Do cardiac output and serum lactate levels indicate blood transfusion requirements in anemia of prematurity?

BACKGROUND: Whether and when to transfuse in anemia of prematurity is highly controversial. Some authors suggest transfusions simply if the hemoglobin (Hb) level is below a defined normal range. Others propose the use of clinical or laboratory parameters in anemic patients to decide whether to transfuse or not. HYPOTHESIS: A decreasing amount of circulating Hb should cause a compensatory increase in cardiac output (CO) and an increase in arterial serum lactate. MATERIALS AND METHODS: In 56 anemic preterm infants (not in respiratory or hemodynamic failure) we analyzed CO after the first week of life using a Doppler sonographic method. At the same time serum lactate levels, Hb levels and oxygen saturation were registered. Nineteen of these patients were given transfusion when they demonstrated clinical signs of anemia by tachycardia > 180/min, tachypnea, retractions, apneas and centralization (group 2). The remaining 37 patients were not transfused (group 1). Serum lactate, CO, heart rate (HR), oxygen delivery, respiratory rate, capillary refill and Hb were analyzed in both groups and in group 2 before and 12-24 h after transfusion. Data between groups 1 and 2 and in group 2 before and after transfusion were compared. RESULTS: In the 56 patients studied no linear correlation between Hb and CO or between Hb and serum lactate was found. Nor could any correlation be demonstrated between the other variables studied. Examining the subgroups separately, a negative linear correlation was demonstrated between serum lactate and oxygen delivery in group 2. No other significant correlations were detected. However, when the pre- and post-transfusion data were compared in group 2 (increase of Hb from 9.45 (SD 3.44) to 12.5 (SD 3.8) g/100 ml), the CO decreased from 281.3 (SD 162.6) to 224 (SD 95.7) ml/kg per min (p < 0.01) and serum lactate decreased significantly from 3.23 mmol/l (SD 2.07) before to 1.71 (SD 0.83) after transfusion. Oxygen delivery was 35.8 (+/- 0.19) ml/kg per min group 1, 27.8 (+/- 0.05) pre- and 43.4 (+/- 0.07) post-transfusion in group 2 (p < 0.01). CONCLUSIONS: CO measurements and serum lactate levels add little information to the decision-making process for blood transfusions, as neither CO nor serum lactate levels correlate with HB levels in an otherwise asymptomatic population of preterm infants. In infants where the indication for blood transfusion is made based on traditionally accepted clinical criteria, serum lactate is an additional laboratory indicator of impaired oxygenation, as it correlates significantly with oxygen delivery. A significant lower oxygen delivery in patients in whom blood transfusion is indicated and an increase in oxygen induced by transfusion demonstrate the value of these criteria in identifying preterm infants who benefit from transfusion.

Elastase alpha 1-proteinase inhibitor and lactoferrin concentrations in endotracheal aspirates of ventilated newborns.

Bacterial colonization of the tracheo-bronchial tree is common and an established risk factor for infection in ventilated newborns. Elastase, a highly active proteinase, and lactoferrin, an iron-binding protein and potential modulator of the inflammatory process, are both major constituents of either azurophilic or primary granules of neutrophilic granulocytes, released by activation of these cells during the inflammatory response. Since both elastase, complexed with its major inhibitor alpha 1-proteinase inhibitor (E alpha 1-Pl), and lactoferrin (Lf) are indicators of granulocyte activation during bacterial infection, they may indicate infectious inflammation at the tracheobronchial site. To study whether these substances in a single suction probe may serve this purpose, we obtained 82 tracheo-bronchial aspirates routinely from 16 ventilated newborns with a median gestational age of 31.5 (range, 25-39) weeks for laboratory analysis and bacterial cultures. Systemic inflammatory response by differential white blood cell count and C-reactive protein (CRP) was monitored simultaneously. The median E alpha 1-Pl level was significantly elevated in culture-positive aspirates (1,005 micrograms/L; range, less than 30-29,240 micrograms/L) in contrast to culture-negative samples (158 micrograms/L; range, less than 30-1,408 micrograms/L). In addition to a diagnostic sensitivity of 77%, E alpha 1-Pl offered a high specificity of 88%, a positive predictive value of 97%, and a negative predictive value of 73%. In contrast, median Lf concentration (10.6; range, 0.3-58.3 mg/L vs. 11.7; range, 1.6-158 mg/L) showed no correlation with culture results. Of the culture-positive aspirates 36% corresponded with systemic signs of an acute inflammatory response, such as elevated I/T-ratio and CRP.(ABSTRACT TRUNCATED AT 250 WORDS)

[Stüve-Wiedemann syndrome in two siblings: focusing on a male patient with the longest actual survival rate]. / Stüve-Wiedemann-Syndrom bei einem Geschwisterpaar: Unter besonderer Berücksichtigung eines Patienten mit zurzeit längster Uberlebensrate.

BACKGROUND: We report on two siblings with Stüve-Wiedemann syndrome (SWS). The older patient, a 16-year-old boy, is -- as to our knowledge -- the longest-term survivor of this syndrome worldwide. The younger sister with the same clinical and radiographic findings died at the age of 10 months. DEFINITION: Characteristic clinical symptoms are: muscular hypotonia, camptodactyly; respiratory insufficiency, swallowing difficulties; reduced sweating with heat intolerance, episodes of hyperthermia. Typical radiographic findings are: progressive bone bowing, unusual bone fractures, abnormal trabecular pattern, middle face hypoplasia. GENETICS: The SWS is identical with the Schwartz-Jampel syndrome (SJS) type 2, which is gene-located on chromosome 1. So far further genetic details of the SWS can be expected in the near future. The genetic transmission is autosomal recessive. In inbred high risk populations the occurrence of the SWS is increased. THERAPY: For the present only symptomatic therapy is available: extended intensive care during infancy, supportive pediatric orthopedics later on.

[Trauma caused by shaking the infant--a special form of child abuse]. / Das Schütteltrauma des Säuglings--eine besondere Form der Kindesmisshandlung.

The shaking of infants is an often underestimated cause of head-injuries in children. Without any external signs the diagnosis can be missed. The combination of subdural hematoma of typically interhemispheric site and retinal bleeding is pathognomonic of the shaked-baby syndrome. It is caused by acceleration-deceleration movements of the head. We present three patients with whiplash-shaken-injuries who were admitted to our hospital with impaired consciousness or in coma. With little external signs of injury more detailed investigations revealed other, older injuries suggesting previous abuse. The outcome was not favourable. Two of the children were discharged with minor or mild psychomotor retardation and one child was severely handicapped. As in the battered-child-syndrome a good history, assessing child specific and familial risk-factors and the socioeconomic background are most important to confirm a diagnosis. This type of injury is usually part of the spectrum of child abuse.

[Unremarkable heart and mediastinal configuration in a newborn infant with totally anomalous pulmonary venous anastomosis to the superior vena cava]. / Unauffällige Herz- und Mediastinalkonfiguration bei einem Neugeborenen mit totaler Lungenvenenfehlmündung in die obere Hohlvene.

A neonate with total anomalous pulmonary venous connection draining via the right cardinal vein into the superior vena cava had a chest-X-ray unsuspicious for congenital heart disease, and initially was treated for neonatal sepsis. But as the clinical state impaired and cyanosis increased, sectorechocardiography revealed the right diagnosis. The child died soon after corrective surgery.

[Postinfectious thrombocytosis as an acute phase reaction: the example of Haemophilus influenzae meningitis]. / Postinfektiöse Thrombozytose als Akute Phase-Reaktion: das Beispiel Haemophilus influenzae-Meningitis.

The postinfectious thrombocytosis occurring in 11 children with Haemophilus influenzae meningitis and/or septicaemia shows regular progress. The rise of thrombocyte concentrations starts around the 5th day after onset of antibiotic therapy, reaches values above 500,000/microliter between the 9th and 12th day, and relapses afterwards to normal values, which are reached around the 20th day. The range of thrombocytosis is influenced by the severity and complications (subdural effusions, secondary infection) of the infection as well as by the age of the patient. An inverse course of serum concentrations of C-reactive protein and thrombocyte concentrations points to the influence of this humoral reaction on the thrombocytic acute phase reaction.

Air embolism and pulmonary interstitial emphysema in a preterm infant with hyaline membrane disease.

A preterm infant with severe hyaline membrane disease requiring extreme mechanical ventilation developed pulmonary air leaks with consecutive shock. The chest roentgenogram showed bilateral pulmonary interstitial emphysema and gas within the heart silhouette as well as in the hepatic veins, inferior v. cava, portal vein, and many abdominal vessels. The respiratory and circulatory failure by massive systemic gas embolism resulted in death.

[Inhibition of meconium induced activation of granulocytes from neonates and adults by pentoxyphylline]. / Inhibition der mekoniuminduzierten Aktivierung neutrophiler Granulozyten durch Pentoxyphyllin im Vollblut Neugeborener und Erwachsener.

BACKGROUND: Neutrophil activation plays a crucial role in the pathogenesis of the meconium aspiration syndrome. Therefore antiinflammatory strategies may offer therapeutic options. The methylxanthinderivative pentoxyphylline (PTX) is known to inhibit the tumor necrosis factor alpha-synthesis and neutrophil degranulation and thus may have beneficial effects on meconium-induced pulmonary inflammation. Effects of PTX on PMN-degranulation in neonatal whole blood have not yet been studied. PATIENTS AND METHODS: Heparin-anticoagulated (3 IE/ml) whole blood of healthy neonates (n = 6) and adult volunteers (n = 6) was incubated for 45 min. Spontaneous PMN-degranulation was compared with meconium-induced (3 mg/ml) and PTX-inhibited (0,025 - 0,4 mg/ml) degranulation by means of elastase (EL) and lactoferrin (LF) release from azurophilic and specific granules. EL- and LF plasma concentration was measured by immunoluminometric methods. RESULTS: Spontaneous degranulation of neonatal PMN was found to be significantly increased after 15 minutes compared with cells from adults (EL and LF concentration: 674 and 660 ng/10 6 PMN vs. 284 and 261 ng/10 6 PMN). At 45 minutes adult PMN showed an acceleration of degranulation in contrast to neonatal cells (EL and LF: 1827 and 1232 ng/10 6 PMN vs. 1400 and 860 ng/10 6 PMN). In presence of PTX (0,4 mg/ml) spontaneous release of EL and LF from neonatal PMN was inhibited by nearly 70 % at 45 min. while degranulation from adult PMN was found to be completely inhibited at 15 min. and reduced by 82 % and 78 % at 45 min. In presence of meconium (3 mg/ml) an increased degranulation of EL from PMN of both neonates and adults (317 % and 170 %) could be observed while LF release was found to be increased from neonatal cells only (267 % and 113 % respectively). PTX inhibited meconium-induced EL release in blood of bath neonates and adults by 63 % and 66 %, while LF release was inhibited by 72 % and 57 % respectively. CONCLUSION: Neonatal PMN exhibit an increased degranulation from azurophilic and specific granules compared with cells from adults. PTX was found to be an effective inhibitor of spontaneous and meconium induced PMN degranulation and may offer new therapeutic options.

Inhibition of granulocyte activation by surfactant in a 2-yr-old female with meningococcus-induced ARDS.

Activated polymorphonuclear neutrophils (PMNs) play a crucial role in acute respiratory distress syndrome (ARDS) via extracellular release of reactive cell products such as elastase. Surfactant has proved valuable in restoring lung function in ARDS. The significance of its immunomodulatory properties with respect to this effect has not yet been clarified. The aim of the present study was to determine the anti-inflammatory effects of surfactant administration in an infant with ARDS. During the acute phase of ARDS in a 2-yr-old female, levels of PMN-derived elastase complexed with alpha1-protease inhibitor (E-alpha1PI) were measured in both arterial and central venous blood samples obtained simultaneously. The results were correlated with oxygen demand and plasma concentrations of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) after endotracheal administration of surfactant (Alveofact 60 mg x kg x body weight(-1)). In the present case, for the first time, a higher E-alpha1PI concentration was detected in arterial blood (4.51 mg x L(-1)) than in central venous blood (2.28 mg x L(-1)). After administration of surfactant, these concentrations and the arteriovenous difference decreased, indicating that during ARDS, most PMN degranulation takes place in the pulmonary vascular bed and is inhibited by surfactant administration. Simultaneously, TNF-alpha and IL-6 plasma concentrations decreased within hours and lung function was restored. This local inhibition of polymorphonuclear neutrophil activation by exogenous surfactant may play a key role in the early improvement in lung function after surfactant administration.

In vitro modulation of induced neutrophil activation by different surfactant preparations.

Endotracheal surfactant administration has gained an important role in the treatment of respiratory failure. Polymorphonuclear neutrophil granulocyte (PMN) activation mediated by chemoattractants, such as interleukin-8 (IL-8), neutrophil-activating peptide-2 (NAP-2) and formylated bacterial oligopeptides, has been found to be involved in the pathophysiology of acute respiratory failure. We investigated potential modulating effects of commercial surfactant preparations (Exosurf, Alveofact, Curosurf and Survanta) on spontaneous and chemoattractant-induced PMN function. Isolated cytochalasin B (CytB)-treated PMNs from healthy adults were incubated with increasing concentrations of surfactant. The response of the cells was measured in terms of elastase release from the lysosomes within 30 min. The PMNs showed no direct activation by any of the surfactants tested. However, when cells were stimulated with suboptimal dosages of chemokines, such as IL-8 (2 nM) or NAP-2 (100 nM), or formyl-methionyl-leucyl-phenylalanine (fMLP) (50 nM), and co-incubated with increasing concentrations of surfactant (0.05-8 mg.mL-1) the release of elastase was markedly modulated depending on the surfactant preparation used. Whilst Exosurf and Alveofact showed only modest effects on the elastase release induced by all three mediators, Curosurf and Survanta markedly inhibited the cellular response in a dose-dependent manner. At concentrations above 1 mg.mL-1, Curosurf and Survanta decreased the IL-8-, NAP-2- and fMLP-induced elastase release by 83, 67 and 90%, and by 82, 75 and 80%, respectively. In conclusion, exogenous surfactant may modulate the inflammatory response of the airways by affecting the chemoattractant-induced polymorphonuclear neutrophil activation. Surfactant preparations with inhibiting properties on neutrophil activation may participate in the prevention of neutrophil-induced lung damage.

[Midazolam (Dormicum) for sedation of children in painful interventions]. / Midazolam (Dormicum) zur Sedierung von Kindern bei schmerzhaften Eingriffen.

In children painful diagnostic and therapeutic investigations require sedation and sometimes local anaesthesia. We tested Midazolam, a new benzodiazepine, for its sedative effect. Midazolam is the first derivate of imidabenzodiazepine and is remarkable for its rapid effect and a short half-life. It has good hypnotic, anxiolytic and amnesic properties. Sleep sets in immediately after intravenous application of Midazolam, and all patients reported anterograde amnesia afterwards. Over 24 months we observed 266 children who had been given Midazolam as a basic sedative before painful investigations. For sleep induction Midazolam was given in a dose of 0.3 mg/kg in children older than 6 years and 0.4 mg/kg in children younger than 6 years. The maximal dose was 15 mg. All patients fell asleep and did not remember anything about the procedure. In 30 patients pulse, blood pressure and respiration rate were measured before and after application of Midazolam. The quality of sleep was determined by the Glasgow-Coma-Scale. We did not observe any side effects.

[Determination of C-reactive protein (CRP) in capillary blood--a comparison with the CPR level in venous serum]. / Bestimmung des C-reaktiven Proteins (CRP) aus Kapillarblut--ein Vergleich mit der CRP-Konzentration in venösem Serum.

C-reactive protein (CRP) has served as a reliable indicator of infectious and inflammatory diseases for a long time. Sequential CRP determinations offer a useful means of monitoring clinical courses and therapeutic effects in patients of any age as its serum concentrations correlate well with clinical symptoms. Especially in pediatric patients, however, venous blood sampling causes many problems. Thus, in our study a new method of CRP analysis from capillary plasma samples was tested and compared with CRP determinations from venous serum samples. 101 pairs of samples simultaneously obtained from 64 pediatric and neonatal patients (mean age of 5.8 months: min. 1 day, max. 5.5 years) were analyzed and compared. A good correlation (r = 0.967) was found for the whole range of measured CRP-concentrations (5-175 mg/l), showing a linear relationship between both methods. Results were analyzed by chi 2-test. Using a cutoff level of 5 mg/l, a sensitivity of 96%, a specificity and a positive predictive value of 98% each and an efficiency of 97% was found. Thus, the CRP determination from capillary blood samples offers a reliable method and a useful alternative for conventional analysis from venous serum.

Variation of alpha 1-antitrypsin glycoprotein microheterogeneity in hepatic postresuscitation disease.

Microheterogeneity of the glycoprotein alpha 1-antitrypsin has been investigated sequentially by high resolution isoelectric focusing in a child with the proteinase inhibitor MS phenotype after near-drowning. A band-splitting with additional cathodal fractions exhibited migration from the most cathodic to the anodic positions of the glycoprotein isoforms in the course of post-resuscitation disease. The pattern may reflect the time- and stage-dependent hypoxic and post-hypoxic effects on hepatocellular metabolic zonation.

[Acute renal failure with high-dose combination therapy with penicillin G and amoxicillin]. / Akutes Nierenversagen unter hochdosierter Kombinationstherapie mit Penicillin G and Amoxicillin.

A 3 year old girl was admitted with suspected bacterial meningitis. The patient's history concerning renal and cerebral function and known allergies had been uneventful until that time. 36 h after initiation of a high dose antibiotic therapy with Penicillin G (0.5 Mega IE/kg/day) and Amoxicillin (400 mg/kg/day) macrohematuria and consecutive anuria was observed. Prerenal cardiocirculatory failure, a Schwartz-Bartter-reaction as well as coagulatory failure could be ruled out. There were no symptoms of hypersensitivity. Sonographic examinations of the kidneys and the urinary tract as well as urinanalysis suggested an acute tubular obstruction and papillary necrosis caused by amoxicillin. After changing the antibiotic regimen to chloramphenicol and induction of diuresis by furosemide and dopamine renal failure could be resolved within 39 h. The patient recovered completely. High dose therapy with amoxicillin (greater than 300 mg/kg/day) includes the risk of tubular obstruction due to cristalluria. Solubility of ampicillin in aqueous fluids (6.5 mg/ml at pH 7) should be supported by sufficient diuresis and urine alkalization.

[Transitory prolongation of QT time in severely ill premature and newborn infants]. / Passagere QT-Zeit-Verlängerung bei schwerkranken Früh- und Neugeborenen.

Over 24 months in a Neonatal Intensive Care Unit 118 electrocardiograms were recorded in the first three days of life. 12 preterm and term newborns had a corrected QT-time-prolongation over 0.44 s. Measurement of the ionized calcium level in these children revealed hypocalcemia in only four as a reason for QT-time-prolongation. One child had hypokalemia, one child suffered from accidental Bupivacain injection. In the other six children no known reasons for QT-time-prolongation could be found. The QT-time-prolongation persisted for a maximum of three months, no inherited QT-syndrome existed. We discuss a correlation of these transitory QT-time-prolongation with asphyxia which preexisted in all six children. Influences on catecholamine receptors of myocardium or changes in central sympathicotonus may be assumed.

[The significance of the initial respiratory parameters in assessing the severity of ARDS in children]. / Die Bedeutung initialer respiratorischer Parameter zur Schweregradbeurteilung beim ARDS im Kindesalter.

In adults, the course and outcome of the acquired respiratory distress syndrome (ARDS) are closely related to the initial respiratory situation. Respiratory indices are frequently used for prognostic purposes and hence for the institution of new techniques such as extracorporeal lung support. The validity of these indices to predict the outcome in pediatric ARDS patients has not been examined as yet. We studied respiratory indices in 69 pediatric ARDS patients. METHODS. Out of 69 pediatric ARDS patients with various underlying diseases (Table 1), we chose 21 with a paO2/FiO2 ratio less than 150 mm Hg at some point to test the prognostic significance of a respiratory severity index (RSI), i.e., mean airway pressure x alveolar-arterial pO2 difference (A-aDo2)/paO2, a respiratory index (RI), i.e., A-aDO2-paO2/paO2, and other respiratory parameters (Table 2). Postsurgical patients, patients with incurable diseases, clearly non-respiratory deaths, and those treated with extracorporeal membrane oxygenation were excluded. We looked for statistical differences between survivors and nonsurvivors and correlations between ventilator days, intensive care unit (ICU) days, and hospital days and these indices. RESULTS. We did not find a significant difference between all respiratory indices tested at admission to the ICU and 24 h later between survivors and nonsurvivors (Table 3). Nonsurvivors initially had significantly higher blood pressures and lower heart rates. Both RSI and RI were significantly correlated to days on the ventilator, days in the ICU, and days in the hospital (Table 4). Initial multiorgan failure was significantly more common in nonsurvivors. CONCLUSIONS. Initial lung dysfunction as indicated by respiratory indices does not predict the outcome in pediatric ARDS. The underlying disease, hemodynamic situation, and age have to be considered in relation to the degree of lung dysfunction to determine new therapeutic strategies such as extracorporeal support.

[Elastase-alpha 1-proteinase inhibitor complex (E alpha 1 PI) and lactoferrin plasma concentrations in viral and bacterial infections]. / Elastase-alpha 1-Proteinaseinhibitorkomplex (E alpha 1 PI) und Lactoferrinplasmakonzentrationen bei viralen und bakteriellen Infektionen.

Typical alterations of the white blood cell count are often missed during the acute course of infectious diseases. Activiation and degranulation of granulocytes are followed by elevation of E alpha 1 PI and lactoferrin plasma concentrations under these conditions. The aim of our study was the evaluation of the diagnostic significance of these granulocyte parameters in relation with the absolute granulocyte count in infected pediatric patients. A total number of 106 patients at the age of 1 day to 16 years were studied. 25 children suffered from viral, 26 from localized and 23 from systemic bacterial infections, 32 children exhibiting no signs of infection served as controls. Results of the study are given as medians and ranges. Total granulocyte count was elevated above controls (4.8; 2.2-12.7/nl) only in patients with localized bacterial infections (13.3; 5.5-36.5/nl). E alpha 1 PI and lactoferrin plasma concentrations correlated well (r = 0.72) and were found to be significantly elevated in patients with localized bacterial infections (856; 363-4820 micrograms/l and 748; 206-2078 micrograms/l) and septicemia respectively (661; 256-2078 micrograms/l and 871; 160-9550 micrograms/l). A clearcut differentiation of septic and locally infected patients was given by the ratio of E alpha 1 PI and total granulocyte counts. Significantly elevated E alpha 1 PI concentrations of patients exhibiting viral infections (295; 86-690 micrograms/l) may suggest effective granulocyte activation under this condition. Finally we conclude that E alpha 1 PI and lactoferin plasma concentration related to total granulocyte counts in infected patients may serve as a helpful indicator of granulocyte activation during the acute course of the disease.

[Hearing disorders in children less than 16 months of age after bacterial meningitis with reference to cerebrospinal fluid elastase]. / Hörstörungen bei Kindern unter 16 Monaten nach bakterieller Meningitis unter Berücksichtigung der Liquorelastase.

Hearing impairment as a sequela of acute bacterial meningitis is a well known complication. Dexamethasone therapy in addition to antibiotics is beneficial in the reduction of deafness, implicating that inflammation may be one reason for hearing impairment. The risk of hearing impairment in different types of bacterial meningitis is well studied. In very young children < 1.5 years of life the incidence of hearing loss and the possible correlation of laboratory data with the development of deafness is yet unknown. We therefore examined the brainstem auditory evoked potentials in 25 children between the first month and the 16th month of life who we treated for meningitis during 3 years in our hospital. 11 children were treated with dexamethasone. In 9 children we found abnormal brainstem auditory evoked potentials, which we controlled every 3 months. 7 children had transient conductive hearing impairment with good recovery during the first year after the disease. In 2 cases we found permanent bilateral sensorineural hearing loss. There was a significant relationship between hearing loss and elastase in cerebrospinal fluid. Dexamethasone reduced this relationship. A screening of hearing should be performed as routine control in all patients with acute meningitis. The association of high elastase in cerebrospinal fluid and later hearing impairment indicates a pathophysiological relation between activation of granulocytes and hearing loss.

Plasma concentration of elastase-alpha 1-proteinase inhibitor complex in surfactant-treated preterm neonates with respiratory distress syndrome.

Although exogenous surfactant replacement improves respiratory distress syndrome (RDS) of immature neonates, it may not prevent subsequent lung damage and development of bronchopulmonary dysplasia associated with polymorphonuclear neutrophil (PMN)-activation. We therefore wanted to assess whether surfactant administration would be associated with activation of circulating PMNs. Since elastase-alpha 1-proteinase inhibitor (E-alpha 1-PI) has proved to be a sensitive indicator of intravascular PMN activation, we studied E-alpha 1-PI plasma concentration in preterm neonates during the treatment of RDS with a bovine surfactant preparation (group I: n = 23). Results were compared with those from a retrospective control group treated by ventilation alone (group II: n = 13), and with a reference group of 92 newborns (group III). Following surfactant administration, median E-alpha 1-PI concentration increased significantly (day 1 80.5 vs Day 2,234 micrograms.l-1), and exceeded the upper limit of the reference range of 274 micrograms.l-1 in seven patients, with a maximal value of 1,881 micrograms.l-1 after multiple surfactant administrations. In contrast, 12 infants from Group II showed no increase in median E-alpha 1-PI levels (Day 1,107 vs Day 2,107 micrograms.l-1), and remained within the reference range (Day 1,125 micrograms.l-1; Day 2,107 micrograms.l-1) of the 92 newborns without respiratory impairment, infection, birth-trauma or asphyxia. From these results, it is concluded that surfactant may trigger a transient, mainly local, inflammatory response, reflected by increased levels of E-alpha 1-PI, and may exert a dose-related pathogenic influence on the course and prognosis of RDS.(ABSTRACT TRUNCATED AT 250 WORDS)