The function of surfactant is impaired during the reimplantation response in rat lung transplants.

In this study we investigated the surfactant function in rat lung transplants at the peak of the reimplantation response in experimental groups with increasing warm ischemic times of the lung transplant. The left and right lungs in five groups of rats were assessed 24 hours after left lung transplantation: rats receiving transplants with lung graft ischemic times of 60 (n = 4), 90 (n = 5), and 120 (n = 5) minutes, donor rats with 120 minutes lung ischemia (n = 5) and normal (nonoperated) rats (n = 6). The reimplantation response was assessed by the ventilation score on chest roentgenograms, measurement of the static lung compliance, and the (serum) protein concentration in the bronchoalveolar lavage fluid. Surfactant in the bronchoalveolar lavage fluid was assessed by measuring the amount and the composition of surfactant phospholipids and the in vitro surfactant function in a pulsating bubble surfactometer. We found that longer ischemic times caused a more severe reimplantation response in the left lung grafts. Although the ventilation scores were equally low in the 60-, 90-, and 120-minute ischemia groups, the lung compliances decreased and the (serum) protein concentrations increased stepwise in correlation with longer ischemic times. The amount of surfactant phospholipids during the reimplantation response was not changed, but the percentage phosphatidyl choline decreased progressively in parallel with the severity of the reimplantation response. Finally, the in vitro function of surfactant from the lung transplants decreased in parallel with the prolongation of the ischemic time, whereas the function of surfactant from donor lungs with 120 minutes of ischemia and from native right lungs was not changed. We conclude that the surfactant function is impaired during the reimplantation response as a result of a high concentration of inhibiting serum proteins and a low percentage of phosphatidyl choline.

Surfactant treatments alter endogenous surfactant metabolism in rabbit lungs.

The effect of exogenous surfactant on endogenous surfactant metabolism was evaluated using a single-lobe treatment strategy to compare effects of treated with untreated lung within the same rabbit. Natural rabbit surfactant, Survanta, or 0.45% NaCl was injected into the left main stem bronchus by use of a Swan-Ganz catheter. Radio-labeled palmitic acid was then given by intravascular injection at two times after surfactant treatment, and the ratios of label incorporation and secretion in the left lower lobe to label incorporation and secretion in the right lung were compared. The treatment procedure resulted in a reasonably uniform surfactant distribution and did not disrupt lobar pulmonary blood flow. Natural rabbit surfactant increased incorporation of palmitate into saturated phosphatidylcholine (Sat PC) approximately 2-fold (P less than 0.01), and secretion of labeled Sat PC increased approximately 2.5-fold in the surfactant-treated left lower lobe relative to the right lung (P less than 0.01). Although Survanta did not alter incorporation, it did increase secretion but not to the same extent as rabbit surfactant (P less than 0.01). Alteration of endogenous surfactant Sat PC metabolism in vivo by surfactant treatments was different from that which would have been predicted by previous in vitro studies.

Transcutaneous PO2 and PCO2 during surfactant therapy in newborn infants with idiopathic respiratory distress syndrome.

We conclude that surfactant treatment in newborn infants with IRDS results in decrease in TcPO2 and an increase in TcPO2 within minutes. The surfactant treatment procedure used in this study was not associated with hypoxemia. During surfactant treatment monitoring of TcPO2 and TcPCO2 is absolutely necessary.

Reduction in adverse effects of mechanical ventilation in rabbits with acute respiratory failure by treatment with extracorporeal CO2 removal and a large fluid volume of diluted surfactant.

The long-term outcome of infants with severe respiratory distress syndrome can be improved by optimizing surfactant therapy and minimizing the risk for pulmonary barovolutrauma and oxygen toxicity. The authors hypothesized that this may be achieved with low frequency ventilation and extracorporeal CO2 removal (LFV-ECCO2R), in combination with intratracheal instillation of a large fluid volume with diluted surfactant. Lung lavaged rabbits were initially ventilated with continuous positive pressure ventilation. The rabbits were randomized to treatment with LFV-ECCO2R and surfactant (experimental group), or surfactant only (control group). In the experimental group, the rabbits were treated with a large volume (16 ml/kg) of diluted surfactant (6.25 mg/ml) at a dose of 100 mg/kg body weight. After surfactant therapy, the FiO2 100% was gradually decreased. During 4 hours, the extracorporeal bloodflow was adjusted to maintain the PaCO2 between 4.0-6.0 kPa. Thereafter, the rabbits were allowed to breathe spontaneously with 2.5 cm H2O continuous positive airway pressure ventilation (CPAP) and 40% oxygen. In the control group, the rabbits received the same surfactant therapy. During the study period, the rabbits remained ventilated with an inspiratory oxygen concentration (FiO2) of 100% for 4 hours. The ventilator flow was adjusted to maintain the PaCO2 between 4.0 and 6.0 kPa. Thereafter, positive-end expiratory pressure was decreased to 2.5 cm H2O and FiO2 was gradually decreased to 40%. In the experimental group, FiO2 was decreased to 40% in a stepwise fashion whereby the PaO2 could be maintained easily within the normal range. Extracorporeal flow rates during perfusion ranged from 20-35 ml/kg/min and were sufficient to keep the PaCO2 and pH within normal limits. After 4 hours, the rabbits could breathe spontaneously with CPAP and 40% oxygen, while normal blood gas values were maintained. All rabbits survived the experiment. In the control group, all rabbits experienced severe hypoxemia, despite FiO2 of 100% oxygen and, during the course of weaning, all rabbits died because of hypoxia. In conclusion, the present study demonstrated that barovolutrauma due to mechanical ventilation, and oxygen toxicity due to high FiO2, can be minimized in an animal model of acute respiratory failure by the combination of LFV-ECCO2R and surfactant therapy.

Large volume instillation of surfactant during extracorporeal life support improves lung function in lung lavaged rabbits.

The sometimes limited effect of surfactant therapy in neonates might be explained in part by an non homogeneous distribution of the surfactant after endotracheal instillation. This distribution can be improved significantly by increasing the fluid volume. The aim of this study was to evaluate the effect of two methods for gas exchange during a large volume instillation of surfactant on the outcome of this treatment in lung lavaged rabbits. In the control group (n = 6) gas exchange was maintained with continuous positive pressure ventilation (CV), whereas in the other group gas exchange was established with extracorporeal life support (ECLS) (n = 6) and intermittent sighs. Five hours after surfactant administration, an identical weaning procedure was started in both groups. The authors found significantly higher PaO2 values in the ECLS group than in the control group in the normocarbia state. All animals in the ECLS group could be weaned to room air maintaining normal blood gases, whereas all the animals in the control group died in the course of weaning. The ventilator efficiency index was significantly higher during the weaning period in the ECLS group, indicating better lung function, than in the control group. The authors conclude that a large volume instillation of surfactant is feasible by applying ECLS and intermittent sighs. Additional studies are needed to elucidate if this combined treatment will be an improvement over current surfactant therapy.

Risk of otitis externa after swimming in recreational fresh water lakes containing Pseudomonas aeruginosa.

OBJECTIVE: To determine whether an outbreak of otitis externa was due to bathing in recreational fresh water lakes and to establish whether the outbreak was caused by Pseudomonas aeruginosa in the water. DESIGN: Matched case-control study. SETTING: The Achterhoek area, the Netherlands. SUBJECTS: 98 cases with otitis externa and 149 controls matched for age, sex, and place of residence. MAIN OUTCOME MEASURES: Odds ratios for type of swimming water and frequency of swimming; presence of P aeruginosa in ear swabs and fresh water lakes. RESULTS: Otitis externa was strongly associated with swimming in recreational fresh water lakes in the previous two weeks (odds ratio 15.5 (95% confidence interval) 4.9 to 49.2) compared with non-swimming). The risk increased with the number of days of swimming, and subjects with recurrent ear disease had a greatly increased risk. The lakes met the Dutch bathing water standards and those set by the European Commission for faecal pollution in the summer of 1994, but P aeruginosa was isolated from all of them, as well as from the ear swabs of 78 (83%) of the cases and 3 (4%) of the controls. CONCLUSIONS: Even when current bathing water standards are met, swimming can be associated with a substantial risk of otitis externa because of exposure to P aeruginosa. People with recurrent ear disease should take special care when swimming in waters containing P aeruginosa.

Surfactant nebulization versus instillation during high frequency ventilation in surfactant-deficient rabbits.

Surfactant nebulization improves lung function at low alveolar doses of surfactant. However, efficiency of nebulization is low, and lung deposition seems to depend on lung aeration. High frequency ventilation (HFV) has been shown to improve lung aeration. We hypothesize that the combination of HFV and surfactant nebulization may benefit lung deposition of surfactant and consequently, lung function. The aim of this study was to compare the effect of surfactant nebulization versus instillation during HFV on lung function, surfactant distribution, and cerebral blood flow. Therefore, severe respiratory failure was induced by lung lavages in 18 rabbits. HFV was applied: frequency = 8 Hz, mean airway pressure = 12 cm H2O, amplitude = 100%, fraction of inspired O2 = 1.0. Technetium-99m-labeled surfactant (Alveofact, 100 mg/kg of BW) was nebulized or instilled (n = 6 each). Six other rabbits did not receive surfactant (control, HFV only). We found that after instillation partial arterial O2 tension increased from 7.0 kPa (95% confidence interval, 6.3-8.0 kPa) to 34 kPa (16-51 kPa), and during nebulization from 7.0 kPa (6.0-9.0 kPa) to 46 kPa (27-58 kPa). Partial arterial CO2 tension decreased after instillation from 6.1 kPa (5.3-7.1 kPa) to 4.8 kPa (3.9-5.6 kPa), and during nebulization, after an initial rise, it decreased from 6.3 kPa (5.3-7.4 kPa) to 4.9 kPa (4.4-5.6 kPa). Both treatments resulted in nonuniform distribution. Surfactant deposition after nebulization was 9.8%. Instillation resulted in a drop of mean arterial blood pressure of 17% (8-31%), and an even more pronounced drop in cerebral blood flow of 39% (18-57%). Nebulization did not affect blood pressure. Cerebral blood flow decreased with a maximum of 27% (10-37%). We conclude that surfactant nebulization during HFV improves lung function in rabbits with severe respiratory failure, without improving distribution, but with less effects on blood pressure and cerebral blood flow, when compared with surfactant instillation.

A comparison of the hemodynamic and respiratory effects of surfactant instillation during interrupted ventilation versus noninterrupted ventilation in rabbits with severe respiratory failure.

The purpose of this study was to evaluate whether avoiding interruption of ventilation during surfactant instillation improves the effects on lung function and surfactant distribution and whether it prevents the adverse effects on blood pressure and cerebral blood flow. The study was performed using rabbits with severe respiratory failure induced by lung lavages. These rabbits were randomized to 99mTc-Nanocoll labeled surfactant instillation through a side lumen of the endotracheal tube without interrupting ventilation or instillation during a short interruption of ventilation. After surfactant instillation with interruption of ventilation, PaO2 rose from 8.7+/-1.3 to 24.9+/-6.4 kPa (mean+/-SEM). Without interruption, PaO2 rose from 8.4+/-0.8 to 32.4+/-4.3 kPa. PaCO2 decreased with interruption from 4.69+/-0.51 to 3.61+/-0.26 kPa and without interruption from 5.06+/-0.41 to 4.13+/-0.23 kPa. Dynamic and static compliance indices were not statistically different after both procedures. Surfactant distribution tended to be less nonuniform after instillation without interrupting ventilation. In contrast, avoidance of interruption of ventilation resulted in less uniform lobar distribution and less peripheral deposition of surfactant. By instillation with interruption, blood pressure increased quickly (28+/-6.6%), followed by a 22+/-5.3% decrease. Blood pressure increased quickly (16+/-4.2%), followed by a 40+/-10% decrease by surfactant instillation without interruption. Cerebral blood flow, measured by an ultrasonic transit time flow probe on the carotid artery, increased quickly (45+/-14%), followed by a 64+/-11% decrease with interruption, whereas it increased 15+/-4.9% (p = 0.06 versus with interruption) and decreased 61+/-13% without interruption of ventilation. Therefore, avoiding interruption of ventilation during surfactant instillation tends to prevent the potential adverse effects of a rapid rise in cerebral blood flow, and furthermore, tends to improve uniformity of surfactant distribution, whereas having no detrimental effect on respiratory function.

Surfactant replacement therapy in surfactant-deficient rabbits: early effects on lung function and biochemical aspects.

Lung-surfactant-deficient rabbits (n = 6) requiring artificial ventilation were subjected to a weaning-off regimen following surfactant replacement therapy. Surfactant-deficient rabbits (n = 6) that did not receive surfactant but underwent the same procedure served as controls. All surfactant-treated rabbits survived (i.e., reestablished spontaneous air breathing) whereas all the control animals died. In the surfactant-treated animals lung function improved in such a way that during the weaning period PaCO2 did not increase and the level of PaO2 remained significantly higher than in the control animals. The static lung compliance and the stability and expansion indices in vitro were significantly higher in the surfactant-treated rabbits. The lamellar body fraction of the lungs of surfactant-treated animals contained a significantly higher amount of surfactant phospholipids than those of the control animals. It is concluded that the animal model used in this study is an excellent tool for testing early effects of different surfactant preparations.

Number and activation of circulating polymorphonuclear leukocytes and platelets are associated with neonatal respiratory distress syndrome severity.

OBJECTIVE: To determine whether number and activation of circulating polymorphonuclear leukocytes (PMNs) and platelets are associated with disease severity in neonatal respiratory distress syndrome (RDS). DESIGN: Prospective study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: Preterm infants with severe (n = 18) or mild to moderate (n = 18) RDS who were consecutively admitted. INTERVENTIONS: PMN and platelet counts and plasma concentrations of elastase-alpha1-proteinase inhibitor (E-alpha1-PI) and thromboxane B2 (TxB2) were recorded each day during the first 5 days of life. E-alpha1-PI-to-PMN and TxB2-to-platelet ratios were calculated to correct for the influence of the PMN and platelet count on elastase and thromboxane release. RESULTS: From day 2, the severe RDS group had lower median PMN counts (1.5 vs 4.5 x 10/L), lower mean platelet counts (136 vs 230 x 10/L), and more elastase and thromboxane release, indicated by higher median E-alpha1-PI-to-PMN (39.2 vs 13.0 ng/10 PMNs on day 2) and TxB2-to-platelet (2.61 vs 0.52 pg/10 platelets on day 3) ratios than the mild-to-moderate group. Lower PMN and platelet counts and higher elastase and thromboxane release were correlated with birth asphyxia (lower 5-minute Apgar scores and umbilical arterial PH values), higher respiratory requirements (fraction of inspired oxygen and peak inspiratory pressure), and decreased values for continuous measures of RDS severity (ventilatory efficiency index and PaO2-to-alveolar oxygen tension ratio). CONCLUSION: Decreased PMN and platelet counts and increased elastase and thromboxane release are correlated with increased RDS severity. Birth asphyxia (hypoxia and acidosis) and tissue injury caused by high-pressure ventilation and hyperoxia may promote this activation process.

Distribution of a second dose of exogenous surfactant in rabbits with severe respiratory failure.

Newborn infants with respiratory distress who fail to respond to surfactant treatment receive a second dose of surfactant. The effect of this strategy on the distribution of surfactant to the lung is unknown. We therefore investigated the distribution of the first (100 mg/kg body weight) and second dose (50 mg/kg body weight) of surfactant (Alveofact) in lung-lavaged rabbits (n = 6). We used 141Ce- and 103Rn-labeled microspheres that were mixed with the first and second dose of surfactant, respectively. Arterial PO2 increased from 5.7 +/- 1.1 to 10.6 +/- 2.0 kPa (p < 0.05) (mean +/- SD) after the first and from 20.1 +/- 3.8 to 30.1 +/- 2.5 kPa (p < 0.05) after the second dose. Thereafter the rabbits were killed, and the lungs were cut into 200 pieces. The radioactivity of Ce and Rn microspheres was measured and distribution histograms were obtained. Histograms of the first, second, and the total dose of surfactant showed similar nonuniform distribution. Correlation coefficients of the Ce and Rn radioactivity in the different lung lobes widely ranged per lung lobe per rabbit. In addition, the percentage of the number of lung pieces that received an amount of surfactant that was less than the calculated endogenous surfactant pool decreased from 12.5 +/- 3.2% to 8.5 +/- 3.0% (p < 0.05) after the first and second dose, respectively. This indicates that the second dose was directed both to areas that initially received surfactant and to areas that were still surfactant-deficient. The surfactant-deficient areas were aerated after this second dose, resulting in a further rise in PO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Disease severity is correlated with plasma clotting and fibrinolytic and kinin-kallikrein activity in neonatal respiratory distress syndrome.

This study was undertaken to determine whether simultaneous activation of clotting, fibrinolysis, and kinin-kallikrein is associated with disease severity in preterm infants with neonatal respiratory distress syndrome (RDS), during the first 5 d of life. In the infants with severe RDS, we found activation of clotting, fibrinolysis, and kinin-kallikrein within 6-12 h of birth, indicated by increased thrombin-antithrombin III complex formation [22.5 ng/ml versus 1.4 ng/ml (median values) in the mild/moderate RDS infants, p < 0.001], increased tissue-type plasminogen activator plasma concentrations [5.1 ng/ml versus 2.6 ng/ml (median values) in the mild/moderate RDS infants, p < 0.01], and increased plasma kallikrein activity [198% versus 189% of maximal activated human plasma (median values) in the mild/ moderate infants, p < 0.01], respectively. Thrombin generation, tissue-type plasminogen activator release, and kallikrein activity did not change significantly in the severe RDS group throughout the study. In these infants, kallikrein activity was accompanied by lower values of plasma kallikrein inhibitory activity. Activation of clotting, fibrinolysis, and kinin-kallikrein was accompanied with a transient decrease of the neutrophil count and a steady decrease of the platelet count in the severe RDS group. The studied parameters of clotting and fibrinolytic and kinin-kallikrein activation were significantly correlated with continuous measures of RDS severity. We, therefore, suggest that this activation process likely contributes to respiratory insufficiency in neonatal RDS.

Leakage of protein into lungs of preterm ventilated rabbits is correlated with activation of clotting, complement, and polymorphonuclear leukocytes in plasma.

We investigated whether leakage of protein in lungs of preterm ventilated rabbits of 28- and 29-d gestational age is correlated with activation of clotting, complement, and polymorphonuclear leukocytes (PMN) in plasma. We found signs of systemic activation of clotting, complement and PMN in ventilated 28-d gestational age rabbits, as indicated, respectively, by increased median plasma fibrin monomer concentrations (83 versus 40% of normal adult rabbit plasma in nonventilated 28-d gestational age rabbits, p < 0.01), decreased median plasma CH50 activity (112 versus 122 U/L in nonventilated 28-d gestational age rabbits, p < 0.05), and increased median plasma beta-glucuronidase concentrations (159 versus 97% of maximal activated adult rabbit plasma in nonventilated 28-d gestational age rabbits p < 0.05). We did not find signs of systemic activation in the ventilated 29-d gestational age group. Higher median total protein concentrations in alveolar wash of the ventilated 28-d gestational age rabbits (2.7 versus 1.3 mg/mL in the nonventilated rabbits. p < 0.01) indicated protein leakage into the lungs, and this protein leakage was more pronounced in the lungs of ventilated 28-d gestational age rabbits than in those of ventilated 29-d gestational age rabbits (2.1 mg/mL, p < 0.01). The total protein concentration in the alveolar wash of all 28-d gestational age rabbits was correlated with the concentration of fibrin monomers (p = 0.51, p = 0.035) and beta-glucuronidase (p = 0.61, p = 0.011), and the CH50 activity (p = -0.73, p = 0.002) in plasma. We conclude that leakage of protein in lungs of preterm ventilated rabbits of 28-d gestational age is correlated with activation of clotting, complement, and PMN in plasma. This activation process may contribute to lung injury by intravascular and intraalveolar deposition of fibrin and formation of proteinaceous edema.

Dose response of thyrotropin-releasing hormone on pulmonary maturation in corticosteroid-treated preterm rabbits.

The dose-response effect of thyrotropin-releasing hormone in enhancing pulmonary maturation was investigated with six dosing regimens. Pregnant does received thyrotropin-releasing hormone (5, 10, or 50 micrograms/kg every 12 hours for four doses or one dose of 20 micrograms/kg) in conjunction with betamethasone beginning on day 25 of gestation, with betamethasone alone or saline solution used as comparison treatment groups. Half of the newborn rabbits received supplemental surfactant therapy after delivery on day 27, and all were ventilated on a ventilator plethysmography system for 30 minutes. There were no differences among the four thyrotropin-releasing hormone doses in surfactant pool sizes, compliances, or proteins leak into or out of the air spaces. The groups that received multiple doses of thyrotropin-releasing hormone had significantly higher perinatal loss rates than the single-dose group. The lungs of the group treated with thyrotropin-releasing hormone plus steroid and the rabbits treated only with steroid were more compliant than the controls without surfactant therapy, and showed significant improvements in protein leak. The addition of thyrotropin-releasing hormone to betamethasone improved several of the protein leak measurements compared with use of betamethasone alone. These results question the necessity of multiple doses of thyrotropin-releasing hormone to induce pulmonary maturation, especially when the higher perinatal mortality and the theoretical long-term effects of fetal hyperthyroidism on thyroid axis function are considered.

Fatal ureaplasmal pneumonia and sepsis in a newborn infant.

Ureaplasma urealyticum was isolated in pure culture from blood tracheal aspirate and lung tissue in a newborn infant, who died of a severe pneumonia within 48 h after birth. The clinical course was characterized by persistent pulmonary hypertension of the newborn (PPHN). Post-mortem examination revealed extensive hyaline membrane formation combined with signs of inflammation in both lungs. The clinical and histopathological picture resembled that of early onset group B haemolytic streptococcal pneumonia/sepsis.

Atypical cellulitis due to group B streptococcus.

In a minority of late-onset Group B streptococcal (GBS) cases in neonates, facial or buccal cellulitis has been described. We report a case of sepsis with GBS, in which an atypical cellulitis in the inguinal area was seen as presenting symptom.

Activation of the plasma clotting, fibrinolytic, and kinin-kallikrein system in preterm infants with severe idiopathic respiratory distress syndrome.

We studied the activation pattern of clotting, fibrinolysis, and kinin-kallikrein during the first 5 d of life in 10 preterm infants with signs of severe idiopathic respiratory distress syndrome (IRDS) after birth (IRDS group) and in 12 healthy preterm infants (reference group). We found systemic activation of clotting, fibrinolysis, and kinin-kallikrein in the IRDS infants within 12 to 24 h of birth, represented by increased median thrombin-antithrombin III complex formation (90 ng/mL versus 10 ng/mL in the reference group, p < 0.05), increased mean tissue-type plasminogen activator plasma concentrations (11.8 ng/mL versus 3.5 ng/mL in the reference group, p < 0.05), and increased mean plasma kallikrein activity (182.6% versus 162.0% of maximal activated human plasma in the reference group, p < 0.05), respectively. Clotting activation was accompanied by a significant decrease of the platelet count. Clotting and fibrinolytic activity decreased in the IRDS group during the first 2 to 3 d of life. Kinin-kallikrein activation was accompanied by decreased plasma kallikrein inhibitor activity values and did not change throughout the study period. Plasma factor XII activity was not significantly increased in the IRDS infants during the first 2 d of life but did significantly increase thereafter. The cause of simultaneous activation of clotting, fibrinolysis, and kinin-kallikrein in our IRDS infants has not yet been clarified. However, this activation process may contribute to lung injury such as that described in the adult respiratory distress syndrome.

Increased tissue-type plasminogen activator antigen release is not accompanied by increased systemic fibrinolytic activity in severe neonatal respiratory distress syndrome.

Intravascular and intraalveolar fibrin depositions in preterm infants with severe respiratory distress syndrome (RDS) have been attributed to activation of clotting. We questioned whether in the face of activated clotting, fibrinolysis is sufficient in these infants. We found, in infants with severe RDS within 6 to 12 h of birth, increased median thrombin-antithrombin III complex formation (11.1 versus 1.3 ng/mL in the group with mild-to-moderate RDS, p < 0.001), indicating activation of clotting. Simultaneously, we found increased tissue-type plasminogen activator antigen (t-PA) release in plasma of these infants represented by increased median t-PA plasma concentrations (8.3 versus 2.5 ng/mL in the group with mild-to-moderate RDS, p < 0.01). This increased t-PA release was not accompanied with more plasminogen and antiplasmin consumption and with more fibrin and fibrinogen degradation than in the infants with mild-to-moderate RDS because plasma plasminogen and antiplasmin activity and total fibrin and fibrinogen degradation product concentrations were similar in both groups. We have found that activated clotting and t-PA plasma concentrations are positively correlated with arterial-to-alveolar oxygen tension ratio and ventilator efficiency index values. Plasminogen and antiplasmin activity, and total fibrin and fibrinogen degradation product concentrations were not correlated with these continuous measures of RDS severity. In neonatal RDS, clotting activity contributes to disease severity. Insufficient fibrinolysis likely facilitates the deleterious effects of activated clotting.

Transcutaneous respiratory electromyographic monitoring.

The integrated diaphragm electromyogram (EMG) signal reflects function from the inspiratory centers to the neuromuscular junction. The feasibility and potential value of transcutaneous diaphragm electromyography (tcEMG) was confirmed in a group of infants using two prototype respiratory EMG monitors. Infants were monitored continuously for periods ranging from hours to days. One hundred were monitored for clinical reasons, looking for disordered respiratory behavior, while 47 were studied for technical/experimental reasons. Reliable measurements of diaphragm EMG activity were obtained, provided fully shielded electrode cables were used. Measurements in 28 ventilated infants and one adult confirmed that, unlike impedance and other non-electrophysiologic measures, tcEMG monitoring is not contaminated by ventilator-induced respiratory movements. The potential value of tcEMG monitoring in ventilated subjects is exemplified by illustrations of: diaphragmatic inactivity from phrenic nerve injury, inadequate central drive, and neuromuscular block; augmented expiratory muscle activity; and progressive increase in inspiratory diaphragmatic activity in the presence of a tension pneumothorax. TcEMG monitoring should prove a worthwhile addition to the available noninvasive respiratory monitoring techniques.