Paediatrics (RCH) - Theses
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ItemOptimising continuous positive airway pressure in preterm infants( 2015)Background: Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) remain common complications of prematurity. Respiratory support may injure the lung and contribute to BPD. Non-invasive methods of respiratory support such as continuous positive airway pressure (CPAP) have the potential to reduce the risk of lung injury but randomised controlled trials comparing early CPAP with mechanical ventilation show no difference in the rates of BPD. In intubated infants, lung recruitment manoeuvres that allow for an ‘open lung’ improve oxygenation and ventilation but there is a paucity of data regarding CPAP strategies and how they impact upon lung behaviour. The series of studies described in this report aim to add to the knowledge regarding lung behaviour and potential complications in very preterm infants receiving CPAP. Method: Five studies of very preterm infants receiving CPAP were designed. These included three studies using respiratory inductive plethysmography and electrical impedance tomography; 1) a physiological study to determine if stepwise increases and decreases in CPAP level would demonstrate hysteresis and thus describe the changes in end-expiratory thoracic volume (∆EEV) and the distribution of ventilation (∆VT) in very preterm infants receiving CPAP from birth; 2) an observational study to describe ∆EEV and ∆VT during extubation to CPAP; and 3) a randomised pilot study comparing ∆EEV and ∆VT in infants extubated to currently used CPAP protocols versus a ‘CPAP recruitment’ manoeuvre. In addition, 4) a laboratory based study to determine whether the stable microbubble test could be used to determine within the first hour of life, which infants would successfully manage CPAP from birth and 5) a case-control study to determine risk factors for the development of pneumothoraces in very preterm infants were conducted. Results: These studies found that 1) it was possible to demonstrate hysteresis in many, but not all, very preterm infants exposed to stepwise increases and decreases in CPAP levels and that ∆EEV and ∆VT were often improved following this manoeuvre; 2) lung behaviour during extubation to CPAP was variable and unpredictable between and within infants; 3) after extubation, there were no differences in ∆EEV following a CPAP recruitment manoeuvre although ∆VT appeared to be more homogeneous when compared with a control group; 4) infants with a stable microbubble count ≥ 8 microbubbles/mm2 in gastric aspirate did not fail CPAP and 5) it may be possible to identify infants at highest risk of pneumothorax on the basis of their inspired fraction of oxygen in the first 12 hours of life. Conclusions: Lung behaviour at different stages of lung disease in very preterm infants receiving CPAP is complex, variable and unpredictable. It is possible to demonstrate hysteresis using CPAP, but optimising CPAP in very preterm infants at the bedside is difficult without tools that provide feedback regarding ∆EEV and ∆VT to clinicians. CPAP protocols that aid an ‘open lung’ require further investigation. Tests of endogenous surfactant status may be used to determine which infants may benefit from CPAP alone and which infants need escalation of respiratory support.
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ItemRespiratory support for children with severe pneumonia and hypoxaemia in a developing country: a randomized trial of bubble CPAP, high flow nasal cannula therapy and standard flow oxygen( 2014)BACKGROUND: Mortality rate from very severe pneumonia in many hospitals is more than 10% even with appropriate antibiotics, standard low flow (LF) oxygen by nasal prongs as recommended by the World Health Organization (WHO) and good supportive care. Bubble CPAP (BCPAP) and humidified high flow nasal cannula (HFNC) oxygen are increasingly used in neonatal care for reducing respiratory distress and hypoxemia. However, there were no published controlled trials (RCT) of the use of BCPAP in children beyond the newborn period with severe pneumonia and hypoxemia in developing countries. AIMS: Our aim was to evaluate the efficacy of BCPAP compared to LF or LF and HFNC therapy in managing children with severe pneumonia and hypoxemia. REGISTRATION: Clinicaltrials.gov identifier: NCT01396759 METHODS: We conducted an open RCT in the Dhaka hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) between August 2011 and July 2013. Children under five years of age who had severe pneumonia and hypoxemia as defined by WHO were randomly allocated to BCPAP, LF or HFNC oxygen therapies. The primary outcome was to determine if there were differences in treatment failure, based on objective clinical criteria. Mortality was our secondary outcome. We established a DSMB which reviewed adverse events and reviewed the planned interim analyses. RESULTS: During the study period 376 children were admitted with study criteria and 225 children were enrolled. There were two interim analyses. Two years into the study 79 children had been allocated to BCPAP, 79 to HFNC and 67 to the LF arms. Baseline and other characteristics were comparable between the 3 intervention groups, and all patients were available for analysis. At the second interim analysis the DSMB recommended stopping the study because of a significant difference in mortality. A total of 31 (14%) children fulfilled the criteria for treatment failure: among them 5 (6%) in BCPAP, 16 (24%) in LF and 10 (13%) in HFNC therapy. There were 23 deaths (10%): 3 (4%) in BCPAP therapy, 10 (15%) in LF therapy, 10 (13%) in HFNC therapy. Children who received BCPAP therapy had significantly lower treatment failure compared to those who received LF therapy (6% vs. 24%; p < 0.003) or LF and HFNC therapy (6% vs. 18%; p = 0.017). Mortality was significantly less in children who received BCPAP therapy compared to those who received LF therapy (4% vs. 15%; p = 0.040) or LF and HFNC therapy (4% vs. 13%; p = 0.035). In multiple logistic regression analysis, after adjusting for potential confounders, children who received BCPAP therapy had significantly less risk (OR = 0.29, 95% confidence interval = 0.09 – 0.88, p = 0.028) of developing treatment failure compared to other intervention groups and BCPAP therapy remained an independent predictor of survival (OR = 0.20, 95% confidence interval = 0.05 – 0.86, p = 0.031) in the management of children with severe pneumonia and hypoxemia. CONCLUSION: In Bangladeshi children under five with severe pneumonia and hypoxemia, compared to standard LF oxygen therapy, BCPAP oxygen therapy was associated with a significant lower probability of treatment failure and mortality. BCPAP should be considered an important option for treating children under five with severe pneumonia and hypoxemia.