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Meconium aspiration syndrome: pathophysiology and prevention.

BACKGROUND: Despite the common occurrence of intrauterine meconium passage and resultant meconium aspiration syndrome (MAS), controversies regarding the pathophysiology and use of appropriate preventive strategies abound. METHODS: Databases from MEDLINE, MD Consult, and the Science Citation Index were searched from 1964 to the present to find relevant sources of information. RESULTS AND CONCLUSIONS: Meconium passage occurs by three distinct mechanisms: (1) as a physiologic maturational event, (2) as a response to acute hypoxic events, and (3) as a response to chronic intrauterine hypoxia. Meconium passage might merely be a marker of chronic intrauterine hypoxia or can predispose to aspiration of meconium and resultant inflammatory pneumonitis, surfactant inactivation, and mechanical airway obstruction. Aspiration can occur in utero with fetal gasping, or after birth with the first breaths of life. Many cases of MAS can be prevented by the strategies addressed in this article, but some will occur despite appropriate preventive techniques. There is not enough evidence to support the use of amnioinfusion as a standard of care for all pregnancies complicated by meconium. Pharyngeal suctioning before delivery of the shoulders is an effective preventive intervention, as is the combination of pharyngeal suctioning followed by intubation and tracheal suctioning. Suctioning of the trachea may be done on a selective basis depending on fetal vigor and consistency of meconium.

Humans↗

Is there a correlation between aortic Doppler velocimetric findings in diabetic pregnant women and fetal outcome?

At present, the role of Doppler velocimetry in monitoring fetal well-being in diabetic pregnancies is controversial. The present study was conducted to determine if fetal aortic velocity waveforms were correlated with fetal outcome in pregnancies complicated by diabetes mellitus. Fetal aortic blood flow was prospectively assessed in 30 pregnant women with insulin-dependent diabetes mellitus. Systolic-diastolic ratios were obtained at 2 week intervals between 18 and 38 weeks of gestation. They were analyzed according to several fetal outcome variables. Infants with presumed fetal distress during labor and neonates with respiratory abnormalities (respiratory distress syndrome, persistent fetal circulation, or transient tachypnea of the newborn) showed statistically significant elevations of aortic Doppler indices (P < 0.031 and < 0.011, respectively). However, these correlations lacked clinical relevance. The infants demonstrated no evidence of fetal distress at birth since Apgar scores were > 7 at 5 min in all but one neonate. No relationship was found between the mean third trimester fetal aortic systolic-diastolic ratios and perinatal death, preterm deliveries, birth weight, Apgar scores at 1 and 5 min, and neonatal metabolic abnormalities. These data demonstrate a poor correlation between fetal aortic Doppler waveform analysis and fetal outcome. Therefore, fetal aortic Doppler velocimetry cannot be used as a means of assessing impending fetal compromise in offspring of diabetic mothers.

Adolescent↗

[Results of extracorporeal membrane oxygenation in 100 newborns with cardiorespiratory insufficiency].

OBJECTIVE: To describe the results of treatment with extracorporeal membrane oxygenation (ECMO) in newborns with severe cardiorespiratory insufficiency. DESIGN: Prospective, descriptive. METHODS: For all 100 newborns treated with ECMO in 1989-1997 in the Academic Hospital Nijmegen, department of Neonatology, the Netherlands, indications for treatment, complications during treatment and mortality within 6 weeks after cessation of ECMO were registered. RESULTS: The 100 children comprised 66 boys and 34 girls, with a mean age of 2 days (range: 1-15). Indications for ECMO treatment were: meconium aspiration syndrome: 39 with 37 survivors (95%), congenital diaphragmatic hernia: 31 with 23 survivors (74%), sepsis or pneumonia: 20 with 14 survivors (70%) and 'others' among which persistent pulmonary hypertension of the newborn: 10 with 8 survivors (80%). Eighteen children died (18%). Causes of death were rebound pulmonary hypertension (9 times), intracranial haemorrhage (4), multi-organ failure (3) and pulmonary problems (2). The most important complications during treatment were bleeding problems (29), clotting problems (20) and infections (11).

Cause of Death↗

Hypoxemia inducing endothelin-1 secretion in meconium aspiration in piglets.

According to our previous study, the secretion of endothelin-1 (ET-1) was induced after meconium aspiration in piglets. In order to determine the role of hypoxemia in the ET-1 secretion during meconium aspiration, 12 piglets were randomly assigned into 2 groups: the hyperoxia and the hypoxia group (6 animals/group). Instillation of meconium (20% in normal saline) was achieved via the endotracheal tube (3 mL/kg) in all these animals. The hyperoxia group was ventilated with 100% oxygen, whereas the hypoxia group was ventilated with only 40% of oxygen. The plasma ET-1 levels, arterial blood gases and hemodynamics were measured at the baseline, 60, 120, 180, and 240 minutes after meconium instillation. The result showed plasma ET-1 levels to be significantly higher in the hypoxia group than the hyperoxia group at 180 and 240 min, respectively (p <0.05 andp <0.01). Besides, the pulmonary arterial pressures were significantly higher in the hypoxia group after 60 min (p <0.05 at 60 min and p <0.01 after 120 min). These results suggested that hypoxemia may be the major factor for inducing ET-1 secretion in meconium aspiration syndrome.

Animals↗

Extracorporeal membrane oxygenation for perinatal and pediatric patients.

Extracorporeal membrane oxygenation (ECMO) is a technique developed to ensure adequate tissue oxygen delivery in patients suffering cardiac and/or respiratory failure. ECMO can provide this delivery without causing the iatrogenic damage associated with high mechanical ventilation pressures, high fraction of inspired oxygen, or high doses of inotropic medications. Though practitioners use a multitude of other, more "conventional," therapies for neonatal respiratory failure, only ECMO has been proven in a randomized, controlled, clinical trial to improve both mortality and morbidity among neonates. Though a randomized controlled trial of ECMO in the neonate has been published, to date no trial in the pediatric, adult, or cardiac population is complete. The Extracorporeal Life Support Organization registry provides data on the over 20,000 ECMO cases performed to date and serves as a resource to refine this supportive therapy. This support is not without complications, and it should be used in appropriate populations, with specific criteria for initiation.

Child↗

Follow-up of infants treated with extracorporeal membrane oxygenation for newborn respiratory failure.

Follow-up studies were conducted to assess the medical and developmental outcome of 92 infants treated with extracorporeal membrane oxygenation at the University of Michigan. Of 118 near-term (greater than 34 weeks' gestation) infants who received extracorporeal membrane oxygenation, 103 (87%) were surviving and available for follow-up at between 1 and 7 years of age. Ninety-two of these children were seen on at least one occasion. Each visit included a history and physical examination, an evaluation by a physical therapist, and developmental testing by a pediatric psychologist. Medical outcome during year 1 found 31% of the children rehospitalized, primarily with respiratory illness. Outpatient-treated lower respiratory tract illness was seen in an additional 31% of the children. New or nonstatic neurologic problems were noted in 6% of the children. Abnormal growth during year 1 occurred in 26% of the children. At last clinic visit 16% of the children exhibited moderate-to-severe neurologic abnormalities, and 8% had moderate-to-severe cognitive delay. Sensorineural hearing loss occurred in 4% of children. Nine percent of the children were receiving speech and language therapy; screening tests showed that an additional 6% had speech and language delay. Overall, at last visit 16 (20%) of the children exhibited some type of handicap. A review of the literature on follow-up studies of non-extracorporeal membrane oxygenation-treated infants with persistent pulmonary artery hypertension produced an impairment rate of 18.5%. Outcome post-extracorporeal membrane oxygenation appears similar to that seen in less ill cohorts of infants treated with more "conventional" therapy. Long-term follow-up of all such infants remains essential.

Child↗

[2 successful treatments with extracorporeal membrane oxygenation in neonates with severe respiratory problems].

We report the successful treatment with extracorporeal membrane oxygenation of two Dutch neonates with severe respiratory insufficiency, due to meconium aspiration syndrome and persistent fetal circulation respectively. During this procedure part of the cardiac output is led outside the body via a venous cannula in the right atrium, oxygenated in a membrane oxygenator, rewarmed to the patient's body temperature in a heat exchanger and returned to the patient via a cannula in the carotid artery debouching into the aortic arch.

Extracorporeal Membrane Oxygenation↗

Severe fetomaternal hemorrhage. A report of four cases.

Four cases of severe fetomaternal hemorrhage (FMH) presented with severe anemia and signs of circulatory failure. One of the patients developed the syndrome of persistent fetal circulation. The diagnosis of FMH was confirmed in all using Kleihauer-Betke tests, which demonstrated abundant fetal erythrocytes in the maternal circulation. Three infants survived after prompt volume replacement and correction of anemia. The only fatality was related to an underlying chromosomal disorder. The majority of reported neonatal deaths due to FMH have occurred when shock was the presenting manifestation.

Adult↗

Treatment of persistent pulmonary hypertension of the newborn without hyperventilation: an assessment of diffusion of innovation.

OBJECTIVE: The treatment of neonates with persistent pulmonary hypertension of the newborn (PPHN) is controversial with no consensus on diagnostic criteria or treatments. Hyperventilation has been the therapeutic mainstay. However, two widely variant alternative approaches have been proposed: ventilation without induced alkalosis, or more aggressive therapies such as high frequency ventilation or extracorporeal membrane oxygenation. We wished to determine the extent to which these alternative treatments have diffused into practice. METHODS: A forced choice questionnaire was mailed to a sample representing 10% of 3740 practicing neonatologists. Sixty percent of those surveyed responded. Data on treatment practices was tabulated. Subanalyses with respect to training era, practice site, and geographic region were performed. RESULTS: In patients with meconium aspiration syndrome, without evidence of PPHN, 36% described their initial management as hyperventilation. If PPHN was confirmed, hyperventilation was used in 90% of patients by 44% of the respondents. Muscular paralysis and inotropic support were also used frequently. Alkali and vasodilator infusion were used less frequently. The gentle ventilation strategy proposed by Wung and James at Columbia Babies Hospital was used infrequently by 47% of respondents. Gentle ventilation was used more frequently by board-certified neonatologists than those not certified. No significant differences in practice were identified by geographic region or era of training. When standard treatment failed, only 40% of the respondents utilized rescue treatments such as high frequency ventilation or extracorporeal membrane oxygenation. CONCLUSIONS: This study documents that gentle ventilation, an easily and inexpensively adopted innovation, has not diffused into practice significantly while more expensive high technology treatments, such as high frequency ventilation and extracorporeal membrane oxygenation, have penetrated more significantly.

Diffusion of Innovation↗

[Development of extracorporeal membrane oxygenation for neonates with severe respiratory failure].

Extracorporeal membrane oxygenation (ECMO) is one of the most highly developed artificial organ treatment of the last decade. Especially for severe neonatal respiratory failure, ECMO has become standard treatment in Japan following the same pattern as in the USA. In the USA, more than 12,000 infants have been registered for ECMO treatment by the Extracorporeal Life Support Organization (ELSO), and their total survival rate is above 80%. Recently, to avoid ligating the carotid artery, most neonates who required ECMO have been supported by a veno-venous (V-V) bypass using a double-lumen catheter via the right internal jugular vein into the right atrium. To prevent bleeding complications, the introduction of Nafamostat Mesilate and the development of a heparin-coated system would be advantageous. Progresses in these instruments and perfusing techniques might enlarge the indications of ECMO. We performed an experiment on fetus ECMO as artificial placenta. The fetuses were incubated for 10-237 hours by A-V ECMO using a centrifugal pump successfully and maturation of the lung was revealed. In the future the fetus ECMO could be introduced clinically as a back-up system for fetal surgeries and incubation for extra-premature infants.

Cystic Adenomatoid Malformation of Lung, Congenita↗

High pulmonary vascular resistance after birth: I. Pathophysiologic considerations and etiologic classification.

The clinical syndrome known as persistent fetal circulation, or persistent pulmonary hypertension of the newborn, is characterized by maintenance of a high pulmonary vascular resistance after birth. The small pulmonary arteries of the fetus have a thick muscular medial layer; they are very reactive, being actively constricted by the low PO2 levels normally present during fetal life. The pulmonary vascular smooth muscle layer is hypertrophied in conditions that result in chronic fetal hypoxia, or a maintained increase in pulmonary arterial pressure. Normally, pulmonary vasodilation occurs rapidly after birth, partly related to physical expansion with gas, but mainly due to the increased PO2 associated with ventilation with air. Based on these developmental considerations, the factors responsible for an increased pulmonary vascular resistance after birth may be classified in three main groups: (A) Acute vasoconstriction due to postnatal hypoxia and aggravated by acidemia; (B) Prenatal increase in pulmonary vascular smooth muscle development; and (C) Decreased cross sectional area of the pulmonary vascular bed due to inadequate numbers of vessels. The various mechanisms that may promote these responses are presented.

Animals↗

Steroids in full term infants with respiratory failure and pulmonary hypertension due to meconium aspiration syndrome.

Persistent pulmonary hypertension of the newborn (PPHN) due to meconium aspiration syndrome (MAS), has a high morbidity and mortality especially in centres with limited access to extra-corporeal membrane oxygenation or nitric oxide therapy. In such a setting, we conducted a pilot study to evaluate the effect of dexamethasone on severe respiratory failure with PPHN due to MAS with a view to exploring possible justification for randomised controlled trials in similar patients. We prospectively managed a consecutive case series of 14 infants over a 3-year period with the above mentioned diagnosis, who were ventilated and with an oxygenation index >25. Dexamethasone was commenced in a dose of 0.5 mg/kg per day and given for up to a maximum of 9 days in a reducing schedule. Differences between time points were analysed using analysis of variance for repeated measures. The mean age of commencing dexamethasone was 79.9 h. There was a rapid, significant improvement (P < 0.05) in the respiratory status in 13 of these infants after commencing dexamethasone, allowing weaning from the ventilator and eventual extubation at a mean age of 8.7 days. One infant died. Two infants had infective episodes. Conclusion. Dexamethasone, if started early in infants with respiratory failure and persistent pulmonary hypertension of the newborn due to meconium aspiration syndrome may be effective in improving gas exchange, and possibly avoiding extra-corporeal membrane oxygenation. A randomised controlled trial of using dexamethasone early in similar patients and setting is warranted.

Analysis of Variance↗

Failure of acute perinatal asphyxia or meconium aspiration to produce persistent pulmonary hypertension in a neonatal baboon model.

OBJECTIVE: Our purpose was to determine whether perinatal asphyxia or meconium aspiration, or both, can produce the physiologic and histologic pulmonary vascular changes associated with the meconium aspiration syndrome. STUDY DESIGN: Twenty neonatal baboons were studied in four groups: 1, control; 2, meconium aspiration; 3, asphyxia (intermittent cord compression); and 4, asphyxia with meconium aspiration. Animals were ventilated for 24 hours under ketamine, diazepam, and pancuronium. Data were analyzed by means of mixed model analysis of measures. RESULTS: Meconium significantly impaired oxygenation (p < 0.001), whereas concurrent asphyxia moderated this effect (p < 0.034). Meconium also increased the need for ventilatory support (p < 0.002). No animal had persistent pulmonary hypertension; neither systemic nor pulmonary systolic pressures differed statistically between the groups. No animal showed evidence of abnormal pulmonary arteriolar muscularization. CONCLUSION: Sublethal perinatal asphyxia or meconium aspiration were insufficient to produce either the physiologic or histologic changes of severe meconium aspiration syndrome. It is unlikely that intrapartum fetal distress alone can produce this syndrome in human neonates.

Acute Disease↗