Assessment of Peak Inspiratory Flow in Young Infants with Acute Viral Bronchiolitis: Physiological Basis for Initial Flow Setting in Patients Supported with High-Flow Nasal Cannula.

OBJECTIVE: To assess the inspiratory demand in young infants with acute viral bronchiolitis to provide a physiological basis for initial flow setting for patients supported with high flow nasal cannula. STUDY DESIGN: Prospective study in 44 infants up to 6 months old with acute viral bronchiolitis, admitted to a pediatric intensive care unit from November 2017 to March 2019. Airflow measurements were performed using spirometry. The primary endpoint was the inspiratory demand as measured by peak tidal inspiratory flow (PTIF). The secondary endpoints were the relationships determined between PTIF, patient weight, and disease severity. RESULTS: Median (Q25-Q75) age and weight of the patients were 37 (20-67) days and 4.3 (3.5-5.0) kg, respectively. Mean PTIF was 7.45 (95% CI 6.51-8.39, min-max: 2.40-16.00) L/minute. PTIF indexed to weight was 1.68 (95% CI 1.51-1.85, min-max: 0.67-3.00) L/kg/minute. PTIF was <2.5 L/kg/minute in 89% (95% CI 75-96) of infants. PTIF was correlated with weight (ρ= 0 .55, P < .001) but not with markers of disease severity, including modified Woods clinical asthma score, Silverman-Andersen score, respiratory rate, fraction of inspired oxygen, and PCO2. CONCLUSIONS: High flow nasal cannula therapy is used commonly to support infants with acute viral bronchiolitis. The efficiency of the device is optimal if the flow setting matches the patient's inspiratory demand. According to our results, a flow rate of <2.5 L/kg/minute would be appropriate in most situations.

Mitochondrial oxidative stress induces leaky ryanodine receptor during mechanical ventilation.

RATIONALE: Ventilator-induced diaphragm dysfunction (VIDD) increases morbidity and mortality in critical care patients. Although VIDD has been associated with mitochondrial oxidative stress and calcium homeostasis impairment, the underling mechanisms are still unknown. We hypothesized that diaphragmatic mitochondrial oxidative stress causes remodeling of the ryanodine receptor (RyR1)/calcium release channel, contributing to sarcoplasmic reticulum (SR) Ca2+ leak, proteolysis and VIDD. METHOD: In mice diaphragms mechanically ventilated for short (6 h) and long (12 h) period, we assessed mitochondrial ROS production, mitochondrial aconitase activity as a marker of mitochondrial oxidative stress, RyR1 remodeling and function, Ca2+ dependent proteolysis, TGFß1 and STAT3 pathway, muscle fibers cross-sectional area, and diaphragm specific force production, with or without the mitochondrial targeted anti-oxidant peptide d-Arg-2', 6'-dimethyltyrosine-Lys-Phe-NH2 (SS31). MEASUREMENTS AND MAIN RESULTS: 6 h of mechanical ventilation (MV) resulted in increased mitochondrial ROS production, reduction of mitochondrial aconitase activity, increased oxidation, S-nitrosylation, S-glutathionylation and Ser-2844 phosphorylation of RyR1, depletion of stabilizing subunit calstabin1 from RyR1, increased SR Ca2+ leak. Preventing mROS production by SS31 treatment does not affect the TGFß1 and STAT3 activation, which suggests that mitochondrial oxidative stress is a downstream pathway to TGFß1 and STAT3, early involved in VIDD. This is further supported by the fact that SS-31 rescue all the other described cellular events and diaphragm contractile dysfunction induced by MV, while SS20, an analog of SS31 lacking antioxidant properties, failed to prevent these cellular events and the contractile dysfunction. Similar results were found in ventilated for 12 h. Moreover, SS31 treatment prevented calpain1 activity and diaphragm atrophy observed after 12 h of MV. This study emphasizes that mitochondrial oxidative stress during 6 h-MV contributes to SR Ca2+ leak via RyR1 remodeling, and diaphragm weakness, while longer periods of MV (12 h) were also associated with increased Ca2+-dependent proteolysis and diaphragm atrophy.

Hyperventilation during exercise in very low birth weight school-age children may implicate inspiratory muscle weakness.

OBJECTIVES: To study the ventilatory response during exercise in 8- to 10-year-old children born in 1998 to 2000 with a birthweight <1500 g (very low birthweight [VLBW]). STUDY DESIGN: We studied 19 VLBW children and 20 full-term children paired for age and sex. A physical activity questionnaire was administered. Lean body mass, spirometry, and maximal inspiratory pressure were assessed at rest. Gas exchange, breathing pattern, and the tension-time index of the inspiratory muscles, a noninvasive indicator of inspiratory muscle effort, were evaluated during a continuous incremental cycling protocol. RESULTS: VLBW children had lower weight, height, lean body mass, and maximal inspiratory pressure than control subjects. Their physical activity level was not different. During exercise, they had a higher respiratory rate and minute ventilation for the same metabolic level (VCO(2)/kg) and a higher tension-time index of the inspiratory muscles for the same exercise level (percentage of maximal oxygen consumption). CONCLUSIONS: The lower inspiratory muscle strength observed in school-age VLBW children resulted in a higher inspiratory effort during incremental exercise. The rapid but not shallow breathing pattern adopted by this population during exercise may have been in response to their lower inspiratory muscle resistance to fatigue. VLBW children complaining of dyspnea should be investigated with exercise testing.

Myocardial adaptation to anemia and red blood cell transfusion in premature infants requiring ventilation support in the 1st postnatal week.

BACKGROUND: Although transfusion practice in very premature infants is becoming more restrictive, little is known about myocardial adaptation to anemia during the 1st postnatal week. OBJECTIVES: To determine the central hemodynamic effects of anemia and red blood cell transfusion in very preterm infants undergoing intensive care. METHODS: Twenty-nine neonates of less than 30 weeks gestational age were treated for respiratory distress syndrome, following a strict protocol. Echocardiographies were performed at the 4th and 6th postnatal days, which corresponded to, respectively, just before and 48 h after an erythrocyte transfusion of 15 ml/kg in the 12 anemic infants. RESULTS: Anemic infants had increased stroke volume [2.1 (1.8-2.3) vs. 1.5 (1.3-1.6) ml/kg] and left ventricular (LV) output [312 (271-345) vs. 206 (177-240) ml/min/kg]. The relationship of the heart rate-corrected velocity of circumferential fiber shortening to LV end-systolic meridional wall stress indicated a higher contractile state in the anemic infants, with a higher y-intercept (p = 0.03) and a steeper slope (p = 0.05) of the regression line than in the nonanemic patients. Posttransfusion, the stroke volume, LV output, shortening fraction, and contractile state decreased to the values observed in the nonanemic infants. CONCLUSIONS: Myocardial contractility was a major component of the circulatory adjustments in the anemic premature infants requiring ventilation support in the early neonatal period. Changes in LV performance associated with anemia were reversed by transfusion with no detrimental effect on right ventricular function, LV preload or the respiratory status of these patients.

Training of aerobic and anaerobic fitness in children with asthma.

OBJECTIVE: To assess the effect of a training protocol on aerobic and anaerobic fitness in children with asthma. STUDY DESIGN: Sixteen boys (mean age: 13 years; range: 10-16 years) with mild-to-moderate asthma participated in a rehabilitation program that included 6 weeks of individualized training on a cycle ergometer. Two groups were randomly formed: the control group (CG, n = 7) and the training group (TG, n = 9), which exercised at an intensity set at the heart rate corresponding to the ventilatory threshold, with 1-minute sprints against the maximal aerobic power (MAP) every 4 minutes. Session duration was 45 minutes, 3 sessions per week. Changes in maximal oxygen uptake (VO(2)max), MAP, short-term peak power (PP), and pulmonary function were assessed. RESULTS: Two patients of the training group did not complete the study. Pulmonary function remained unchanged in both groups. Improvement in both aerobic and anaerobic fitness was significant only in the training group (TG vs CG): VO(2)max +18% +/- 2.1% versus +9% +/- 4.5% (P <.05), MAP +32% +/- 5% versus 12% +/- 7% (P <.05), PP +21% +/- 5.7% versus +8.8% +/- 10% (P <.01). CONCLUSION: Exercise training with high-intensity bouts is well tolerated in children with mild-to-moderate asthma. When included in a global rehabilitation program, this type of training improves both aerobic and anaerobic fitness. Anaerobic activities should be considered in sports rehabilitation programs for children with asthma.