Use of permissive hypercapnia in the ventilation of infants with respiratory syncytial virus infection

We wished to retrospectively evaluate the effects of permissive hypercapnia (PHY) on barotrauma, mortality and length of stay when applied to ventilated infants with respiratory syncytial virus (RSV) bronchiolitis. Nineteen control infants with RSV induced respiratory failure were treated with conventional ventilation (April 1991–January 1994), after which time PHY was adopted as unit policy. A further 28 infants were then treated with PHY (January 1994–April 1996). Demographic and physiological data were collected from admission, and outcome variables including length of stay, barotrauma and mortality were recorded. The PHY group showed a significantly higher mean pCO₂ (7.6 vs 5.2 kPa), a lower mean pH (7.34 vs 7.40), and a reduction in maximal peak inspiratory pressures (25 vs 30 cmH₂O). Mortality, barotrauma, use of neuromuscular blockade and nosocomial infection did not differ between groups. There was a trend towards increased length of ventilation in the PHY group (median 7 vs 5 days). Conclusion Based on this retrospective data we can show no benefit for the use of permissive hypercapnia as a ventilatory strategy in this patient group. A prospective randomised controlled trial is warranted to accurately assess the outcome variables and cost implications of this strategy. Received: 22 June 1998 / Accepted in revised form: 25 August 1998     

Chest wall rigidity in two infants after low-dose fentanyl administration

Since its introduction into clinical practice, it has been known that fentanyl and other synthetic opioids may cause skeletal muscle rigidity. Involvement of the respiratory musculature, laryngeal structures, or the chest wall may impair ventilation, resulting in hypercarbia and hypoxemia. Although most common with the rapid administration of large doses, this rare adverse effect may occur with small doses especially in neonates and infants. We present 2 infants who developed chest wall rigidity, requiring the administration of neuromuscular blocking agents and controlled ventilation after analgesic doses of fentanyl. Previous reports regarding chest wall rigidity after the administration of low-dose fentanyl in infants and children are reviewed, the pathogenesis of the disorder is discussed, and treatment options offered.     

Cardiopulmonary interaction during partial liquid ventilation in surfactant-treated preterm lambs

Gas ventilation following instillation of perfluorochemical (PFC) liquid, partial liquid ventilation (PLV), improves gas exchange and pulmonary mechanics in neonatal animals and humans with severe respiratory distress. The effect of PLV on cardiac contractility, performance, pulmonary blood flow and ductal shunt has not been fully described. To this end, we evaluated these indices of cardiopulmonary function in eight conventionally gas ventilated, surfactant-treated premature lambs (125 days gestation) before and during PLV. Animals were instrumented with central venous and aortic lines. Serial evaluation of arterial blood chemistry/pressure, and pulmonary mechanics was performed; cardiac contractility, performance, pulmonary blood flow and ductal shunts were serially assessed by echocardiography. As compared to conventional gas ventilation, during PLV there was a significant decrease in left ventricular meridian (22.5 ± 6.6 SE vs 8.1 ± 1.4 SE g/cm², P < 0.02) and circumferential wall stress (54.1 ± 16.5 vs 24.4 ± 3.8 SE g/cm², P < 0.04) at end systole. The fall in wall stress at end systole was associated with a significant decrease in left ventricular internal diameter (1.2 ± 0.05 SE vs 1.04 ± 0.045 SE cm; P < 0.01). There were no significant changes in heart rate, systemic arterial and central venous pressures, systemic vascular resistance, left ventricular shortening and ejection fractions during PLV. The decrease in wall stress was associated with a significant decrease in mean airway pressures (15.9 ± 1.1 SE vs 9.9 ± 0.2 SE cmH₂O; P < 0.05) and ostensibly a change in intrathoracic pressures during PLV. There were no significant differences in blood flows (pre vs during PLV; ml/min/kg): pulmonary (226 ± 62 SE vs 293 ± 65 SE), aortic (237 ± 36 SE vs 204 ± 21 SE), and left to right ductal (119 ± 25 SE vs 105.5 ± 26 SE) measured before and during PLV. Conclusion Cardiac output and pulmonary blood flow do not change significantly during PLV and therefore do not appear to contribute to improved gas exchange. This stable cardiac performance occurs at lower wall stress and thereby more advantageous energetic conditions. Received: 18 July 1996 and in revised form: 28 May 1997 / Accepted: 31 May 1997     

Cat-scratch disease simulating a malignant process of the chest wall

Cat-scratch disease is a well-known cause of regional adenopathy in immunocompetent children. Rarely, patients may present with symptoms simulating a neoplastic disease. The case of a 12-year-old boy with fever, swelling of the chest wall and hepatosplenic nodules is reported. Histological analysis of biopsy specimen obtained from the chest wall lesion and the liver revealed granulomatous reaction without malignant cells. Serological investigations were positive for Bartonella species. The symptoms and the lesions disappeared after oral antibiotic therapy (ciprofloxacin) was started. The patient remained symptom-free 12 months later. Conclusion The present case emphasizes the wide spectrum of clinical manifestations associated with cat-scratch disease which should be investigated as differential diagnosis of manifestations suggesting a neoplastic disease in children. Received: 10 February 1998 / Accepted in revised form: 5 August 1998     

Impact of new treatments for respiratory failure on outcome of infants with congenital diaphragmatic hernia

Term and near-term newborn infants with congenital diaphragmatic hernia (CDH), symptomatic in the first 24 h of life or diagnosed antenatally, without other significant malformations were treated at our hospital with high-frequency oscillatory ventilation (HFOV) as a primary modality of ventilation and elective delay in surgical repair after a period of stabilisation. When unresponsive to HFOV, infants were treated with surfactant, inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) to achieve pre-operative stabilisation. From October 1994 to August 1998, 28 newborn infants with CDH were managed with such treatment; mean birth weight was 3184 ± 535 g and gestational age 38.5 ± 1.85 weeks. Age at operation was 68 ± 35 h. In 9 cases, large diaphragmatic defects required the use of a prosthetic patch (Gore-tex). HFOV was used for primary ventilation in inborn patients (n = 16); outborn infants (n = 12) were placed on HFOV at admittance. A total of 15 patients (53%) were stabilised using only HFOV. Bovine surfactant was administered in 12 infants and 4 responded. iNO was used in eight infants and five responded. ECMO was used in three outborn patients and one survived. Overall, out of 28 infants, 25 survived (89%). Neurological examination (Amiel-Tison and Grenier) of 15 infants showed transient anomalies at 6 months in 40% of infants, while a normal neurological examination was present in all patients at 1 year. The development quotient (Griffiths scales) was within normal values in ten and mildly abnormal in two infants tested at 1 year. Conclusion Management based on early HFOV, eventually associated with surfactant, iNO and ECMO to achieve preoperative stabilisation, resulted in a good survival rate (89%) and good neurodevelopmental outcome at 1 year of age in infants with CDH. Received: 10 November 1998 and in revised form: 3 March 1999 / Accepted: 16 March 1999     

Resuscitation at birth

It is only in recent years that the techniques used for resuscitation at birth have come under critical review and there have been very few controlled trials to assess their efficacy. Recent studies have indicated that the large majority of asphyxiated term babies can be resuscitated using air rather than 100% oxygen, possibly reducing damage from oxygen free radicals during re-perfusion. Physiological studies have shown that inflation pressures of 25–30 cmH₂O maintained for up to 1 s, only result in approximately 40% of the mean inspiratory volume achieved by babies who breathed spontaneously at birth. These spontaneous inflation volumes can be matched either by maintaining the first inflation for 3 s, or by using pressures of up to 50 cmH₂O for 300 ms, a pattern adopted by spontaneously breathing babies. Bag and mask systems are even less effective, often depending on the Head paradoxical reflex to stimulate respiration rather than producing adequate tidal exchange. Face mask T-piece devices provide more effective ventilatory exchange and are easier to use. Conclusion Although the pattern of ventilatory support in current use often leads to successful resuscitation of asphyxiated babies at birth, more physiological and randomised controlled studies are needed to refine techniques in order to limit babies' exposure to potentially damaging hypoxia to the minimum. Received: 19 January 1998 / Accepted: 19 January 1998     

Unusual site for oesophageal perforation in an extremely low birth weight infant

A male infant born at 26 weeks gestation became unwell at 10 days of age with blood-stained pharyngeal aspirates. The chest radiograph revealed a feeding tube in the right pleural cavity, indicating a perforation of the thoracic oesophagus. The infant had had a chest drain inserted on the right side on two previous occasions. These had been allowed to remain across the mediastinum at the site of the subsequent perforation. The infant was successfully managed conservatively with no long-term sequelae The unusual site of the perforation led us to conclude that pressure necrosis from the drains was a contributing factor in the aetiology. Conclusion Oesophageal perforations in the neonate, in contrast to the adult, can be managed conservatively. Received: 11 March 1997 and in revised form 24 February 1998 / Accepted: 3 March 1998     

Growth hormone treatment increases CO2 response, ventilation and central inspiratory drive in children with Prader-Willi syndrome

We studied whether the beneficial effects of growth hormone (GH) treatment on growth and body composition in PWS are accompanied by an improvement in respiratory function. We measured resting ventilation, airway occlusion pressure (P_0.1) and ventilatory response to CO₂ in nine children, aged 7–14 years, before and 6–9 months after the start of GH treatment. During GH treatment, resting ventilation increased by 26%, P_0.1 by 72% and the response to CO₂ by 65% (P < 0.002, <0.04 and <0.02, respectively). This observed increase in ventilatory output was not correlated to changes in body mass index. Conclusion Treatment of children with Prader-Willi syndrome (PWS) seems to have a stimulatory effect on central respiratory structures. The observed increase in ventilation and inspiratory drive may contribute to the improved activity level reported by parents of PWS children during growth hormone therapy. Received: 28 April 1998 / Accepted: 6 April 1999     

A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants

This study was carried out to assess the feasibility of late cord clamping of 45 s in preterm infants delivered mainly by caesarean section and the effects on post-partal adaptation and anaemia of prematurity. Prior to delivery, 40 infants of <33 gestational weeks were randomised to either 20 s or 45 s of late cord clamping. After the first shoulder was delivered, oxytocin was given intravenously to the mother in order to enhance placento-fetal transfusion while the infant was held below the level of the placenta. The 20 infants in group 1 (20 s) had a mean birth weight of 1070 g and a mean gestational age of 29 + 4/7 weeks versus 1190 g and 30 weeks in group 2 (45 s). On day 42 of life there were ten infants without transfusions in group 2 versus three in group 1 (P < 0.05). Out of the 20 infants in group 1, 19 and 15/19 in group 2 were delivered by caesarean section. There were no significant differences in Apgar scores, temperature on admission, heart rate, blood pressure and requirements for artificial ventilation. Conclusion Delayed cord clamping of 45 s is feasible and safe in preterm infants below 33 weeks of gestation. It is possible to perform the procedure at caesarean section deliveries and it should be performed whenever possible. It reduces the need for packed red cell transfusions during the first 6 weeks of life. Received: 10 February 2000 / Accepted: 12 April 2000     

A detailed analysis of changes in serum C-reactive protein levels in neonates treated for bacterial infection

A prospective study was undertaken to characterize the rate of increase, time of peak values and rates of decrease in serum concentrations of C-reactive protein (CRP) in a group of infants treated for neonatal bacterial infection. A total of 176 consecutively admitted neonates with birth weight >1500 g and without mechanical ventilation or central lines in situ, who received antibiotic therapy for suspected bacterial infection, were enrolled. The changes in serum CRP concentration in 60 of 63 infants who had CRP values above 20 mg/l 24–48 h after the beginning of treatment were analysed in detail. Initial increase rates in serum CRP levels of up to 4.5 mg/l per h were documented peak were reached at a mean of 19.5 h after antibiotic therapy had been initiated, but in some patients an increase in serum CRP levels occurred up to 40–48 h after the beginning of treatment. The mean serum half-life of CRP in infected neonates was 21 h (range 11.2–38 h). Conclusion In neonates with bacterial infection (defined by a combination of clinical signs and increased C-reactive protein and immature-total quotient values) no differences in the overall pattern nor in any of the particular phases of the C-reactive protein response curves could be observed between neonates with positive (n = 13) or negative blood cultures (n = 47). Received: 18 July 1997 / Accepted in revised form: 5 May 1998     

A Japanese family with autosomal dominant growth hormone deficiency

We report a 1-year-old Japanese boy and his father with isolated growth hormone deficiency II. In both cases, a G → A transition of the first base of the donor splice site of intron 3 of the growth hormone-1 gene was detected. All unaffected family members were homozygous normal. Conclusion This is the fourth reported case of autosomal isolated growth hormone deficiency II with a G → A transition. The CG dinucleotide at the exon 3-intron 3 junction of the growth hormone-1 gene appears to be a hot spot for point mutations. Received: 1 July 1998 / Accepted in revised form: 16 December 1998     

The effects of body positioning on sucking behaviour in sick neonates

Some infants show better oxygenation in the prone position compared to the supine position while they are bottle-fed; however, the reason for this phenomenon is not clear. The purpose of this study was to obtain a better understanding of the effects of body position on the oral feeding performance, i.e. the sucking pressure, frequency, efficiency, and ventilation. A total of 14 infants (12 full-term, 2 preterm), who often showed O₂ desaturation (SpO₂ < 90) during oral feeding, were enrolled in the study. The infants were fed either in the supine position or in the prone position throughout feeding. Oxygen saturation was recorded with a pulse oxymeter. The sucking pressure was measured with a 1 mm I.D. silicone tube inserted into the artificial nipple. The ventilation volume during bottle feeding was measured with a pneumotachograph. The prone position resulted in better oxygenation (97.2 ± 0.6% prone, 92.5 ± 0.9% supine, P < 0.05) and larger tidal volume (6.4 ± 0.8 ml/kg prone and 4.9 ± 0.6 ml/kg supine, P < 0.05), although the minute ventilation during bottle-feeding was not different from that in the supine position. In the prone position, the sucking pressure and frequency were higher and the duration of each suck was shorter. Conclusion Sucking in the prone position may to some extent reduce disadvantages of oral feeding on ventilation. Received: 18 January 2000 / Accepted: 9 May 2000     

Persistent pulmonary hypertension of the term neonate: a strategy for management

The management of 32 consecutive term infants referred with persistent pulmonary hypertension of the newborn were reviewed. Despite indices suggesting severe cardiorespiratory failure with a median alveolar-arterial oxygen gradient of 591 torr (inter-quartile range 432–618) and oxygenation index of 31 (18–44), all but one patient responded to conventional treatment with inhaled nitric oxide and high frequency oscillatory ventilation. Conclusion Patients should be referred early to centres where maximal conventional support can be offered before consideration for extracorporeal membrane oxygenation. Received: 6 August 1998 / Accepted in revised form: 3 March 1999     

Risk factors for type I diabetes mellitus in children in Austria

The aim of this study was to investigate environmental risk factors in the development of type 1 diabetes mellitus in a population-based case-control study. Parents of all patients with manifestation of type 1 diabetes between 1989 and 1994 in Vienna were asked to complete a questionnaire (n = 114). Control children (n = 495), matched for age and sex, were randomly recruited from all schools in Vienna. Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015). Children with diabetes were more likely to be second- or third-born children (P < 0.05) and fewer went to kindergarten than the control group children (P = 0.007). No significant difference in duration of gestation, percentage of delivery by caesarean section, birth weight or length was found. Neonatal jaundice was more often observed in the patient group (P = 0.038). Breast feeding was reported by 82.7% of mothers of diabetic children and by 81% of mothers of control children, and the duration of breast feeding was longer in patients than in controls (n.s.). Conclusion In our study, the development of type 1 diabetes mellitus was associated with higher paternal age and neonatal jaundice. No correlation could be found with dietary intake of cow's milk products in early infancy, vaccination and other environmental factors. Received: 5 May 1998 / Accepted in revised form: 27 August 1998     

Early vitamin K deficiency bleeding after maternal phenobarbital intake: management of massive intracranial haemorrhage by minimal surgical intervention

Vitamin K deficiency bleeding within the first 24 h of life is caused in most cases by maternal drug intake (e.g. coumarins, anticonvulsants, tuberculostatics) during pregnancy. Haemorrhage is often life-threatening and usually not prevented by vitamin K prophylaxis at birth. We report a case of severe intracranial bleeding at birth secondary to phenobarbital-induced vitamin K deficiency and traumatic delivery. Burr hole trepanations of the skull were performed and the subdural haematoma was evacuated. Despite the severe prognosis, the infant showed an unexpected good recovery. At the age of 3 years, neurological examinations were normal as was the EEG at the age of 9 months. CT showed close to normal intracranial structures. Conclusion This case report stresses the importance of antenatal vitamin K prophylaxis and the consideration of a primary Caesarean section in maternal vitamin K deficiency states and demonstrates the successful management of massive subdural haemorrhage by a limited surgical approach. Received: 4 July 1997 and in revised form: 30 October 1997 / Accepted: 7 November 1997     

The complement component C4 in sudden infant death

The aim of the present study was to compare partial deletions of the complement C4 gene in victims of totally unexplained sudden infant death (SID) (n = 89) and borderline SID (n = 15) with and without slight infections prior to death, in cases of infectious death (n = 19), and in living infants with and without infections (n = 84). The SID and borderline SID groups were pooled. In this total SID group slight infections prior to death was associated with deletion of either the C4A or the C4B gene (P = 0.033), and the SID victims with such infections had a higher deletion frequency than the controls (P = 0.039). There were no differences between the living infants with and without upper airway infections. Conclusion The present study confirms that partial deletions of the C4 gene in combination with slight upper airway infections may be a risk factor in sudden infant death. Received: 8 June 1998 / Accepted in revised form: 7 September 1998     

Ureaplasma urealyticum colonization and bronchopulmonary dysplasia: a comparative prospective multicentre study

To determine the role of tracheal colonization at birth with Ureaplasma urealyticum and other pathogenic bacteria with regard to the development of bronchopulmonary dysplasia (BPD), 97 premature infants with very low birth weight (<1500 g) were followed prospectively over 30 days in a multicentre study. Of those infants, 35 were colonized with Ureaplasma urealyticum (group Ia), 22 with other pathogenic bacteria (group Ib) and 40 infants with sterile tracheal aspirates served as controls (group II). Colonization with Ureaplasma urealyticum or with pathogenic bacteria independently increased the risk of developing BPD as compared to the controls (OR 2.55; 95% CI [1.11, 5.87]). Among Ureaplasma urealyticum and bacterial colonized infants, duration of mechanical ventilation and oxygen requirement were significantly longer than among controls (P < 0.05); during the interval of 11 to 35 days of life, every additional day of ventilation significantly increased the risk of BPD (OR 1.22; CI [1.12, 1.32]). The rate of oxygen supplementation, which was similar in both groups during the first 2 weeks of life, was significantly higher among the colonized infants at day 21 (0.38 ± 0.18 and 0.39 ± 0.16 vs 0.31 ± 0.13, P < 0.05) and at day 28 (0.38 ± 0.21 and 0.34 ± 0.15 vs 0.28 ± 0.12, P < 0.05). For infants still ventilated at age of 28 days, Ureaplasma urealyticum and bacterial colonization were associated with a significant higher risk for BPD than for uncolonized controls (OR 5.53; [1.27, 24.02]. Association of Ureaplasma urealyticum and of bacterial colonization and BPD was not weakened after adjustments were made in a multivariate analysis for other significant risk factors. Conclusion Ureaplasma urealyticum colonization is as an important risk factor in the development of bronchopulmonary dysplasia as bacterial colonization even after treatment with surfactant. Received: 23 January 1997 and in revised form: 30 December 1997 / Accepted: 5 January 1998     

Hearing in newborn infants of opiate-addicted mothers

To investigate effects of maternal drug abuse on neonatal hearing, auditory brain-stem evoked potentials were recorded in 132 consecutive newborn infants of mothers who had taken heroin or methadone during pregnancy, alongside 1016 neonates with and 483 hospitalized neonates without risk factors, as defined by the Joint Committee on Infant Hearing. In infants antenatally exposed to opiates, the rate of severe bilateral hearing impairment (≥50 dB) did not differ from that of hospitalized neonates without risk factors (1.5% vs 2.5%). In contrast, intra-uterine toxoplasmosis, syphilis, or cytomegalovirus infection, bilirubin serum concentrations >25 mg/dl, craniofacial anomalies, and mechanical ventilation for 5 days or more were independently associated with increased rates of severe hearing impairment by analysis of all 1631 infants studied. Conclusion Newborns of opiate-addicted mothers are not at increased risk for early onset hearing loss. Received: 1 July 1998 / Accepted: 17 November 1998     

The role of acoustic rhinometry in the diagnosis of adenoidal hypertrophy in pre-school children

Adenoidal hypertrophy is a common problem in pre-school children and diagnosis depends mostly on evaluation of clinical symptoms and signs. Investigative techniques to assess adenoidal size often do not add to this information. Recent reports have suggested a role for acoustic rhinometry in this situation. A total of 49 children consecutively referred to the Department of Otorhinolaryngology, University of Mainz, with evidence of adenoidal enlargement underwent acoustic rhinometry pre- and postoperatively and were compared to an age-matched control group from a local kindergarten school. Adenoidal size was visually estimated at surgery and questionnaires were completed by parents of symptomatic children. Acoustic rhinometry was not able to differentiate controls (mean nasopharyngeal cross-sectional area 1.34 +/− 0.47 cm², n = 35) from symptomatic children admitted for adenoidectomy (mean nasopharyngeal cross-sectional area 1.66 +/− 0.83 cm², n = 42, P = 0.53). Acoustic rhinometry was advantageous for patients with adenoidal hypertrophy in two situations. Firstly a subgroup of patients with complete nasopharyngeal obstruction could be identified (P = 0.03) and secondly all patients with a postnasal space less than 1.2 cm² clinically benefited from adenoidectomy. Conclusions Acoustic rhinometry, in general, is not suitable for assessing adenoidal size in pre-school children. Physical limitations of currently available acoustic rhinometers are likely to explain the limited clinical value of this investigative technique. Received: 26 February 1998 / Accepted in revised form: 22 June 1998     

Elevated platelet activating factor in the tracheal aspirate at birth and signs of intra-uterine inflammation in infants with neonatal pulmonary emphysema

To investigate the pathophysiology of the neonatal pulmonary emphysema, we assayed platelet activating factor (PAF) in the tracheal aspirates of the low birth weight infants. A total of 29 neonates (birth weight <1750 g) who required mechanical ventilation were enrolled. Tracheal aspirates were obtained within 48 h and blood samples collected within 24 h of life. PAF was assayed on the basis of its ability to cause aggregation of washed rabbit platelets. PAF was significantly elevated in four infants who showed pulmonary emphysema within the 1st week of life (median 24 pg/g lipid phosphorus, range 9.9–200) compared with those detected in the other three groups of infants; infants with respiratory distress syndrome (RDS) in whom chronic lung disease (CLD) did not develop (median 1.8 pg/g lipid phosphorus, range 0–30; P < 0.05), infants without RDS nor CLD (median 0.64 pg/g lipid phosphorus, range 0–14; P < 0.05) and infants with other types of CLD (median 1.1 pg/g lipid phosphorus, range 0–1.8; P < 0.01). The four infants who developed pulmonary emphysema within the 1st week of life, had significantly elevated serum IgM and neutrophilia at birth. The increased amount of PAF in the tracheal aspirates shows the presence of inflammation in the lung at birth. The elevated serum IgM level and neutrophilia indicate that the inflammation begins in utero. Conclusion Our data suggest that neonatal pulmonary emphysema is caused by intra-uterine inflammation increasing platelet activating factor in the lungs. Platelet activating factor may play a role in aggravating the process of pulmonary emphysema. Received: 20 July 1998 / Accepted: 14 February 1999