Surfactant therapy and extracorporeal life support

I read with great interest the article by Hermon and coworkers [1], who reported that surfactant application in children with severe respiratory failure treated with extracorporeal membrane oxygenation was associated with improved lung volume and pulmonary mechanics. Although these findings must be confirmed in prospective studies, they are very promising. Based on a series of animal studies, more than 10 years ago we advocated use of a combination of surfactant therapy and extracorporeal life support in the treatment of severe respiratory failure. We found that one effective option is to combine intratracheal instillation of a large fluid volume with diluted surfactant and LFV-ECCO2R (low frequency ventilation and extracorporeal carbon dioxide removal). In animal studies using 141 Ce-labelled microspheres mixed with the surfactant [2,3], we observed that, followin

Bench-to-bedside review: Paediatric viral lower respiratory tract disease necessitating mechanical ventilation – should we use exogenous surfactant?

Treatment of infants with viral lower respiratory tract disease (LRTD) necessitating mechanical ventilation is mainly symptomatic. The therapeutic use of surfactant seems rational because significantly lower levels of surfactant phospholipids and proteins, and impaired capacity to reduce surface tension were observed among infants and young children with viral LRTD. This article reviews the role of pulmonary surfactant in the pathogenesis of paediatric viral LRTD. Three randomized trials demonstrated improved oxygenation and reduced duration of mechanical ventilation and paediatric intensive care unit stay in young children with viral LRTD after administration of exogenous surfactant. This suggest that exogenous surfactant is the first beneficial treatment for ventilated infants with viral LRTD. Additionally, in vitro and animal studies demonstrated that surfactant associated proteins SP-A and SP-D bind to respiratory viruses, play a role in eliminating these viruses and induce an inflammatory response. Although these immunomodulating effects are promising, the available data are inconclusive and the findings are unconfirmed in humans. In summary, exogenous surfactant in ventilated infants with viral LRTD could be a useful therapeutic approach. Its beneficial role in improving oxygenation has already been established in clinical trials, whereas the immunomodulating effects are promising but remain to be elucidated

Unloading work of breathing during high-frequency oscillatory ventilation: a bench study

INTRODUCTION: With the 3100B high-frequency oscillatory ventilator (SensorMedics, Yorba Linda, CA, USA), patients' spontaneous breathing efforts result in a high level of imposed work of breathing (WOB). Therefore, spontaneous breathing often has to be suppressed during high-frequency oscillatory ventilation (HFOV). A demand-flow system was designed to reduce imposed WOB. METHODS: An external gas flow controller (demand-flow system) accommodates the ventilator fresh gas flow during spontaneous breathing simulation. A control algorithm detects breathing effort and regulates the demand-flow valve. The effectiveness of this system has been evaluated in a bench test. The Campbell diagram and pressure time product (PTP) are used to quantify the imposed workload. RESULTS: Using the demand-flow system, imposed WOB is considerably reduced. The demand-flow system reduces inspiratory imposed WOB by 30% to 56% and inspiratory imposed PTP by 38% to 59% compared to continuous fresh gas flow. Expiratory imposed WOB was decreased as well by 12% to 49%. In simulations of shallow to normal breathing for an adult, imposed WOB is 0.5 J l(-1 )at maximum. Fluctuations in mean airway pressure on account of spontaneous breathing are markedly reduced. CONCLUSION: The use of the demand-flow system during HFOV results in a reduction of both imposed WOB and fluctuation in mean airway pressure. The level of imposed WOB was reduced to the physiological range of WOB. Potentially, this makes maintenance of spontaneous breathing during HFOV possible and easier in a clinical setting. Early initiation of HFOV seems more possible with this system and the possibility of weaning of patients directly on a high-frequency oscillatory ventilator is not excluded either

Factors Associated with Prolonged Antibiotic Therapy in Neonates with Suspected Early-Onset Sepsis

Early-onset sepsis (EOS) is a rare but profoundly serious bacterial infection. Neonates at risk of EOS are often treated with antibiotics. The start of empiric antibiotic therapy can successfully be reduced by the implementation of the EOS calculator. However, once started, antibiotic therapy is often continued despite a negative blood culture. To decrease the burden of antibiotic therapy, it is necessary to know whether the clinician’s reasons are based on objective factors. Therefore, we performed a retrospective single-centre cohort study to identify the factors associated with prolongation of antibiotic therapy in neonates with suspected EOS but a negative blood culture. Maternal, clinical, and laboratory data of neonates with a gestational age of ≥32 weeks, admitted between January 2019 and June 2021, were collected. Among neonates with a negative blood culture, we compared neonates with prolonged (≥3 days) to neonates with discontinued (&lt;3 days) antibiotic therapy. The clinician’s reported reasons for prolonging therapy were explored. Blood cultures were positive in 4/146 (2.7%), negative in 131/146 (89.7%), and not obtained in 11/146 (7.5%) of the neonates. The incidence of EOS was 0.7 per 1000 neonates. Of the 131 neonates with a negative blood culture, 47 neonates (35.9%) received prolonged antibiotic therapy. In the prolonged group, the mean gestational age was higher (38.9 versus 36.8 weeks), and spontaneous preterm birth was less prevalent (21.3% versus 53.6%). Prolonged treatment was associated with late onset of respiratory distress, respiratory rate, hypoxia, apnoea and bradycardia, pale appearance, behavioural change, and elevated CRP levels. The most reported reasons were clinical appearance (38.3%), elevated CRP levels (36.2%), and skin colour (10.6%). Prolonging empiric antibiotic therapy despite a negative blood culture is common in suspected EOS. Clinical signs associated with prolongation are uncommon and the reported reasons for prolongation contain subjective assessments and arbitrary interpretations that are not supported by the guideline recommendations as arguments for prolonged therapy.</p

Factors Associated with Prolonged Antibiotic Therapy in Neonates with Suspected Early-Onset Sepsis

Early-onset sepsis (EOS) is a rare but profoundly serious bacterial infection. Neonates at risk of EOS are often treated with antibiotics. The start of empiric antibiotic therapy can successfully be reduced by the implementation of the EOS calculator. However, once started, antibiotic therapy is often continued despite a negative blood culture. To decrease the burden of antibiotic therapy, it is necessary to know whether the clinician’s reasons are based on objective factors. Therefore, we performed a retrospective single-centre cohort study to identify the factors associated with prolongation of antibiotic therapy in neonates with suspected EOS but a negative blood culture. Maternal, clinical, and laboratory data of neonates with a gestational age of ≥32 weeks, admitted between January 2019 and June 2021, were collected. Among neonates with a negative blood culture, we compared neonates with prolonged (≥3 days) to neonates with discontinued (&lt;3 days) antibiotic therapy. The clinician’s reported reasons for prolonging therapy were explored. Blood cultures were positive in 4/146 (2.7%), negative in 131/146 (89.7%), and not obtained in 11/146 (7.5%) of the neonates. The incidence of EOS was 0.7 per 1000 neonates. Of the 131 neonates with a negative blood culture, 47 neonates (35.9%) received prolonged antibiotic therapy. In the prolonged group, the mean gestational age was higher (38.9 versus 36.8 weeks), and spontaneous preterm birth was less prevalent (21.3% versus 53.6%). Prolonged treatment was associated with late onset of respiratory distress, respiratory rate, hypoxia, apnoea and bradycardia, pale appearance, behavioural change, and elevated CRP levels. The most reported reasons were clinical appearance (38.3%), elevated CRP levels (36.2%), and skin colour (10.6%). Prolonging empiric antibiotic therapy despite a negative blood culture is common in suspected EOS. Clinical signs associated with prolongation are uncommon and the reported reasons for prolongation contain subjective assessments and arbitrary interpretations that are not supported by the guideline recommendations as arguments for prolonged therapy.</p

Soluble adhesion molecules as markers for sepsis and the potential pathophysiological discrepancy in neonates, children and adults

Sepsis is a severe and life-threatening systemic inflammatory response to infection that affects all populations and age groups. The pathophysiology of sepsis is associated with aberrant interaction between leukocytes and the vascular endothelium. As inflammation progresses, the adhesion molecules that mediate these interactions become shed from cell surfaces and accumulate in the blood as soluble isoforms that are being explored as potential prognostic disease biomarkers. We critically review the studies that have tested the predictive value of soluble adhesion molecules in sepsis pathophysiology with emphasis on age, as well as the underlying mechanisms and potential roles for inflammatory shedding. Five soluble adhesion molecules are associated with sepsis, specifically, E-selectin, L-selectin and P-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. While increased levels of these soluble adhesion molecules generally correlate well with the presence of sepsis, their degree of elevation is still poorly predictive of sepsis severity scores, outcome and mortality. Separate analyses of neonates, children and adults demonstrate significant age-dependent discrepancies in both basal and septic levels of circulating soluble adhesion molecules. Additionally, a range of both clinical and experimental studies suggests protective roles for adhesion molecule shedding that raise important questions about whether these should positively or negatively correlate with mortality. In conclusion, while predictive properties of soluble adhesion molecules have been researched intensively, their levels are still poorly predictive of sepsis outcome and mortality. We propose two novel directions for improving clinical utility of soluble adhesion molecules: the combined simultaneous analysis of levels of adhesion molecules and their sheddases; and taking age-related discrepancies into account. Further attention to these issues may provide better understanding of sepsis pathophysiology and increase the usefulness of soluble adhesion molecules as diagnostic and predictive biomarkers

Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure

Introduction Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of mechanical ventilation with heliox in these patients is unclear. The objective of this prospective cross-over study was to determine the effects of mechanical ventilation with heliox 60/40 versus conventional gas on respiratory system resistance, air-trapping and CO2 removal. Methods Mechanically ventilated, sedated and paralyzed infants with proven RSV were enrolled within 24 hours after paediatric intensive care unit (PICU) admission. At T = 0, respiratory system mechanics including respiratory system compliance and resistance, and peak expiratory flow rate were measured with the AVEA ventilator. The measurements were repeated at each interval (after 30 minutes of ventilation with heliox, after 30 minutes of ventilation with nitrox and again after 30 minutes of ventilation with heliox). Indices of gas exchange (ventilation and oxygenation index) were calculated at each interval. Air-trapping (defined by relative change in end-expiratory lung volume) was determined by electrical impedance tomography (EIT) at each interval. Results Thirteen infants were enrolled. In nine, EIT measurements were performed. Mechanical ventilation with heliox significantly decreased respiratory system resistance. This was not accompanied by an improved CO2 elimination, decreased peak expiratory flow rate or decreased end-expiratory lung volume. Importantly, oxygenation remained unaltered throughout the experimental protocol. Conclusions Respiratory system resistance is significantly decreased by mechanical ventilation with helio

Imposed work of breathing during high-frequency oscillatory ventilation: a bench study

INTRODUCTION: The ventilator and the endotracheal tube impose additional workload in mechanically ventilated patients breathing spontaneously. The total work of breathing (WOB) includes elastic and resistive work. In a bench test we assessed the imposed WOB using 3100 A/3100 B SensorMedics high-frequency oscillatory ventilators. METHODS: A computer-controlled piston-driven test lung was used to simulate a spontaneously breathing patient. The test lung was connected to a high-frequency oscillatory ventilation (HFOV) ventilator by an endotracheal tube. The inspiratory and expiratory airway flows and pressures at various places were sampled. The spontaneous breath rate and volume, tube size and ventilator settings were simulated as representative of the newborn to adult range. The fresh gas flow rate was set at a low and a high level. The imposed WOB was calculated using the Campbell diagram. RESULTS: In the simulations for newborns (assumed body weight 3.5 kg) and infants (assumed body weight 10 kg) the imposed WOB (mean ± standard deviation) was 0.22 ± 0.07 and 0.87 ± 0.25 J/l, respectively. Comparison of the imposed WOB in low and high fresh gas flow rate measurements yielded values of 1.63 ± 0.32 and 0.96 ± 0.24 J/l (P = 0.01) in small children (assumed body weight 25 kg), of 1.81 ± 0.30 and 1.10 ± 0.27 J/l (P < 0.001) in large children (assumed body weight 40 kg), and of 1.95 ± 0.31 and 1.12 ± 0.34 J/l (P < 0.01) in adults (assumed body weight 70 kg). High peak inspiratory flow and low fresh gas flow rate significantly increased the imposed WOB. Mean airway pressure in the breathing circuit decreased dramatically during spontaneous breathing, most markedly at the low fresh gas flow rate. This led to ventilator shut-off when the inspiratory flow exceeded the fresh gas flow. CONCLUSION: Spontaneous breathing during HFOV resulted in considerable imposed WOB in pediatric and adult simulations, explaining the discomfort seen in those patients breathing spontaneously during HFOV. The level of imposed WOB was lower in the newborn and infant simulations, explaining why these patients tolerate spontaneous breathing during HFOV well. A high fresh gas flow rate reduced the imposed WOB. These findings suggest the need for a demand flow system based on patient need allowing spontaneous breathing during HFOV