Transfusion-related acute lung injury treated with surfactant in a neonate

A term, male neonate suddenly developed respiratory distress and severe cyanosis while undergoing exchange transfusion for hyperbilirubinaemia. Transfusion-related acute lung injury was diagnosed. Because of persistent hypoxaemia despite aggressive treatment, two doses of surfactant were administered, resulting in marked improvement. Conclusion: Transfusion-related acute lung injury may occur in neonates, and may be successfully treated by surfactant replacement.     

Surfactant decreases pulmonary vascular resistance and increases pulmonary blood flow in the fetal lamb model of congenital diaphragmatic hernia

INTRODUCTION: Experiments using animal models of neonatal respiratory distress syndrome have shown a decrease in pulmonary vascular resistance (PVR) with surfactant replacement, whereas studies with the lamb model of congenital diaphragmatic hernia (CDH) have demonstrated improvement in oxygenation and lung mechanics with this therapy. The aim of the present study was to measure the effects of surfactant replacement therapy on the pulmonary hemodynamics of the lamb model of CDH. METHODS: Ten lambs with surgically created CDH and five control lambs were instrumented at term, with the placental circulation intact. Ultrasonic flow probes were positioned around the main pulmonary artery and the common origin of the left and right pulmonary arteries to record total lung and main pulmonary artery blood flow. Catheters were inserted to record systemic, pulmonary, and left atrial pressure. Five CDH animals received 50 mg/kg of surfactant by tracheal instillation just before delivery. All 15 animals were then ventilated for 4 hours. RESULTS: Correcting the surfactant deficiency in the CDH lamb resulted in a significant increase in pulmonary blood flow, a decrease in PVR, and a reduction in right-to-left shunting. These improvements in hemodynamics were associated with a significant improvement in gas exchange over 4 hours. CONCLUSION: The fetal lamb model of CDH has elevated PVR in comparison to controls. Prophylactic surfactant therapy reduces this resistance and dramatically increases pulmonary blood flow while reducing extrapulmonary shunt. A surfactant deficiency may be partially responsible for the persistent pulmonary hypertension in neonates with CDH.     

Selective intrabronchial instillation of surfactant in a patient with pneumonia: a preliminary report

The efficacy of treatment with exogenous surfactant has been reported in children with respiratory failure due to severe pneumonia. Its effect in adults with similar features has not been established. We therefore administered 240 mg of surfactant to a 71 year old man, who had developed right lower lobe pneumonia and hypoxaemia following abdominal aortic surgery. After this treatment, the patient's oxygenation, evaluated by arterial oxygen tension/fraction of inspired oxygen (PaO2/FIO2) ratio during artificial ventilation, gradually improved, and ventilator settings could be reduced whilst maintaining PaO2 at the appropriate level. Although the precise mechanism by which surfactant improves respiratory failure due to pneumonia is unclear, administration of the drug may have overcome a quantitative deficiency of endogenous surfactant attributable to the antagonistic effect of pulmonary exudates and reduced production following damage to type II pneumocytes. The present case provides an indirect suggestion of a possible causal relationship between the improvement of oxygenation and administration of surfactant in adult respiratory failure caused by pneumonia.     

Prevention of respiratory failure after hydrochloric acid aspiration by intratracheal surfactant instillation in rats

Because the surfactant system probably is involved in the pathophysiology of respiratory failure caused by hydrochloric acid (HCl) aspiration, we investigated the effects of different ventilation strategies and intratracheal surfactant instillation at different time intervals on the course of pulmonary gas exchange after HCl aspiration in rats. In this study rats were anesthetized and mechanically ventilated via a tracheostomy. Respiratory failure was induced by intratracheal instillation of 3 mL/kg 0.1 N HCl. Animals (n = 49) were divided into nine groups: Groups 1 and 2 through 9 were ventilated with peak airway pressure/positive end-expiratory pressure of 14/2 and 26/6 cm H2O, respectively; Groups 3 and 4 received surfactant (200 mg/kg) intratracheally, 1 and 10 min after HCl aspiration; Groups 5 and 6 received saline, 1 and 10 min after HCl aspiration; Groups 7 and 8 received surfactant, 60 and 90 min after HCl aspiration; Group 9 received saline instead of HCl. Gas exchange deteriorated in Groups 1, 2, 5, 6, 7, and 8, whereas respiratory failure could be prevented in Groups 3 and 4. After deterioration of gas exchange, surfactant treatment prevented further decrease of PaO2 values in Group 7, whereas no effect on gas exchange was observed in Group 8; intratracheal instillation of saline had no effect on gas exchange (Group 9). These results suggest that surfactant should be given as early as possible after aspiration of gastric contents to prevent development of respiratory failure.     

A comparative study of human immunodeficiency virus culture, polymerase chain reaction and anti-human immunodeficiency virus immunoglobulin A antibody detection in the diagnosis during early infancy of vertically acquired human immunodeficiency virus infection

Asynchrony of delivered and spontaneous breaths in mechanically ventilated infants may impair gas exchange and prolong the need for assisted ventilation. We conducted a randomized, controlled trial of a patient-triggered, flow-synchronized ventilator on 30 preterm infants with respiratory distress syndrome who weighed between 1100 and 1500 gm at birth. Entry criteria included radiographic evidence of respiratory distress syndrome and the need for mechanical ventilation and surfactant replacement therapy. Patients were assigned to either conventional time-cycled, pressure-limited ventilation or patient-triggered, flow-synchronized ventilation in an assist/control mode. Otherwise clinical management was identical. Time to extubation was the primary outcome measure. Patients treated with flow-synchronized ventilation were weaned more rapidly and had a significantly shorter mean time to extubation than those treated with time-cycled, pressure-limited ventilation, 119 versus 271 hours, p = 0.0152. In addition, there was no difference in the rate of complications between the two groups. There were, however, considerable reductions in patient charges of $4344 per patient in the flow-synchronized ventilation group.     

Morphological investigation of the neonatal lung with respiratory distress syndrome which was maximally distended with Somentor 33 and formalin (author's transl)]

The importance of morphological immaturity of the lung in the development of the respiratory distress syndrome was investigated. Atelectatic lungs of newborns were maximally expanded with a mineral oil of low kinematic viscosity (Somentor 33) or 10% Formalin. With this method, surface active forces of peripheral air spaces should not impede expansion of the lungs. 27 lungs of neonates who died of respiratory distress syndrome and 10 lungs of neonates without primary respiratory problems were examined. Following maximal expansion of the lungs with the respiratory distress syndrome show a hypercellular densely cellular tissue of the pulmonary segments, much like glanduloid hyperplasia with small peripheral air spaces and long distances for diffusion of the respiratory gases. The lungs of newborns without respiratory distress syndromes are well alveolar following expansion and show an optimal morphology for gas diffusion. A lack of a surfactant should have significant consequences in small air spaces.     

Breast reconstruction through tissue expansion

In this article the pathophysiology and diagnosis of neonatal respiratory distress syndrome as a primarily form of surfactant deficiency is disclosed. Attention is paid to surfactant composition, productive and secretion in the alveoli and metabolic turnover as well. From clinical point the view basic principles concerning the surfactant replacement is discussed. Surfactant minimizes the surface tension and friction between the gas molecules and lung tissues during breathing. It also helps keep lung tissues dry and alveoli patent. At 26 to 28 weeks of gestation alveolar ducts and bronchioles are present but pulmonary capillaries are not in close contact with them. Alveoli may not even be distinguishable. Surfactant develops all through gestation but does not surge until about the 34th week. Infants born before 35 weeks of gestation are at risk for respiratory distress syndrome which is at first characterised by decrease of lung compliance. It leads to progressive respiratory failure.     

Effect of surfactant on respiratory failure associated with thoracic aneurysm surgery

OBJECTIVE: To study the effects of surfactant administration on the left lung after surgical repair of descending aortic aneurysms on postoperative respiratory failure. DESIGN: Randomized, prospective, controlled study. SETTING: Clinical investigation. PATIENTS: Eleven patients with respiratory failure associated with thoracic aneurysm surgery. INTERVENTION: Eleven adult patients with acute respiratory failure (PaO2/FIO2 <300 torr [<40 kPa]) after surgical repair of descending aortic aneurysms. The artificial surfactant (30 mg/kg) was given to the operated side of the lung by intrabronchial instillation in six patients (surfactant group), whereas nothing was instilled in the other five patients (control group). MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters, blood gas, and peak inspiratory pressure were measured at the end of surgery, before surfactant instillation, and at 2, 6, 12, 24, and 48 hrs after surfactant instillation. At the end of surgery, the mean +/- SEM values of the PaO2/FIO2 ratio were 204 +/- 25 torr (27.2 +/- 3.3 kPa) in the surfactant group and 240 +/- 26 torr (32.0 +/- 3.5 kPa) in the control group. After 2, 6, 12, and 48 hrs, improvements in the PaO2/FIO2 ratios were observed in the surfactant group, whereas the control group showed no improvement. Two hours after surfactant instillation, the mean value in the PaO2/FIO2 ratio was significantly higher in the surfactant group (318 +/- 24 torr [42.4 +/- 3.2 kPa]) (p < .05) compared with the control group values (240 +/- 34 torr [32 +/- 4.5 kPa]). CONCLUSION: Surfactant administration immediately after surgery restored gas exchange in postoperative respiratory failure associated with thoracic aneurysm surgery.     

A mathematical approximation for the solution of a static indentation test

The aim of this study was to compare the incidence of acute adverse events and long-term outcome of two different surfactant dosing procedures in respiratory distress syndrome (RDS). The effects of two surfactant dosing procedures on the incidence of transient hypoxia and bradycardia, gas exchange, ventilatory requirements and 28 d outcome were compared. The patients, comprising 102 infants (birthweight 600-2000 g) with RDS on mechanical ventilation with FiO2 > or = 0.4, were randomized at 2-24 h to receive 200 mg kg(-1) of Curosurf; in 56 it was given by bolus delivery, and in 55 by a simplified technique (dose given in 1 min via a catheter introduced through a side-hole in the tracheal tube adaptor. The baby's position was not changed and ventilation was not interrupted). Two additional surfactant doses (100 mg kg(-1)) were also given, by the same method, if ventilation with FiO2 > or = 0.3 was needed 12 and 24 h after the initial dose. The number of episodes of hypoxia and/or bradycardia was similar in both groups. A slight and transient increase in PaCO2 was observed in the side-hole group. The efficacy of the surfactant, based on oxygenation improvement, ventilator requirements, number of doses required and incidence of air leaks, was similar. No differences were observed in the incidence of intraventricular haemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia or survival. In conclusion, a simplified surfactant dosing procedure not requiring fractional doses, ventilator disconnection, changes in the baby's position or manual bagging was found to be as effective as bolus delivery. The number of dosing-related transient episodes of hypoxia and bradycardia was not decreased by the slow, 1 min, side-hole instillation procedure.     

High-frequency partial liquid ventilation in respiratory distress syndrome: hemodynamics and gas exchange

Partial liquid ventilation using conventional ventilatory schemes improves lung function in animal models of respiratory failure. We examined the feasibility of high-frequency partial liquid ventilation in the preterm lamb with respiratory distress syndrome and evaluated its effect on pulmonary and systemic hemodynamics. Seventeen lambs were studied in three groups: high-frequency gas ventilation (Gas group), high-frequency partial liquid ventilation (Liquid group), and high-frequency partial liquid ventilation with hypoxia-hypercarbia (Liquid-Hypoxia group). High-frequency partial liquid ventilation increased oxygenation compared with high-frequency gas ventilation over 5 h (arterial oxygen tension 253 +/- 21.3 vs. 17 +/- 1.8 Torr; P < 0.001). Pulmonary vascular resistance decreased 78% (P < 0.001), pulmonary blood flow increased fivefold (P < 0.001), and aortic pressure was maintained (P < 0.01) in the Liquid group, in contrast to progressive hypoxemia, hypercarbia, and shock in the Gas group. Central venous pressure did not change. The Liquid-Hypoxia group was similar to the Gas group. We conclude that high-frequency partial liquid ventilation improves gas exchange and stabilizes pulmonary and systemic hemodynamics compared with high-frequency gas ventilation. The stabilization appears to be due in large part to improvement in gas exchange.     

Severe myelotoxicity of oral etoposide in heavily pretreated patients with non-Hodgkin''s lymphoma or chronic lymphatic leukemia

In this study we aimed to determine the incidence of herpes simplex virus (HSV) in the lungs of burns patients, and its association with the presence of adult respiratory distress syndrome (ARDS) and pneumonia. Haematoxylin and eosin (H&E), and immunohistochemical (IHC) staining for HSV was performed on lung tissue from 54 patients who had died following burn injury and from nine control cases. Polymerase chain reaction (PCR) for HSV deoxyribonucleic acid (DNA) was performed on a subset both of burns cases and controls. No viral inclusions were detected in H&E sections, but 50% of the burns cases were positive for HSV by IHC staining; no control cases were positive. Nuclear and cytoplasmic immunopositivity for HSV was seen in macrophages and epithelial lining cells. HSV was strongly associated with ARDS (p=0.007), but not with pneumonia (p=0.577). The relative risk of HSV infection was higher for cases with ARDS (2.21) than for those with pneumonia (1.26). PCR for HSV DNA was positive in three out of five burns cases, and in one out of five control cases. Immunohistochemical staining is more sensitive for the detection of herpes simplex virus than haematoxylin and eosin staining for detection of viral inclusions. Burns cases have a high incidence of pulmonary herpes simplex virus infection. Polymerase chain reaction results may not be fully representative due to problems of tissue necrosis postmortem. Pulmonary herpes simplex virus is strongly associated with adult respiratory distress syndrome and the two may be causally linked. Early detection and treatment of pulmonary herpes simplex virus in burns patients may reduce pulmonary complications and mortality.     

Pulmonary distribution and efficacy of exogenous surfactant in lung-lavaged rabbits are influenced by the instillation technique

Surfactant bolus instillation has been reported to cause changes in arterial blood pressure (BP) and cerebral blood flow velocities which may increase the risk of intraventricular haemorrhage. To avoid these effects, slow tracheal infusion was evaluated as a possible alternative method of surfactant administration. Saline lung lavages were performed in 13 anesthetized and artificially ventilated adult rabbits to produce respiratory distress syndrome. Curosurf (CS, 200 mg/kg) labeled with 14C-dipalmitoyl-phosphatidylcholine (-DPPC) and/or red microspheres (RMS) was instilled into the trachea either as a single bolus (n = 8) or by infusion during 45 min via a side-channel within the wall of the tracheal tube (n = 5). An arterial cannula was placed for monitoring of blood gases and BP. To determine surfactant distribution, the lungs were cut into 60-70 pieces and radioactivity and/or the number of RMS were measured in each piece. The distribution of RMS was closely related to the distribution of 14C-DPPC (r = 0.96). Bolus instillation of CS led to a prompt and sustained increase in PaO2 (from < 10.5 to > 40 kPa within 2 min), a transient decrease in BP, and a reasonably homogeneous pulmonary surfactant distribution. Tracheal infusion of CS changed neither BP nor PaO2 during the observation period of 60 min. The pulmonary distribution of CS was extremely uneven after infusion. The distribution of exogenous surfactant and its effects on gas exchange are influenced by the instillation method. An inadequate instillation technique may add to the causes of "poor response" after surfactant replacement.     

Pulmonary follow-up 2.5 years after a randomized, controlled, multiple dose bovine surfactant study of preterm newborn infants

Forty-seven preterm infants, who were previously enrolled in a prospective, randomized, blinded study at birth to assess the effects of multiple doses of exogenous bovine surfactant to prevent respiratory distress syndrome, underwent lung function evaluation and review of their medical histories at 2 1/2 years of age. During their initial hospitalization there were no differences between the 17 control infants and the 30 surfactant-treated infants in the duration of ventilator or oxygen therapy and the incidence of bronchopulmonary dysplasia. At the follow-up both groups were similar in chronological and corrected ages, weights, lengths, and sex ratios and there were no differences in the occurrence of allergy, asthma, bronchiolitis, eczema, pneumonia, and wheezing. In addition, there was no significant difference regarding the incidence of chest illnesses lasting either 3 or 7 days and in the total number of required rehospitalizations. Functional residual capacity (FRC), tidal volume (VT/kg), compliance (Crs/kg), resistance (Rrs), and time constant of the respiratory system were not significantly different between the two groups at 2 1/2 years of age. We conclude that bovine surfactant, when given during the neonatal period, has little long-term effect on lung function. Neonatal bovine surfactant therapy neither improves nor produces any adverse effects on the developing respiratory system.     

Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction

A 66-year old man was admitted to our hospital because of vomiting, diarrhea and progressive dyspnea. Acute respiratory distress syndrome (ARDS) due to bilateral pneumonia was diagnosed and he was also in septic shock. The patient had a history of partial hepatectomy for hepatoma, and suffered from liver cirrhosis. Emergency bronchoalveolar lavage (BAL) revealed abundant gram-positive cocci and polymorphonuclear leukocytes in the collected sample. Blood culture revealed corynebacterium. Treatment consisted of mechanical ventilation and administration of fluids, effective antibiotics, and high-dose methylprednisolone (MPS). MPS was administered from the onset of ARDS with a starting dose of 1,000 mg, which was gradually reduced to 60 mg over 8 days. Pulmonary infiltrates shown on the chest X-ray film were alleviated, and arterial blood gas data rapidly improved. The patient was successfully extubated on the 10th hospital day, and discharged on the 30th hospital day. Serial BAL and plasma levels of inflammatory cytokines decreased rapidly in parallel with the improvement of the patient's clinical condition. This is a case report of severe bacterial pneumonia that was successfully treated with effective antibiotics and high-dose MPS for several days from the onset of ARDS.     

Acute effects of inhaled nitric oxide in adult respiratory distress syndrome

This study evaluated the dose-response effect of inhaled nitric oxide (NO) on gas exchange, haemodynamics, and respiratory mechanics in patients with adult respiratory distress syndrome (ARDS). Of 19 consecutive ARDS patients on mechanical ventilation, eight (42%) responded to a test of 10 parts per million (ppm) NO inhalation with a 25% increase in arterial oxygen tension (Pa,O2,) over the baseline value. The eight NO-responders were extensively studied during administration of seven inhaled NO doses: 0.5, 1, 5, 10, 20, 50 and 100 ppm. Pulmonary pressure and pulmonary vascular resistance exhibited a dose-dependent decrease at NO doses of 0.5-5 ppm, with a plateau at higher doses. At all doses, inhaled NO improved O2 exchange via a reduction in venous admixture. On average, the increase in Pa,O2, was maximal at 5 ppm NO. Some patients, however, exhibited maximal improvement in Pa,O2 at 100 ppm NO. In all patients, the increase in arterial O2 content was maximal at 5 ppm NO. The lack of further increase in arterial O2 content above 5 ppm partly depended on an NO-induced increase in methaemoglobin. Respiratory mechanics were not affected by NO inhalation. In conclusion, NO doses < or =5 ppm are effective for optimal treatment both of hypoxaemia and of pulmonary hypertension in adult respiratory distress syndrome. Although NO doses as high as 100 ppm may further increase arterial oxygen tension, this effect may not lead to an improvement in arterial O2 content, due to the NO-induced increase in methaemoglobin. It is important to consider the effect of NO not only on arterial oxygen tension, but also on arterial O2 content for correct management of inhaled nitric oxide therapy.     

Surfactant proteins A and D: disease markers

The abundant and restricted expression of surfactant proteins SP-A and SP-D within the lung makes these collectins specific markers for lung diseases. The measurement of SP-A and SP-D in amniotic fluids and tracheal aspirates reflects lung maturity and the production level of the lung surfactant in infants with respiratory distress syndrome (RDS). The SP-A concentrations in bronchoalveolar lavage (BAL) fluids are significantly decreased in patients with acute respiratory distress syndrome (ARDS) and also in patients at risk to develop ARDS. The prominent increase of these proteins in BAL fluids and sputum is diagnostic for pulmonary alveolar proteinosis (PAP). The concentrations of SP-A and SP-D in BAL fluids from patients with idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with collagen vascular diseases (IPCD) are rather lower than those in healthy controls and the SP-A/phospholipid ratio may be a useful marker of survival prediction. SP-A and SP-D appear in the circulation in specific lung diseases. Their serum concentrations significantly increase in patients with PAP, IPF and IPCD. The successive monitoring of serum levels of SP-A and SP-D may predict the disease activity. The serum SP-A levels increase in patients with ARDS. SP-A is also a marker for lung adenocarcinomas and can be used to differentiate lung adenocarcinomas from other types and metastatic cancers from other origins, and to detect metastasis of lung adenocarcinomas.     

Liver fibrosis

Surfactant abnormalities may contribute to the impairment of gas exchange observed in Pneumocystis carinii pneumonia. Analysis of rat bronchoalveolar lavage (BAL) lipid extracts from normal controls, steroid controls, trimethaprim-sulfamethoxazole (TMP-SMX) controls, TMP-SMX/P. carinii pneumonia controls, and P. carinii pneumonia animals reveal similar total phospholipid and total protein levels. However, there was a marked reduction in phosphatidylglycerol (PG) from the BAL of P. carinii pneumonia rats as compared with control animals, with a decrease from 4.91 +/- 1.29 nmol/mg protein to 0.46 +/- 0.57 nmol/mg protein (p<0.05) and a decrease, as a percent of total phospholipids, from 7.7% +/- 0.88% to 0.91% +/- 0.59% (p<0.001). Furthermore, in vitro surface activities of BAL lipid extracts from control and P. carinii pneumonia rats revealed minimum surface tension increases from 9.38 +/- 1.71 mN/m in controls to 16.36 +/- 0.83 mN/m in P. carinii pneumonia rats (p<0.05) and likewise maximum surface tension increases from 22.14 +/- 4.34 mN/m to 38.57 +/- 2.07 mN/m (p<0.01). Of interest, the surface activity of PG-deficient P. carinii pneumonia BAL lipid extracts is completely restored to that of normal controls by the addition of exogenous PG. These findings suggest that a functionally abnormal surfactant occurs in P. carinii pneumonia and that this may account, in part, for the impairment of gas exchange observed in this disorder.     

The pulmonary surfactant system: physiology, pathologies associated with its alteration and exogenous administration as therapeutic and diagnostic agent]

Pulmonary surfactant is a lipoproteic mixture synthesized and secreted by alveolar type II cells. Its principal property is to reduce the surface tension by lining on the alveolar surface. Surfactant deficiency is the major factor responsible for the respiratory distress syndrome of the newborn (RDS) and the adult respiratory distress syndrome (ARDS). Since 1980, the exogenous administration of surfactant for the treatment of these syndromes is being studied. In this work the exogenous surfactant preparations, the delivery techniques and the dosing schedule is discussed. The utilization of the exogenous natural surfactant (ENS) as precursor of a radiopharmaceutical labeled with 99mTc (99mTc-ENS) for aerial lung scintigraphy is also discussed.     

Lipoleiomyosarcoma of the mediastinum

Two infants presenting with respiratory distress in the first 24 h of life are described. Both patients underwent extensive investigation before the diagnosis of surfactant protein B-deficiency was reached. Both children died within 2 months of birth. Parental consanguinity was known to be a feature in the first case, who proved to have a previously unrecognized mutation of the surfactant protein B gene. In the second case, a history of parental consanguinity was not sought from the Caucasian family, but was later volunteered by the parents themselves. Case 2 proved to have the "common" surfactant protein B-deficient genotype. The key to diagnosis is having a high index of suspicion in any term or near-term newborn with severe respiratory distress; parental consanguinity must be excluded. Surfactant protein B-deficiency can be readily diagnosed from bronchoalveolar lavage specimens; a simple, inexpensive procedure which is well tolerated in newborns.