morphine and Pneumonia

The pathogenesis of neonatal meconium aspiration syndrome (MAS) involves meconium-induced lung inflammation and surfactant inactivation. Bronchoalveolar lavage (BAL) with diluted surfactant facilitates the removal of meconium. CHF5633, one of the most promising synthetic surfactants, is effective in neonatal respiratory distress syndrome. Here we investigated its efficacy via BAL in an experimental MAS model.. Experimental MAS was induced at birth in near-term newborn rabbits by intratracheal instillation of reconstituted human meconium. First, undiluted CHF5633 was compared with a porcine-derived surfactant (Poractant alfa) via intratracheal bolus (200 mg/kg). Second, the efficacy of BAL with diluted CHF5633 (5 mg/mL, 20 ml/kg) alone, or followed by undiluted boluses (100 or 300 mg/kg), was investigated.. Meconium instillation caused severe lung injury, reduced endogenous surfactant pool, and poor survival. CHF5633 had similar benefits in improving survival and alleviating lung injury as Poractant alfa. CHF5633 BAL plus higher boluses exerted better effects than BAL or bolus alone in lung injury alleviation by reversing phospholipid pools and mitigating proinflammatory cytokine mRNA expression, without fluid retention and function deterioration.. CHF5633 improved survival and alleviated meconium-induced lung injury, the same as Poractant alfa. CHF5633 BAL plus boluses was the optimal modality, which warrants further clinical investigation.. To explore the efficacy of a synthetic surfactant, CHF5633, in neonatal lung protection comparing with Poractant alfa in a near-term newborn rabbit model with meconium-induced lung injury. Similar effects on improving survival and alleviating lung injury were found between CHF5633 and Poractant alfa. Optimal therapeutic effects were identified from the diluted CHF5633 bronchoalveolar lavage followed by its undiluted bolus instillation compared to the lavage or bolus alone regimens. Animals with CHF5633 lavage plus bolus regimen exerted neither substantial lung fluid retention nor lung mechanics deterioration but a trend of higher pulmonary surfactant-associated phospholipid pools.

Topics: Animals; Animals, Newborn; Female; Humans; Infant, Newborn; Lung Injury; Meconium; Meconium Aspiration Syndrome; Phospholipids; Pneumonia; Pulmonary Surfactants; Rabbits; Surface-Active Agents; Swine; Therapeutic Irrigation

Since inflammation and oxidative stress are fundamental in the pathophysiology of neonatal meconium aspiration syndrome (MAS), various anti-inflammatory drugs have been used in experimental and clinical studies on MAS. This pilot study evaluated therapeutic potential of N-acetylcysteine in modulation of meconium-induced inflammation and oxidative lung injury. Oxygen-ventilated adult rabbits were intratracheally given 4 ml/kg of meconium (25 mg/ml) or saline (Sal, n = 6). Thirty minutes later, meconium-instilled animals were treated with intravenous N-acetylcysteine (10 mg/kg, Mec + NAC, n=6) or were non-treated (Mec, n = 6). All animals were oxygen-ventilated for additional 5 hours. Total and differential blood leukocyte counts were determined at baseline, and at 1, 3 and 5 h of the treatment. After sacrificing animals, left lung was saline-lavaged and total and differential cell counts in the bronchoalveolar lavage fluid were determined. Right lung was used for biochemical analyses and for estimation of wet-dry weight ratio. In lung tissue homogenate, thiobarbituric acid-reactive substances (TBARS), dityrosine, lysine-lipid peroxidation (LPO) products, and total antioxidant status (TAS) were detected. In isolated lung mitochondria, TBARS, dityrosine, lysine-LPO products, thiol group content, conjugated dienes, and activity of cytochrome c oxidase were estimated. To evaluate systemic effects of meconium instillation and NAC treatment, TBARS and TAS were determined also in plasma. To evaluate participation of eosinophils in the meconium-induced inflammation, eosinophil cationic protein (ECP) was detected in plasma and lung homogenate. Meconium instillation increased oxidation markers and ECP in the lung and decreased TAS (all P<0.05). NAC treatment reduced ECP and oxidation markers (all P<0.05, except of dityrosine in homogenate and conjugated dienes in mitochondria) and prevented a decrease in TAS (P<0.01) in lung homogenate compared to Mec group. In plasma, NAC decreased TBARS (P<0.001) and ECP, and increased TAS (both P<0.05) compared to Mec group. Concluding, N-acetylcysteine diminished meconium-induced inflammation and oxidative lung injury.

Topics: Acetylcysteine; Age Factors; Animals; Antioxidants; Biomarkers; Disease Models, Animal; Humans; Infant, Newborn; Inflammation Mediators; Leukocytes; Lipid Peroxidation; Lung; Lung Injury; Meconium; Meconium Aspiration Syndrome; Mitochondria; Oxidative Stress; Pneumonia; Pulmonary Edema; Rabbits; Thiobarbituric Acid Reactive Substances; Time Factors

To examine the effects of pentoxifylline (PTX) on regional pulmonary and systemic inflammation after meconium aspiration, we studied 26 anesthetized and ventilated adult rats for 3 hours. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally. After instillation of meconium, PTX (20 mg/kg, i.a.; n = 9) or saline (n = 8) was given to the subjects. Nine rats that were ventilated and not instilled with meconium served as sham group. Meconium instillation resulted in increased bronchoalveolar lavage (BAL) fluid tumor necrosis factor-α (TNF-α; P = 0.004 and P = 0.002, respectively), protein (P = 0.005 and P = 0.001, respectively) levels, and arterial oxygenation index (OI) in PTX and saline groups. PTX treatment prevented the increase of BAL fluid TNF-α, protein concentrations, and OI in the meconium-instilled lungs but had no statistically significant effect. These results indicate that meconium aspiration induces severe inflammation in the lung. PTX treatment affects the TNF-α production in the lungs and it may attenuate meconium-induced derangements.

Topics: Animals; Arteries; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Humans; Infant, Newborn; Lung; Meconium; Meconium Aspiration Syndrome; Pentoxifylline; Pneumonia; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

The effects of dexamethasone on in vitro airway reactivity associated with lung inflammation were investigated in rabbits with meconium aspiration. Oxygen-ventilated adult rabbits received an intratracheal bolus of 4 ml/kg body weight of saline (Sal, n = 4) or human meconium (25 mg/ml). Thirty minutes later, meconium-instilled animals intravenously received 0.5 mg/kg of dexamethasone (Dexa, n = 6), or were left without treatment (Meco, n = 5). The animals were ventilated for a further 5 hr and then sacrificed. The left lungs were lavaged with saline, and the white blood cell (WBC) count was estimated. Tracheal and right-lung tissue strips were placed into organ chambers with Krebs-Henseleit solution. Cumulative doses of histamine (10(-8)-10(-3) mol/l) and acetylcholine (10(-8)-10(-3) mol/l) were added to the chambers, and recordings of contractions were made after a 30-min loading phase with a tension of 4 grams, and another 30-min adaptation phase with a tension of 2 g. Tracheal smooth muscle in vitro reactivity to histamine was higher in the Meco than in the Sal group, and dexamethasone decreased the reactivity compared to the Meco group (P < 0.05). Lung tissue in vitro reactivity to histamine was slightly higher in the Meco than in the Sal group (P > 0.05), and dexamethasone decreased the reactivity compared to both the Meco and Sal groups (P < 0.05). No between-group differences were observed in tracheal or lung in vitro reactivity to acetylcholine (P > 0.05). In the Meco group, blood WBC (P > 0.05) and neutrophil (P < 0.05) counts were lower than in the Sal and Dexa groups. Lung neutrophils and eosinophils were higher in both the Meco and Dexa groups than in the Sal group (P < 0.01). Dexamethasone decreased neutrophils (P < 0.05) compared to the Meco group. Meconium-induced airway hyperreactivity to histamine and lung inflammation were alleviated by dexamethasone.

Topics: Animals; Anti-Inflammatory Agents; Dexamethasone; Disease Models, Animal; Humans; In Vitro Techniques; Infant, Newborn; Lung; Meconium; Meconium Aspiration Syndrome; Muscle, Smooth; Pneumonia; Rabbits; Trachea; Treatment Outcome

Neonatal meconium aspiration often produces severe respiratory distress due to an inflammatory pulmonary injury, but the extension of this damaging reaction to the noncontaminated lung regions is still uncertain. To investigate the presence of generalized pulmonary inflammatory response, 31 anesthetized and ventilated neonatal piglets (1-3 d) were studied. Meconium (n = 16) or saline (n = 15) was instilled unilaterally into the right lung, and analysis of the lung tissue or bronchoalveolar lavage (BAL) fluid from both lungs was performed after 12 h. Meconium increased the wet/dry weight ratio, histologic tissue injury score and tissue myeloperoxidase activity as well as BAL fluid total cell count in the contaminated lung. Tumor necrosis factor-alfa concentrations in BAL fluid did not however differ significantly. Furthermore, in the meconium-instilled lungs the tissue and lavage fluid catalytic activity of phospholipase A2 (PLA2) and tissue PLA2 group-I and group-II concentrations were significantly elevated. Although BAL fluid catalytic activity of PLA2 was moderately increased also in the meconium noninstilled lung, significant inflammatory injury in this lung was absent. The results thus indicate that meconium aspiration induces severe local inflammation and lung injury, but significant generalized pulmonary inflammatory damage in the pathogenesis of meconium aspiration syndrome is unlikely.

Topics: Animals; Animals, Newborn; Blood Pressure; Humans; Infant, Newborn; Lung; Meconium; Meconium Aspiration Syndrome; Organ Size; Pneumonia; Swine

Meconium aspiration syndrome is a major contributor to neonatal respiratory distress in infants and it has been sporadically recognized in neonatal animals. This investigation was designed to study the short and long term effects of meconium and amniotic fluid in the lungs of neonatal rats. Seven-day-old rats (n = 123) divided in three groups were intratracheally inoculated with saline solution, amniotic fluid or meconium. Rats were euthanatized on 1, 3, 7, 14, 28, 56 and 112 postinoculation days (PID) and the lungs were examined by light microscopy. Saline solution did not induce any change while amniotic fluid elicited only a mild foreign body response which disappeared by PID 14. In contrast, meconium induced an exudative alveolitis characterized by recruitment of neutrophilsn in the bronchoalveolar spaces. Meconium also induced atelectasis, hyperinflation and thickening of alveolar septa all of which had disappeared by PID 14. Starting at PID 7, neutrophils were progressively replaced by macrophages, giant cells, and some fibroblasts. There were sporadic foci of mineralization starting at PID 14 and lasting up to PID 112. Some mineralized foci became lined with cuboidal epithelial cells at PID 28. Meconium was slowly degraded but still evident by PID 112. It was concluded that inoculation of meconium in neonatal rats induces acute microscopic changes typical of meconium aspiration syndrome. The long term lesions induced by meconium consisted of persistent multifocal histiocytic alveolitis and bronchiolitis reaction with occasional foci of calcification.

Topics: Amniotic Fluid; Animals; Animals, Newborn; Coloring Agents; Female; Intubation, Intratracheal; Lung; Male; Meconium; Pneumonia; Pregnancy; Pulmonary Alveoli; Rats; Rats, Inbred F344; Tissue Fixation

Aspiration of meconium produces an inflammatory reaction resulting in necrotic changes in lung tissue. To further investigate the mechanisms of the meconium-induced early pulmonary injury, twenty 10-12-d-old piglets were studied for lung tissue ultrastructural and apoptotic changes and phospholipase A2 activity. Twelve piglets received an intratracheal bolus (3 mL/kg) of a 20-mg/mL (thin, n = 6) or 65-mg/mL (thick, n = 6) mixture of human meconium, and control piglets (n = 5) received the same amount of intratracheal saline. Three ventilated piglets with no aspiration were also studied. Pulmonary hemodynamics and systemic oxygenation were followed for 6 h after meconium or saline insufflation. In the control groups, the pulmonary tissue showed open alveolar spaces and intact vascular walls, whereas meconium administration resulted in severe pneumonitis, with alveolar spaces filled with inflammatory exudate. Meconium instillation additionally resulted in edematous changes in the vascular walls and alveolar epithelium, whereas type II pneumocytes were intact. The amount of apoptotic cells was increased, especially in the respiratory epithelium, and the catalytic activity of phospholipase A2 in lung tissue samples was significantly elevated after thick meconium instillation. This activity rise proved to be mainly because of human group I phospholipase A2, introduced by meconium. Our data thus show that aspiration of meconium leads to severe lung tissue inflammation with early ultrastructural changes in the pulmonary alveolar walls and is associated with apoptotic cell death in the epithelium, already during the first hours after the insult. These results further suggest that high phospholipase A2 activity, mainly introduced into the lungs within the meconium, may have an important role in the initiation of these alterations in neonatal lungs.

Topics: Animals; Animals, Newborn; Apoptosis; Humans; Instillation, Drug; Intubation, Intratracheal; Lung; Meconium; Microscopy, Electron; Peroxidase; Phospholipases A; Phospholipases A2; Pneumonia; Swine

It is uncertain how often the passage of meconium in utero is a response to some event causing fetal distress as opposed to being simply the physiologic functioning of a maturing intestinal tract. The extent to which meconium may produce injury or inflammation in pulmonary and placental tissues after intrauterine exposure is also unclear. This study was a retrospective review of 123 cases, 79 stillborn and 44 liveborn less than one month of age, autopsied at The Johns Hopkins Hospital, and showing histologic evidence of intrauterine meconium exposure by aspirated meconium or meconium macrophages in placental tissues. Of 55 cases with pulmonary inflammation, 13 (24%) had fetal pneumonia, 5 (9%) had postnatal bronchopneumonia, and 37 (67%) had inflammation secondary to meconium aspiration. There was inflammation of the umbilical cord in 31 (41%) of the 75 cases with available slides, 11 (15%) had funisitis associated with chorioamnionitis and 18 (58%) were secondary to meconium exposure. There were 19 cases with focal injury of cord vessels from meconium, two of which had cord ulceration. Inflammation of the membranes and chorionic plate was present in 24 (33%) of the 72 cases where it could be assessed, and was due to chorioamnionitis in 11 (46%) and to meconium in 13 (54%). In general, meconium-related inflammations was much less severe in the membranes than in the cord. There were 67 (54%) cases with definite or probable evidence of fetal distress. In 38 (48%) stillborns no cause of fetal death in utero was identified and in 18 (41%) liveborns there was no known prenatal problem. The results support the concept that meconium passage in utero may occur either as a response to fetal distress or as a physiologic process. Inflammation in the lung and placental tissues, and vascular injury in the umbilical cord may arise secondary to in utero exposure to meconium.

Topics: Female; Fetal Death; Fetus; Humans; Infant, Newborn; Inflammation; Meconium; Meconium Aspiration Syndrome; Placenta; Placenta Diseases; Pneumonia; Pregnancy; Retrospective Studies; Umbilical Cord; Vascular Diseases

In a thirty-month prospective study pleural effusions were found on chest radiographs in 33 of 1482 newborns admitted to intensive care units. Congenital heart disease was the most common cause, accounting for eleven cases. Meconium aspiration was the most common respiratory disease associated with neonatal pleural effusion. Infants whose effusions were first noted after the second day of life were likely to have heart disease (p = 0.02). Infants with moderate or large effusions were unlikely to have heart disease (p = 0.04). Prolonged pleural effusion was associated with a prolonged need for supplemental oxygen. Survivors whose effusions lasted three or more days were at increased risk for needing supplemental oxygen for more than twenty-one days (p = 0.07). The overall mortality was 48 percent (sixteen of thirty-three infants died).

Topics: Cardiovascular Diseases; Heart Defects, Congenital; Humans; Infant, Newborn; Lung; Lung Diseases; Meconium; Pleural Effusion; Pneumonia; Prognosis; Prospective Studies; Radiography; Risk; Streptococcus agalactiae

The short-term effects of muscle relaxation with pancuronium bromide on arterial blood gas values, heart rate, and arterial blood pressure were studied in 49 neonates receiving mechanical ventilation. After pancuronium administration, mean PaO2 increased from 61.9 +/- 30.0 to 80.9 +/- 52.8 mm Hg (P = 0.006), mean PaCO2 decreased from 40.1 +/- 13.0 to 37.5 +/- 13.3 mm Hg (P = 0.03), and mean heart rate rose from 146.2 +/- 24.9 to 161.0 +/- 20.5 beats/min (P less than 0.001). Arterial blood pressure did not change significantly. When results were analyzed by diagnosis (meconium aspiration syndrome, hyaline membrane disease, pneumonia), only infants with meconium aspiration syndrome had a significant improvement in oxygenation (P = 0.008). Six of 18 patients with hyaline membrane disease responded to muscle relaxation, with a decrease in PaO2 of 10 mm Hg or more. No significant correlation was found between change in PaO2 and birth weight, gestational age, postnatal age, or change in heart rate. A weak correlation (r = -0.37, P less than 0.006) was observed between change in PaO2 and change in PaCO2. Although the reasons for the divergence in response in different groups of patients are not entirely clear, the risk of deterioration with pancuronium therapy should be kept in mind, particularly if treatment in an infant with hyaline membrane disease is being considered.

Topics: Blood Gas Analysis; Blood Pressure; Heart Rate; Humans; Hyaline Membrane Disease; Hypoxia; Infant, Newborn; Meconium; Pancuronium; Pneumonia; Pneumonia, Aspiration; Respiration, Artificial

Chest physical therapy for neonates with pulmonary dysfunction is a growing specialty of physical therapy practice. The purpose of this article is to provide physical therapists current information regarding chest physical therapy for the newborn infant. The neonatal diagnoses for which chest physical therapy is useful or has good rationale are discussed. Common complications are reviewed that affect physical therapy and medical treatment for infants with respiratory diseases and prematurity. Specific indications, contraindications, and precautions for physical therapy techniques are listed. Chest physical therapy evaluation and treatment are described and rationale for the application of various techniques is provided. Literature is reviewed dealing with the effects of chest physical therapy on neonates with pulmonary dysfunction. The strengths and weaknesses of each reviewed study are analyzed and suggestions for direction of future research for physical therapists are provided.

Topics: Adult; Bronchopulmonary Dysplasia; Child; Humans; Infant, Newborn; Infant, Newborn, Diseases; Meconium; Percussion; Physical Therapy Modalities; Pneumonia; Posture; Respiratory Distress Syndrome, Newborn; Respiratory Tract Diseases

Topics: Amniotic Fluid; Drowning; Food; Foreign Bodies; Gases; Gastric Juice; Gastroesophageal Reflux; Humans; Infant, Newborn; Lung; Meconium; Nitrogen Dioxide; Peptide Hydrolases; Phosgene; Pneumonia; Pneumonia, Aspiration; Pneumonia, Lipid; Saliva; Smoke

The bacteriology of tracheal aspirates from 28 intubated newborn babies was studied. There was no correlation between such colonization and the respiratory distress syndrome. Endotracheal suction of intubated infants did provide a reliable specimen source for determining the etiology of perinatal pneumonia. Presence of polymorphonuclear leukocytes in the aspirate correlated well with infection. Anaerobic bacteria were found to play a role in three of the five cases of pneumonia.

Topics: Bacteria; Critical Care; Exudates and Transudates; Female; Humans; Infant Care; Infant, Newborn; Infant, Newborn, Diseases; Intubation, Intratracheal; Male; Meconium; Pneumonia; Pneumonia, Aspiration; Respiratory Distress Syndrome, Newborn; Trachea

Topics: Adolescent; Albumins; Bronchitis; Child; Child, Preschool; Cystic Fibrosis; Female; Genes, Recessive; Heterozygote; Humans; Infant; Infant, Newborn; Life Expectancy; Male; Meconium; Pneumonia; Sodium Chloride; Sweat

The clinical course and follow-up of 14 neonates who developed acute renal failure are reported. Renal failure in these patients was secondary to major perinatal disorders, e.g., hyaline membrane disease, pneumonia, hemorrhage, or sepsis. Thirteen patients had hypoxia and nine were in shock when renal failure developed. Five patients died during the acute stage of renal failure. Of nine survivors, five patients sustained residual renal damage.

Topics: Acute Kidney Injury; Anuria; Follow-Up Studies; Humans; Hyaline Membrane Disease; Infant, Newborn; Infant, Newborn, Diseases; Meconium; Pneumonia; Shock

We investigated the effects of meconium on the lungs of an adult rabbit model to distinguish between mechanical obstruction of airways and chemical pneumonitis. After the rabbits were anesthetized and intubated, 20% human meconium in saline was instilled into the trachea. Arterial and mixed venous blood gases, functional residual capacity, cardiac output vascular pressures, calculated venous admixture, and pulmonary vascular resistance were measured. Sections of affected lung tissue were examined microscopically. The results were consistent with an early mechanical obstruction of airways with gradual development of chemical pneumonitis over 48 hours.

Topics: Airway Obstruction; Animals; Carbon Dioxide; Functional Residual Capacity; Inhalation; Lung; Meconium; Oxygen; Partial Pressure; Pneumonia; Pulmonary Atelectasis; Rabbits

Meconium staining of the placenta and/or fetal body was present at birth in 10.3 per cent of 42,000 live-born infants, but present disproportionately in 18.1 per cent of 788 neonatal deaths. The neonatal mortality rate was 3.3 per cent in the stained group and 1.7 per cent in the nonstained group. Among infants who died, the incidence of erythroblastosis was quadrupled and that of cardiovascular malformation was doubled in the stained group. Meconium staining was associated with a decrease in the expected frequency of hyaline membranes and atelectasis even in premature infants; hypotheses for this phenomenon were presented. Meconium staining of the fetus or placenta requires several hours of exposure. As a hypothesis, the observed increase of deaths in stained neonates may be related to the stresses of cumulative or chronic hypoxia which may occur after the initial passage of meconium if delivery is prolonged.?23AUTHOR

Topics: Amniotic Fluid; Autopsy; Birth Weight; Congenital Abnormalities; Erythroblastosis, Fetal; Female; Fetal Diseases; Hemorrhage; Humans; Hyaline Membrane Disease; Hypoxia; Infant, Newborn; Infant, Newborn, Diseases; Meconium; Obstetric Labor Complications; Placenta; Pneumonia; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Pulmonary Atelectasis; Time Factors

Topics: Birth Weight; Chromatography, Thin Layer; Gestational Age; Humans; Infant, Newborn; Intubation, Intratracheal; Lung; Meconium; Pharynx; Phosphatidylcholines; Pneumonia; Pneumonia, Aspiration; Prognosis; Respiratory Distress Syndrome, Newborn; Sphingomyelins; Trachea

Topics: Amniotic Fluid; Animals; Bronchi; Cesarean Section; Enterococcus faecalis; Escherichia coli; Extraembryonic Membranes; Exudates and Transudates; Female; Fetal Diseases; Fibrin; Gastric Juice; Gestational Age; Inflammation; Injections; Ink; Klebsiella pneumoniae; Leukocytes; Lung; Meconium; Pneumonia; Pregnancy; Pulmonary Alveoli; Rabbits; Staphylococcus

Topics: Diatrizoate; Enema; Fluoroscopy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Intestinal Obstruction; Meconium; Methods; Pneumonia

Topics: Asphyxia Neonatorum; Brain Damage, Chronic; Follow-Up Studies; Humans; Infant, Newborn; Infant, Premature; Inhalation; Meconium; Pneumonia; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Tetanus

Topics: Anti-Bacterial Agents; Catheterization; Cystic Fibrosis; Germany, East; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Obstruction; Meconium; Pneumonia; Postoperative Complications; Staphylococcal Infections

Topics: Asphyxia Neonatorum; Humans; Hyaline Membrane Disease; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Meconium; Pneumonia; Pneumothorax; Respiratory System Abnormalities; Respiratory Tract Diseases