Mekonium aspiration syndrome MAS ) also known as meconium neonatal aspiration is a medical condition that affects newborns. It describes the spectrum of disorders and pathophysiology of newborns born in meconium stained amniotic fluid (MSAF) and has meconium in their lungs. Therefore, MAS has varying degrees of severity depending on what conditions and complications develop after the birth process. Furthermore, the pathophysiology of MAS is multifactorial and highly complex which is why it is a major cause of morbidity and mortality in term infants.
Video Meconium aspiration syndrome
What is meconium?
The word meconium comes from the Greek word m? K? Nion meaning juice from opium poppy as a tranquilizing effect on fetuses observed by Aristotle. A
Meconium is a dark, sticky green substance containing gastrointestinal secretion, amniotic fluid, bile acids, bile, blood, mucus, cholesterol, pancreatic secretions, lanugo, vernix caseosa and cellular debris. Meconium accumulates in the fetal digestive tract during the third trimester of pregnancy and is the first intestinal fluid released within the first 48 hours after birth. Particularly, since meconium and all the contents of the gastrointestinal tract are located 'extracorporeal', the constituents are hidden and are not usually recognized by the fetal immune system.
For meconium in the amniotic fluid that successfully causes MAS, it must enter the respiratory system during a period when fluid-filled lung transitions into an air-containing organ that is able to exchange gas. A
Maps Meconium aspiration syndrome
Prevalence
1 in every 7 pregnancies have MSAF and, from these cases, about 5% of these babies develop MAS. MSAF was observed at 23-52% in pregnancy at 42 weeks therefore, the MAS frequency increased as the length of pregnancy increased, resulting in the greatest prevalence occurring in post-pregnancy pregnancy. In contrast, preterm delivery is not often associated with MSAF (only about 5% of total MSAF). Interestingly, MAS rates fall in populations where delivery is induced in women who have a pregnancy beyond 41 weeks. There are many suspected factors before disposal that are considered to increase the risk of MAS. For example, the risk of MSAF is higher in African American, African and Pacific Islander mothers, compared to mothers of other ethnic groups. A
Signs, Symptoms and Diagnosis
Respiratory distress in infants born through dark MSAF as well as meconium blocking airways is usually sufficient to diagnose MAS. In addition, newborns with MAS may experience other types of respiratory disorders such as tachypnea and hypercapnia. Sometimes it is difficult to diagnose MAS because it can be confusing with other diseases that also cause respiratory problems, such as pneumonia. In addition, lung ultrasound can be a fast, easy and inexpensive imaging technique to diagnose lung diseases like MAS.
Cause
The main theories of the meconium part into the amniotic fluid are caused by fetal maturity or from fetal stress as a result of hypoxia or infection. Other factors that drive the passage of meconium in utero include placental insufficiency, maternal hypertension, pre-eclampsia and use of maternal drugs from tobacco and cocaine. However, it should be noted that the exact mechanisms for meconium ducts into the amniotic fluid are not fully understood and may be a combination of several factors. A
Mekonium Path as a result of Distress Fetal
There may be an important link between fetal distress and hypoxia with MSAF. It is believed that fetal distress develops into fetal hypoxia which causes the meconium defecate fetus that produces MSAF and then possibly MAS. Other stressors that cause fetal distress, and therefore the meconium part, are included when the umbilical venous oxygen saturation is below 30%.
Fetal hypoxia pressures during labor can stimulate colonic activity, by increasing intestinal peristalsis and relaxing the anal sphincter, which results in a meconium trajectory. Then, by inhaling intrauterine or from the first few breaths after delivery, MAS may develop. Furthermore, thick meconium aspiration causes airway obstruction that causes more severe hypoxia.
It is important to note that the relationship between fetal distress and meconium sections is not a definite cause-effect relationship because more than Ã,¾ infants with MSAF are strong at birth and have no distress or hypoxia. In addition, fetal pressure often occurs in the absence of meconium as well.
Meconium Passage as Fetal Maturity Result
Although meconium is present in the digestive tract early in development, MSAF rarely occurs before 34 weeks of gestation.
Fetal bowel peristalsis is present at the beginning of 8 weeks' gestation and anal sphincter develops about 20-22 weeks. Control of the anal sphincter is not well known, but the fetus regularly defecates into the amnion cavity even without any disturbance. The presence of intestinal enzymes has been found in the amniotic fluid of women as early as 14-22 weeks pregnant. Thus, suggest there is a free part of the intestinal contents into the amniotic fluid. A
Motilin is found in higher concentrations in the postmenstrual fetal gastrointestinal tract rather than prematurely. Similarly, intestinal parasympathetic innervation and myelination also increase in subsequent pregnancies. Therefore, the increased incidence of MAS in post-term pregnancy may reflect the maturation and development of peristalsis in the digestive tract in newborns. A
Pathophysiology
Because MAS describes the spectrum of newborn disturbances born through MSAF, without any congenital or other underlying respiratory disorders, there are many hypothesized mechanisms and causes for the onset of this syndrome. Long-term consequences may arise from this disorder, for example, infants with MAS have higher rates of developmental neural development defects due to poor respiration. A
Air Channel Obstruction
In the first 15 minutes of meconium aspiration, there is greater airway obstruction leading to increased pulmonary resistance, decreased lung compliance, acute hypoxemia, hypercapnia, atelectasis and respiratory acidosis. After 60 minutes of exposure, meconium moves further into the smaller airways. Once inside the bronchioles and alveoli terminals, meconium triggers inflammation, pulmonary edema, vasoconstriction, bronchoconstriction, airway collapse and inactivation of surfactants (Mokra and Calkovska, 2013; Mokra et al., 2013). A Fetal Hypoxia
The area of ​​the lung that does not or only partially participate in ventilation, due to obstruction and/or destruction, will become hypoxic and the inflammatory response may occur consequently. Partial obstruction will cause air traps and hyperinflation of certain lung areas and pneumothorax may occur. Chronic hypoxia will lead to an increase in smooth muscle tone of the pulmonary vessels and persistent pulmonary hypertension leading to respiratory and circulatory failure. A
Infection
The most common microorganisms, Gram-negative stems, and endotoxins are found in MSAF samples at a higher level than clear amniotic fluids, for example 46.9% of patients with MSAF also have endotoxins. Microbial invasion of the amniotic cavity (MIAC) is more common in patients with MSAF and this may eventually lead to an intra-amniotic inflammatory response. MIAC is associated with high concentrations of cytokines (such as IL-6), chemokines (such as IL-8 and monocytes-1 chemo protein), complementary, phospholipase A 2 and matrix decomposition enzymes. Therefore, such mediators in the amniotic fluid during MIAC and intra-amniotic infections may, when aspirated in utero , induce lung inflammation within the fetus. A
Pulmonary Inflammation
Meconium has a complex chemical composition, making it difficult to identify a single agent responsible for several emerging diseases. As meconium is stored in the intestine, and some are not exposed to the immune system, when it becomes aspirated the innate immune system is recognized as a foreign and dangerous substance. The immune system, which is present at birth, responds within minutes with low specificity and no memory to try to remove microbes. Meconium may lead to chemical pneumonitis because it is a potent activator of inflammatory mediators that include cytokines, supplements, prostaglandins and reactive oxygen species.
Meconium is a source of pro-inflammatory cytokines, including tumor necrosis factor (TNF) and interleukin (IL-1, IL-6, IL-8), and mediators produced by neutrophils, macrophages and epithelial cells that can injure the lung tissue directly. or indirectly. For example, proteolytic enzymes are released from the neutrophilic grains and this can damage the lung membrane and the surfactant protein. In addition, active leukocytes and cytokines produce reactive nitrogen and oxygen that have cytotoxic effects. Oxidative stress produces vasoconstriction, bronchoconstriction, platelet aggregation and accelerated cell apoptosis. Recently, it has been hypothesized that meconium is a potential activator of toll-like receptors (TLRs) and complement, a key mediator in inflammation, and thus may contribute to an inflammatory response in MAS. A
Meconium contains a large amount of phospholipase A 2 , a potent proinflammatory enzyme, which can be directly (or through arachidonic acid stimulation) causing surfactant dysfunction, lung destruction epithelial, tissue necrosis and increased apoptosis. Meconium can also activate coagulation cascade, production of platelet activating factor (PAF) and other vasoactive substances that can cause capillary endothelium damage and basal membrane. Injury to the alveolocapillary membrane results in leakage of fluids, plasma proteins, and cells into the interstitial and alveolar spaces (Mokra et al./,>, 2013). Surfactant Inactivation
Surfactants are synthesized by type II alveolar cells and are made of complex phospholipids, proteins and saccharides. It serves to lower surface tension (to allow lung expansion during inspiration), stabilize the alveoli at the end of expiration (to prevent alveolar collapse) and prevent pulmonary edema. Surfactants also contribute to lung and defense protection as they are also anti-inflammatory agents. Surfactants increase the removal of the inhaled particles and the old cells away from the alveolar structure. A
The level of surfactant inhibition depends on the concentration of surfactant and meconium. If the concentration of the surfactant is low, even a very dilute meconium may inhibit the function of the surfactant, whereas at high surfactant concentrations, the effects of meconium are limited. Meconium may affect the mechanism of surfactants by preventing surfactants from spreading on the alveolar surface, decreasing the concentration of surfactant proteins (SP-A and SP-B), and by altering the viscosity and surfactant structure. Some morphological changes occur after exposure to meconium, the most prominent being the airway epithelial detachment of the stroma and the shedding of epithelial cells into the airways. This shows a direct adverse effect on lung alveolar cells due to the introduction of meconium to the lungs. A
Persistent Pulmonary Hypertension
Persistent pulmonary hypertension (PPHN) is a failure of the fetal circulation to adapt to extra-uterine conditions after birth. PPHN is associated with various respiratory diseases, including MAS (as 15-20% of infants with MAS develop PPHN), but also pneumonia and sepsis. The combination of hypoxia, lung vasoconstriction and ventilation/perfusion mismatch may trigger PPHN, depending on the concentration of meconium in the respiratory tract. PPHN in newborns is the leading cause of death in MAS. A
Apoptosis
Apoptosis is an important mechanism in the clearance of injured cells and in tissue repair, but too much apoptosis can cause harm, such as acute lung injury. Meconium induces apoptosis and DNA cleavage of lung airway epithelial cells, this is detected by the presence of fragmented DNA in the airways and in the core of the alveolar epithelium. Meconium induces an inflammatory reaction in the lungs because there is an increase in autophagocytic cells and caspase level 3 after exposure. After 8 hours of exposure to meconium, in fetal rabbits, the total number of apoptotic cells was 54%. Therefore, most of the lung damage caused by meconium may be due to damage to the airway epithelial barrier from apoptosis.
Treatment
Most babies born through MSAF do not require treatment (other than routine postpartum care) because they show no signs of respiratory distress because only about 5% of babies born through MSAF develop MAS. However, infants who develop MAS need to be given to a neonatal unit where they will be closely observed and given the required treatment. Observations included monitoring heart rate, respiratory rate, oxygen saturation and blood glucose (to detect worsening respiratory acidosis or development of hypoglycemia). In general, MAS treatment is more supportive.
Help Ventilation Technique
In the case of MAS, there is an additional oxygen requirement for at least 12 hours to maintain oxygen saturation of hemoglobin at 92% or more. The severity of respiratory distress can vary significantly between newborns and MAS, as some require little or no additional oxygen demand, in severe cases, mechanical ventilation may be necessary. A
To clear the airways from meconium, tracheal suctioning can be used, the efficacy of this method is questionable and can cause damage. However, additional oxygen may be given to the baby to help maintain ideal oxygen levels. The desired oxygen saturation is between 90-95% and PaO 2 may be as high as 90mmHg. In cases where there is a thick meconium deep inside the lungs, mechanical ventilation may be necessary. In extreme cases, extracorporeal membrane oxygenation (ECMO) may be used in infants who fail to respond to ventilatory therapy. While in ECMO, the body can have time to absorb meconium and for all perturbations to resolve it. There is a very good response to this treatment, as the survival rate at ECMO is over 94%. A
Baby ventilation with MAS can be a challenge and, since MAS can affect each individual differently, ventilation may need to be adjusted. Some newborns with MAS may experience homogeneous lung changes and others may experience inconsistent and uneven changes in their lungs. It is common for sedation and muscle relaxants to be used to optimize ventilation and minimize the risk of pneumothorax associated with dyssynchronous breathing. A
Inhalation Nitric Oxide
Inhaled nitric oxide (iNO) acts on the smooth muscle of the blood vessels causing selective pulmonary vasodilation. It is ideal in the treatment of PPHN as it causes vasodilation inside the ventilated area of ​​the lung thus reducing the perfusion-ventilation mismatch and thus, increasing oxygenation. Treatment using iNO reduces the need for ECMO and mortality in newborns with hypoxic respiratory failure and PPHN as a result of MAS. However, about 30-50% of infants with PPHN do not respond to iNO therapy. A
Anti-inflammatories
Because inflammation is a very big problem in MAS, the treatment consists of anti-inflammatory. A
Glucocorticoids
Glucocorticoids (GC) have strong anti-inflammatory activity and work to reduce migration and activation of neutrophils, eosinophils, mononuclear and other cells. GCs reduce the migration of neutrophils to ergo lungs, reducing their adherence to endothelium. Thus, there is a reduction in the action of mediators that are released from these cells and therefore, the reduced response of inflammation.
GC also has a genomic action mechanism where, after attaching to the glucocorticoid receptor, the activated complex moves into the nucleus and blocks mRNA transcription. Ultimately, it affects whether various proteins are produced or not. Inhibiting nuclear factor transcription (NF-? B) and protein activator (AP-1) weaken the expression of pro-inflammatory cytokines (IL-1, IL-6, IL-8 and TNF etc.), enzymes (PLA 2 , COX-2, iNOs, etc.) and other biologically active substances. The anti-inflammatory effect of GC is also shown by increasing lipocortin activity that inhibits the PLA activity 2 and therefore, decreases the production of arachidonic acid and mediators from the pathway of lipoxygenase and cyclooxygenase. A
Antiinflammatory should be administered as soon as possible because the effects of these drugs can be reduced even just an hour after meconium aspiration. For example, the early administration of dexamethasone significantly increases gas exchange, reduces ventilatory pressure, decreases the number of neutrophils in the bronchoalveolar area, reduces the formation of edema and oxidative lung injury. A
However, GC may increase the risk of infection and this risk increases with the dose and duration of glucocorticoid treatment. Other problems may arise, such as aggravation of diabetes mellitus, osteoporosis, skin atrophy and growth retardation in children. A
Phosphodiesterase Inhibitors
Phosphodiesterases (PDE) degrade cAMP and cGMP and, in the newborn respiratory system with MAS, various PDE isoforms may be involved due to their pro-inflammatory and delicate muscle contraction activity. Therefore, selective and selective PDE inhibitors are potentially used in MAS therapy. However, the use of PDE inhibitors can cause cardiovascular side effects. Non-selective PDE inhibitors, such as methylxanthines, increase cAMP and cGMP concentrations in cells that lead to bronchodilation and vasodilation. In addition, methylxanthines decreases the concentration of calcium, acetylcholine and monoamine, it controls the release of various mediators of inflammation and bronchoconstriction, including prostaglandins. Selective PDE inhibitors target one subtype of phosphodiesterase and in MAS the activities of PDE-3, PDE-4, PDE-5 and PDE-7 can be increased. For example, Milrinone (selective PDE3 inhibitor) increases oxygenation and neonatal survival with MAS.
Cyclooxygenase Inhibitors
Arachidonic acid is metabolized, via cyclooxygenase (COX) and lipoxygenase, to various substances including prostaglandins and leukotrienes, which exhibit strong pro-inflammatory and vasoactive effects. By inhibiting COX, and more specifically COX-2, (either through selective or non-selective drugs) inflammation and edema may be reduced. However, COX inhibitors can induce peptic ulcer and cause hyperkalemia and hypernatremia. In addition, COX inhibitors have not shown a good response in MAS treatment.
Antibiotics
Meconium is usually sterile however, it can contain a variety of bacterial cultures so that the right antibiotics may need to be prescribed. A
Surfactant Treatment
Lung rinse with dilute surfactant is a new treatment with potentially beneficial results depending on how early it is given to the newborn with MAS. This treatment is promising because it has a significant effect on air leakage, pneumothorax, the need for ECMO and death. Early intervention and use in newborns with mild MAS is more effective. However, there is a risk because large volumes of fluid gradually into the lungs of newborns can be harmful (especially in severe cases of MAS with pulmonary hypertension) because it can exacerbate hypoxia and cause death.
Previous treatments
Initially, it was believed that MAS developed as a result of meconium as a physical blockage of the airways. Thus, to prevent newborns, born through MSAF, from MAS development, suctioning the oropharyngeal and nasopharyngeal areas prior to shoulder delivery followed by tracheal aspiration was used for 20 years. This treatment is believed to be effective because it is reported to significantly reduce the incidence of MAS compared with newborns who were delivered through untreated MSAF. Subsequent research, concluding that oropharyngeal and nasopharyngeal suctioning before delivery of the shoulders in infants born through MSAF did not prevent MAS or its complications. In fact, this can cause more problems and damage (eg mucosal damage), so this is not the recommended preventive treatment. Aspiration may not significantly reduce the incidence of MAS as part of meconium and aspiration may occur in-utero. Thus making excessive and useless suctioning because meconium may already be deep inside the lungs at birth. A
Historically, amnioinfusion has been used when MSAF is present, which involves infusion of transervical fluid during labor. The idea is to thin thick meconium to reduce its pathophysiological potential and reduce MAS cases, because MAS is more common in cases of thick meconium. However, there are associated risks such as cord prolapse and prolongation of labor. The National Institute of Health and Clinical Excellence (NICE) UK guidelines recommend the use of amnioinfusion in women with MSAF.
Prevention
In general, the incidence of MAS has decreased significantly over the past two decades as the number of post-term deliveries has decreased. Currently, delivery is induced in women who have been pregnant for more than 41 weeks of pregnancy.
Prevention during Pregnancy
Prevention during pregnancy may include amnioinfusion and antibiotics but the effectiveness of these treatments is questionable. A
Prevention during Partition
As mentioned earlier, suctioning of oropharyngeal and nasopharyngeal is not an ideal preventive treatment for strong babies and depression (not breathing).
Future Research
Research is being focused on developing both successful methods to prevent MAS as well as effective treatment. For example, investigations are underway in the efficiency of anti-inflammatory agents, surfactant replacement therapy and antibiotic therapy. Further research needs to be done on pharmacological properties, for example, glucocorticoids, including doses, administration, timing or any drug interactions. In addition, there is still research being conducted on whether meconium intubation and suction in newborns with MAS is beneficial, dangerous or only overdone and overdeveloped. In general, there is still no generally accepted therapeutic protocol and an effective treatment plan for MAS.
See also
- Aspiration pneumonia
References
External links
- eMedicine article on meconium aspiration syndrome
Source of the article : Wikipedia
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