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. Author manuscript; available in PMC: 2022 Jun 1.
Published in final edited form as: Curr Opin Pediatr. 2021 Jun 1;33(3):319–324. doi: 10.1097/MOP.0000000000001009

Prone Positioning in Children with Respiratory Failure Due to COVID-19

Matthew K Leroue 1, Aline B Maddux 1, Peter M Mourani 2
PMCID: PMC8544610  NIHMSID: NIHMS1717958  PMID: 33782242

Abstract

Purpose of Review:

Acute respiratory distress syndrome (ARDS) is a common manifestation of severe COVID-19. Prone positioning has been used successfully in adult patients with ARDS and has been shown to decrease mortality. The efficacy of prone positioning in pediatric ARDS is less clear. In this review, we discuss the physiologic principles and literature on prone positioning in adults and children relative to COVID-19.

Recent Findings:

There are limited published data on prone positioning in respiratory failure due to COVID-19. The use of proning in non-intubated patients with COVID-19 may improve oxygenation and dyspnea but has not been associated with improved outcomes. Initial adult cohort studies of intubated patients undergoing prone positioning in severe ARDS related to COVID-19 have shown an improvement in mortality. While the use of proning in children with severe COVID-19 is recommended, data supporting its use is scarce.

Summary:

Additional studies to evaluate the efficacy of prone positioning in pediatric ARDS are needed to provide evidence for or against this treatment strategy in children. Given the unknown evolution of this pandemic, collaborative research efforts across pediatric centers provides the greatest opportunity to develop a data driven approach to use of this potential therapy

Keywords: COVID-19, Acute Respiratory Distress Syndrome, Prone Position, Pediatrics

Introduction

Approximately 20% of hospitalized adult patients with coronavirus disease 2019 (COVID-19) develop acute respiratory distress syndrome (ARDS) [1]. Adults with COVID-19 who develop ARDS have a case fatality rate that ranges from 30 to 60% [2]. Pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often are asymptomatic or have minor symptoms such as fever and cough [3–5]. Of children with COVID-19, 2.5% require hospitalization and far fewer, 0.8% require intensive care unit (ICU) admission [6]. In a large retrospective case series by the Children’s Hospital of Philadelphia Care Network which included a cohort of 7256 children tested for SARS-CoV-2, 424 (12%) tested positive but only 12 patients (2.8%) required mechanical ventilation with two deaths reported [5].

The management of respiratory failure due to COVID-19 has evolved but high-quality supportive care with non-invasive and invasive mechanical ventilation remains a cornerstone of management for these patients. The use of prone positioning in patients with COVID-19 may help spontaneously breathing patients and is recommended for mechanically ventilated patients with respiratory failure due to COVID-19 [7–9]. This review will discuss the physiologic principles of prone positioning, the benefits of prone positioning in ARDS including in COVID-19, and the implications for children with respiratory failure due to COVID-19.

Physiologic Principles of Prone Positing

Prone positioning was first described in the 1970s as a strategy to reduce pleural pressure gradients and restore aeration to the dorsal lungs in patients with severe pulmonary disease [10, 11]. Prone positioning was associated with improved oxygenation and used as rescue therapy for refractory hypoxemia. Mechanistic studies in human and animal models have demonstrated that improved oxygenation is related to two key physiologic changes: 1) improved aeration and alveolar recruitment of the dorsal lungs and 2) optimization of ventilation and perfusion matching and reduction of shunt fraction (Figure 1) [12–14].

Figure 1:

Figure 1:

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In the supine position, competitive forces from the chest wall, heart, and abdominal compartment lead to preferential ventilation of more anterior lung units (L) with collapse of more posterior lung units. Simultaneously, the posterior aspect of the lung receives a greater proportion of pulmonary blood flow, resulting in ventilation/perfusion mismatch. When prone, these competitive forces are reduced with more uniform aeration of lung units. A more uniform distribution of pulmonary blood flow in the prone position results in greater ventilation/perfusion matching. Black arrows indicate the force of gravity from heart and abdominal compartment; thicker arrows indicate greater force. Circles represent lung units with size of the circle indicative of degree of collapse.

During supine ventilation, the dorsal lungs are compressed by the weight of the heart, which contributes 3 to 5 cmH2O of pressure to the underlying tissue [15]. When supine, the ventral lungs achieve greater inflation due to increased regional alveolar ventilation, which in combination with the weight of the chest wall and ventral lungs, leads to impaired ventilation of the dorsal lungs [12]. The gravitational upward movement of the abdominal compartment differentially compresses the dorsal lungs. The resultant decreased dorsal ventilation, combined with relative increased perfusion of the dorsal lungs, leads to V/Q mismatching and hypoxemia [14, 15]. Prone positioning, while variably impacting chest wall compliance, reduces the competitive forces from the heart, ventral lungs, and abdominal compartment [13, 15]. This allows for better recruitment of the atelectatic dorsal lungs, overall improved lung compliance, and more uniform aeration [16]. Because less than 25% of pulmonary perfusion is mediated by gravitational forces, pulmonary blood flow is relatively preserved while prone, resulting in improved V/Q matching [14].

Prone ventilation has been shown to reduce ventilator induced lung injury through more homogenous ventilation, reducing shear strain and atelectrauma on the alveoli and regional overdistention [14, 15]. Prone positioning may also potentiate the benefits of higher positive end expiratory pressure (PEEP) ventilation strategy due to more homogenous distribution of airway pressures. Lung recruitment and improved V/Q matching may also enhance cardiac output through decreased pulmonary vascular resistance and lower right ventricular afterload[17].

Animal models and limited human studies have demonstrated that prone positioning reduces proinflammatory mediators such as IL-6 and IL-8, presumably by reducing ventilator induced lung injury [18, 19].

Physiologic Principles of Prone Positioning in Children

Pediatric pulmonary physiology results in differential responses to therapeutic interventions employed to treat ARDS, including prone positioning. Higher chest wall compliance, lower functional residual capacity (FRC), and decreased airway diameter modify the interaction between the severely injured lung and prone positioning [20]. Children, especially infants, have a more compliant chest wall due to a non-ossified rib cage, decreased muscle mass, and horizontal insertion of the diaphragm [21]. The higher compliance of the chest wall facilitates greater V/Q mismatching as more compliant lung regions are preferentially ventilated and at risk of overdistension. Prone positioning likely results in a decrease in chest wall excursion compared to adults. The immature chest wall also has lower chest wall recoil and lower FRC, again, due to low muscle mass, horizontal rib and diaphragm insertion and non-ossified chest wall [22]. In fact, FRC in infants is approximately 15–20% of vital capacity compared to 35% in adults, and these discrepancies are exacerbated in context of lung disease. The FRC in immature lungs more closely approximates closing capacity, placing children at higher risk of atelectrauma during ARDS. Prone positioning may result in more homogenous recruitment of alveoli with higher PEEP, and result in a greater proportion of alveoli ventilated above the lower inflection point of the lung hysteresis curve [23, 24]. Finally, the relatively smaller airway diameter in children results in exponentially increased resistance from edema and/or secretions. Prone positioning facilitates secretion clearance and, to the degree secretions impede ventilation and oxygenation in respiratory failure due to COVID-19, children may benefit from this effect of prone positioning [25].

Benefit of Prone Positioning in ARDS

Early randomized controlled trials of prone positioning included the full spectrum of ARDS severity and did not demonstrate broad benefit in mortality or ventilator free days but showed an improvement in PaO2/FiO2 (P/F) ratios, indicating better oxygenation, especially in severely hypoxemic patients [26–28].

In 2013, the Prone Positioning in Severe Acute Respiratory Distress Syndrome (PROSEVA) trial became the first randomized control study to demonstrate mortality benefit and decreased duration of ventilation in patients undergoing prone positioning [29]. Adults with severe ARDS requiring mechanical ventilation with a PEEP >5 cmH20 and a P/F ratio <150 mmHg were randomized within 36-hours of mechanical ventilation and were maintained on a low tidal volume ventilation strategy of 6 ml/kg, and a plateau pressure <30 cmH2O. The protocol required patients to be placed prone within 1 hour of randomization and to remain prone for at least 16 consecutive hours. There were very strict criteria for returning to the supine position and cross over from supine to prone was prohibited except in life-threatening hypoxemia. The prone group had a significant reduction in mortality at 28 and 90 days, higher rates of successful extubation, improved oxygenation, and significantly more ventilator free days.

Unlike prior studies, the PROSEVA trial design targeted a more severely ill cohort and applied a very strict proning protocol early in the ARDS course [12, 30]. Results of the PROSEVA trial have been supported by several meta-analyses demonstrating a benefit to prone positioning in patients with moderate to severe ARDS, specifically when implemented early and utilized for >12 hours [31–33].

Prone Positioning in Pediatric ARDS

Studies evaluating prone positioning for pediatric ARDS occurred concurrently with adult research. Similar to adult data, several small pediatric studies suggested improvements in oxygenation with prone positioning, particularly when applied early and to children with severe lung injury [34–36]. This research led to a multicenter, randomized control trial conducted between 2001 and 2004 [37]. The study included 102 patients who were enrolled within 48 hours of meeting criteria for acute lung injury defined as a P/F ratio <300 mmHg. Patients were placed in prone position within 4 hours of enrollment and remained prone 20 hours per day for up to 7 days. The primary outcome was ventilator free days to day 28. Sedation and ventilator management were protocolized. Despite improvements in oxygenation during prone positioning, there were no differences between groups in the primary or secondary outcomes at the planned interim analysis and the study was stopped due to futility. A secondary analysis did not find differences in serious safety events including unintentional extubation, sedation requirements, or feeding practices between the patients treated in the supine or prone positions [38]. Experts continue to question whether prone positioning may prove to be an effective therapy in children with the most severe forms of lung injury [39]. In fact, the ongoing Prone and Oscillation Pediatric Clinical Trial (PROSpect) is evaluating the efficacy of prone positioning and high-frequency oscillatory in children with severe ARDS utilizing a two by two factorial, randomized scheme [40].

The use of prone positioning remains highly variable in children with ARDS. The Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study found that among patients admitted to 145 PICUs worldwide, 10% of patients with ARDS were treated with prone positioning [41]. The use of prone positioning was more common in younger children and patients with direct lung injury. It was employed more frequently in smaller PICUs, centers without an ECMO program, and in middle income compared to high income countries. Specifically, it was employed less frequent in North America compared with other regions globally. This study also found that, when utilized, the duration of prone positioning was highly variable. The 2015 Pediatric Acute Lung Injury Consensus Conference guidelines did not recommend prone positioning for routine use, but recommended consideration as an option in severe ARDS [42].

Prone Positioning in COVID-19

Prone Positioning in Non-intubated COVID-19 Patients

Awake prone positioning or proning in non-intubated (PINI) patients has been used as a strategy to improve oxygenation in patients with COVID-19 in the absence of invasive ventilation. The feasibility and utility of PINI in COVID-19 has been described in several case reports and cohort studies, suggesting that it may improve oxygenation and dyspnea [43–47].

In one multicenter, prospective observational cohort study by the COVID-19 Spanish ICU Network, 199 patients supported by heated high flow nasal cannula including 55 (28%) who were also treated with PINI for > 16 hours per day were evaluated. They found no differences in the rates of intubation, ICU length of stay, ICU discharge, or mortality [48]. Similarly, Coppo and colleagues preformed a single center prospective cohort study of patients requiring supplemental oxygenation or continuous positive airway pressure [49]. All patients enrolled in the study were kept prone for at least three hours. While they found that P/F ratios improved significantly in the prone position, only 50% of patients maintained improved oxygenation after returning supine and there was no change in rates of intubation between responders and non-responders

Data remains insufficient to strongly recommend for or against PINI and the lack of stringent protocols for PINI strategies give little guidance for implementation or which patients may benefit. However, this low-cost, safe intervention is reasonable to consider though should not delay intubation [8]. Several randomized controlled trials currently underway may provide additional insight [50, 51].

Prone Positioning in Intubated COVID-19 Patients

The use of prone positioning in intubated patients with respiratory failure due to COVID-19 is limited to cohort studies, though early results seem promising. Similar to the data found in PINI, intubated patients with respiratory failure due to COVID-19 disease demonstrate improved oxygenation with prone positioning [1, 52]. Shelhamer and colleagues published a cohort study of 261 patients who were mechanically ventilated with severe COVID-19 associated ARDS, 62 (24%) of whom underwent prone positioning [53]. Patients were proned for at least 16 hours and had a P/F ratio <150 mmHg on PEEP of at least 10 cmH20 and required an FiO2 >0.6. The prone group demonstrated improved oxygen saturation index between days 1 through 3 and improved oxygen saturation index, oxygenation index, and P/F ratio between days 4 through 7. While there was no difference in ventilator free days, mortality was significantly reduced in the prone group. These findings and others substantiate recommendations by the National Institutes of Health, World Health Organization, and Surviving Sepsis Campaign to recommend prone positioning in adult, intubated patients with severe ARDS due to COVID-19 [7–9].

Pediatric Proning in COVID 19

There is a paucity of data evaluating the efficacy of prone positioning in pediatric patients with COVID-19 associated ARDS. In a single case report, Alseoudy described the use of awake prone positioning for a two-year-old patient with post-extubation hypoxemia with COVID-19. Prone positioning improved oxygenation in this patient, coinciding with adult literature [54]. Awake proning has been described in bronchiolitis and may decrease work of breathing in infants and is well tolerated [55]. There has been no published data describing prone positioning in intubated pediatric patients with respiratory failure due to COVID-19. The use of prone positioning in children with severe ARDS has been recommended based on expert opinion [56].

While it appears to be safe to prone pediatric patients when adhering to strict protocols, there can be risk of serious safety events at institutions with less experience or fewer safety protocols in place [38]. Proning in awake pediatric patients is limited by the developmental ability of pediatric patients to adhere to such practices but may have utility in patients who can comply with prone positioning whether by direction from providers or by patient preference.

Determining the efficacy of prone positioning in respiratory failure due to COVID-19 is challenging due to the low incidence of severe disease, infrequent occurrence of traditionally studied outcomes in ARDS research (e.g., mortality), heterogeneous patient populations, and variation in clinical practice across sites [57]. If these challenges are to be overcome, it will necessitate collaboration amongst centers to generate sufficient sample sizes, identification of outcomes with ample event rates to detect meaningful differences, and novel statistical designs to manage methodologic limitations [58]. Until these data are available, it is imperative for pediatric intensivists to carefully consider the evidence of prone positioning in adults with respiratory failure due to COVID-19, physiologic differences between pediatric and adult lung disease, and relative infrequency of poor outcomes in children with COVID-19 [3].

For patients with respiratory failure due to COVID-19, prone positioning, including PINI, may be beneficial, especially in those with severely impaired oxygenation, but should not delay more proven therapies such as invasive mechanical ventilation. While prone positioning in intubated patients is feasible for most PICUs, safety measures should be in place to avoid patient harm, especially given the infrequent use of this intervention (Table 1). Additionally, safety events and functional outcomes, particularly those related to ancillary treatments associated with prone positioning (e.g. sedation, neuromuscular blockade) should be monitored to ensure that patients are not harmed from this therapy. Additional studies on the utility of prone positioning for ARDS in children, such as the PROSpect, will provide further evidence for or against this treatment strategy.

Table 1:

Institutional Measures to Ensure Safe Prone Practices

Institutional Preparation

  • Clinical Practice Guideline in place to identify patients who would benefit from prone positioning, detailing timing and duration of prone positioning, and contraindications.

  • Regular training, including simulation, for staff on how to perform prone maneuver.

  • Nutritional guidelines for enteral feeding in prone positioning

Procedural Preparation

  • Confirm endotracheal tube positioning

  • Discuss sedation and neuromuscular blockade plan

  • Appropriate cushioning available to prevent pressure ulcers

  • Checklist and timeout policies in place for prone positioning procedure to ensure safety and consistency

  • Appropriate staff on hand to perform prone maneuver (2–3 nurses, 1–2 respiratory therapists, 1 physician)

Post-Procedural Care

  • Regular monitoring to prevent pressure and eye injuries

  • Appropriate sedation and neuromuscular blockade prescription for safety including monitoring for secondary effects.

  • Policy in place with clear indications for discontinuing prone positioning and/or for escalating therapy in context of an ARDS treatment algorithm.
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Conclusion

Given the unknown evolution of this pandemic, special attention should be given to the management of pediatric patients with COVID-19 and collaborative research efforts across pediatric centers provides the greatest opportunity to address these important clinical questions and ensure optimal outcomes for our patients.

Key Points.

  1. Prone positioning has been shown to be an effective treatment strategy in adult patients with severe ARDS when initiated early and when patients are kept in prone position for 12 or more hours.

  2. Early data in adult patients with respiratory failure related to COVID-19 show that prone positioning may be beneficial in intubated and non-intubated patients.

  3. Data supporting prone positioning in pediatric acute respiratory distress syndrome from any cause is limited and evidence of clear benefit is lacking.

  4. Multi-center, collaborative research efforts are needed to determine the efficacy of prone positioning in respiratory failure related to COVID-19.

Footnotes

Conflicts of Interest: None

References

* of special interest

** of outstanding interest

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