F. Reiterer

Activation of the clotting system during extracorporeal membrane oxygenation in term newborn infants

OBJECTIVES To determine the degree of clotting activation that occurs with the usual anticoagulation regimen with systemic heparinization. METHODS To allow a standardized comparison of the patients, this study focused on the first 48 hours of extracorporeal membrane oxygenation (ECMO) in term newborn infants. The ECMO perfusion circuit consisted of a roller pump, silicone membrane lungs, and silicone rubber tubing. Coagulation was controlled routinely by measuring prothrombin time, fibrinogen, antithrombin III, and reptilase time. Platelet counts, activated clotting time, and heparin concentration were controlled regularly. The following specific activation markers of the clotting system were measured: prothrombin activation fragment 1 + 2(F1+2), thrombin-antithrombin III complexes, and D-dimer. Measurements were done before the start of ECMO, after 5 minutes, and at hours 1, 2, 3, 4, 6, 12, 24 and 48. RESULTS All seven term infants had excessively high levels of clotting activation markers within the first 2 hours of ECMO: F1+2, 11.6(+/- O.9) nmol/L (mean +/- SEM); thrombin-antithrombin, 920(+/- 2.2) microg/L; D-dimer, 15.522(+/- 3.689) ng/L. During the next 46 hours of ECMO, F1+2 and thrombin-antithrombin III complexes decreased from those high values, whereas D-dimer did not. The increase of activation markers was accompanied by low fibrinogen, low platelet counts. and prolongation of reptilase time. CONCLUSIONS These findings fit the pattern of consumptive coagulopathy during neonatal ECMO, especially in the first 24 hours.

Congenital central hypoventilation syndrome (Ondine's curse syndrome) in two siblings: Delayed diagnosis and successful noninvasive treatment

Congenital central hypoventilation syndrome (CCHS, Ondines curse syndrome) is a rare respiratory disorder; less than 100 cases have been reported. Familiality of the disease has been discussed, but only few familial cases have been reported so far. In this report we describe the occurrence of CCHS in two male siblings. Diagnosis was established only at the age of 4 years in the first case, although the patient had disease related symptoms since early infancy. The second patient was one of dizygotic twins, he was diagnosed with CCHS at the age of 8 months. Up to that age only moderate desaturations had been observed. The other twin was unaffected by the disease. Both patients were successfully treated by nocturnal positive-pressure ventilation via a specially adapted face mask. They show satisfactory physical and neurologic development.

Partial liquid ventilation combined with inhaled nitric oxide in acute respiratory failure with pulmonary hypertension in piglets

This study was a prospective, randomized, controlled design to evaluate gas exchange, lung mechanics, and pulmonary hemodynamics during partial liquid ventilation (PLV) combined with inhaled nitric oxide (NO) in acute respiratory failure (ARF) with pulmonary hypertension (PH). ARF with PH was induced in 12 piglets weighing 9.7-13.7 kg by repeated lung lavages and the continuous infusion of the stable endoperoxane analog of thromboxane. Thereafter the animals were randomly assigned either for PLV or conventional mechanical ventilation (CMV) at a fractional concentration of inspired O2(Fio2) of 1.0. Perfluorocarbon (PFC) liquid (30 mL kg-1) was instilled into the endotracheal tube over 5 min followed by 5 mL kg-1h-1. All animals were treated with different concentrations of NO (1-10-20 ppm) inhaled in random order. Continuous monitoring included ECG, right atrial (Pra), mean pulmonary artery (Ppa), pulmonary capillary(Ppc′), and mean arterial (Pa) pressures, arterial oxygen saturation, and mixed venous oxygen saturation measurements. During PLV Pao2/Fio2 increased significantly from 8.2 ± 0.4 kPa to 34.8 ± 5.1kPa (p < 0.01), whereas Pao2/FiO2 remained constant at 9.5 ± 0.4 kPa during CMV. The infusion of the endoperoxane analog resulted in a sudden decrease of Pao2/Fio2 from 34.8 ± 5.1 kPa to 14.1 ± 0.4 kPa (p < 0.01) in the PLV group and from 9.5 ± 0.4 kPa to 6.9 ± 0.2 kPa(p < 0.05) in the control group. Inhaled NO significantly improved oxygenation in both groups (Pao2/Fio2: 45.7 ± 5.3 kPa during PLV and 25.9 ± 4.7 kPa during CMV). During inhalation of NO mean Ppa decreased significantly from 7.8 ± 0.26 kPa to 4.2 ± 0.26 kPa (p < 0.01) in the PLV group and from 7.4 ± 0.26 kPa to 5.1 ± 0.13 kPa (p < 0.01) in the control group. As documented in the literature PLV significantly improves oxygenation and lung mechanics in severe ARF. In addition, when ARF is associated with severe PH, the combined treatment of PLV and inhaled NO improves pulmonary hemodynamics resulting in better oxygenation.

Venous thrombosis in and after extracorporeal membrane oxygenation: detection and follow-up by color Doppler sonography

The purpose of our study was to evaluate thrombosis of venous vessels during and after extracorporeal membrane oxygenation (ECMO) using color Doppler sonography. We prospectively performed serial color Doppler sonography investigations in 30 ECMO patients [age: newborn to 3 years, male:female = 20:10, venoarterial (VA) ECMO = 18, venovenous (VV) ECMO = 12]. During ECMO obstruction and/or thrombosis of the superior vena cava (SVC) was observed in 2 neonates on VA ECMO. Furthermore, a thrombotic clot from an initially open duct of Arantii with partial portal vein thrombosis, reaching into the inferior vena cava (IVC), occurred despite adequate heparinization. After ECMO, late septic SVC thrombus occurred in one neonate. IVC thrombus was observed in two pediatric VV ECMO patients. The overall incidence of venous clots was 20 % (6 of 30). Routine color Doppler sonography monitoring of vessels in children on and after ECMO was found to be useful for early detection of venous thrombosis. It enabled consequent administration of appropriate therapy as well as follow-up after decannulation and reconstruction.

Spontaneous gastrointestinal perforation in very-low-birth-weight infants – a rare complication in a neonatal intensive care unit

Over a 6-year period (1989–1995), gastrointestinal (GI) perforation was diagnosed in nine preterm infants (mean gestional age 27 weeks, mean birth weight 872 g). Three presented with necrotizing enterocolitis (NEC), two with indwelling-tube-induced perforation of the stomach, one with small-left- colon syndrome, and another with meconium ileus. Spontaneous intestinal perforation occurred in two similar very-low-birth-weight (VLBW) infants, in the distal ileum, on days 8 and 9 of life, respectively. The only clinical sign was extensive abdominal distension, and abdominal X-ray studies revealed free peritoneal air. All findings were distinct from those associated with NEC. Their further clinical course was complicated by reperforation on day 32 and 39, respectively. They subsequently recovered and presented without GI problems at the corrected ages of 4 and 2 months, respectively. In contrast to high mortality of 57% in the group with non-spontaneous intestinal perforations, spontaneous perforation seems to have a good prognosis even in VLBW infants if diagnosed and treated promptly.

The influence of head position on the intracranial pressure in preterm infants with posthemorrhagic hydrocephalus

In order to measure the intracranial pressure (ICP) of 8 newborn with posthemorrhagic hydrocephalus (group A) we used the noninvasive technique via the anterior fontanel (Ladd monitor). The ICP was monitored in two different head positions (30° elevated, horizontal). The median measurements were: elevated head position, 13 mm Hg, horizontal head position, 16 mm Hg. For comparative reasons, we also measured the ICP of 12 healthy newborns (group B). The median results were: elevated head position, 4 mm Hg, horizontal head position, 6.5 mm Hg. Significant differences were found between groups.

Meconium aspiration syndrome--a 21-years' experience from a tertiary care center and analysis of risk factors for predicting disease severity.

Aim of this study was to describe the course of perinatal factors in neonates with meconium aspiration syndrome (MAS) from 1990 to 2010 and to determine risk factors for a severe course of the disease.All neonates with MAS hospitalized in our level III neonatal intensive care unit from 1990 to 2010.Retrospective analysis of trends of perinatal factors in neonates with MAS over time and of the association of these factors with severe MAS (need for invasive mechanical ventilation for ≥7 days, or need for high frequency oscillation or need for extracorporeal membrane oxygenation).We included 205 neonates with MAS, 55 had severe MAS (27%). MAS incidence and absolute number of MAS cases per year decreased during the observation period (p=0.003 and 0.005, respectively) as well as rates of outborn deliveries (p=0.004), duration of invasive mechanical ventilation (p=0.004), and hospital stay (p=0.036). Incidence and absolute number of severe MAS cases per year decreased (p=0.008 and 0.006, respectively), though the percentage of severe MAS among all neonates with MAS did not change. Risk factors for severe MAS were acute tocolysis (odds ratio 18.2 (95% confidence interval 2.1-155.3), p<0.001) fetal distress (3.4 (1.8-6.4), p<0.001), and severe and moderate birth asphyxia (4.4 (2.0-9.7), p=0.001 and 2.9 (1.5-5.6), p=0.009).The incidence and absolute numbers of MAS and severe MAS cases changed during the study period as well as neonatal management. Acute tocolysis, fetal distress, and asphyxia were associated with severe MAS.

Evaluation of bedside pulmonary function in the neonate: From the past to the future

Pulmonary function testing and monitoring plays an important role in the respiratory management of neonates. A noninvasive and complete bedside evaluation of the respiratory status is especially useful in critically ill neonates to assess disease severity and resolution and the response to pharmacological interventions as well as to guide mechanical respiratory support. Besides traditional tools to assess pulmonary gas exchage such as arterial or transcutaenous blood gas analysis, pulse oximetry, and capnography, additional valuable information about global lung function is provided through measurement of pulmonary mechanics and volumes. This has now been aided by commercially available computerized pulmonary function testing systems, respiratory monitors, and modern ventilators with integrated pulmonary function readouts. In an attempt to apply easy‐to‐use pulmonary function testing methods which do not interfere with the infant́s airflow, other tools have been developed such as respiratory inductance plethysmography, and more recently, electromagnetic and optoelectronic plethysmography, electrical impedance tomography, and electrical impedance segmentography. These alternative technologies allow not only global, but also regional and dynamic evaluations of lung ventilation. Although these methods have proven their usefulness for research applications, they are not yet broadly used in a routine clinical setting. This review will give a historical and clinical overview of different bedside methods to assess and monitor pulmonary function and evaluate the potential clinical usefulness of such methods with an outlook into future directions in neonatal respiratory diagnostics. Pediatr Pulmonol. 2015; 50:1039–1050.

Sonographically guided cannula positioning for extracorporeal membrane oxygenation

Drainage problems due to catheter malpositioning are acutely life-threatening in patients undergoing extracorporeal membrane oxygenation. In order to reduce these complications we introduced sonographically guided catheter positioning. We compare the outcome in a group of patients with blind cannula positioning to that in a group with sonographically guided catheter positioning. Our results show that neonates and young infants especially are at high risk of drainage problems due to catheter malposition and that their outcome could be markedly improved by introducing sonographically guided cannula insertion.

Non-invasive oscillometric blood pressure measurement in very-low-birthweight infants: a comparison of two different monitor systems

Sir, Over the last 20 y, non-invasive oscillometric blood pressure measurement has become a widespread and accepted technique, even in very-low-birthweight infants (VLBW), for use when invasive measurement is inappropriate or impossible. However, the accuracy of this oscillometric method is still under debate (1–3). The aim of this study was to compare two different commonly used oscillometric systems for blood pressure measurement in VLBW-infants: HP-Monitor CMS Model 68 S with Modul HP M-1008B (HP) (HewlettPackard Co., Palo Alto, CA, USA) and Dinamap 8100 (Dinamap). (Critikon Inc., Tampa, FL, USA) In 20 VLBW-infants, paired measurements were obtained by making a single measurement with each system within 3–5 min, whereby the sequence of the devices was randomized. Series of paired blood pressure measurements were obtained by making records six times a day. Gestational age and birth weight of the patients were 28 (25–31) wk (mean and range) and 841 (540–1200) g, respectively. Age, body weight and circumference of the extremities at the time of taking the measurement series were 14 (1–79) d (median and range), 972 (570–1470) g, and 6 (4.5– 7.3) cm, respectively. The patients had neither clinical signs of cardiac failure nor received inotropic agents at the time of measurement. Measurements were performed using the cuff size recommended by the manufacturers. For each paired measurement the same cuff size, extremity and position of the infant were used. In a total of 44 series, 2 (1–6) (median and range) series per patient, 264 paired measurements were performed. A total of 72 paired measurements were excluded, either because the heart rate exceeded normal values (4) or because of movements of the extremity during measurement. A total of 192 paired measurements, i.e. 5 (2–6) (median range) per series, were analysed. In 63 paired measurements cuff size 1 was used and in 129 cuff size 2 was used. The cuff width to arm circumference ratio was 0.48 0.04. A total of 42 paired measurements were performed on the upper and 150 on the lower extremity. In 98 paired measurements Dinamap was used first and in 94 paired measurements HP was used first. No difference (paired t-test;p> 0.05) was observed in heart rate during paired measurements: 154 13 per min with Dinamap and 155 12 per min with HP. Systolic, diastolic and mean blood pressures measured with Dinamap were 65.2 11.9 mmHg, 39.4 8.1 mmHg and 47.9 9.3 mmHg, respectively; and with HP, 59 10.4 mmHg, 35.2 8.1 mmHg and 43.3 8.4 mmHg, respectively. The mean differences (Dinamap minus HP) for systolic, diastolic and mean blood pressures were 6.2 10.3 mmHg, 4.2 8.8 mmHg and 4.6 9.0 mmHg, respectively. Figures 1–3 show the differences between Dinamap and HP, based on a graphical technique suggested by Bland and Altmann (5). Mean blood pressure values measured with Dinamap were higher than with HP in our study. 95% prediction intervals of the mean differences (Dinamap minus HP)