Effect of inhaled nitric oxide on neutrophil respiratory burst.
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Administration, Inhalation↗
Biomedical subjects
W Kachel
Publications and source records attributed to W Kachel.
A prospective, randomized, multicenter trial of high-frequency oscillatory ventilation compared with conventional ventilation in preterm infants with respiratory distress syndrome receiving surfactant.
OBJECTIVES: To compare high-frequency oscillatory ventilation (HFOV) and intermittent positive pressure ventilation (IPPV) as a primary ventilation mode in preterm infants with respiratory distress syndrome. Primary end points were survival and maintenance of the randomized ventilation mode. STUDY DESIGN: Prospective, multicenter, randomized clinical trial. SETTING: Level III neonatal intensive care units at three university children's hospitals. PATIENTS: Ninety-six premature infants (gestational age < 32 weeks) randomly assigned to HFOV or IPPV within the first 2 hours of life. All patients received a natural surfactant. No differences were found between the study groups with respect to the demographic data or the severity of respiratory distress syndrome. Infants were stratified at randomization, by birth weight, into two groups: 750 to 1000 gm (n = 32) and 1001 to 1500 gm (n = 64). The centers involved complied with a study protocol that planned a reduction in respiratory pressures when the infant's oxygen requirement had reached a fractional concentration of inspired oxygen of 0.6. RESULTS: Five patients in the HFOV group died, and eight patients did not respond to the randomized ventilation mode; whereas four patients in the IPPV group died, and nine were switched to HFOV. No differences were found in gas exchange or ventilator support over the first 72 hours. Premature infants with a birth weight < 1000 gm had a significantly shorter course to reach fractional concentration of inspired oxygen of 0.21 while receiving IPPV than those receiving HFOV (9.3+/-4.5 days vs 27.5+/-10.2 days, p = 0.01). No differences were found between the groups in extraalveolar air (HFOV seven; IPPV, seven) and intracranial bleeding (HFOV, nine; IPPV, eight). CONCLUSION: After surfactant treatment, HFOV, as a primary ventilation mode in premature infants with respiratory distress syndrome, is as safe and efficacious as conventional ventilation.
Female↗
[The role of extracorporeal membrane oxygenation (ECMO) in current neonatology].
Two hundred term or near-term neonates were referred to an ECMO center for severe PPHN associated diseases. In 2 time periods from 1987 to 1991 and from 1992 to December 1995 alternative treatment modes were tried in an attempt to obviate ECMO. During the first time period patients underwent a trial of high-frequency oscillatory (HFOV) ventilation before ECMO. In the second time period patients first received inhaled NO followed by HFOV in non-responders. If this also failed HFOV was combined with iNO. In both time periods about 40% of the patients were spared ECMO treatment by these alternative treatment modalities. INO only benefited 15% of the ECMO candidates who apparently had fared just as well on HFOV alone in the preceding time period. While patients who were improved by iNO were spared HFOV with its potential severe complications, i.e. air leaks and cardiocirculatory instability. More extended long-term studies will have to show which of these 2 treatment modalities (iNO or HFOV) should be given-first priority in an attempt to avoid ECMO in neonates with severe respiratory failure.
Extracorporeal Membrane Oxygenation↗
A new side effect of inhaled nitric oxide in neonates and infants with pulmonary hypertension: functional impairment of the neutrophil respiratory burst.
INTRODUCTION: Inhaled nitric oxide (NO) may be beneficial in the treatment of pulmonary hypertension, both of the newborn and in the adult respiratory distress syndrome. Up to now, serious systemic side effects have not been reported. OBJECTIVE: The effect of inhaled NO on superoxide anion production by neutrophils. DESIGN: Prospective study of a consecutive series of 15 neonates and infants. SETTING: Neonatal and paediatric ICUs with a total of 17 beds (university hospital). MEASUREMENTS AND RESULTS: Superoxide anion production was determined by a flow cytometric method using dihydrorhodamine 123 (DHR) as an oxidative probe after the priming of neutrophils with N-formyl-methionyl- leucylphenylalanine (fMLP) or with Escherichia coli. The generated fluorescence was expressed as relative fluorescence intensity (RFI). Inhalation of NO for more than 24 h reduced the superoxide anion production by neutrophils stimulated with E. coli to below baseline values before NO inhalation (mRFI = 158 +/- 25 vs 222 +/- 24; P = 0.03). This decrease was more pronounced after more than 72 h (mRFI = 133 +/- 17). At this time, superoxide anion production by fMLP-stimulated neutrophils was also decreased (mRFI = 40 +/- 3, vs 57 +/- 5; P = 0.03). The reduced capacity of superoxide production persisted throughout therapy with NO and lasted up to more than 4 days after the end of NO inhalation. CONCLUSION: The results suggest that inhalation of NO in patients with pulmonary hypertension causes reduced superoxide anion production by neutrophils stimulated with E. coli or with fMLP. To determine the clinical importance of this systemic side effect with respect to bacterial infections, a randomized controlled study is necessary.
Administration, Inhalation↗
Inhaled nitric oxide for avoidance of extracorporeal membrane oxygenation in the treatment of severe persistent pulmonary hypertension of the newborn.
UNLABELLED: Inhaled nitric oxide (NO) is thought to provide a noninvasive therapeutic alternative to extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). OBJECTIVE: Since January 1993, we have studied inhalation of NO in PPHN patients meeting the ECMO criteria of our institution. We focused on the questions of whether or not the need for ECMO could be obviated and whether differences could be found between NO responders and nonresponders. DESIGN: NO gas was delivered via conventional IPPV ventilation in incrementally increasing concentrations from 20 to 80 ppm. PATIENTS: NO therapy was attempted in ten ECMO candidates with clinical and echocardiographical evidence of PPHN (mean OI 51.9, SD 10.4). RESULTS: At various NO levels (30-60 ppm), five patients showed a significant increase in mean PaO2 (range 32.9-85.9 mmHg). Improvement was transient in three patients (6-10 h) and prolonged in two others (54-80 h); in the latter cases, ECMO was avoided. Five patients did not respond at all to treatment. Responders and nonresponders differed in their mean respiratory tidal volume (8.9 vs 4.18 ml/kg, P <0.05). CONCLUSIONS: In our study, inhalation of NO obviated the necessity of ECMO therapy in only two out of ten PPHN patients. Thus, we would discourage any overoptimistic expectations about the effectiveness of NO therapy in PPHN until larger clinical trials have been performed.
Administration, Inhalation↗
Inhaled nitric oxide during extracorporeal membrane oxygenation for the treatment of severe persistent pulmonary hypertension of the newborn.
Inhaled nitric oxide (NO) as a complementary treatment was studied in 10 neonates during extracorporeal membrane oxygenation (ECMO) therapy of various persistent pulmonary hypertension of the newborn (PPHN)-associated diseases. At individually different levels of inhaled NO (20-80 ppm), the mean Pao2 increased by 59.7% in 6 responders, but it remained unchanged in 4 nonresponders. Adverse side effects of the NO inhalation were tolerable. It was associated with a reversible decrease of the mean arterial blood pressure in 1 patient. During prolonged NO inhalation, the methemoglobin (met-Hb) level increased to 0.9-4.6% in 6 patients. Based on these preliminary results, we conclude that inhaled NO during ECMO can improve oxygenation in some PPHN patients. Further studies with control groups are needed to determine whether inhaled NO can shorten ECMO treatment or improve the rate of survival among PPHN patients.
Administration, Inhalation↗
Influence of early postnatal dexamethasone therapy on ventilator dependency in surfactant-substituted preterm infants.
We examined 26 preterm infants with respiratory distress syndrome in a randomized controlled prospective study to determine whether early postnatal dexamethasone therapy (< 2 h; 0.5 mg/kg per day) over 5 days in addition to substitution of surfactant (100 mg/kg) facilitates extubation and the course of RDS. Control (n = 12) and treated (n = 14) groups were comparable in birthweight (mean +/- SD: 1219 +/- 292 versus 1446 +/- 442 g), gestational age (29.3 +/- 2.2 versus 30.6 +/- 2.7 weeks), prenatal characteristics and initial respiratory and blood gas parameters. In both groups one infant died. Infants in the dexamethasone group responded better to surfactant (12/14 versus 3/12; p < 0.01), were extubated earlier (6.6 versus 14.2 days; p < 0.02) and required less time on supplemental oxygen (4.2 versus 12.5 days; p < 0.02). Pulmonary complications tended to be lower in the dexamethasone group (1/14 versus 4/12), as was the frequency of retinopathy (2/14 versus 6/12; p < 0.05). We conclude that early postnatal dexamethasone therapy improves response to surfactant therapy resulting in better weaning and earlier extubation in premature infants.
Anti-Inflammatory Agents↗
Neutrophil respiratory burst in term and preterm neonates without signs of infection and in those with increased levels of C-reactive protein.
Developmental immaturities in neonatal host defense predispose the neonates to an increased mortality rate during bacterial infections. Early diagnosis is of great clinical importance, but, especially in neonates, is sometimes very difficult. The ability to generate reactive oxygen species, the so-called respiratory burst, is essential for neutrophils to kill infectious microorganisms. Therefore, changes of respiratory burst may reflect increased susceptibility of neonates to infections and may be useful for the early detection of infections. Superoxide anion production was determined by a flow cytometric method using dihydrorhodamine 123 (DHR) as an oxidative probe after priming of neutrophils with PBS buffer (spontaneous burst), with N-formyl-methionyl-leucyl-phenylalanine (fMLP), or with Escherichia coli. During the study period, the spontaneous percentage of activated cells in whole blood as well as the percentage of activated cells in stimulation with fMLP was lower in adults (n = 100; PBS, 1.0 +/- 0.1%; fMLP, 8.3 +/- 0.9%) compared with neonates without signs of infection (n = 143). Among the latter, the percentage of activated cells (PBS and fMLP assay) varied with respect to gestational age and hours of life: lowest values were measured in preterm newborns with gestational age less than 32 wk and between 25 and 120 h of life. The same correlation to gestational age was true for total neutrophil cell counts. In neonates with increased levels of C-reactive protein during the first 5 d of life (n = 43), the percentages of activated cells after PBS and fMLP incubation were higher than those of neonates without signs of infection. The relationship of neutrophil respiratory burst and neutrophil cell counts to gestational age might reflect at least in part a reason for the increased susceptibility of neonates to infections. Furthermore, determination of respiratory burst may prove to be a new laboratory parameter of neonatal infection.
Adult↗
Neonatal neutropenia in low birthweight premature infants.
Neutropenia, as defined by common reference values, occurs often in neonates. Its incidence, causes, and clinical consequences have not been studied extensively in premature neonates. Of 208 consecutive infants with birthweight up to 2000 g, 121 (58%) had neutropenia. Low gestational age and low birthweight correlated with the incidence of neutropenia. Less than half of the neutropenic episodes could be attributed to infections, the others were related to specific perinatal events and due to drug therapy or were of unknown cause. Neutropenia following treatment with certain antibiotics was the most common cause of neutropenia occurring after the second week of life. The high incidence of neutropenia in premature neonates raises questions about application of these reference ranges to low birthweight infants and suggests the need for new reference values.
Anti-Bacterial Agents↗
[Persistent fetal circulation syndrome].
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Extracorporeal Membrane Oxygenation↗
Prognosis and outcome of neonates treated either with veno-arterial (VA) or veno-venous (VV) ECMO.
A comparison was done between neonates requiring veno-arterial (VA) ECMO (too small jugular vein, inability to insert a 12 Fr double lumen catheter or cardio-circulatory instability) and neonates treated with veno-venous (VV) ECMO in the same period of time. From 1991-1995 ECMO was done in 48 neonates after failure of maximum conventional treatments, NO-inhalation and HFOV. 30/48 babies were treated with VV-ECMO, with a switch to VA-ECMO later on in 3 of them. In 18 infants VA-ECMO was installed primarily. Differences between the VA- and VV-ECMO group were: the OI was higher in the VV-treated babies (62 +/- 20 vs. 48 +/- 13, p < 0.03), as were birth weight (3385 +/- 570 vs. 2963 +/- 653 g, p < 0.04), gestational age (39.7 +/- 1.6 vs. 37.9 +/- 2.7 weeks, p < 0.01) and MAP (18.7 +/- 2.2 vs. 17.1 +/- 2.4 cm H2O, p < 0.05). Severe ICH's occurred more frequently in the VA-treated babies (29 vs. 7%, p < 0.05), the rate of other complications was equal. The mortality rates were 43% (VA) and 15% (VV), p < 0.05. About one third of neonatal ECMO candidates will be treated with VA-ECMO, even if the VV-ECMO technique is available. Need for VA-ECMO implies--due to a higher number of preterm babies and a greater severity of illness before ECMO--a higher incidence of ICH's and a higher mortality rate.
Birth Weight↗
High-frequency oscillatory ventilation and nitric oxide: alternative or complementary to ECMO.
One hundred and seventy-seven term or near-term neonates were referred to an ECMO center for severe PPHN-associated diseases. In 2 time periods from 1987 to 1991 and from 1992 to April 1995 alternative treatment modes were tried in an attempt to obviate ECMO. During the first time period patients underwent trial high-frequency oscillatory ventilation before ECMO. In the second time period patients first received inhaled NO followed by HFOV in a non-responders. If this also failed HFOV was combined with INO. In both time periods about 40% of the patients were spared ECMO treatment by these alternative treatment modalities. INO only benefited 15% of the ECMO candidates who apparently had fared just as well on HFOV alone in the preceding time period. While patients who were improved by INO were spared HFOV with its potential severe complications, i.e. air leaks and cardiocirculatory instability, more extended long-term studies will have to show which of these 2 treatment modalities (INO or HFOV) should be given first priority in an attempt to avoid ECMO in neonates with severe respiratory failure.
Administration, Inhalation↗
Ophthalmic findings in partial monosomy 4p (Wolf syndrome) in combination with partial trisomy 10p.
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Abnormalities, Multiple↗
[Eye manifestations of shaken baby syndrome. A case presentation].
UNLABELLED: Violent shaking is a type of child abuse which may cause intracranial hemorrhages combined with retinal and vitreous bleeding. Fundus bleeding is similar to that in Terson syndrome. However, in the shaken baby syndrome the intraocular hemorrhages may precede both the clinical and radiologic recognition of subdural haematoma. CASE REPORT: We present a 4-months-old baby with convulsions and additional extensive bleeding of the fundus. Neither the ocular findings nor the seizures could be explained by minimal lesions of external trauma. Repeated cranial computed tomography showed increasing intracerebral bleeding with consecutive brain atrophy. Fundus bleeding completely disappeared. CONCLUSION: When child abuse is suspected, ophthalmological examination is most important to detect fundus bleeding, which, in the absence of birth trauma or any other supportive evidence of external trauma or other diseases, is the leading symptom of the shaken baby syndrome.
Battered Child Syndrome↗
Serum concentrations of granulocyte colony-stimulating factor in healthy term and preterm neonates and in those with various diseases including bacterial infections.
The neonate is uniquely susceptible to severe and overwhelming bacterial infections. One of the most important deficits in the neonatal host defense system seems to be a quantitative and qualitative deficiency of the myeloid and the phagocytic system. Future optimal therapy of neonatal sepsis may include the use of adjuvant immunologic therapy. Granulocyte colony-stimulating factor (G-CSF) has been shown to induce neutrophilia and to enhance mature effector neutrophil function. To evaluate the role of G-CSF with respect to infection, we examined serum levels of G-CSF in term and preterm neonates, using an enzyme-linked immunosorbent assay method. G-CSF levels in healthy neonates showed peak levels up to 7 hours after birth, followed by an increase in total neutrophil cell (TNC) counts. Both G-CSF levels determined between 4 and 7 hours after birth and peak TNC counts correlated with the gestational age of the neonates. The state of nutrition, maternal treatment with glucocorticoids, maternal infection and hypertension, and the mode of delivery influenced peak G-CSF levels. Neonates with signs of infection between 4 and 7 hours after birth had higher levels of G-CSF than did healthy neonates (1,312 +/- 396 pg/mL v 176 +/- 19 pg/mL). In conclusion, the presented results of serum concentrations of G-CSF in relation to TNC counts and various diseases suggests an important role of G-CSF in the regulation of granulopoiesis during the neonatal period.
Bacterial Infections↗
[Results of extracorporeal membrane oxygenation (ECMO) and perspectives for the asphyctic newborn infant].
Extracorporeal life support with membrane oxygenation (ECMO) has been successfully introduced into the management of asphyctic neonates. Two case studies are given to show the importance of this method in antenatal obstetric management.
Asphyxia Neonatorum↗
Neurological findings in newborn infants after extracorporeal membrane oxygenation, with special reference to the EEG.
Seventeen newborn infants were treated with extracorporeal membrane oxygenation (ECMO). Two died shortly after the start of ECMO due to the underlying disease, two died later in the course due to a lack of recovery of lung function and two others died weeks after ECMO from renal damage and a cardiac defect. Of the survivors, nine are developing normally (aged between one and four years) and two are severely disabled because of infarctions of the left hemisphere, acquired before and after ECMO. Intermittent-discontinuous EEGs did not indicate a poor prognosis if normalization of the EEG occurred within seven days. However, infarcted areas on ultrasonography, persistent EEG changes or deteriorating findings indicated disability or early death.
Brain↗
[Extracorporeal membrane oxygenation (ECMO) in acute cardiovascular failure caused by myocarditis].
Main indication for extracorporeal membrane oxygenation (ECMO) is respiratory failure in the newborn. Less frequently ECMO is used for cardiac support. We report on a 4 months old boy, who suddenly fell ill with an acute viral myocarditis and heart failure (left-ventricular shortening fraction lowered to 17%). After failure of conventional management and resuscitation (twice) due to asystolic, veno-arterial ECMO was installed for a total time of 4 days. Under ECMO there was complete recovery of left-ventricular function; the infant was discharged 1 month after admission to hospital. ECMO-therapy should not only be considered in children with respiratory failure, but also in those with potentially reversible cardiac failure.
Echocardiography↗