Correlation among cytokines, bronchopulmonary dysplasia and modality of ventilation in preterm newborns: improvement with melatonin treatment

Improved survival because of advances in neonatal care has resulted in an increased number of infants at risk for chronic lung disease. Even though the etiology of lung injury is multifactorial, recent animal and clinical data indicate that pulmonary damage depends in large part on the ventilatory strategies used. Ventilator-associated lung injury was believed to result from the use of high pressure, thus, the term barotraumas. This trauma is believed to involve free-radical damage. Oxidant injury is a serious cause of lung injury. In the present study, 110 newborns with respiratory distress syndrome were studied; 55 were treated with melatonin and the other 55 with placebo. All the subjects were mechanically ventilated with or without guaranteed volume. Proinflammatory cytokines [interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha] were measured in tracheobronchial aspirate and the clinical outcome was evaluated. Melatonin treatment reduced the proinflammatory cytokines and improved the clinical outcome. The beneficial action of melatonin presumably related to its antioxidative actions.     

Inspired gas temperature in ventilated neonates

The warming and humidification of inspired gases for ventilated neonates are routine. There are no data on the temperature of the gas at the airway opening in ventilated neonates. Is the inspired gas temperature at the airway opening, as expected and set on the humidifier, around 37°C? We aimed to measure temperature at the airway opening and compare this with the circuit temperature. This was an observational study in a neonatal intensive care unit. Twenty‐five mechanically ventilated infants were studied. All had humidifiers with chamber temperature set at 36°C and the circuit temperature set at 37°C. Two temperature probes were inserted and rested at the circuit‐exit and at the airway opening, and temperatures were measured for 2 min in each infant. At this time, the circuit temperature was also noted. The mean (SD) temperature at the airway opening in infants nursed in incubators was 34.9 (1.2)°C, compared with radiant warmers where the mean (SD) was 33.1 (0.5)°C. The mean (SD) difference in temperature from the circuit temperature probe to the airway opening was greater under radiant warmers, with a mean (SD) drop of 3.9 (0.6)°C compared with a mean (SD) drop of 2.0 (1.3)°C in the incubators. In conclusion, the temperature at the circuit temperature probe does not reflect the temperature at the airway opening. Inspired gas temperatures are lower than the expected 37°C with the normal circuits and usual humidifier settings. Pediatr Pulmonol. 2004; 38:50–54. © 2004 Wiley‐Liss, Inc.     

经鼻双水平通气在治疗新生儿呼吸窘迫中的作用简

目的 探讨经鼻双水平通气（N-BiPAP）在治疗新生儿呼吸窘迫（RDS）中的作用.方法 对83例RDS新生儿进行分组,观察组接受N-BiPAP治疗,对照组接受经鼻持续正压通气（NCPAP）治疗.结果 T3时两组pH、PaO2及PaO2/ FiO2均明显上升,且PaCO2显著下降,观察组改变程度较对照组更为显著;观察组氧疗时间及住院费用明显低于对照组;观察组死亡1例,并发症率35.7%,对照组死亡3例,并发症率43.9%,两组患儿死亡率及并发症率均无明显统计学差异.结论 经鼻双水平通气可缓解新生儿呼吸窘迫症状,且治疗费用低、安全性好.     

An experimental model for the measurement of inspired gas temperatures in ventilated neonates

OBJECTIVE: To determine the inspired gas temperature at points from the endo-tracheal tube (ETT) circuit manifold to the tip of the ETT in a model neonatal lung. DESIGN: A model lung attached to standard ventilator circuit, autofeed chamber and humidifier was ventilated using typical pressure-limited, time cycled settings. Temperatures were measured at various distances along the ETT using a K-type thermocouple temperature probe. RESULTS: The inspired gas temperature dropped from the circuit temperature probe site (40 degrees C) to the proximal end of the ETT (37 degrees C). The temperature dropped further as it passed through the exposed part of the ETT (34 degrees C) but then warmed again on entering the lung model so that the inspired gas at the distal end of the ETT was 37 degrees C. Statistically significant differences were found with a one-way ANOVA P-value of <0.0001. The differences between each pair of mean temperatures were statistically significant (all P<0.001) except when comparing the proximal end of the ETT with midway down the ETT (Bonferroni's Multiple Comparison Test, P>0.05). CONCLUSIONS: Inspired gas temperature drops as it passes through the circuit temperature probe site, the proximal end of the ETT and the exposed part of the ETT. The inspired gas rewarms on entering the model lung and exits the ETT at the desired temperature. The effect of measuring temperature closer to the patient, setting the circuit temperature higher and/or increasing the ambient temperature through which the circuit passes, need to be evaluated.     

A drop in gas temperature in the external part of the endotracheal tube is problematic during neonatal respiratory support

During neonatal respiratory support, maintaining optimal humidity minimizes the risk of airway occlusion and chronic lung disease. With neonatal respiratory support using a heated humidifier,condensation following decreases in temperature within the unheated part of the inspiratory circuit represents a serious problem, due to the resulting drop in absolute humidity. Several reports describing the temperature/humidity gradient in the unheated inspiratory limb have excluded the endotracheal tube (ETT). The present study investigated the extent to which the temperature gradient in the ETT affects breathing gas conditioning in premature infants, who display tiny minute volumes. By measuring temperature/dew point at various sites along the inspiratory circuit, including inside the ETT, we evaluated the effects of temperature change in the ETT using an in vitro model of a micropremie on mechanical respirator care in an incubator. We confirmed significant moisture loss (absolute humidity loss; 7.5-10.1 mg/L) with decreasing gas temperature in the ETT external to the body, with subsequent drying of the gas (relative humidity drop, 10.7-22.3%) as temperature increased in the ETT inside the body. The present results suggest that temperature decreases in the ETT represent an important issue in the respiratory care of very premature infants.     

新生儿机械通气撤机失败的影响因素及预测指标分析

目的探讨导致新生儿机械通气撤机失败的影响因素及寻找预测指标减少撤机失败率。方法回顾性分析我院2015年1月至2019年12月新生儿重症监护病室350例机械通气时间≥72 h并存活的新生儿。根据撤机48 h内是否再次插管,分为撤机成功组与撤机失败组。比较两组撤机前一般情况、临床变量、呼吸机设置及血气分析,撤机后无创通气模式及雾化情况。单因素及多因素分析确定高危因素,并预测指标价值。结果47例(13.4%)发生撤机失败。单因素分析显示15个变量是撤机失败的影响因素(P<0.05)。Logistic回归分析示机械通气时间长、吸痰耐受能力差、多脏器损害、高PCO 2、撤机时自主呼吸及心率快是撤机失败的高危因素(P<0.05)。PCO₂预测撤机失败价值高,AUC为0.819(0.738,0.900),P<0.001。结论多种因素与撤机失败相关,应针对高危因素进行干预,撤机前进行充分预测评估以减少撤机失败率。     

Effects of antenatal corticosteroid treatment on pulmonary ventilation and circulation in neonatal lambs with hypoplastic lungs

Our aim was to determine whether antenatal corticosteroids improve perinatal adaptation of the pulmonary circulation in lambs with lung hypoplasia (LH). LH was induced in 12 ovine fetuses between 105 and 140 days gestation (term approximately 147 days); in 6 of these the ewe was given a single dose of betamethasone (11.4 mg im) 24 hr before delivery (LH + B). All lambs, including a control group (n = 6), were delivered at approximately 140 days and ventilated for 2 hr during which arterial pressures, pulmonary blood flow (PBF), and ventilating pressure and flow were recorded. During ventilation, respiratory system compliance was lower in both LH + B and LH groups than in controls. Pulmonary vascular resistance (PVR) was lower in LH + B lambs than in LH lambs and similar to controls; PBF was reduced in LH lambs but was restored to control levels by betamethasone. The mean density of small arteries of LH + B lambs was similar to that of LH lambs (P = 0.06) and lower than in controls; the thickness of the media of small pulmonary arteries from LH + B lambs was similar to that in LH lambs and thicker than in controls. VEGF mRNA levels were not different between groups. PDGF mRNA levels in LH + B lambs were higher than in LH lambs; a similar trend (P = 0.06) was seen for PECAM-1. SP-C mRNA levels were greater in both LH and LH + B lambs than in controls. Effects of betamethasone were greater on indices of pulmonary circulation than ventilation. We conclude that a single dose of maternal betamethasone 24 hr prior to birth has significant favorable effects on the postnatal adaptation of the pulmonary circulation in lambs with LH.     

The biphasic ventilatory response to hypoxia in preterm infants is not due to a decrease in metabolism

The mechanism underlying the biphasic ventilatory response to hypoxia in neonates is poorly understood. Because alveolar P_CO2 (P_ACO2) decreases and remains low during hypoxia, it has been argued that a decrease in metabolism may occur. We hypothesized that if the late decrease in ventilation during hypoxia is due to a decrease in CO₂ production, an increase in P_ACO2 should abolish it. We studied 27 preterm infants [birth weight, 1,700 ± 41 g (mean ± SEM); study weight, 1,760 ± 36 g; gestational age 32 ± 0.2 weeks; postnatal age, 17 ± 1 days]. A flow-through system and Beckman analyzers were used to measure ventilation and alveolar gases. Metabolism was expressed as changes in oxygen consumption. Infants were studied randomly during hypoxia alone (15% O₂ + N₂, n = 55) and during hypoxia plus CO₂, (0.5% CO₂, n = 30; 2% CO₂, n = 10). Each experiment consisted of 2 minutes of control measurements (21% O₂), 5 minutes of measurements during hypoxia alone or hypoxia plus CO₂, followed by 2 minutes of recovery (21% O₂). We found a biphasic response to hypoxia with or without CO₂ supplementation, the percent change in ventilation from initial peak hyperventilation to late hypoventilation at 5 minutes being -16 ± 2 on 15% O₂; -9 ± 3 on 15% O₂; + 0.5% CO₂ and -15 ± 9 on 15% O₂; + 2% CO₂; (P < 0.05).The decrease in ventilation was primarily due to a significant decrease in frequency; tidal volume increased. Oxygen consumption decreased similarly with the various inspired gas mixtures during hypoxia. These findings indicate that the decrease in ventilation during hypoxia is unlikely to be solely due to a decrease in metabolism since the late decrease in ventilation following initial hyperventilation still occurred despite the elimination of a fall in P_ACO2. We speculate that the mechanism underlying the late decrease in ventilation is likely of central origin, probably mediated through the release of inhibitory neurotransmitters. Pediatr Pulmonol. 1996; 22:287–294. © 1996 Wiley-Liss, Inc.     

Ventilatory failure during resistive loaded breathing in the newborn primate

Previous investigations have shown that ventilatory failure during severe inspiratory resistive loading (IRL) in the 21-day-old infant primate occurs secondary to a decrease in respiratory frequency, that is, central failure. To examine the response of the more immature newborn to IRL, minute ventilation (V′_E), arterial blood gases and pH, minute diaphragmatic electromyogram (EMG) activity, peak inspiratory airway pressure, and the centroid frequency (Fc) of the diaphragmatic EMG power spectrum were measured in four unanesthetized tracheotomized 2-day-old monkeys during various levels of IRL, until either (1) ventilatory failure occurred (ventilatory failure run) or (2) normocapnia was sustained for 1 hr (successful trial). During successful trials, minute ventilation, breathing frequency, tidal volume, Fc, and P_aCO₂ were sustained at baseline levels and an increase in minute EMG activity and peak inspiratory airway pressure were observed. In contrast, during ventilatory failure runs, minute ventilation and tidal volume fell and P_aCO₂ rose compared to their respective baseline values. Respiratory frequency did not change. The decline in tidal volume occurred despite significant increases in minute diaphragmatic EMG activity and peak inspiratory airway pressure. No shifts in Fc were noted, suggesting that peripheral diaphragmatic fatigue did not occur. We conclude that ventilatory failure during IRL in the 2-day-old monkey is due to the animal's inability to defend tidal volume as opposed to central failure. Pediatr Pulmonol. 1998; 26:312–318. © 1998 Wiley-Liss, Inc.     

Comparison of lung volume measurements by antero-posterior chest X-ray and the SF6 washout technique in mechanically ventilated infants

While anterior/posterior chest x-rays (CXR) are routinely performed to estimate lung volume (LV) and adjust ventilator settings, the precise measurement of LV requires additional sophistication. In 31 infants ventilated because of surfactant deficiency (n = (23), bronchopulmonary dysplasia (n = 7), or pulmonary hypoplasia (n = 1) with either intermittent positive pressure (n = 18) or high frequency oscillation (n = 13) gestational age 23–39 weeks (median 26 weeks); birthweight 550–2780 g (median 840 g); age at measurement 1–91 days (median 6 days); weight at study time (WST) 675–3000 g (median 938 g), we investigated whether LV, as measured by the sulfur hexafluoride (SF₆) washout technique, could by estimated from CXR by: (1) the sum (A+B) of the right (A) and left (B) lung fields areas; 2) the product (LxW) of the distances from the right apex to the right costophrenic angle (L) and between both costophrenic angles (W); (3) the diaphragm position relative to the posterior parts of the ribs (DP); and (4) the lung radiolucency (RL, grades 0–4). Correlations between A+B (r = 0.44) or LxW (r = 0.37) and LV were poor, but improved when A+B, LxW, and LV were normalized to WST: (A+B)/WST vs. LV/WST (r = 0.74), and LxW/WST vs. LV/WST (r = 0.67). DP (r = 0.13) and RL (Spearman's rho = 0.17) did not correlate with LV/WST. A multiple linear regression analysis led to the following best-fit equation: LV/WST = 2.58 (A+B)/WST − 5.47 DP + 42.2 (r = 0.83). We concluded that an estimate of LV from CXR lacked sufficient accuracy. DP and RL did not correlate with LV measured by SF₆ washout. Pediatr Pulmonol. 1998; 26:265–272. © 1998 Wiley-Liss, Inc.     

Increased incidence of sighs (augmented inspiratory efforts) during synchronized intermittent mandatory ventilation (SIMV) in preterm neonates

A reflex resulting in a deep, sigh-like inspiratory effort (augmented breath) is frequently triggered during synchronized mechanical ventilation in preterm infants. We studied the incidence of augmented inspiratory efforts and their effect on ventilation and lung compliance during conventional IMV and synchronized IMV (SIMV) in 15 preterm neonates (GA 26.7 ± 1.5 wks (mean ± SD), BW 925 ± 222 g, age 1–8 days). Augmentation of spontaneous inspiratory effort was defined as an esophageal pressure deflection occurring coincident with a synchronized mechanical breath and exceeding the previous unassisted spontaneous effort by more than 50%. The incidence of augmented breaths was higher during SIMV (11.1 ± 7.7%; P < 0.01) than during conventional IMV (5.1 ± 6.1%). However, when the synchronized breaths were triggered late (200–300 msec) after the onset of inspiration, augmented breaths occurred no more frequently than during conventional IMV (6.0 ± 4.7%). The incidence of augmented breaths correlated inversely with dynamic lung compliance (P = 0.014), but was not significantly influenced by a change in PEEP. Although inspiratory effort increased nearly three times during the augmented breaths, tidal volume increased only 12%. The change in tidal volume was limited because the augmented effort reached its maximal negativity only approximately 500 ms after the beginning of the synchronized, mechanical breath and at a time when the mechanical breath had already ended. For this reason the augmented effort did not contribute significantly to minute ventilation, but only prolonged inspiration. Dynamic lung compliance did not change significantly after an augmented breath. The results indicate that augmented inspiratory efforts are more common in preterm neonates ventilated with SIMV than with conventional IMV, but do not contribute significantly to ventilation. Pediatr. Pulmonol. 1997; 24:195–203. © 1997 Wiley-Liss, Inc.     

Community-based validation of assessment of newborn illnesses by trained community health workers in Sylhet district of Bangladesh

Objectives  To validate trained community health workers' recognition of signs and symptoms of newborn illnesses and classification of illnesses using a clinical algorithm during routine home visits in rural Bangladesh.
Methods  Between August 2005 and May 2006, 288 newborns were assessed independently by a community health worker and a study physician. Based on a 20-sign algorithm, sick neonates were classified as having very severe disease, possible very severe disease or no disease. The physician's assessment was considered as the gold standard.
Results  Community health workers correctly classified very severe disease in newborns with a sensitivity of 91%, specificity of 95% and kappa value of 0.85 ( P  < 0.001). Community health workers' recognition showed a sensitivity of more than 60% and a specificity of 97–100% for almost all signs and symptoms.
Conclusion  Community health workers with minimal training can use a diagnostic algorithm to identify severely ill newborns with high validity.     

Lung function tests in neonates and infants with chronic lung disease: global and regional ventilation inhomogeneity

This review considers measurement of global and regional ventilation inhomogeneity (VI) in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy (CLDI). We focus primarily on multiple-breath inert gas washout (MBW) and electrical impedance tomography (EIT). The literature is critically reviewed and the relevant methods, equipment, and studies are summarized, including the limitations and strengths of individual techniques, together with the availability and appropriateness of any reference data. There has been a recent resurgence of interest in using MBW to monitor lung function within individuals and between different groups. In the mechanically ventilated, sedated, and paralyzed patient, VI indices can identify serial changes occurring following exogenous surfactant. Similarly, global VI indices appear to be increased in infants with CLDI and to differentiate between infants without lung disease and those with mild, moderate, and severe lung disease following preterm birth. While EIT is a relatively new technique, recent studies suggest that it is feasible in newborn infants, and can quantitatively identify changes in regional lung ventilation following alterations to ventilator settings, positive end expiratory pressure (PEEP), and administration of treatments such as surfactant. As such, EIT represents one of the more exciting prospects for continuous bedside pulmonary monitoring. For both techniques, there is an urgent need to establish guidelines regarding data collection, analysis, and interpretation in infants both with and without CLDI.     

Patient transitions relevant to individuals requiring ongoing ventilatory assistance: A Delphi study

BACKGROUND:

Various terms, including ‘prolonged mechanical ventilation’ (PMV) and ‘long-term mechanical ventilation’ (LTMV), are used interchangeably to distinguish patient cohorts requiring ventilation, making comparisons and timing of clinical decision making problematic.

OBJECTIVE:

To develop expert, consensus-based criteria associated with care transitions to distinguish cohorts of ventilated patients.

METHODS:

A four-round (R), web-based Delphi study with consensus defined as >70% was performed. In R1, participants listed, using free text, criteria perceived to should and should not define seven transitions. Transitions comprised: T1 – acute ventilation to PMV; T2 – PMV to LTMV; T3 – PMV or LTMV to acute ventilation (reverse transition); T4 – institutional to community care; T5 – no ventilation to requiring LTMV; T6 – pediatric to adult LTMV; and T7 – active treatment to end-of-life care. Subsequent Rs sought consensus.

RESULTS:

Experts from intensive care (n=14), long-term care (n=14) and home ventilation (n=10), representing a variety of professional groups and geographical areas, completed all Rs. Consensus was reached on 14 of 20 statements defining T1 and 21 of 25 for T2. ‘Physiological stability’ had the highest consensus (97% and 100%, respectively). ‘Duration of ventilation’ did not achieve consensus. Consensus was achieved on 13 of 18 statements for T3 and 23 of 25 statements for T4. T4 statements reaching 100% consensus included: ‘informed choice’, ‘patient stability’, ‘informal caregiver support’, ‘caregiver knowledge’, ‘environment modification’, ‘supportive network’ and ‘access to interprofessional care’. Consensus was achieved for 15 of 17 T5, 16 of 20 T6 and 21 of 24 T7 items.

CONCLUSION:

Criteria to consider during key care transitions for ventilator-assisted individuals were identified. Such information will assist in furthering the consistency of clinical care plans, research trials and health care resource allocation.