically [[COX-2]], (either through selective or non-selective drugs) inflammation and oedema can be reduced. However, COX inhibitors may induce [[Peptic ulcer disease|peptic ulcers]] and cause [[hyperkalemia]] and [[hypernatremia]]. Additionally, COX inhibitors have not shown any great response in the treatment of MAS.<ref name=":7" />

=== Antibiotics ===
Meconium is typically sterile however, it can contain various cultures of bacteria so appropriate antibiotics may need to be prescribed.<ref name=":10" />

=== Surfactant treatment ===
[[Lung lavage]] with diluted [[surfactant]] has potential benefits depending on how early it is given in newborns with MAS. This treatment shows promise as it has an effect on air leaks, [[pneumothorax]], the need for [[Extracorporeal membrane oxygenation|ECMO]] and death. Early intervention and using it on newborns with mild MAS is more effective. However, there are risks as a large volume of fluid instillation to the lung of a newborn can be dangerous (particularly in cases of severe MAS with [[pulmonary hypertension]]) as it can exacerbate [[Hypoxia (medical)|hypoxia]] and lead to mortality.<ref>{{Cite journal|last1=Choi|first1=HJ|last2=Hahn|first2=S|last3=Lee|first3=J|last4=Park|first4=BJ|last5=Lee|first5=SM|last6=Kin|first6=HS|last7=Bae|first7=CW|date=2012|title=Surfactant Lavage Therapy for Meconium Aspiration Syndrome: A Systematic Review and Meta-Analysis|journal=Neonatology|volume=101|issue=3|pages=183–191|doi=10.1159/000329822|pmid=22067375 |doi-access=free}}</ref>

=== Previous treatments ===
Originally, it was believed that MAS developed as a result of the meconium being a physical blockage of the airways. Thus, to prevent newborns, who were born through MSAF, from developing MAS, suctioning of the [[oropharyngeal]] and [[nasopharyngeal]] area before delivery of the shoulders followed by [[trachea]]l aspiration was utilised for 20 years. This treatment was believed to be effective as it was reported to significantly decrease the incidence of MAS compared to those newborns born through MSAF who were not treated.<ref>{{Cite journal|last1=Carson|first1=BS|last2=Losey|first2=RW|last3=Bowes Jr|first3=WA|last4=Simmons|first4=MA|date=1976|title=Combined Obstetric and Pediatric Approach to Prevent Meconium Aspiration Syndrome|journal=Am J Obstet Gynecol|volume=15|issue=126|pages=172–175|doi=10.1016/0002-9378(76)90525-1|pmid=984149 }}</ref> This claim was later disproved and future studies concluded that oropharyngeal and nasopharyngeal suctioning, before delivery of the shoulders in infants born through MSAF, does not prevent MAS or its complications.<ref name=":1" /> In fact, it can cause more issues and damage (e.g. [[Mucous membrane|mucosal]] damage), thus it is not a recommended preventative treatment.<ref name=":9" /> Suctioning may not significantly reduce the incidence of MAS as meconium passage and aspiration may occur ''in-utero.'' Thereby making the suctioning redundant and useless as the meconium may already be deep within the lungs at the time of birth.<ref name=":10" />

Historically, [[amnioinfusion]] has been used when MSAF was present, which involves a transcervical infusion of fluid during labour. The idea was to dilute the thick meconium to reduce its potential pathophysiology and reduce cases of MAS, since MAS is more prevalent in cases of thick meconium.<ref name=":1" /> However, there are associated risks, such as [[umbilical cord prolapse]] and prolongation of labour. The UK National Institute of Health and Clinical Excellence (NICE) Guidelines recommend against the use of amnioinfusion in women with MSAF.<ref name=":8" />