PAEDIATRIC RESPIRATORY FAILURE. Tang Swee Fong Department of Paediatrics University Kebangsaan Malaysia Medical Centre
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1 PAEDIATRIC RESPIRATORY FAILURE Tang Swee Fong Department of Paediatrics University Kebangsaan Malaysia Medical Centre
2 Outline of lecture Bronchiolitis Bronchopulmonary dysplasia Asthma ARDS
3 Bronchiolitis
4 Bronchiolitis - Epidemiology Deaths (100) Hospitalisations (57, ,00 2-3% of children <12 months) Hospital charges: >$1.7 billion in ,000 to 199,000 deaths in children <5 years of age (mainly in resourcelimited countries) Outpatient care (800,00 children - 20% of birth cohort) Hall CB, et al. New Engl J Med 2009;360: Nair H, et al. Lancet 2010;375:
5 Bronchiolitis - Management Lack of curative therapy Bronchodilators Corticosteroids Wheeze Clinicians should not administer albuterol (or salbutamol) to infants and children with diagnosis of bronchiolitis AAP Guidelines 2014
6 Hypertonic saline Draw fluid from submucosal and adventitial spaces replenishes air liquid surface and improve clearance of airway
7 Double-blind RCT 3%HS vs 0.9%NS 68 patients (HS: 33; NS:35) Mild to moderate acute viral bronchiolitis
8 Major outcomes Hypertonic saline Group 1 (HS) N=33 Normal saline Group II (NS) N=35 p value Days until fit to discharge (mean + SD) Days until discharge (mean + SD) Severity score D1 (33, 35) Severity score D2 (33, 34) Severity score D3 (29, 31) Severity score when fit to discharge (33, 35) 1 1 (N Group I, N Group II) Flores P, et al. Pediatr Pulmonology 2016;51:418-25
9 Major outcomes Hypertonic saline Group 1 (HS) N=33 Normal saline Group II (NS) N=35 p value Days until fit to discharge (mean + SD) Days until discharge (mean + SD) Severity score D1 (33, 35) Severity score D2 (33, 34) Severity score D3 (29, 31) Severity score when fit to discharge (33, 35) 1 1 (N Group I, N Group II) Flores P, et al. Pediatr Pulmonology 2016;51:418-25
10 Minor outcomes Hypertonic saline Group 1 (HS) N=33 Normal saline Group II (NS) N=35 p value Supplemental oxygen, duration (h) Further doses of salbutamol 17 (51.5) 23 (65.7) Nebulised epinephrine 9 (27.3) 23 (14.3) Systemic corticosteroids 8 (24.2) 10 (28.6) Antibiotics 18 (54.5) 13 (37.1) Patients in HS group had significantly more Cough (46% vs 20%, p=0.025) Rhinorrhoea infants with bronchiolitis (58% vs 31%, p=0.03) Our results do not support the use of HS in Flores P, et al. Pediatr Pulmonology 2016;51:418-25
11 10 hospitals in UK 317 infants (HS: 158; NS: 159) 3% HS vs standard therapy Thorax 2014;69:
12 SABRE (hypertonic Saline in Acute Bronchiolitis Rct and Economic evaluation Hazard ratio: 0.95, (95%CI: ) Hazard ratio: 0.97, (95%CI: ) This study does not support the use of nebulised HS in the treatment of acute bronchiolitis over usual care with minimal handlings Everard M, et al. Thorax 2014;69:
13 Retrospective, cohort study Single centre 135 patients Pediatr Crit Care Med 2017;18:e106-e111
14 Cumulative fluid balance (ml/kg) Early fluid overload prolongs mechanical ventilation *p<0.05 *p<0.01 * ** * * 92.6% had a positive cumulative fluid balance starting on day of admission Duration of mechanical ventilation positively correlated with mean cumulative fluid balance Study day No association between fluid status and OSI Ingelse SA, et al. Pediatr Crit Care Med 2017;18:e108-e111
15 (Pediatr Crit Care Med 2017;18:e106-e111) Early fluid overload independent predictor of prolonged mechanical ventilation
16 New Engl J Med 2006;354: Crit Care Med 2012;40:2883-9
17 (Crit Care Res Pract 2011;854142) p<0.02, 95%CI 1.09 (1.00, 1.18) p<0.02, 95%CI (-0.42, -0.01)
18 Judicious fluid management
19 Lancet 2017;369:930-9 Aim HFWHO provided enhanced respiratory support Shorter time to weaning off oxygen Treatment arm HFWHO (1L/kg to maximum of 20 L, maximum FiO 2 of 0.6) Control arm standard therapy (cold wall oxygen 100% via nasal cannulae at low flow to a maximum of 2L/min)
20
21 HFWHO treatment failure and care escalation (ITT) Treatment failure Standard therapy N (%) HFWHO N (%) p value Difference (95%CI) 33 (33) 14 (14) % (8-30) Crossover 32 (32) 1 (1) < % (17-44) Rescued 20 (20) ICU transfer 17 (12) 14 (14) % (-7 to 16) Kepreotes E, et al. Lancet 2017;369:930-9
22 HFWHO HFWHO - summary and standard therapy were both effective early use did not alter overall course of bronchiolitis prevented deterioration in significantly more infants able to reverse deterioration in 63% This study provides evidence for the use of HFWHO at a maximum of 1L/kg per min (FIO 2 0.6) in the management of children with bronchiolitis of moderate severity for whom standard therapy with oxygen at 2L/min has failed or have used HFWHO from the outset Kepreotes E, et al. Lancet 2017;369:930-9
23 Bronchiolitis management in 2017 Supplemental oxygen Minimal handling Provision and judicious use of fluids
24 Chronic lung disease of infancy (Bronchopulmonary dysplasia) BPD complicated with pulmonary hypertension associated with increased morbidity and mortality
25 18 patients with BPD Pulmonary pressure assessment: Echocardiography and cardiac catheterisation PH medication: Sildenafil alone - 12, Sildenafil + Bosentan 5, Bosentan alone 1
26 Clinical improvement A decrease in Ross functional class by at least one degree Haemodynamic improvement A decrease in pulmonary hypertension severity by one level
27 Ross functional class over time Echocardiographic score over time vs , p< Moderate or severe PH 72% vs 17% moderate PH, p<0.001
28 PAH-targeted therapy can be useful for infants with BPD and PH on optimal treatment of underlying respiratory and cardiac disease (Class IIa; Level ofevidence C) Circulation 2015;132
29 Asthma Magnesium sulphate infusion
30 Pediatr Crit Care Med 2016;17:e29-33 Prospective randomised open-label trial 6-16 year old with severe asthma Emergency department iv MgSO 4 50mg/kg bolus vs high dose infusion 50mg/kg/hr for 4 hours
31 Outcomes Main outcomes Bolus High dose infusion p value LOS < 24 hrs, n (%) 2 (10.5) 9 (47.4) Absolute risk reduction 37%; 95% CI, 10-63; NNT, 3 LOS (hr) (mean + SD) Cost (US$) (mean + SD) Irazuzta et al. Pediatr Crit Care Med 2016;17:e29-33
32 Outcomes Main outcomes Bolus High dose infusion p value Early utilisation of high-dose prolonged MgSO 4 infusion expedites discharge from emergency department with significant reduction in healthcare cost LOS < 24 hrs, n (%) 2 (10.5) 9 (47.4) Absolute risk reduction 37%; 95% CI, 10-63; NNT, 3 LOS (hr) (mean + SD) Cost (US$) (mean + SD) Irazuzta et al. Pediatr Crit Care Med 2016;17:e29-33
33 ..if a little is good, more is even better? Comparatively easy to use Relatively good side effect profile Inexpensive? Higher dose short term infusion useful adjunct
34 Acute Respiratory Distress Syndrome
35 Pediatr Crit Care Med 2016;17:101-9 Alveolar dead space fraction = (PaCo 2 PetCO 2 ) / PaCO 2
36 AVDSf
37 AVDSf AUROC 0.76; (95% CI, ; p<0.001) Better than OI or PaO 2 /FiO 2 Yehya N, et al. Pediatr Crit Care Med 2016;17:101-9
38 Pediatr Crit Care Med 2017;18:e229-e234 Oxygenation
39 Pediatr Crit Care Med 2017;18:e229-e mechanically ventilated patients Responders: >10% increase in OI
40 Changes in oxygenation and regional ventilation Responders (n=4) Non-responders (n=8) Baseline 60 min Baseline 60 min OI % change in OI N/A N/A PaO 2 /FiO SpO 2 /FiO Responders proportion of ventilation increased in dorsal lung (49% to 57%) Improvement in ventilation homogeneity Lupton-Smith A, et al.. Pediatr Crit Care Med 2017;18:e229-e234
41 Novel insights on ventilation distribution on turning prone Not all infants and children respond positively Degree of response variable Ventilation becomes more homogenous with time improving V/Q matching Highlights clinical utility of electrical impedance tomography to aid in identifying those more likely to respond
42 JPEN J Parentr Enteral Nutr 2016? Nutrition delivery to children pards? Provision of adequate nutrition improved clinical outcomes
43 Caloric intake Protein intake ICU mortality with adequate caloric intake, 34.6% vs 60.5%, p=.025 ICU mortality with adequate protein intake, 14.3% vs 60.2%, p=.002 Significantly associated with ventilator-free days
44 JPEN J Parentr Enteral Nutr 2016 Adequate nutrition delivery improves clinical outcome Protein delivery may have potentially more impact than caloric intake
45 Pediatri Crit Care Med 2017;18:
46 Guidelines for provision and assessment of nutrition support therapy Reiterates importance of nutritional assessment Need for renewed focus on Accurate estimation of energy needs Attention to optimising protein intake Optimal route and timing of nutrient delivery still debated and investigated enteral nutrition preferred route of delivery
47 Open-labelled RCT Expected length of stay > 72 hours JAMA, 2016;316: JAMA 2016;316: PaO 2 (mmhg) SpO 2 (%) Conservative Conventional Up to Unplanned early termination
48 Oxygen-ICU: ICU mortality Conservative PaO2 70 to 100 mmhg SpO2 94%-98% Conventional PaO2 up to 150 mmhg SpO2 97%-100% Girardis M, et al. JAMA 2015;316:1583-9
49 Oxygen therapy, No. (%) Conservative (n=216) Conventional (n=218) Absolute risk JAMA 2016;316: p value reduction (95%CI) Primary outcome Mortality 25 (11.6) 44 (20.2) Secondary outcome Shock Liver failure Bacteraemia 8 (3.7) 4 (1.9) 11 (5.1) 23 (10.6) 14 (6.4) 22 (10.1) ( ) NNT ( ) ( ) ( )
50 Potential impact to current practice Mindful of the potential harms of hyperoxia in critically ill patients Judicious use of supplemental oxygen titrating to maintain normoxia
51 Am J Respir Crit Care Med 2017;195:331-8
52 Clinical outcome by ARDS Subphenotype Subphenotype 1 (n=727) Subphenotype 2 (n=273) p value 60-d mortality, % < d mortality, % <0.001 Ventilator-free days, median 19 3 <0.001
53 Clinical outcome by ARDS Subphenotype Subphenotype 1 (n=727) Subphenotype 2 (n=273) p value 60-d mortality, % < d mortality, % <0.001 Ventilator-free days, median 19 3 <0.001 Interaction between ARDS Subphenotype and Fluid Management Strategy Fluid management strategy Subphenotype 1 Subphenotype 2 p value Conservative (n=349) Liberal (n=367) Conservative (n=142) Liberal (n=131) 60-d mortality, % d mortality, % Ventilator-free days, median
54 Lancet Respir Med 2014
55 Association between phenotype assignment and clinical outcome ARMA cohort ALVEOLI cohort Phenotype 1 (n=308) Phenotype 2 (n=155) p value Phenotype 1 (n=404) Phenotype 2 (n=145) p value 90-d mortality 23% 44% % 51% <0.001 Ventilator-free days Organ-failure free days < < < <0.001 Differences in response to PEEP strategy (ALVEOLI cohort only) Phenotype 1 (n=404) Phenotype 2 (n=145) Low PEEP (n=202) High PEEP (n=202) Low PEEP (n=71) High PEEP (n=74) p value 90-d mortality 33 (16%) 48 (24%) 36 (51%) 31 (42%) Ventilator-free days 20 (10-25) 21 (3-24) 2 (0-21) 4.5 (0-20) Organ-failure free days 22 (11-26) 22 (9-26) 4 (0-18) 6.5 (0-21) 0.003
56 Amer J Respir Crit Care Med 2017;195:3:280-1
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58 2026/2027 PAEDIATRIC RESPIRATORY FAILURE
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60 Thank you
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