Objectives :
• Definition :
• AECC
• BERLIN
• PALICC
• Risk factors
• Pathophysiology
• Clinical features
• Management Strategy
• Reference

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.

THE EVOLUTION
• What about Pediatrics ARDS?
• But… no pediatricians or pediatric intensivists on the committee
• Needs of kids not addressed

Acute Respiratory Distress Syndrome, The Berlin Definition2012 American Medical Association: JAMA, June 20, 2012—
Vol 307, No. 23

• Formulated between 2012 and 2014
• Published recommendations in 2015

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 )

bronchial dilatation within areas of
ground-glass opacification
B-lines, spared areas, pleural line thickening, and subpleural
consolidations.

Pathophysiology :

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

• Approach to ARDS :

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

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

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

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

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)

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

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

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)

• 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

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

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)

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

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

Sedation scales
• COMFORT scale
• <11: over sedated
• 11-22: Moderate sedation
• >22: under sedated
• Modified Ramsay sedation scale

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

Refractory hypoxemia
• Recruitment maneuvers
• HFO
• Prone positioning
• Others

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.

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

Ventilation – HFOV

Airway pressure release ventilation (APRV)
• Truncated
• APRV as primary mode for ARDS , increased mortality

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

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

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)

• 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

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

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