Evaluation of the impact of oximeter averaging times on automated FiO2 control in routine NICU care: a randomized cross-over study.

Objective: Changes in oximeter averaging times have been noted to affect alarm settings. Automated algorithms (A-FiO2) assess FiO2 faster than oximeter averaging, potentially impacting their effectiveness. Methods: In a single NICU routinely using 15 fabian-PRICO A-FiO2 systems, neonates were randomly exposed to SpO2 averaging time settings switched every 12 h among short (2-4 s), medium (10 s), and long (16 s) oximeter averaging times for the entire duration of their A-FiO2 exposure. Primary endpoints were the percent time in the set SpO2 target range (dependent on PMA), SpO2 < 80%, and SpO2 > 98%, excluding FiO2 = 0.21. Results: Ten VLBW neonates were enrolled over 11 months. At entry, they were 17 days old (IQR: 14-19), with an adjusted gestational age of 29 weeks (IQR: 27-30). The study included data from 272 days of A-FiO2 control (34% short, 32% medium, and 34% long). Respiratory support was predominantly non-invasive (53% NCPAP, 40% HFNC, and 6% NIPPV). The aggregate SpO2 exposure levels were 67% (IQR: 55-82) in the target range, 5.4% (IQR: 2.0-10) with SpO2 < 80%, and 1.2% (IQR: 0.4-3.1) with SpO2 > 98%. There were no differences in the target range time between the SpO2 averaging time settings. There were differences at the SpO2 extremes (p ≤ 0.001). The medium and long averaging were both lower than the short, with the difference larger than predicted. Multivariate analysis revealed that these findings were independent of subject, ventilation mode, target range, and overall stability. Conclusions: This A-FiO2 algorithm is effective regardless of the SpO2 averaging time setting. There is an advantage to the longer settings, which suggest an interaction with the controller.

Cell Membrane-Derived Microvesicles in Systemic Inflammatory Response.

Human body reacts to physical, chemical and biological insults with a complex inflammatory reaction. Crucial components and executors of this response are endothelial cells, platelets, white blood cells, plasmatic coagulation system, and complement. Endothelial injury and inflammation are associated with elevated blood levels of cell membrane-derived microvesicles. Increased concentrations of microvesicles were found in several inflammatory reactions and diseases including acute coronary syndromes, stroke, vasculitis, venous thromboembolism, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, anti-phospholipid antibody syndrome, inflammatory bowel disease, thrombotic thrombocytopenic purpura, viral myocarditis, sepsis, disseminated intravascular coagulation, polytrauma, and burns. Microvesicles can modulate a variety of cellular processes, thereby having an impact on pathogenesis of diseases associated with inflammation. Microvesicles are important mediators and potential biomarkers of systemic inflammation. Measurement of inflammatory cell-derived microvesicles may be utilized in diagnostic algorithms and used for detection and determination of severity in diseases associated with inflammatory responses, as well as for prediction of their outcome. This review focuses on the mechanisms of release of microvesicles in diseases associated with systemic inflammation and their potential role in the regulation of cellular and humoral interactions.

Heart failure treated with low-dose milrinone in a full-term newborn.

A term newborn with a hypocontractile myocardium complicating persistent pulmonary hypertension of the newborn was successfully treated with a low-dose phosphodiesterase III inhibitor milrinone. Echocardiography diagnosed heart failure with a left ventricular ejection fraction of 35% and a left ventricular shortening fraction of 18% and severe persistent pulmonary hypertension of the newborn with oxygenation index of 28. Milrinone was started at an initial dose of 50 mcg/kg, followed by continuous infusion of 0.20 mcg/kg/min. With lowdose milrinone oxygenation index decreased to 3 within 6 hours, left ventricular ejection fraction and left ventricular shortening fraction increased to 57%, and 30%, respectively. Low doses of milrinone might be promising in the treatment of heart failure and persistent pulmonary hypertension of the newborn in term newborns.

Severe tentorial haemorrhage of the term newborn with a favourable outcome--case report.

The traumatic intracranial haemorrhage still remains a serious complication of instrumental deliveries with an uncertain prognosis. Regarding tentorial haemorrhage, surprisingly few clinical neurological data are available. Most of the references in literature are older case reports, associated frequently with an unfavourable outcome. We report a newborn after a serious tentorial haemorrhage with an excellent neurodevelopmental outcome. Computed tomography (CT) scan of our patient demonstrated an extensive bilateral tentorial haemorrhage extending to the foramen magnum. The newborn showed a good respiratory effort, but a neurological impairment including anisocoria, apathy, hypotonia, incomplete grasp and Moro reflex. Despite these signs, the development at 9 and 18 months of age was appropriate. The aim of this report is to accentuate that the prognosis of infants with tentorial haemorrhage should be always evaluated carefully with main respect to clinical signs. The outcome of the newborn even after a large tentorial haemorrhage can be surprisingly without a serious neurological deficit. Spontaneous breathing without support, normal blood pressure and absence of seizures are clinical indicators that may be associated with a good outcome despite an extensive tentorial haemorrhage.

Successful treatment of profound hypothermia of the newborn.

UNLABELLED: We report a case of a profoundly hypothermic newborn with a core temperature of 25 degrees C with a successful recovery and normal neurological outcome at 3 and 6 months. This term male infant had been exposed to a temperature of -3 degrees C for approximately 30 min. Slow re-warming, using external modalities was used in addition to volume expansion, heparinization, antibiotics and sedation. There is limited information available concerning the safest and most effective method of re-warming hypothermic newborns. Slow re-warming has been advocated as it replicates the normal physiological process in a neonate, which minimizes a negative therapy impact. CONCLUSION: The most significant decision regarding treatment is the identification of the most appropriate method and speed of re-warming. This report supports recommendations for gradual re-warming of a severely hypothermic newborn. Physiological cardiovascular mechanisms seemed to be intact during slow re-warming; this might be applicable to the treatment of profound hypothermia of the newborn.

Critically ill newborns with multiple organ dysfunction: assessment by NEOMOD score in a tertiary NICU.

BACKGROUND: The neonatal multiple organ dysfunction score (NEOMOD) predicts mortality during the first 28 days of life, and provides information on organ functions influencing mortality. AIM: To test the predictive and descriptive accuracy of NEOMOD in very low birth weight (VLBW) infants. METHODS: The system was used in 112 infants. It evaluates the central nervous system (CNS), coagulation, respiratory, gastrointestinal (GIT), cardiovascular (CVS), renal system, and acid-base balance in 24-h intervals during the first 28 days of life. RESULTS: A NEOMOD of > or =9 was associated with 100% mortality. A receiver operating characteristic (ROC) curve was used for assessing the accuracy of NEOMOD score in prediction of mortality. The area under curve (AUC) attained by NEOMOD was 0.93 for mortality. CONCLUSIONS: The NEOMOD evaluates daily the severity of the multiple organ dysfunction syndrome (MODS) and is an accurate predictor of mortality.

New antimycobacterial 2,3-dihydro-1-alkylindole-2-thiones.

A series of 2,3-dihydroindole-2-thiones was evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, M. fortuitum, two strains of M. intracellulare and three strains of M. avium. 2,3-Dihydro-1-methyl-2-thioxoindole-3-one and 2,3-dihydro-1-butyl-2-thioxoindole-3-one were the most active substances against potentially pathogenic strains, being more active than isoniazide.

Congenital diaphragmatic hernia associated with esophageal atresia, tracheoesophageal fistula, and truncus arteriosus in a premature newborn.

The occurrence of coexisting congenital diaphragmatic hernia (CDH) and esophageal atresia (EA) with distal tracheoesophageal fistula (TEF) is extremely rare and is considered highly lethal. The combination of CDH with EA/TEF and truncus arteriosus communis (TAC) has not been reported in the literature to date. The authors describe a premature neonate with this association.

New antimycobacterial S-alkylisothiosemicarbazones.

In connection with a systematic study of antimycobacterial agents against potentially pathogenic strains the series of 12 S-alkylisothiosemicarbazones was evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, M. fortuitum, two strains of M. intracellulare and three strains of M. avium. Quinoline-4-carbaldehyde-S-hexyl-isothiohydrazone was found to be more active against potentially pathogenic strains than isoniazide.

[New Apgar score? A multi-centre study dealing with the evaluation of the neonate NEOMOD scoring system for the first day of life]. / Nove apgar skóre? multicentrická studie hodnocení novorozence skórovacím systémem NEOMOD první den zivota.

OBJECTIVE: To compare the predictive accuracy of the NEOMOD score and the Apgar score as concerns prediction of mortality and affection of the central nervous system (CNS) in neonates. DESIGN: Prospective multi-centre clinical study. SETTING: Mother and Child Care Institute, Prague; Thomayer's Faculty Hospital with a Policlinic, Prague. METHODS: All neonates with a gestation age > or =35 weeks of pregnancy, hospitalised in the intensive care units of the cooperating hospitals in the period 1998-2002, were included in the study. For all the neonates, the NEOMOD score was established in the first 24 hours and the Apgar score was established in the 1st, 5th and 10th minutes of their lives. The aim was to establish the predictive accuracy of the scoring systems for mortality and affection of CNS in the first 28 days of life. RESULTS: 620 patients participated in the study; 16 patients (1.90%) died by the 28h day. The predictive accuracy for mortality expressed as AUS - the area under receiver operating characteristic (ROC) curve reached the highest level for NEOMOD AUC = 0.96. AUC for the Apgar score was 0.84 in the 1st minute; it was 0.84 in the 5th minute and it was 0.88 in the 10th minute. The predictive accuracy for affection of CNS was AUC = 0.76 in the case of NEOMOD; in the case of Apgar, AUC was 0.71, 0.74 and 0.77 in the 1st, 5th and 10th minute, respectively. CONCLUSION: The NEOMOD system proved a high accuracy in the prediction of neonatal mortality in a group of patients with a gestation age > or =35 weeks of pregnancy. The predictive accuracy of NEOMOD was higher than that of the Apgar score. The predictive accuracy of both the NEOMOD and Apgar scores for affection of CNS in the neonatal period was low.

[The first experience with linezolide in treatment of nosocomial septic condition in premature neonates]. / První zkusenosti s linezolidem pri terapii nozokomiálního septického stavu u nedonogených novorozencu.

OBJECTIVE: Nosocomial infections caused by the coagulase-negative staphylococci are among the most frequent complications in an intensive care unit for neonates. The authors describe three cases of successful treatment of this complication in which the new antibiotic Linezolide was used. DESIGN: Analysis of three clinical cases. SETTING: Mother and Child Care Institute, Prague. METHODS: Description of cases of nosocomial sepsis in 3 immature neonates where the usual treatment of multiresistant strains of coagulase-negative staphylococci, based on the use of Vankomycin, was not successful. CONCLUSION: Administration of Linezolide proved to be very effective in all of the described cases. In spite of the high effectiveness and relative safety of this preparation, its precise role in the treatment of infection-related complications caused by coagulase-negative staphylococci has not yet been established. For the time being, we recommend administering this preparation only in strictly indicated cases after the usual therapy fails.

[Multiresistant tuberculosis in the Czech Republic (1999-2001)]. / Multirezistentní tuberkulóza v Ceské republice (1999-2001).

BACKGROUND: Multidrug-resistant (MDR) tuberculosis, defined as a disease caused by Mycobacterium tuberculosis strains, which are resistant to more antituberculous drugs (at least to isoniazid and rifampicin), is a problem frequently discussed in the Czech Republic. Cases of specific disease refractive to causal antituberculous therapy are associated with the risk of the spread of the causative agent among the population. METHODS AND RESULTS: The National Reference Laboratory for Mycobacteria collected 2813 Mycobacterium tuberculosis strains isolated by Czech mycobacteriological laboratories in 1999 to 2001. All strains were tested for susceptibility to basic antituberculous drugs and then the MDR strains were further tested for susceptibility/resistance to other antituberculous and antibacterial drugs. The MDR strains were studied by DNA analysis (DNA fingerprinting restriction analysis, RFLP-Restriction Fragment Length Polymorphism) as well. Thirty-nine patients who had MDR tuberculosis were excretors of 56 Mycobacterium tuberculosis strains. In average, MDR tuberculosis accounted for 1.96% (1.7-2.4) of all cases of bacillary tuberculosis. The most frequent type of the multidrug resistance was that resistant to four basic antituberculous drugs (isoniazid, rifampicin, ethambutol and streptomycin). It was confirmed in 48.2% multidrug resistant strains. CONCLUSIONS: Isepamicin, clofazimin, capreomycin and amikacin are considered to be the most promising antituberculosis drugs. Based on RFLP profiles, 61.5% of strains were placed into 8 clusters while the other strains remained unclustered. No significant differences in geographical distribution and population structure were found between the excretors of clustered strains and those of unclustered strains. Preliminary comparison with restriction profiles of the MDR Mycobacterium tuberculosis strains in the international database suggests the uniqueness of Czech strains showing the profiles not found elsewhere to date.

[Pseudo-hydrothorax in peripheral venous catheterization in an extremely premature neonate--case report]. / Vznik pseudofluidotoraxu pri zavedení periferního venózního katétru u extrémne nezralého novorozence--kazuistika.

The authors describe very rare complication (pseudopleural effusion) after peripheral venous cannulation (Introcan-W 24G3/4 through v. axilaris) in extremely premature newborn with birth weight 600 grams, which lead to worsening of patient's respiratory insufficiency. Ultrasonographic examination confirmed extrapleural process without necessity of surgical intervention. Cannula extraction and infusion interruption were followed by spontaneous regression of the complication, thereafter artificial ventilation was discontinued and baby was discharged.

Postnatal increase of procalcitonin in premature newborns is enhanced by chorioamnionitis and neonatal sepsis.

BACKGROUND: To determine the influence of chorioamnionitis and neonatal sepsis on procalcitonin (PCT) levels in very-low-birth-weight (VLBW) infants within the first week of life. DESIGN: PCT serum levels were measured in cord blood 1 h after delivery and on day 3 and day 7 of life. Chorioamnionitis and neonatal sepsis within the first week were monitored. RESULTS: Chorioamnionitis was present in eight of 37 patients (21.6%). PCT on day 3 was increased in both the "No chorioamnionitis" (2.54 ng mL(-1), SEM 0.51) and "Chorioamnionitis" (6.96 ng mL(-1), SEM 2.93) groups of VLBW infants compared with the 1st hour values (0.45 and 0.58 ng mL(-1) SEM 0.07 and 0.11, respectively, P < 0.001) of the same patients. The postnatal gain was higher in the "Chorioamnionitis" group (P < 0.01). Neonatal sepsis was diagnosed (after exclusion) in 12 of 32 patients (37.5%). Mean values of maximum PCT in patients with and without sepsis were 8.41 ng mL(-1) (SEM 1.87) and 3.02 ng mL(-1) (SEM 1.38), respectively (P < 0.05). Sensitivity to sepsis of PCT, ratio of immature to total neutrophils (I : T), and C-reactive protein (CRP) were 75%, 50% and 25%, respectively. CONCLUSIONS: In the group of VLBW infants the PCT level within 72 h of delivery was markedly increased in patients with chorioamnionitis. Compared with I : T and CRP, PCT appears to be a more sensitive marker of neonatal sepsis.

[Procalcitonin--a marker of systemic infection and multiorgan dysfunction: characteristics of the gene and protein]. / Prokalcitonin--marker systémové infekce a multiorgánové dysfunkce: charakteristika genu a proteinu.

Procalcitonin (PCT) is a protein consisting of 116 aminoacids with molecular weight 13 kDa. It is encoded by CALC-1 gene. According to the basic and clinical research results PCT appears to be a highly sensitive and specific marker reflecting severity of the systemic inflammatory response to infectious stimuli. Despite the investigation focused on CALC-1 gene, little is known about the biology of PCT and cellular sources of PCT during inflammation. One of the possible sources may be human peripheral blood mononuclear cells. PCT is an indicator of bacterial infections minimally stimulated by viral infections, autoimmune diseases and tumors.

Characterization of multiple organ dysfunction syndrome in very low birthweight infants: a new sequential scoring system.

To define multiple organ dysfunction in newborns, we established a sequential scoring system NEOMOD (Neonatal Multiple Organ Dysfunction Score). It was developed to describe the process of increasing physiologic derangement in critically ill newborns. It provides, during the first 28 days of life, information concerning function of organ systems having a primary influence on mortality in very low birth weight (VLBW) infants. Our scoring system has been used in 142 VLBW infants. It evaluates moderate (1 point) or severe dysfunction (2 points) in 7 organ systems (central nervous system, cardiovascular, renal, respiratory, and gastrointestinal systems, and hemocoagulation and acid-base balance) in 24-h intervals from day 1 to 28 of life. Maximum possible value of NEOMOD was 14 points. Receiver operating characteristic curve was used for assessing predictive accuracy of maximum NEOMOD score obtained by daily scoring for mortality rate. AUC (area under curve) attained by NEOMOD was 0.95 for mortality within the first 28 days and 0.91 for hospital mortality, respectively. In the study group, NEOMOD score of > or = 9 was associated with 100% mortality. An analysis of specific organ dysfunctions in the non-survivors group (n = 16) disclosed, in all patients, dysfunction of more than two organ systems 24 h before death. Similar to critically ill adults, secondary multiple organ dysfunction can be described also in a majority of critically ill VLBW infants. NEOMOD scores may help to evaluate daily the severity of the syndrome and risk of death.

[Reconstruction of the diaphragm with a polytetrafluoroethylene patch in neonates with congenital diaphragmatic hernia]. / Rekonstrukce bránice polytetrafluoroetylenovou záplatou u novorozencu s vrozenou bránicní kýlou.

The authors present their experience with the reconstruction of the diaphragm with a synthetic polytetrafluoroethylene patch in a group of 66 neonates with a congenital diaphragmatic hernia. After preoperative stabilization 53 neonates (80%) were operated, simple reconstruction of the diaphragm was made in 39 neonates (74%), reconstruction of the diaphragm with a polytetrafluoroethylene patch was indicated in 14 patients (26%). Nine patients recovered after reconstruction of the diaphragm by a synthetic patch without complications. The only relapse of diaphragmatic hernia when using a patch was recorded in a neonate with a bilateral diaphragmatic hernia, sternal cleft and omphalocele. After simple reconstruction of the diaphragm there was no relapse of hernia. The total mortality in the group was 27% (18 neonates). After surgery five neonates died. Two of them died of serious haemorrhagic complications during extracorporeal membrane oxygenation and three died after operations performed at borderline oxygenation and ventilation values and subsequent deterioration of the general condition. In four of them a polytetrafluoroethylene patch (GORE-TEX) was used. Reconstruction of the diaphragm by a polytetrafluoroethylene patch is a suitable surgical method in the treatment of neonates with a congenital diaphragmatic hernia. Indication for the use of a patch is agenesis of the diaphragm and major diaphragmatic defects with hypoplastic borders. The use of a non-absorbable synthetic patch is from the aspect of the long-term effect on growth and the development of skeletal deformities equivocal and will call for further detailed studies.

[Chorioamnionitis and early-onset neonatal sepsis do not significantly affect levels of interleukin-6 in very low birth weight neonates]. / Chorioamniitis a casná novorozenecká sepse neovlivnují významne hladinu interleukinu-6 u novorozencu velmi nízké porodní hmotnosti.

OBJECTIVE: To determine the influence of maternal chorioamnionitis and neonatal sepsis on interleukin-6 (IL-6) levels in cord blood and in blood obtained from very low birth weight (VLBW) infants within the first two hours of life. DESIGN: Prospective clinical study. SETTING: Institute for the Care of Mother and Child, Prague. METHODS: We measured the serum levels of IL-6 in 30 consecutive VLBW infants born in our institute. IL-6 levels were evaluated in cord blood and in neonatal blood within 2 hours after delivery. Maternal chorioamnionitis and neonatal sepsis within the first 72 hours of life were monitored. RESULTS: Maternal chorioamnionitis was detected in 7 of 30 patients (23.3%). There was no significant increase in IL-6 level in cord blood of newborns with maternal chorioamnionitis (p = 0.42). Serum level of IL-6 in this group did not differ from the level in newborns of mothers without signs of intraamniotic infection (p = 0.39). Neonatal early-onset sepsis was diagnosed in 7 of 30 patients (23.3%). There was no influence of neonatal sepsis on IL-6 level in cord blood (p = 0.98) and IL-6 level in neonatal blood (p = 0.19). We did not find any correlation between the group "chorioamnionitis positive" and "sepsis positive" (p = 0.31). CONCLUSION: IL-6 in cord blood or in neonatal blood within 2 hours of life was not enough sensitive and specific marker of maternal chorioamnionitis as well as for early-onset neonatal sepsis in the group of very low birth weight infants.

Development of multiple organ failure in critically ill newborns under AT III substitution.

Criteria for the AT III substitution were fulfilled by 33 infants. Mean birth weight was 1321 g (480 g up to 2860 g), and mean gestational age was 29 weeks (23-39 weeks). AT III substitution in dosing of 5 u/kg/hr was administered to all patients as well as standard heparin 10 u/kg/hr. Initial plasma level of AT III in the study group prior to start of the substitution was 45 +/- 17% activity of normal plasma of adult donor. The value increased up to 90 +/- 32% after 24 hours and up to 113 +/- 38% at the end of the therapy. Eight patients died (24%). Considerable decrease of the Neonatal Therapeutic Intervention Scoring System (NTISS), indicating a level of multiple organ dysfunction, was observed as early as after the first 48 hours of AT III therapy in the entire group (p < 0.01). Extensive increase of platelet count (p < 0.05) occurred after 48 hours of AT III therapy in survivors. Except for a severe sepsis in one case, no clinical signs of increased bleeding occurred during the AT III therapy, and the clinical signs of pre-existing bleeding even disappeared in 5 cases. Analysis of the group of 8 deceased patients revealed irreversible organ dysfunction in 7 cases present prior to the start of AT III substitution. In conclusion, during the AT III substitution, no bleeding, no clinical side effects but improvement in multiple organ dysfunction including increase in platelet count was recorded.