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Paediatric acute respiratory distress syndrome (PARDS)

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When does respiratory failure become PARDS, and how should we manage it?

Peter, a 2-month-old boy, is admitted to the paediatric ward on high-flow nasal oxygen with presumed bronchiolitis. Over the day, his oxygen requirement dramatically increased to the point of requiring intubation

He is transferred to the regional PICU, where ventilation becomes increasingly challenging, with high airway pressures and poor oxygenation. You spend a challenging night responding to ventilator alarms and dramatic desaturations.

During the morning handover, the PICU consultant suspects PARDS, and you discuss the next steps in his management.


Does this child meet the criteria? How can we improve his ventilation?

Paediatric acute respiratory distress syndrome (PARDS) has been historically hard to define. The definition was initially extrapolated from adult syndrome (simply known as ARDS). This was never ideal because of significant differences between adults and children.

Firstly, ARDS requires invasive measurement via an arterial blood gas (ABG) of PaO2. We tend to opt for surrogate or alternative measures of arterial gases in children—except in those with arterial access—and rely on oxygen saturations as a surrogate. This means that the condition could be underdiagnosed, and those who did fit the criteria often self-select as being more severe, as they were already intubated. 

The second major issue was using the PaO2/FiO2 ratio to define PARDS. The PaO2/FiO2 ratio is heavily influenced by ventilation pressures and strategies, both of which vary significantly between PICUs – much more so than their adult counterparts. 

So, the Paediatric Acute Lung Injury Consensus Conference (PALICC) was formed to decide on a definition. They first met in 2015 and again in 2023. What followed was the publication of the PALICC-2 executive summary for the diagnosis and management of PARDS. 

What is PARDS?

ALICC-2 (2023) decided on the following criteria for diagnosis of PARDS:

Age: Nil specific cutoff, but excludes those with perinatal lung disease
Timing: within 7 days of known insult 
Origin of oedema: not fully explained by cardiac failure or fluid overload.
Chest imaging: new bi/unilateral opacities consistent with parenchymal disease, not explained by effusion or atelectasis.
Oxygenation:
If mechanically ventilated – the oxygenation index ≥ 4 or the oxygenation saturation index ≥5
If on NIV (oronasal CPAP or BiPAP) – Spo2/Fio2 ≤ 250 or PaO2/FIO2 ≤ 300 

 Oxygenation index is calculated as follows:

Mean airway pressure (MAP) × FiO2 × 100÷PaO2


Oxygenation saturation index is calculated as follows:

MAP × FiO2 × 100÷SpO2

Or use a calculator (e.g. MDCalc) if you don’t want to make a mistake!

Determining the severity of PARDS

Severity can be determined four hours after the initial criteria are met based on the following:

Mechanically ventilated-PARDS: 

  • Mild/moderate if OI <16 or OSI <12
  • Severe if OI ≥16 or OSI ≥12

NIV-PARDS:

  • Mild/moderate if paO2/FIO2 >100 or Spo2/FIO2 > 150
  • Severe if PaO2/FIO2 ≤100 or SPO2/FIO2 ≤150

 For those children with pre-existing cyanotic heart disease:

PARDS if an acute deterioration is not explained by cardiac disease


For those with pre-existing chronic lung disease:

PARDS If there is acute deterioration from baseline oxygenation

Possible vs At Risk of PARDS

It’s worth noting that they made a distinction between patients meeting the criteria for PARDS and children classified as possible PARDS or at-risk of PARDS:

Criteria for possible PARDS:

Nasal continuous airway positive pressure/bilevel positive airway pressure or high-flow nasal cannula (≥ 1.5 L/kg/min or ≥ 30 L/min): Pao2/Fio2 ≤ 300 or Spo2/Fio2 ≤ 250

Criteria for at-risk of PARDS:

Oxygen supplementation (via any interface) to maintain Spo2 ≥ 88% but not meeting the definition for PARDS or possible PARDS.

Back to Peter

Based on the criteria, you agree that Peter meets the definition for PARDS.

As Peter has an arterial line, you draw a blood gas and stratify him as severe based on his oxygenation index. 

You consult the PALICC-2 consensus document for treatment guidelines and realise there are 151 different recommendations across nine domains (including sedation, monitoring, fluids and nutrition).

You decide to focus on optimising Peter’s ventilation and sedation..

Lung-protective ventilation

PALICC-2 recommends a lung protective strategy. What does ‘lung-protective’ mean?

All ventilators do work – they create pressure, volume, oxygenation. This is transferred to the patient’s lungs. We want to limit this damage to the (already damaged) lungs and accept a trade-off in permissive hypoxaemia and hypercapnia.

Practically, we use initial volumes of 6-8mls/kg, reduced to 4-6mls/kg if airway pressures are particularly high, aiming for a pH ≥7.20 (permissive hypercapnia). Oxygen saturations should be 92-97%; however, sats <92% are acceptable in severe cases if PEEP is optimised (see below). You should use central venous oxygen saturations are used when accepting sats of <92%. 

The results of the Oxy-PICU trial, published in December 2023, are worth mentioning. This was a UK-based, multi-centre randomised controlled trial in 15 PICUs looking at the difference in outcomes between conservative (88-92%) vs liberal (>94%) saturation targets. It was an open-label, randomised, controlled trial. The primary outcome of this study was the duration of organ support at 30 days. They found that the duration of organ support was significantly lower in the conservative group, with a probabilistic index of 0.53 (95% CIs 0.50-0.55) and an adjusted odds ratio of 0.84 (0.72-0.99). Prespecified adverse events were reported in 3% of 939 in the conservative group vs 4% of 933 in the liberal group. 

The authors concluded there was a “small, but significant, greater probability of a better outcome in terms of duration of organ support at 30 days or death when compared with a liberal oxygenation target”. They felt that the widespread adoption of this approach could help improve outcomes and reduce costs for the sickest children admitted to intensive care. Many paediatric intensive care units are therefore adopting a SpO2 target of 88-92% as default (including for children with PARDS).

PALICC-2 advises optimising sedation to achieve the desired minute ventilation and oxygenation goals, focusing on daily reviews. If ventilation targets are not being met with sedation alone, neuromuscular blockade should be used at the lowest effective dose in combination with sedation. 

You look at Peter’s ventilator settings and see he has a peak pressure of 34 with a PEEP of 15.

He seems quite active and triggers the ventilator frequently with variable volumes. He is not receiving any infusion of a neuromuscular blocking agent. What should we do?


You opt to increase his sedation gradually whilst adding in an infusion of rocuronium.

You decrease his targeted tidal volume to 4-6mls/kg but increase his respiratory rate to maintain his minute ventilation, aiming for a target SpO2 of 88-92%.

His peak pressure is now at 28 with a PEEP of 15, achieving SpO2 88-92% and pH >7.2.

You gradually increase his sedation while adding an infusion of rocuronium and decrease his targeted tidal volume to 4-6mls/kg.

If peak pressure is ≤ 28cm or driving pressure (plateau pressure – PEEP) ≤ 15cm H2,O aim for tidal volumes of 6-8mls/kg

If struggling to meet these pressure limits, aim for tidal volumes of 4-6mls/kg

PEEP should be titrated up according to oxygen requirement in-line with original ARDSNET recommendations:

For the sickest patients who fail to improve despite the above recommendations, there are several additional options. These, however, lack evidence and are so weakly supported by PALICC-2.

When conventional measures fail…

Despite your best efforts, Peter’s oxygenation does not improve. You consider your options.

What does PALICC-2 say about them?

Proning – no recommendation either way.

High-frequency oscillatory ventilation (HFOV) – no recommendation either way.

Inhaled nitric oxide (NO) is not routinely recommended but may be useful in selected populations, e.g., those with pulmonary hypertension or right ventricular dysfunction. It can also be considered a rescue or bridge to ECMO

Corticosteroids – recommends against the routine use in PARDS (unless caused by SARS-CoV-2).

Surfactant – recommends against the routine use in PARDS.

Your team decides to prone Peter and start inhaled nitric oxide as a potential rescue therapy while discussing a possible transfer to VV-ECMO with the regional ECMO centre.

He does not have SARS-COV-2, so you do not give him corticosteroids.

Thankfully, his ventilation slowly improves, and you can de-prone him and stop the nitric oxide.

After many more days of invasive ventilation, he is extubated and begins to wean with non-invasive respiratory support.

The Evidence

The PALICC-2 recommendations were produced after an extensive systematic review. Topics were chosen from the 2015 PALICC guidelines, and new key topics were identified by each PALICC-2 subgroup (eleven in total!).

The GRADE approach was used to summarise evidence and produce guidelines for practice, and where applicable, meta-analyses were performed to obtain pooled estimates from similar studies. 

The GRADE approach to systematic review is “a transparent framework for developing and presenting summaries of evidence for making practice recommendations”. It is the most widely adopted tool for grading the quality of evidence. 

The group graded recommendations as strong or conditional based on the certainty of the evidence reviewed. Strong recommendations were only made when a “large net positive impact” was abundantly clear if the action was implemented. 

Take-homes

The development of paediatric-specific ARDS diagnostic criteria was essential to allow the development of guidelines and research for PARDS.

The PALICC group has produced a consensus definition that allows diagnosis and stratification as well as identifying those with possible or at risk of developing PARDS

A lung protective ventilation strategy is central to the management of PARDS.

PALICC recommend permissive hypercapnia aiming for pH of ≥7.20.

Permissive hypoxia is tolerable, provided PEEP is optimised and central venous saturations are monitored.

There is no consensus on the routine use of proning or high-frequency oscillatory ventilation – although the PROSpect trial is currently comparing conventional vs oscillatory ventilation and prone vs supine positioning.

PALICC states that Inhaled nitric oxide (iNO) can be considered as a rescue or bridge to ECMO in severe cases

Note that iNO does have a role in other populations/conditions not discussed in this article.

About PICSTAR

PICSTAR is a trainee-led research network open to all doctors, nurses and allied health trainees within Paediatric Intensive Care.  We are the trainee arm of the Paediatric Critical Care Society – Study Group (PCCS-SG) and work with them on research, audit and service evaluation.

If you would like to join PICSTAR and get involved in projects, have ideas you would like to propose or get advice/mentorship via PCCS-SG, don’t hesitate to contact us at picstar.network@gmail.com. See their website for more: https://pccsociety.uk/research/picstar/

References

  1. Emeriaud G, López-Fernández YM, Iyer NP, Bembea MM, Agulnik A, Barbaro RP, Baudin F, Bhalla A, Brunow de Carvalho W, Carroll CL, Cheifetz IM, Chisti MJ, Cruces P, Curley MAQ, Dahmer MK, Dalton HJ, Erickson SJ, Essouri S, Fernández A, Flori HR, Grunwell JR, Jouvet P, Killien EY, Kneyber MCJ, Kudchadkar SR, Korang SK, Lee JH, Macrae DJ, Maddux A, Modesto I Alapont V, Morrow BM, Nadkarni VM, Napolitano N, Newth CJL, Pons-Odena M, Quasney MW, Rajapreyar P, Rambaud J, Randolph AG, Rimensberger P, Rowan CM, Sanchez-Pinto LN, Sapru A, Sauthier M, Shein SL, Smith LS, Steffen K, Takeuchi M, Thomas NJ, Tse SM, Valentine S, Ward S, Watson RS, Yehya N, Zimmerman JJ, Khemani RG; Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) Group on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2). Pediatr Crit Care Med. 2023 Feb 1;24(2):143-168. doi: 10.1097/PCC.0000000000003147. Epub 2023 Jan 20. PMID: 36661420; PMCID: PMC9848214.
  2. Peters MJ, Gould DW, Ray S, Thomas K, Chang I, Orzol M, O’Neill L, Agbeko R, Au C, Draper E, Elliot-Major L, Giallongo E, Jones GAL, Lampro L, Lillie J, Pappachan J, Peters S, Ramnarayan P, Sadique Z, Rowan KM, Harrison DA, Mouncey PR; Oxy-PICU Investigators of the Paediatric Critical Care Society Study Group (PCCS-SG). Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial. Lancet. 2023 Dec 1:S0140-6736(23)01968-2. doi: 10.1016/S0140-6736(23)01968-2. Epub ahead of print. PMID: 38048787.
  3. What is GRADE? | BMJ Best Practice
  4. PROSpect Study – The PRone and OScillation Pediatric Clinical Trial (PROSpect) is designed to study the effects of prone positioning and HFOV for PARDS (prospect-network.org)
  5. Inhaled Nitric Oxide Use in Pediatric Hypoxemic Respiratory Failure – PMC (nih.gov)

Authors

  • Olly can usually be found working as a consultant in emergency medicine with a special interest in paediatrics, whilst also doing shifts in paediatric retrieval. When not working he will normally be trying to keep up with his two young daughters.

  • Kieran is enjoying PICM training at both RHC Glasgow and RHCYP Edinburgh. Away from work he enjoys hillwalking, travelling, football and the pub, and is working on ways to involve his new baby boy in all of these activities

  • PICSTAR is a trainee-led research network open to all doctors, nurses and allied health trainees within Paediatric Intensive Care. We are the trainee arm of the Paediatric Critical Care Society – Study Group (PCCS-SG) and work with them on research, audit and service evaluation. If you would like to join PICSTAR and get involved in projects, have ideas you would like to propose or get advice/mentorship via PCCS-SG, don’t hesitate to get in touch with us at picstar.network@gmail.com. See their website for more: https://pccsociety.uk/research/picstar/

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