Prone Positioning

Definition of mild:

• Symptomatic (any acute COVID-19 related symptoms)
• AND respiratory rate <24/min
• WITHOUT pneumonia or hypoxia

A conditional recommendation is one for which the desirable effects probably outweigh the undesirable effects (weak recommendation FOR an intervention) or undesirable effects probably outweigh the desirable effects (weak recommendation AGAINST an intervention) but appreciable uncertainty exists. This implies that not all will be best served by this recommendation and decisions can be made by the patient and caregiver based on patient values, resources and setting with a clear understanding of the ensuing harms and benefits.

Definition of moderate illness

• Pneumonia (clinical or radiological) OR hypoxia (SpO2 <94% in adults with no underlying lung disease)
• AND respiratory rate ≤30/min
• AND SpO2 ≥90% on room air

Critical illness:

• Requirement for high-level respiratory support: noninvasive ventilation, high-flow oxygen (≥20 litres per minute) or invasive mechanical ventilation
• OR acute respiratory distress syndrome (PaO2/FiO2 ratio of <300)
• OR sepsis
• OR shock

Prone positioning, or proning, is an inexpensive non-pharmacological intervention which is postulated to improve oxygenation by recruiting alveoli that are better perfused and hence decrease the ventilation- perfusion mismatch in COVID-19 pneumonia with acute respiratory distress syndrome (ARDS).

In ventilated patients with COVID-19 ARDS, the guidelines group decided to strongly recommend proning, as there is unambiguous evidence of this intervention in decreasing mortality in patients with non-COVID-19 ARDS who require invasive ventilation. The assumption underpinning this recommendation is that COVID-19 ARDS is not significantly different from non-COVID-19 ARDS.

There have been 4 randomized controlled trials recruiting patients with moderate to severe COVID-19 studying awake self-positioning or proning against standard of care without prone positioning. The studies were marked by substantial heterogeneity, particularly in the duration of prone positioning. Compliance with the intervention was also of concern; all trials reported that the intended duration of prone positioning was not achieved. Hence, we decided not to pool these studies in a meta-analysis.

Due to the paucity of randomized trial evidence, observational cohorts reporting outcomes of interest were analyzed. There were 6 studies in non-intubated hypoxemic patients with COVID-19 included in our evidence summary. A meta-analysis of these revealed that awake proning /self-prone positioning improves oxygenation in the short term, as measured by PaO2, SpO2, PaO2/FiO2 ratio and SpO2/FiO2 ratio. The number of hours of self-prone positioning per day varied substantially between studies.

This led to only a conditional recommendation of awake proning /self-prone positioning in moderate and severe COVID-19, and in those with critical COVID-19 not receiving invasive mechanical ventilation, and a strong recommendation for proning in patients on invasive mechanical ventilation in critical COVID-19.

Date of latest search: 17^th July 2021.

Date of completion & presentation to Expert Working Group: 19^th July 2021.

Date of planned update: 17^th January 2022

Evidence synthesis team: Lenny Vasanthan T, Deva Jedidiah, Richard Kirubakaran, Priscilla Rupali and Bhagteshwar Singh

The Respiratory Therapy and Other Supportive Therapy Group met on 19^th July 2021 to consider Prone Positioning as a treatment for COVID-19. A further focused meeting with critical care physicians in the group took place on 5^th August 2021, discussing prone positioning in severe to critical COVID-19, which was followed up by email discussions achieving consensus among group members. Conflict of interest declarations were reviewed by the Steering Committee; none were found to be relevant to prone positioning.

A summary and then more detailed explanations of the Expert Working Group's (EWG) judgements follow.

Problem

The COVID-19 pandemic in India with more than 30 million cases and over 0.39 million deaths has significantly impacted and stressed the health structure of the country. With a shortage of intensive care unit beds, oxygen and trained personnel the country is facing a major health crisis. The group judged the problem to be of utmost priority.

Desirable effects

The panel agreed that the evidence is lacking to suggest that proning has a clinically significant effect on all-cause mortality, progression to NIV /high flow nasal canula. Progression to IMV and also need for ICU was not signficant. Studies suggest that proning may have a clinically significant effect on PaO2/FiO2, Pao2, SpO2 and reduction in respiratory rate, though the evidence was graded as very uncertain. The expert working group (EWG) also noted potential improvement in oxygenation and based on RCTs ^11-14, though these data were not pooled. Proning in critically ill patients with ARDS does not have equipoise. It is known to have a mortality benefit. Discussion was held and it was felt that we need to look at evidence in critical COVID-19 requiring intubation. However, intensivists were of the view that proning as a modality to improving oxygenation in severe ARDS is known. Hence the panel concluded that proning has a small desirable effect.

Undesirable effects

The data from some RCTs suggested that the adverse events like bedsore and dislodging of IV lines were less common in the groups with prone positioning in the RCTs, though it was unclear how valid it would be to conclude this based on small, heterogeneous trials. Anecdotally mild hypotension has been observed by some working group members who have provided the intervention (based on unpublished evidence, personal clinical experience). However, the EWG concluded that the undesirable effects of proning were thought to be trivial.

Certainty of evidence

Using GRADE methodology, the evidence synthesis team rated certainty of evidence as very low for all the outcomes.

Values

The EWG felt that there is no important uncertainty or variability on how people would value the main outcomes.

Balance of effects

The expert working group felt that the balance of effects probably favours the intervention. The group discussed at length about desirable effects about improvement in oxygenation, reduced escalation of care. Accidental disconnections and dislodging of tubes are apparently common in the ward, even though the opposite was suggested by some RCTs. But where feasible it is a good intervention to implement, with mitigation measures in place for potential undesirable effects.

Resources required

The resources required would include trained manpower (however existing staff could be redeployed), material resources, and a hospital facility capable of managing patients with ARDS. Proning schedules may be difficult to implement unless they are made part of routine care and led by a specific supervising lead. Proning may decrease oxygen requirements and hence may bring down capital costs as well. Intensive care units have 1:1 staffing but this is not the same in other wards and hence additional resources required vary according to the setting. The costs of these resources would also vary depending on the setting.  The group includes clinicians in different types of Indian hospitals who have a good idea of drug and hospitalization costs.

Certainty of evidence of required resources

No studies reporting this were reviewed by the group but the clinicians in the group were aware of the difficulties in generalizing costs, as mentioned above, and hence felt that there was low certainty of evidence for required resources to implement this intervention.

Cost effectiveness

The group discussed that even though there was no research evidence that evaluated cost in an Indian context, it probably favors the intervention, as this intervention was of clinical benefit and would not be high relative to others. The group felt that despite the additional manpower that may or may not be needed, this is an intervention that should be implemented wherever possible choosing the right kind of setting and patient population.

Equity

The intervention itself is cheap and probably will have no impact on equity although appropriate implementation may require an appropriate setting and in some cases adequate personnel.

Acceptability

The group felt that this intervention is likely to have wide acceptance by all the relevant stakeholders (policy-makers, patients and clinicians), even though it is uncomfortable and hence patients might be initially reluctant, but this would be overcome if patient were motivated based on the improvement in their clinical status.

Feasibility

This is a feasible intervention but mechanisms need to be put in place for proning protocols.

The working group discussions concluded that awake prone positioning was a reasonably feasible intervention for patients with moderate and severe COVID-19 disease. The practical challenges include patient related factors such as degree of respiratory distress (it may be difficult or unsafe to have a patient with severe distress to maintain an awake prone positioning), patient habitus (it may be difficult in obese individuals), level of co-operation. Often mild sedation, anxiolysis and/or analgesics may be required to facilitate prone positioning. The duration of awake prone management that leads to best outcomes is unknown. Even though there is no strong evidence to show benefit in overall outcome, due to the physiological effects on oxygenation and ventilation, it is plausible that awake prone ventilation when combined with Non-Invasive ventilation or high-flow oxygen therapy, could be an effective form of respiratory support that may reduce oxygen requirements, reduce the need for invasive ventilation, ICU care or death. System related factors such as nurse-patient ratios, availability of allied health practitioners or physiotherapists, location of patients (ICU vs wards) may determine the ease with which awake prone ventilation may be carried out.

With regard to prone ventilation in invasively ventilated patients, prone ventilation for COVID-19 patients with Moderate to Severe ARDS may have a mortality benefit (especially if PaO2/FiO2 ratios are 60% and when carried out for at least 16 hours) as with other forms of ARDS. This reflects best practice in units where staff are familiar with this process.

Contraindications to prone ventilation include raised intracranial pressure, increased intrabdominal pressure, vertebral injuries or instability, severe haemodynamic instability. Common complications include dislodgement of tubes (Endotracheal or Nasogastric), excessive discharge of oral and gastric secretions, facial and tongue oedema, eye injuries, pressure related injuries to dependent areas. Patients must be frequently monitored for these, while in prone position.

No subgroup analysis was performed by individual studies or in the meta-analysis.

Considered decisions have to be made based on individual patient’s condition and response to prone positioning, resources and experience of clinicians attending to the patient.

No specific recommendations can be made regarding the following subgroups of interest based on available evidence:

• Pre-existing chronic lung disease
• Obesity
• Co-existing cardiac failure (acute/chronic)
• Age > 65 years
• Spine or chest wall deformities
• Pre-existing neurological disease with deficits
• Pregnancy

Prone positioning in hospitalized moderate to non-intubated critical patients is a low risk and low-cost intervention with small benefits in improving oxygenation and preventing escalation of care. The side effects related to the practice are minimal, however there is lack of well-defined protocols for the practice. While further studies are warranted and as the data emerge, the group will monitor and evaluate the clinical relevance, benefits and the best set protocols for the awake self-prone positioning.

There is considerable heterogeneity in implementation of the intervention in various studies precluding a clear cut answer to its efficacy, however since it is a low cost, feasible intervention it is being practiced everywhere. However, the group felt that the following could be considered:

1. RCT comparing full-prone position and semi-prone positions in awake patients with COVID-19 and early ARDS, measuring the effect on mortality and requirement of invasive mechanical ventilation.
2. Studies comparing the effect of prone position in mechanically ventilated patients with COVID-19 with severe ARDS vs. in patients with ARDS of other infectious etiologies.

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Covid Management Guidelines India Group - Other Supportive Management Working Group. Prone Positioning. Covid Guidelines India; Published online on November 05th, 2021; URL: https://indiacovidguidelines.org/prone-positioning/  (accessed ).