Peter C. Rimensberger

Inhaled Nitric Oxide Versus Aerosolized Iloprost in Secondary Pulmonary Hypertension in Children With Congenital Heart Disease Vasodilator Capacity and Cellular Mechanisms

Background —Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each. Methods and Results —A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng · kg−1 · min−1 for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48±0.38 to 0.27±0.16 (P <0.001). Similarly, iloprost decreased the ratio from 0.49±0.38 to 0.26±0.11 (P <0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6±11.9 to 34.7±21.4 nmol/L during iNO (P <0.01), and plasma cAMP increased from 55.7±22.9 to 65.1±21.2 nmol/L during iloprost inhalation (P <0.05). Conclusions —In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.

Treatment of a persistent postoperative chylothorax with somatostatin

Chylothorax is a rare but potentially serious complication of pediatric cardiac operations. We report the case of a 4-month-old boy who underwent a Senning procedure for correction of D-transposition of the great vessels. A persistent postoperative chylothorax developed, necessitating continuous drainage, despite conservative treatment over 3 weeks. Thereafter, continuous somatostatin infusion for 14 days led to the reduction and finally cessation of chyle production. This treatment allowed early enteral feeding and avoided further surgical intervention.

Lung recruitment during small tidal volume ventilation allows minimal positive end-expiratory pressure without augmenting lung injury.

OBJECTIVES Ventilation with positive end-expiratory pressure (PEEP) above the inflection point (P(inf)) has been shown to reduce lung injury by recruiting previously closed alveolar regions; however, it carries the risk of hyperinflating the lungs. The present study examined the hypothesis that a new strategy of recruiting the lung with a sustained inflation (SI), followed by ventilation with small tidal volumes, would allow the maintenance of low PEEP levels (<P(inf)) without inducing additional lung injury. DESIGN Prospective, randomized, controlled ex vivo study. SETTING An animal laboratory in a university setting. SUBJECTS Isolated nonperfused lungs of adult Sprague-Dawley rats. INTERVENTIONS We studied the effect on compliance and lung injury in four groups (n = 10 per group) of lavaged rat lungs. One group (group 1) served as a control; their lungs were inflated at PEEP < P(inf) but not ventilated. The other three groups were ventilated with small tidal volumes (5 to 6 mL/kg) for 2 hrs with the following interventions: group 2, PEEP < P(inf) without SI; group 3, PEEP < P(inf) after a SI to 30 cm H2O for 30 secs; and group 4, PEEP > P(inf). MEASUREMENTS AND MAIN RESULTS In groups 2 and 4, static compliance decreased after ventilation (p < .01). Histologically, group 2 (PEEP < P(inf) without SI) showed significantly greater injury of small airways, but not of terminal respiratory units, compared with group 1. Group 3 (PEEP < P(inf) after a SI), but not group 4, showed significantly less injury of small airways and terminal respiratory units compared with group 2. CONCLUSIONS We conclude that small tidal volume ventilation after a recruitment maneuver allows ventilation on the deflation limb of the pressure/volume curve of the lungs at a PEEP < P(inf). This strategy a) minimizes lung injury as well as, or better than, use of PEEP > P(inf), and b) ensures a lower PEEP, which may minimize the detrimental consequences of high lung volume ventilation.

Pediatric Acute Respiratory Distress Syndrome: Consensus Recommendations From the Pediatric Acute Lung Injury Consensus Conference

OBJECTIVE To describe the final recommendations of the Pediatric Acute Lung Injury Consensus Conference. DESIGN Consensus conference of experts in pediatric acute lung injury. SETTING Not applicable. SUBJECTS PICU patients with evidence of acute lung injury or acute respiratory distress syndrome. INTERVENTIONS None. METHODS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published, data were lacking a modified Delphi approach emphasizing strong professional agreement was used. MEASUREMENTS AND MAIN RESULTS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published data were lacking a modified Delphi approach emphasizing strong professional agreement was used. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the following topics related to pediatric acute respiratory distress syndrome: 1) Definition, prevalence, and epidemiology; 2) Pathophysiology, comorbidities, and severity; 3) Ventilatory support; 4) Pulmonary-specific ancillary treatment; 5) Nonpulmonary treatment; 6) Monitoring; 7) Noninvasive support and ventilation; 8) Extracorporeal support; and 9) Morbidity and long-term outcomes. There were 132 recommendations with strong agreement and 19 recommendations with weak agreement. Once restated, the final iteration of the recommendations had none with equipoise or disagreement. CONCLUSIONS The Consensus Conference developed pediatric-specific definitions for acute respiratory distress syndrome and recommendations regarding treatment and future research priorities. These are intended to promote optimization and consistency of care for children with pediatric acute respiratory distress syndrome and identify areas of uncertainty requiring further investigation.

Electrical impedance tomography: a method for monitoring regional lung aeration and tidal volume distribution?

ObjectiveTo demonstrate the monitoring capacity of modern electrical impedance tomography (EIT) as an indicator of regional lung aeration and tidal volume distribution.Design and settingShort-term ventilation experiment in an animal research laboratory.Patients and participantsOne newborn piglet (body weight: 2 kg).InterventionsSurfactant depletion by repeated bronchoalveolar lavage, surfactant administration.Measurements and resultsEIT scanning was performed at an acquisition rate of 13 images/s during two ventilatory manoeuvres performed before and after surfactant administration. During the scanning periods of 120 s the piglet was ventilated with a tidal volume of 10 ml/kg at positive end-expiratory pressures (PEEP) in the range of 0–30 cmH2O, increasing and decreasing in 5 cmH2O steps. Local changes in aeration and ventilation with PEEP were visualised by EIT scans showing the regional shifts in end-expiratory lung volume and distribution of tidal volume, respectively. In selected regions of interest EIT clearly identified the changes in local aeration and tidal volume distribution over time and after surfactant treatment as well as the differences between stepwise inflation and deflation.ConclusionsOur data indicate that modern EIT devices provide an assessment of regional lung aeration and tidal volume and allow evaluation of immediate effects of a change in ventilation or other therapeutic intervention. Future use of EIT in a clinical setting is expected to optimise the selection of appropriate ventilation strategies.

Acute lung injury in children: Therapeutic practice and feasibility of international clinical trials*

Objectives: To describe mechanical ventilation strategies in acute lung injury and to estimate the number of eligible patients for clinical trials on mechanical ventilation management. In contrast to adult medicine, there are few clinical trials to guide mechanical ventilation management in children with acute lung injury. Design: A cross-sectional study for six 24-hr periods from June to November 2007. Setting: Fifty-nine pediatric intensive care units in 12 countries in North America and Europe. Patients: We identified children meeting acute lung injury criteria and collected detailed information on illness severity, mechanical ventilatory support, and use of adjunctive therapies. Interventions: None. Measurements and Main Results: Of 3823 patients screened, 414 (10.8%) were diagnosed with acute lung injury by their treating physician, but only 165 (4.3%) patients met prestablished inclusion/exclusion criteria to this trial and, therefore, would have been eligible for a clinical trial. Of these, 124 (75.2%) received conventional mechanical ventilation, 27 (16.4%) received high-frequency oscillatory ventilation, and 14 (8.5%) received noninvasive mechanical ventilation. In the conventional mechanical ventilation group, 43.5% were ventilated in a pressure control mode with a mean tidal volume of 8.3 ± 3.3 mL/kg; and there was no clear relationship between positive end-expiratory pressure and Fio2 delivery in the conventional mechanical ventilation group. Use of adjunctive treatments, including nitric oxide, prone positioning, surfactant, hemofiltration, recruitment maneuvers, steroids, bronchodilators, and fluid restriction, was highly variable. Conclusions: Our study reveals inconsistent mechanical ventilation practice and use of adjunctive therapies in children with acute lung injury. Pediatric clinical trials assessing mechanical ventilation management are needed to generate evidence to optimize outcomes. We estimate that a large number of centers (∼60) are needed to conduct such trials; it is imperative, therefore, to bring about international collaboration.

Lung recruitment and lung volume maintenance: a strategy for improving oxygenation and preventing lung injury during both conventional mechanical ventilation and high-frequency oscillation

Objective: To determine whether using a small tidal volume (5 ml/kg) ventilation following sustained inflation with positive end-expiratory pressure (PEEP) set above the critical closing pressure (CCP) allows oxygenation equally well and induces as little lung damage as high-frequency oscillation following sustained inflation with a continuous distending pressure (CDP) slightly above the CCP of the lung.¶Material and methods: Twelve surfactant-depleted adult New Zealand rabbits were ventilated for 4 h after being randomly assigned to one of two groups: group 1, conventional mechanical ventilation, tidal volume 5 ml/kg, sustained inflation followed by PEEP > CCP; group 2, high-frequency oscillation, sustained inflation followed by CDP > CCP.¶Results: In both groups oxygenation improved substantially after sustained inflation (P < 0.05) and remained stable over 4 h of ventilation without any differences between the groups. Histologically, both groups showed only little airway injury to bronchioles, alveolar ducts, and alveolar airspace, with no difference between the two groups. Myleoperoxidase content in homogenized lung tissue, as a marker of leukocyte infiltration, was equivalent in the two groups.¶Conclusions: We conclude that a volume recruitment strategy during small tidal volume ventilation and maintaining lung volumes above lung closing is as protective as that of high-frequency oscillation at similar lung volumes in this model of lung injury

Use of analgesic and sedative drugs in the NICU: integrating clinical trials and laboratory data.

Recent advances in neonatal intensive care include and are partly attributable to growing attention for comfort and pain control in the term and preterm infant requiring intensive care. Limitation of painful procedures is certainly possible, but most critically ill infants require unavoidable painful or stressful procedures such as intubation, mechanical ventilation, or catheterization. Many analgesics (opioids and nonsteroidal anti-inflammatory drugs) and sedatives (benzodiazepines and other anesthetic agents) are available but their use varies considerably among units. This review summarizes current experimental knowledge on the effects of sedative and analgesic drugs on brain development and reviews clinical evidence that speaks for or against the use of common analgesic and sedative drugs in the NICU but avoids any discussion of anesthesia during surgery. Risk/benefit ratios of intermittent boluses or continuous infusions for the commonly used sedative and analgesic agents are discussed in the light of clinical and experimental studies. The limitations of extrapolating experimental results from animals to humans must be considered while making practical recommendations based on the currently available evidence.

Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group

Electrical impedance tomography (EIT) has undergone 30 years of development. Functional chest examinations with this technology are considered clinically relevant, especially for monitoring regional lung ventilation in mechanically ventilated patients and for regional pulmonary function testing in patients with chronic lung diseases. As EIT becomes an established medical technology, it requires consensus examination, nomenclature, data analysis and interpretation schemes. Such consensus is needed to compare, understand and reproduce study findings from and among different research groups, to enable large clinical trials and, ultimately, routine clinical use. Recommendations of how EIT findings can be applied to generate diagnoses and impact clinical decision-making and therapy planning are required. This consensus paper was prepared by an international working group, collaborating on the clinical promotion of EIT called TRanslational EIT developmeNt stuDy group. It addresses the stated needs by providing (1) a new classification of core processes involved in chest EIT examinations and data analysis, (2) focus on clinical applications with structured reviews and outlooks (separately for adult and neonatal/paediatric patients), (3) a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles, (4) consensus, unified terminology with clinical user-friendly definitions and explanations, (5) a review of all major work in thoracic EIT and (6) recommendations for future development (193 pages of online supplements systematically linked with the chief sections of the main document). We expect this information to be useful for clinicians and researchers working with EIT, as well as for industry producers of this technology.

Ventilation practices in the neonatal intensive care unit: a cross-sectional study

OBJECTIVE To assess current ventilation practices in newborn infants. STUDY DESIGN We conducted a 2-point cross-sectional study in 173 European neonatal intensive care units, including 535 infants (mean gestational age 28 weeks and birth weight 1024 g). Patient characteristics, ventilator settings, and measurements were collected bedside from endotracheally ventilated infants. RESULTS A total of 457 (85%) patients were conventionally ventilated. Time cycled pressure-limited ventilation was used in 59% of these patients, most often combined with synchronized intermittent mandatory ventilation (51%). Newer conventional ventilation modes like volume targeted and pressure support ventilation were used in, respectively, 9% and 7% of the patients. The mean tidal volume, measured in 84% of the conventionally ventilated patients, was 5.7 ± 2.3 ml/kg. The mean positive end-expiratory pressure was 4.5 ± 1.1 cmH(2)O and rarely exceeded 7 cmH(2)O. CONCLUSIONS Time cycled pressure-limited ventilation is the most commonly used mode in neonatal ventilation. Tidal volumes are usually targeted between 4 to 7 mL/kg and positive end-expiratory pressure between 4 to 6 cmH(2)O. Newer ventilation modes are only used in a minority of patients.