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  1. Objectives : • Definition : • AECC • BERLIN • PALICC • Risk factors • Pathophysiology • Clinical features • Management Strategy • Reference
  2. Definition : • Acute respiratory distress syndrome (ARDS) is an acute, diffuse, inflammatory form of lung injury and life-threatening condition in seriously ill patients, characterized by:  poor oxygenation, pulmonary infiltrates, and acute onset. On a microscopic level, the disorder is associated with capillary endothelial injury and diffuse alveolar damage. • ARDS is defined by the patient's oxygen in arterial blood (PaO2) to the fraction of the oxygen in the inspired air (FiO2). These patients have a PaO2/FiO2 ratio of less than 300.
  3. THE EVOLUTION • What about Pediatrics ARDS? • But… no pediatricians or pediatric intensivists on the committee • Needs of kids not addressed
  4. Acute Respiratory Distress Syndrome, The Berlin Definition2012 American Medical Association: JAMA, June 20, 2012— Vol 307, No. 23
  5. • Formulated between 2012 and 2014 • Published recommendations in 2015
  6. Clinical features: • Commonly presents with : • Dyspnea • Anxiety • Agitation • Increased WOB • Chest x-ray shows bilateral infiltrates (hallmark : bilateral pulmonary infiltrates on chest radiography • PaO2/ FiO2 ratio of 300 mm Hg , in absence of suspected cardiogenic pulmonary edema )
  7. bronchial dilatation within areas of ground-glass opacification B-lines, spared areas, pleural line thickening, and subpleural consolidations.
  8. Pathophysiology :
  9. ARDS Loss of the alveolar capillary permeabili ty barrier Damage to the lung epithelium and vascular endothelium Presence of protein-rich edema fluid in the alveoli Dysregulated inflammation and inappropriate activity of leukocytes and platelets Uncontrolled activation of coagulation and suppression of fibrinolysis Loss of surfactant
  10. • Approach to ARDS :
  11. Management : • PICU management is mandatory . • Goals : Treatment of the underlying disorder Provide adequate oxygenation and ventilation Treatment of the associated multiple organ dysfunction. • Assess ABC
  12. Initial Strategy : •Worsening respiratory distress, Increasing WOB, SpO2 = 90-92% •Intubated •P-SIMV mode •Maintenance fluids – 70% •Sedo-analgesia: IV midazolam-fentanyl infusion •Broad spectrum antibiotics •COVID PCR negative •? Trial of NIV
  13. Should NIV trial have been given? • Benefit: Improve gas exchange, ⤓ WOB, avoid MV, complications, ICU stay • Risk: No response & deterioration, final outcome can be worse Why? Pediatric studies: Reduced need mechanical ventilation esp. mild-moderate Evidence Only mild ARDS Provided trained staff & close monitoring Immunodeficiency – individualize decision Practice
  14. Should NIV trial have been given? … Evidence for more caution • More preintubation NIV duration worse the outcomes compared with no preintubation NIV • If NIV doesn’t improve oxygenation/clinical parameters • Intubation : sooner the better • Longer the duration of NIV before intubation , worse the outcome May 2021 • Volume 49 • Number 5
  15. Ventilation - Which mode? • Adequate oxygenation and ventilation, • Prevent ventilator-induced lung injury Why? • No outcome data on influence of mode (C or A) during conventional MV PALICC guideline • PC vs. VC can be based on unit protocol & familiarity Practice Avoid • Overdistension (volutrauma and barotrauma), • Minimize the cyclic opening and closing of alveoli (atelectrauma) • Minimize biochemical mediator induced lung/organ injury (biotrauma)
  16. Ventilation - Volumes & Pressures: Vt, Pplat • Adequate oxygenation and ventilation, • Prevent ventilator-induced lung injury Why? • ARDS Network trial: • Adults - Lower Vt (6 mL/kg vs. 12mL/kg) ⤓ mortality ⤒ VFD ( ventilation free day ). • Limited plateau pressure (30cm H2O) Evidence • Vt < physiologic range for age/body weight • 3–6 mL/kg – poor compliance, 5–8 mL/kg – preserved compliance • Pplat < 28 cm H2O (29–32 cm H2O - reduced chest wall compliance) Practice – PALICC guideline
  17. SpO2 & PaCO2…. PALICC guideline Mild PARDS (PEEP<10): 92–97% PARDS with PEEP > 10: 88–92% Insufficient data exist to recommend a lower Spo2 limit Spo2 < 92%: Monitor central venous saturation and markers of oxygen delivery Saturation targets Tolerable PaCO2 Moderate-to-severe PARDS: Consider permissive hypercapnia pH 7.15–7.30 Exceptions – intracranial hypertension, severe PAH, select CHD, hemodynamic instability, significant ventricular dysfunction Bicarbonate supplementation is not routinely recommended
  18. Monitoring PALICC guideline All children with or at risk of PARDS should receive the minimum clinical monitoring : RR, HR, Spo2, NIBP Specific alarms when monitored variables are outside predefined ranges Vt & compliance  predicted body weight (gender + height/ulna length) Exhaled Vt should be continuously monitored to prevent injurious ventilation Pinsp monitored to prevent VILI – Ppeak (pressure mode) / Pplat (vol. mode)
  19. • To guide volume expansion in fluid restrictive strategy • To evaluate the impact of ventilation and disease on right & left cardiac function • To assess oxygen delivery Why? • no pediatric RCTs Evidence • Moderately elevated PEEP (10–15 cm H2O) • In severe PARDS, PEEP > 15 may be needed, limit plateau pressure • Closely monitor oxygen delivery, compliance, hemodynamics Practice – PALICC guideline PALICC guideline Suspected cardiac dysfunction  echocardiography Consider peripheral arterial catheter in severe PARDS – continuous monitoring of arterial blood pressure & ABG Insufficient evidence to recommend • Pulse contour with transpulmonary dilution technology, • Pulmonary artery catheters • Ultrasonic cardiac output monitoring • Transesophageal aortic Doppler • Noninvasive monitoring of cardiac output • Central venous oxygenation monitoring • B-type natriuretic peptide measurements Monitoring – hemodynamics
  20. Fluid management • Adequate intravascular volume, end-organ perfusion, optimal delivery of oxygen Why? • No pediatric RCTs Evidence • After initial fluid resuscitation & stabilization - goal-directed fluid management Adequate intravascular volume + prevent positive fluid balance • Goal-directed protocol = total fluid intake, output, & net balance Practice – PALICC guideline
  21. FLUIDS AND ARDS • For every 1% increase in daily FO %- OI increase by 0.9 • 83.3% of non-survivors had fluid overload, as compared to 38.8% of survivors, (P 0.002)
  22. Corticosteroids • Dysregulated inflammation occurring in ARDS Why? • Systematic reviews (adult) - mixed results • Meduri et al. – safe, ⤓ duration of mech. ventilation, ICU & LOS, mortality • Pediatric data: No benefit / longer duration of mechanical ventilation Evidence • Corticosteroids cannot be recommended as routine therapy in PARDS • Further study - specific patient populations, specific dosing and delivery regimens Practice – PALICC guideline
  23. Sedation • Facilitate tolerance to mechanical ventilation • Optimize oxygen delivery, oxygen consumption, work of breathing Why? Evidence • PALICC guideline Practice PALICC guideline Minimal yet effective targeted sedation Valid, reliable pain & sedation scales to monitor, target, and titrate sedation & to facilitate interprofessional communication Sedation monitoring, titration, & weaning should be managed by a goal-directed protocol with daily sedation goals collaboratively Physiologically stable, patients should receive a periodic assessment of their capacity to resume unassisted breathing Individualized sedation weaning plan, objective withdrawal scoring & assessment of patient tolerance • Nurse-driven sedation protocol • 2,900 mechanically ventilated children across 31 PICUs • No reduction in duration of mech. Ventilation ….. but more wakeful state, lower exposure to sedative meds • Long-term - No difference in functional status or mental health risk • Need for additional investigations
  24. Sedation scales • COMFORT scale • <11: over sedated • 11-22: Moderate sedation • >22: under sedated • Modified Ramsay sedation scale
  25. Neuromuscular blockers • Important adjunct to sedation for mechanically ventilated patients • To facilitate tolerance to mechanical ventilation • Optimal oxygen delivery, consumption, WOB & lung mechanics Why? • Adult clinical trials/guidelines - support NMB use in early severe ARDS • Mostly cis-atracurium. Rocuronium, vecuronium - ⤒ myopathy, neuropathy • No pediatric RCT Evidence Practice – PALICC guideline PALICC guideline If sedation alone is inadequate to achieve effective mechanical ventilation  NMB Minimal yet effective NMB with sedation Monitored & titrated to the goal depth established by the interprofessional team. Monitoring : effective ventilation, clinical movement, Consider daily NMB holiday to allow periodic assessment of level of NMB & sedation. Improved OI with continuous NMB
  26. Refractory hypoxemia • Recruitment maneuvers • HFO • Prone positioning • Others
  27. Ventilation – recruitment manoeuvres • Increased PEEP or sustained inflation to reopen regions of lung collapse • Open lung strategy by preventing lung collapse & atelectotrauma Why? • Adult studies - sustained inflation or high levels of PEEP - improve oxygenation in higher lung compliance (early ARDS with atelectasis or inflammatory edema) compared to those with decreased chest wall compliance Evidence • Careful recruitment maneuvers to improve severe oxygenation failure • By slow incremental & decremental PEEP steps • Sustained inflation not recommended Practice – PALICC guideline No data - impact of recruitment maneuvers on mortality or duration of mech. vent. Sustained inflation  heterogeneous overdistension.
  28. Ventilation – HFOV • Open lung strategy by preventing lung collapse & atelectotrauma Why? • Early adults studies of HFOV – promising • OSCILLATE & OSCAR - no benefit and potential harm; applicability to children ? • Pediatric studies – no clear benefit Evidence • Availability • experts - HFO has a role • Ongoing PROSPeCT may provide clarity Practice – PALICC guideline HFOV - alternative mode: Moderate-to-severe PARDS - Pplat > 28 cm H2O No clinical evidence of reduced chest wall compliance Optimal lung volume  Exploration of the potential for lung recruitment  Stepwise increase & decrease of Paw  Continuous monitoring (oxygenation, Co2, hemodynamics) High-frequency jet ventilation not recommended, ~ severe air leak syndrome High-frequency percussive ventilation not recommended ~ secretion-induced collapse
  29. Ventilation – HFOV
  30. Airway pressure release ventilation (APRV) • Truncated • APRV as primary mode for ARDS , increased mortality
  31. Ventilation – prone positioning • Improve lung mechanics & oxygenation in mechanically ventilated patients Why? Evidence • Not recommended as routine therapy • Considered an option in cases of severe PARDS Practice – PALICC guideline 1999 systematic review (20 studies) - improved oxygenation, adverse events rare Three more meta-analyses - 2008 (13 studies) improve oxygenation without significant effect on mortality - Follow-up study of 10 trials - decreased mortality only in severe ARDS - 2014 (11 RCT) – significant reduction mortality when coupled with lung protective vent. Included PROSEVA study - 50% mortality reduction in severe ARDS Multicenter RCT in pediatrics - safe, but no difference in duration of mechanical ventilation, mortality, or other health outcomes PROSpect study – ongoing
  32. Inhaled nitric oxide • Pulmonary vasodilator to increase blood flow to areas with adequate ventilation, improving ventilation/perfusion mismatch & oxygenation Why? Evidence Practice – PALICC guideline PALICC guideline Not recommended for routine use in PARDS. Consider - documented PAH / severe RV dysfunction May consider - severe PARDS: rescue / bridge ECMO When used, prompt assessment of benefit Insufficient evidence to support use Transient improvement in oxygenation Does not reduce mortality May be harmful, ~ renal impairment
  33. Something much simpler… When to transfuse red blood cells ? PALICC guideline Clinically stable children with evidence of adequate oxygen delivery - Trigger for RBC transfusion : 7.0 g/Dl (excluding cyanotic heart disease, bleeding, and severe hypoxemia)
  34. • Augment systemic oxygen delivery to allow the injured lungs to rest & recover • Significant risk; substantial resources & expertise • Strong evidence in neonates & potential benefit in adults; use in children ⤒ Why? • Adults: mixed results CESAR trial: cost-effective, ⤒ 6-month survival • EOLIA trial: No significant difference in 60-day mortality • PARDS lacking; survival to hospital discharge - 60% Evidence Practice – PALICC guideline Consider in severe PARDS - cause reversible or lung transplantation. Strict criteria difficult; when lung protective strategies result in inadequate gas exchange. Structured evaluation of case history & clinical status Serial evaluation of ECMO eligibility > single-point assessment. Consider quality of life & likelihood of benefit should be assessed. Should not be deployed - life-sustaining measures limited Extreme hypercarbia & mild-to-moderate hypoxia may benefit from new extracorporeal devices with partial respiratory support ECLS
  35. Other important issues… Nutrition A nutrition plan to facilitate recovery, maintain growth, meet metabolic needs. Enteral nutrition, when tolerated, in preference to parenteral. Enteral nutrition monitoring, advancement, maintenance - goal-directed protocol collaboratively established by the interprofessional team. Weaning Daily assessment of extubation readiness to avoid prolonged ventilation. Spontaneous Breathing Trials and/or Extubation Readiness Tests should be performed Endotracheal suctioning ET suctioning - cautious to minimize the risk of derecruitment Insufficient data to support open or closed suctioning system Severe PARDS – minimize the potential for derecruitment Routine instillation of isotonic saline prior to suctioning not recommended May be indicated for lavage to remove thick tenacious secretions
  36. Other therapies. Surfactant Surfactant dysfunction is part of the known pathophysiology No benefit for outcomes such as mortality, ventilation time, or LOS Further studies Other therapies with no proven benefit Helium-oxygen mixture Inhaled or IV prostaglandins therapy Plasminogen activators Fibrinolytics Inhaled β-adrenergic receptor agonists or ipratropium N-acetylcysteine Dornase alpha in non CF population