Am. J. Trop. Med. Hyg., 104(5), 2021, pp. 1676–1686 doi:10.4269/ajtmh.20-1445 Copyright © 2021 by The American Society of Tropical Medicine and Hygiene Awake Proning as an Adjunctive Therapy for Refractory Hypoxemia in Non-Intubated Patients with COVID-19 Acute Respiratory Failure: Guidance from an International Group of Healthcare Workers Willemke Stilma,1,2* Eva Åkerman,3,4 Antonio Artigas,5,6 Andrew Bentley,7,8 Lieuwe D. Bos,1 Thomas J. C. Bosman,1 Hendrik de Bruin,1 Tobias Brummaier,9,10 Laura A. Buiteman-Kruizinga,1,11 Francesco Carcò,12 Gregg Chesney,13 Cindy Chu,9,10 Paul Dark,14,15,16 Arjen M. Dondorp,10,17 Harm J. H. Gijsbers,18 Mary Ellen Gilder,19 Domenico L. Grieco,20,21 Rebecca Inglis,22 John G. Laffey,23,24 Giovanni Landoni,12,25 Weihua Lu,26 Lisa M. N. Maduro,18 Rose McGready,9,10 Bairbre McNicholas,23 Diego de Mendoza,27,28,29 Luis Morales-Quinteros,27,30 Francois Nosten,9,10 Alfred Papali,31,32 Gianluca Paternoster,33 Frederique Paulus,1,2 Luigi Pisani,1,17,34 Eloi Prud’homme,35 Jean-Damien Ricard,36,37,38 Oriol Roca,39 Chiara Sartini,12 Vittorio Scaravilli,40 Marcus J. Schultz,1,10,17 Chaisith Sivakorn,41 Peter E. Spronk,42 Jaques Sztajnbok,43 Youssef Trigui,44 Kathleen M. Vollman,45 and Margaretha C. E. van der Woude46 1 Department of Intensive Care, Amsterdam University Medical Centers, Location ‘AMC’, Amsterdam, The Netherlands; 2Faculty of Health, Center of Expertise Urban Vitality, Amsterdam University of Applied Science, Amsterdam, The Netherlands; 3Division of Nursing, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden; 4Function of Perioperative Medicine and Intensive Care, Department of Intensive Care, Karolinska University Hospital, Stockholm, Sweden; 5Department of Intensive Care, Hospital de Sabadell, CIBER Enfermedades Respiratorias, Sabadell, Barcelona, Spain; 6Autonomous University of Barcelona, Sabadell, Barcelona, Spain; 7Acute Intensive Care Unit, Manchester University NHS Foundation, Manchester, United Kingdom; 8Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom; 9Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand; 10Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; 11Department of Intensive Care, Reinier de Graaf Hospital, Delft, The Netherlands; 12Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; 13Division of Emergency Medicine-Critical Care, Department of Emergency Medicine, NYU Grossman School of Medicine, New York, New York; 14Critical Care Medicine, NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester, United Kingdom; 15Division of Infection, Immunity and Respiratory Medicine, NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester, United Kingdom; 16Humanitarian and Conflict Response Institute, University of Manchester, Manchester, United Kingdom; 17Faculty of Tropical Medicine, Mahidol–Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand; 18Department of Rehabilitation Medicine, Amsterdam University Medical Centers, Location ‘AMC’, Amsterdam, The Netherlands; 19Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 20Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; 21Department of Anesthesiology and Intensive Care Medicine, Catholic University of the Sacred Heart, Rome, Italy; 22Lao-Oxford- Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahosot Hospital, University of Oxford, Vientiane, Lao People’s Democratic Republic; 23Department of Anaesthesia and Intensive Care, MedicineGalway University Hospitals, Galway, Ireland; 24School of Medicine, Disciplines of Anaesthesia and Intensive Care Medicine, National University of Ireland, Galway, Ireland; 25School of Medicine, Vita Salute San Raffaele University, Milan, Italy; 26Department of Critical Care Medicine, Yijishan Hospital of Wannan Medical College, Wuhu, China; 27Intensive Care Department, Hospital Universitari Sagrat Cor. Grupo Quironsalud, Barcelona, Spain; 28Emergency Department, Hospital Universitari Sagrat Cor. Grupo Quironsalud, Barcelona, Spain; 29Ciber Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; 30Institut d’ Investigacio I Innovacio Parc Taulı́ I3PT, Universidad Autonoma de Barcelona, Barcelona, Spain; 31Division of Pulmonary and Critical Medicine, Atrium Health, Charlotte, North Carolina; 32School of Medicine, University of Maryland, Baltimore, Maryland; 33Department of Cardiovascular Anaesthesia and ICU, San Carlo Hospital, Potenza, Italy; 34Section of Operational Research, Doctors with Africa CUAMM, Padova, Italy; 35Intensive Care Unit, Détresse Respiratoire Infections Sévères, Assistance Publique Hôpitaux de Marseille, Marseille, France; 36DMU ESPRIT- Enseignements et Soins de Proximité, Recherche, Innovation et Territoires, Université de Paris, Paris, France; 37Infection, Antimicrobiens, Modélisation, Evolution (IAME), Université de Paris, Paris, France; 38Service de Médecine Intensive Réanimation, Hôpital Louis Mourier, Assistance Publique – Hôpitaux de Paris, Colombes, France; 39Servei de Medicina Intensiva, Hospital Vall d’Hebron, Barcelona, Spain; 40Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milan, Italy; 41Department of Clinical Tropical Medicine, Mahidol University, Bangkok, Thailand; 42Expertise Center for Intensive Care Rehabilitation Apeldoorn, Gelre Hospitals Apeldoorn, Apeldoorn, The Netherlands; 43Intensive Care Unit, Instituto de Infectologia Emilio Ribas, São Paulo, Brazil; 44Service des Maladies Respiratoires, Centre Hospitalier D’Aix-en-Provence, Aix-en-Provence, France; 45Clinical Nurse Specialist/Critical Care Consultant, Advancing Nursing LLC, Northville, Michigan; 46Intensive Care Unit, Zuyderland Medisch Centrum, Location ‘Heerlen’, Heerlen, The Netherlands Abstract. Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6–12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs. * Address correspondence to Willemke Stilma, Department of In- tensive Care, Amsterdam University Medical Centers, Location ‘AMC’, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. E-mail: w.stilma@amsterdamumc.nl 1676 GUIDANCE FOR AWAKE PRONING IN HYPOXEMIC COVID-19 PATIENTS 1677 INTRODUCTION LMICs? Members could participate in more than one sub- group, by members’ preferences. COVID-19 acute respiratory failure may cause severe hyp- Quality of evidence was scored from very high to very low, oxemia.1 Many patients need to be hospitalized for supple- and the strength of each recommendation was given as strong mentary oxygen. If this fails, that is, when hypoxemia is or weak considering indirectness of evidence and magnitude refractory to oxygen therapy, invasive ventilation is often of effects. For LMICs, the availability, affordability, safety, needed. and feasibility of awake proning in patients with acute re- In intubated and invasively ventilated patients with spiratory failure were used to refine the recommendations if moderate-to-severe acute respiratory distress syndrome, necessary.10 prone positioning can improve oxygenation and has been shown to improve survival.2,3 Benefit of prone positioning may not be restricted to invasively ventilated patients––at least in RESULTS theory, non-intubated patients could also benefit from being Reports from the subgroups: Evidence for benefit. The placed in a prone position.4,5 The so-called awake proning is a number of studies investigating awake proning is rapidly in- cheap intervention, and thus very attractive from an economic creasing, but thus far, randomized clinical trials remain absent. viewpoint. Awake proning, however, could be or become Published studies were heterogeneous with regard to several uncomfortable if incorrectly performed, especially when it aspects––for example, supplementary oxygen during awake needs to be provided for many hours. It may also come with proning was provided using diverse interfaces, from simple complications such as shoulder injuries,6,7 pressure ulcers,8 oxygen supplementation via a nasal prong or cannula11–14 or a and aspiration of gastric content.9 Venturi mask14 to continuous positive airway pressure We invited a group of healthcare professionals with known (CPAP),15–18 HFNO,4,12,19,20 and NIV21; the exact positions interest or expertise in awake proning or with practical knowl- taken during awake proning also differed widely; thresholds edge regarding care for patients with acute respiratory failure for awake proning varied, from pulse oximetry as high as in low- and middle-income countries (LMICs), to develop a set > 94%15,22 to as low as < 90%11; duration of awake proning of pragmatic recommendations for use of this intervention. varied too, from 30 minutes to several hours4,5,11,15,21,23 or The goal was to develop a guidance enriched with illustrations even longer13,19,20,22,24; and proning could be applied more for a better understanding and local training of healthcare pro- times per day,4,5,21 or until low oxygen saturations resolved.14 fessionals. Information on awake proning mainly originated in Awake proning improves oxygenation4,5,11,12,15,19,25 and resource-rich settings in high-income countries––the group also reduces dyspnea.13,21,22 The improvements in oxygen- translated the available information into recommendations for ation are seen within minutes after the start of awake pron- use in resource-restricted settings in LMICs. ing.11 The effects of awake proning on oxygenation are maintained for up to one hour after turning back to supine15 METHODS but disappear after 6–12 hours.12,26 Awake proning also re- duces dyspnea sensation and work of breathing by improving An international group of healthcare professionals was in- ventilation–perfusion.14,19,21,22,25 Despite this benefit, awake vited by the study leads (W. S., L. D. B., L. P., M. J. S., and proning is not always tolerated.5,12,14,21,27 F. P.). Communication and writing within the group and three It remains uncertain whether awake proning can prevent subgroups was merely by email correspondence and tele- invasive ventilation. Several studies show a low intubation rate conferences, and a central shared online document was used with the use of awake proning.12,14,21 Two studies suggest to draft the current guidance. prevention of intubation,20,22 but this is not confirmed in other Several literature searches in Medline were performed, us- investigations in invasively ventilated patients,15,28,29 nor in ing different combinations of search terms like “coronavirus patients with severe hypoxemia receiving NIV,4 nor in patients disease,” “coronavirus disease 2019,” “COVID-19,” “SARS- receiving HFNO.30 It is highly uncertain whether awake proning CoV-2,” “prone positioning” and “awake proning,” “non- can be used as a rescue therapy, that is, to avoid intubation in intubated,” “non-invasive,” “oxygen therapy,” “high flow nasal patients who already fulfill the criteria for immediate intubation. oxygen (HFNO),” “non-invasive ventilation (NIV),” “respiratory It remains unclear whether the effects of awake proning monitoring,” and “ratio of oxygen saturation (ROX) index.” depend on the way supplemental oxygen is administered, Searches had to be updated several times, as publications albeit that improvements in oxygenation are described with all continued to appear in the literature during the writing of forms of oxygen supplementation, that is, via nasal cannula or this report. A final search in Medline was performed in late oxygen mask,11–13,15,19,28,31 CPAP,15,21 HFNO,12,20,24,27,30,31 October 2020. In addition to these Medline searches, Internet and NIV.4,21 Some studies suggest that “early” awake proning searches, mainly through the Google search machine and (i.e., when oxygen can still be supplied via a simple interface using the comparable terms, were performed to explore the like a nasal cannula)11,12,22,28 could have a better effect than gray literature and search for webinars on awake proning. “late” awake proning (i.e., when oxygen needs to be supplied Information was bundled and dealt within three subgroups via HFNO or CPAP).15,21,24,32 A change in pulse oximetry regarding the following questions: 1) What is the evidence for readings or respiratory rate (RR) induced by awake proning benefit of awake proning for acute respiratory failure in gen- could be useful parameters to define responders versus eral, and in COVID-19 pneumonia in particular? 2) What are the nonresponders. In one study, a rise of SpO2 > 95% is asso- recommendations and suggestions for practical application of ciated with a lower intubation rate.28 awake proning for acute respiratory failure in general, and in Persistent hypoxemia despite supplementary oxygen was COVID-19 pneumonia? 3) Should recommendations for use used as an indication in all studies, albeit with considerable of awake proning differ between high-income countries and variation in the degree of hypoxia. Literature remains vague 1678 STILMA AND OTHERS regarding other indications, and also contraindications for potential increase on pulse oximetry readings and a reduction awake proning. Based on the studies identified by the in dyspnea, coughing, and sputum production could increase searches and consensus within the group, indications and following the position change––this is usually short-lasting. It (relative) contraindications for awake proning were formulated can be useful to know if the patient normally sleeps face down (Table 1). Consensus was not based on robust evidence, and (e.g., prone), to adjust this information. Patients could find may depend on various factors such as available resources, awake proning uncomfortable, but this may be mitigated and local expertise––for example, in a hospital ward environ- through supportive nursing care and noticing the marked im- ment with a low nurse-to-patient ratio, it may be challenging to provements of pulse oximetry readings. Family can stay with safely use light sedation in the management of a severely patients who are proning, and use of mobile devices to spend dyspneic patient who will receive awake proning. time and communicate with relatives should be stimulated. If Reports from the subgroups: Practical application of use of sedatives or anxiolytics is being considered to facilitate awake proning. Based on the studies identified by the prone positioning in non-intubated patients, this should be searches and consensus within the group, recommendations and undertaken in a closely monitored location, with access to suggestions for practical application of awake proning in COVID- continuous oxygen saturation, blood pressure, and electro- 19 patients were formulated (Table 2). The group considers it es- cardiogram monitoring. Pain medication could be considered, sential to train local teams in terms of correct and safe use of awake as pain related to stiffness of shoulders and neck could proning, especially when light sedation is used. Ideally, an “awake develop. proning team” consists of two healthcare professionals, including Frequent assessment for tolerability, at least within 10 at least one doctor, and a nurse or a physical therapist. One pro- minutes after the start of proning, is considered important. In fessional should provide team leadership. The team will assist the some patients, it may be necessary to start benzodiazepine, patient to take the correct position and ascertains continuation of clonidine, or dexmedetomidine, but only if the setting allows; oxygenation supplementation––extra oxygen during positioning also, morphine in low dosages could be useful in a severely could be considered. The healthcare professional should assist in dyspneic patient. In those cases, proper monitoring, including proper positioning of the limbs. Supporting materials, such as continuous or intermittent pulse oximetry, blood pressure, and pillow blocks, cushions, or rolled blankets, should be closely at maybe electrocardiogram could be useful. hand. To minimize the risks of awake proning, a practical checklist The vast majority of patients will receive supplemental ox- or “proning bundle” can be checked every time a patient is placed ygen through interfaces like a nasal prong or cannula, a face in the prone position33 (Table 3). mask, CPAP via a mask, or a ventilation hood, HFNO, or For awake proning to be successful, the group thinks mo- NIV.15–17,19 There is no evidence as to which interface is best in tivational support to the patient is one key to success. Before patients who receive prone positioning. Nasal interfaces and proning, why awake proning could work, what it is like to be in masks seem more practical and better tolerated than hoods,5 a prone position, and how to maintain a proper position should especially in elderly patients.15 One current multicenter ran- be explained to the patient and family members if present. A domized clinical trial is testing the efficacy of different TABLE 1 Indications and contraindications to apply awake proning Indications SpO2/FiO2 ratio < 315 Acute respiratory failure requiring any supplemental oxygen to maintain saturation > 90% Able to follow instructions in their native language Absolute contraindications in the ward and ICU setting Anticipated difficult airway Cardiogenic pulmonary edema as a cause for respiratory failure Respiratory rate of above 40/min or accessory muscle use Unreliable SpO2 tracing Immobile or extremely limited mobility Inability to tolerate proning due to anatomic concerns (e.g., injury or wound on the ventral surface of the body) Spinal instability Glaucoma or other condition with acutely elevated intraocular pressure Severe head trauma with high ICP Absolute contraindications in the ward, but relative contraindication in the ICU setting Severe oxygenation problems defined as PaO2/FiO2 < 100 mmHg4 or, alternatively, SpO2/FiO2 < 140 mmHg60 Altered mental status or inability to follow commands Inability to communicate with care team or call for help verbally or with call bell Hemodynamic instability defined as requiring vasopressor support (i.e., a systolic blood pressure < 90 mmHg or mean arterial pressure less than 65 mmHg despite appropriate volume resuscitation) Inability to reposition self for comfort without assistance Relative contraindications in the ward and ICU setting Facial injury Neurological issues (e.g., frequent seizures) Morbid obesity (BMI > 40) Pregnancy (2/3rd trimesters) Pressure ulcers Concomitant type II respiratory failure, unless chronic, stable, and compensated (pH > 7.36). If awake proning is considered, it should be trialed, and a blood gas should be taken within 30 minutes to ensure no deterioration in hypercapnia. BMI: body mass index; FiO2: oxygen concentration; ICP: intracranial pressure; PaO2: arterial blood oxygen concentration; SpO2: peripheral oxygen saturation. GUIDANCE FOR AWAKE PRONING IN HYPOXEMIC COVID-19 PATIENTS 1679 TABLE 2 Recommendations and suggestions for practical application of awake proning in COVID-19 patients (with grading) Domain Recommendation Grading Considerations for use in LMICs* 1 Indications Suggest: Consider awake proning in Low-quality evidence Where pulse oximetry is not available, it patients with acute respiratory failure would be reasonable to trial awake requiring supplemental oxygen proning for COVID-19 patients with to maintain saturation > 93%.11,15,22 cyanosis, marked tachypnea, or other evidence of respiratory distress. 2 Indications Suggest: Consider awake proning in Expert opinion No additional considerations. patients able to follow instructions. 3 Indications Recommend: Use awake proning during Expert opinion In settings without tocography and the 1st and 2nd trimesters in pregnant Doppler, fetal monitoring using clinical women with additional monitoring of auscultation of the fetal heart rate the position and the fetus. should be performed. 4 Contra-indications Suggest: Use awake proning in the 3rd Expert opinion In settings without tocography and trimester of pregnancy with additional Doppler, fetal monitoring using clinical monitoring with caution and on an auscultation of the fetal heart rate individual risk–benefit basis. should be performed. 5 Contra-indications Recommend against: Awake proning in Low-quality evidence Where mechanical ventilation is not patients with extreme respiratory available or affordable, a trial of awake distress requiring immediate proning may be performed as a rescue intubation.15,20,22,28,29 maneuver. 6 Contra-indications Suggest against: Awake proning in Low-quality evidence No additional considerations. patients with impaired consciousness. 7 Preparation Strongly recommend: Preparing the Expert opinion Visual aids may be useful to illustrate the patient and the family for what it is like to family what will happen. Caregivers will be in a prone position, what can be often become a key component of the expected, and how to maintain this proning team. position. Widely available fleece blankets can be used instead of pillows to reduce costs. 8 Preparation Recommend: Preparation for Expert opinion Examples of recommended preparations complications (safe airway, suctioning, for complications include having the and pressure ulcers). equipment necessary for emergency intubation prepared nearby in case it is required, having a functioning suction machine with a clean suction catheter available at all times, and ensuring careful padding of all pressure areas and daily pressure area surveillance. 9 Monitoring Strongly recommend: Minimum Expert opinion Where available, a multiparametric monitoring of pulse rate and peripheral monitor or a handheld or tabletop pulse oxygen saturation. oximeter is preferable to a fingertip pulse oximeter (not easily seen or heard from a distance and may automatically switch off after a certain time period).61 Whatever device is used, the alarm should be set to alert staff if SpO2 drops below 90%. When there are insufficient pulse oximeters available for continuous monitoring, intermittent monitoring should be carried out as frequently as staffing and equipment allow. 10 Monitoring Recommend: Monitoring respiratory rate, Expert opinion While safety is high, feasibility depends on work of breathing (use of respiratory the local level of staffing.62 muscles), and dyspnea. 11 Monitoring Suggest: Possibility of monitoring Expert opinion Feasibility relies on the availability of pulse respiratory status by using the ROX oximetry. index. 12 Monitoring Recommend: Monitoring of Expert opinion We recommend a noninvasive blood hemodynamic parameters (MAP and pressure measurement at least once an SBP). hour where possible (expert opinion). 13 Monitoring Suggest: Visual care monitoring by open Expert opinion This is a pragmatic measure that improves wards in event of high surge capacity. patient safety and makes efficient use of staff and PPE. 14 Monitoring Suggest against: Awake proning in Expert opinion This recommendation may not apply in conventional hospital wards for settings where no higher level of care is patients with severe respiratory failure. available. 15 Oxygen supply Recommend: Use of any available Expert opinion Oxygen is a scarce resource in at least method of oxygen delivery during one-quarter of hospitals in LMICs.52 awake proning. The choice among oxygen concentrators, cylinders, or centralized (continued) 1680 STILMA AND OTHERS TABLE 2 Continued Domain Recommendation Grading Considerations for use in LMICs* systems will depend on local availability and option assessment.63 Reservoir masks may represent feasible and affordable option. Attention should be paid to ensuring the tubing is not kinked in the prone position and in the case of a reservoir mask that the bag is fully inflated. 16 Oxygen supply Suggest: Use of CPAP or HFNO for Low-quality evidence Availability and affordability of CPAP and delivery of higher FiO2, depending on HFNO systems is variable but generally the locally available expertise. low.64 Feasibility of HFNO is low because of high oxygen demands. 17 Position Suggest: Train multidisciplinary proning Expert opinion Where insufficient staff are available, care teams in approaches on awake and givers can also provide support.65 sedated proning with one person having the lead. 18 Position Suggest: Have a slightly lateral position to Expert opinion Some patients prefer to keep their head turn the face. central rather than turned to the side (see Figure 2 for a configuration of padding to accommodate this). 19 Position Suggest: Avoid a closed packed shoulder Expert opinion No additional considerations. by keeping the shoulder of the raised arm around 80° abduction.35 20 Position Suggest: Full flexion of the knees if Expert opinion Extra pillows may be needed. Widely possible and maximum range ankle available fleece blankets can be used motion. instead of pillows to reduce costs. 21 Position Suggest: Use analgesia when low back Expert opinion pain becomes a problem. 22 Position Recommend: Supportive padding above Expert opinion Folded fleece blankets can be used for and below the gravid uterus when this purpose. pregnant women are proned (Figure 1). 23 Position Suggest: A semi-lateral prone position in Expert opinion No additional recommendations. pregnant woman in the 2nd/3rd trimester as an alternative (Figure 1). 24 Hydration and nutrition Recommend: Maintain normovolemia. Expert opinion No additional recommendations. 25 Hydration and nutrition Suggest: Allow oral intake unless there is Expert opinion No additional recommendations. a high risk of intubation. 26 Hydration and nutrition Suggest: Stay in the supine position for Expert opinion No additional recommendations. one hour after oral feeding in the supine position. 27 Risk management Recommend: Have equipment for Expert opinion This only applies to centers where endotracheal intubation nearby and mechanical ventilation is available. frequently checked. 28 Risk management Recommend: Have an intravenous port Expert opinion No additional recommendations. available for sudden clinical deterioration. 29 Risk management Recommend: Have materials for Expert opinion Where electrical suction devices are not (endotracheal or nasal) suctioning available, a manual suction pump or standby. bulb suction can be used. 30 Risk management Suggest: Start reverse CPR until a team is Expert opinion CPR should only be commenced once ready to get the patient in the supine staff attending the patient are wearing position. N95 respirators/masks or equivalent. CPAP = continuous positive airway pressure; CPR = cardiopulmonary resuscitation; HFNO = high-flow nasal oxygen; LMICs = low- and middle-income countries; MAP = mean arterial pressure; NIV = noninvasive ventilation; PPE = personal protective equipment; SBP = systolic blood pressure. * Considerations regarding feasibility, availability, safety and affordibility.10 interfaces for supplemental oxygen during awake proning in Some refinements could increase safety of awake proning patients with COVID-19 acute respiratory failure.34 and may allow acceptance for a longer period of time. Sug- In patients with mild hypoxemia, “self-proning” could be gested positions are illustrated in Figures 1 and 2. A slightly possible, eventually with the help of a family member. In lateral prone position allows a patient to turn the face to one patients with severe hypoxemia, “assisted proning” is side, which can be supported by a pillow or rolled blanket likely to be superior to “self-proning,” as patients may placed under one side of the chest, and a raised arm em- need all of their energy to breathe, and thus need help. As- bracing the pillow (the “front crawl” or “swimmers position”). sistance also prevents dislocation of the interfaces for supple- While in the prone position, the patient faces the armpit of the mental oxygen and any indwelling catheter. Assistance may raised arm of which the elbow is flexed at ∼90°, and the prevent an increase in oxygen consumption induced by contralateral arm remains aligned with the body. A maximum changing the position, especially in older, frail, pregnant, and closed packed position of the shoulder is avoided by keeping obese patients. the shoulder of the raised arm at ∼80° abduction, or even lower GUIDANCE FOR AWAKE PRONING IN HYPOXEMIC COVID-19 PATIENTS 1681 TABLE 3 Safe awake proning checklist Preparation Proning After turning/during proning Patient Patient Patient Identity Self-proning Comfort Explanation procedure Assisted proning Document chosen position (prone and lateral) Document duration of procedure Document position of arms Consent Materials Materials Materials Pillows and slide sheet Sufficient room between the head and Provide emergency buzzer, mobile shoulders for oxygen supply phone, and improvised rattle Crash cart In pregnant women, special attention to alleviate pressure on the gravid uterus Oxygen available Suction equipment available Monitoring: pulse oximetry if available Check Check Vital signs: SpO2, RR, HR, and BP Oxygen supply continued Vital signs: SpO2, RR, HR, and BP IV access IV access Nurse call system Nurse call system Baby monitor in case of pregnancy Additional external fetal monitoring Medication Pain: paracetamol 4 dd 1 g Anxiety: low-dose benzodiazepine Oxazepam 10 mg po Midazolam 1–2 mg po Emergencies Emergencies Emergencies Emergency team for the supine position Emergency team for the supine position Emergency team for the supine position Crash cart (intubation equipment) Crash cart (intubation equipment) Crash cart (intubation equipment) available available available and know where to find BP = blood pressure; HR = heart rate; IV = intravenous; RR = respiratory rate; SpO2 = peripheral oxygen saturation. Based on the WHO surgical checklist and Safe prone checklist.66 if possible.35 The upper arm and shoulder blade are positioned head-up position, between the sessions, if allowed, and should not in a straight horizontal line to protect the shoulder, and arm be placed in a prone position for at least 1 hour after oral intake. repositioning is encouraged, if pain or stiffness occurs. Slight Fluids should be given intravenously, if needed. However, sips of adjustments or repositioning of the legs and hip should be water could be taken with the bed in a more upright position. encouraged to prevent pressure ulcers and meralgia par- Direct visual care and monitoring of patients during awake esthetica. The latter complication is a result of compression proning is facilitated by designated areas for cohorts of pa- injury of the lateral femoral cutaneous nerve.36 The side of the tients. Monitoring of RR, accessory muscle use, and work of swimmers position changes frequently, preferably every 2 or 3 breathing could help identifying patients who need escalation hours. Full flexion of the knees should be possible, with a of care. The ROX index,37 defined as the ratio of SpO2/FiO2 to maximum range of ankle motion to prevent stiffness and RR, has been proposed for monitoring. This index combines pointed feet. In patients with lower back pain, a semi-prone or three parameters that assess a patient’s respiratory status. lateral position could be taken. If this does not provide relief for Improvement in the ROX index during awake proning could the lower back pain, pain medication could be considered. indicate a lesser likelihood for intubation,38 but experience As patients in prone position may need urgent intubation, with the ROX index in patients with COVID-19 acute re- they should remain fasting. Fasting is also advisable because spiratory failure is still very limited. of an increased risk for aspiration when in a prone position. Pa- In case of cardiac arrest in a prone position, “reverse car- tients should thus be encouraged to take oral feeds in supine, diopulmonary resuscitation (CPR)”39,40 can and must be FIGURE 1. Awake proning in a 9-month pregnant woman. Both 3/4 prone and full prone options are shown. Suggested position is an indication and could be adapted based on patient preferences. This figure appears in color at www.ajtmh.org. 1682 STILMA AND OTHERS FIGURE 2. Visual aid to facilitate awake proning implementation in a resource-limited setting. Suggested position is an indication and could be adapted based on patient preferences. Adapted with permission from a prone positioning checklist developed by Dr. Rebecca Inglis in Lao PDR.67 This figure appears in color at www.ajtmh.org. started until a team is available to turn the patient back to include a lack of human resources, training, and challenges supine.41 This team should be identified and always be readily with infrastructure and equipment.49 available. Emergency endotracheal intubation equipment and The group recognizes the limitation of staffing in many materials must be close by and regularly checked for imme- LMICs and that a “proning team” may not always be feasible. diate use alongside relevant emergency drugs. The guidance by one trained healthcare professional, or two in Finally, the group suggests awake proning should not be an obese or a noncooperative patient, however, is seen as one withheld in pregnant patients,42–47 but supplemental oxygen minimal requirement to proceed with this intervention. It is should be provided such that pulse oximetry remains ³ 95%.43 always important that a patient can be turned back to supine To prevent aortocaval compression in pregnant patients,48 with urgency to allow emergency procedures such as CPR. additional measures can be taken by organizing extra pillows Training of staff becomes pivotal in limited-resource settings, and monitoring. as it is possible to spare time and resources when exact ma- Reports from the subgroups: Recommendations for neuvers are known by the team. Figures 1 and 2 provide ad- awake proning in LMICs. As awake proning does not require ditional training material. particular resources, it should be considered in hypoxemic Oxygen is listed as an essential medication by the WHO50 patients with COVID-19 acute respiratory failure who do not but remains a very limited resource in many settings.51–53 respond to simple supplementary oxygen in settings where Low-flow supplemental oxygen via nasal prongs, sponge- resources are limited. The group considers awake proning tipped catheters, or face masks are increasingly available and with any available method of respiratory support a safe in- affordable, although one-quarter of hospitals surveyed in an tervention, also in LMICs. Awake proning may prevent the LMIC study reported gaps in oxygen supply.52 Facemasks need for invasive ventilation which is important for settings with reservoir allow increasing FiO2 significantly and should be with limited numbers of ventilators.14,32 In fact, at times, strongly considered (Figure 2). High-flow nasal oxygen and awake proning may be the only option to improve oxygenation NIV are feasible in LMICs, but not widely available. They come in settings. Limitations regarding awake proning in LMICs at additional costs for the interfaces and devices. They also GUIDANCE FOR AWAKE PRONING IN HYPOXEMIC COVID-19 PATIENTS 1683 come with technical challenges and practical concerns, as intensive care units in LMICs. Also, the group consisted of they depend on a reliable source of oxygen and electricity. various types of healthcare workers, including (ICU) doctors, Continuous positive airway pressure and HFNO apparatuses (ICU) nurses, and physiotherapists. may rapidly use up oxygen supplies; indeed, HFNO consumes This work also has limitations. We emphasize that this is oxygen at more than four times the rate of low flow oxygen not a systematic review, but rather a clinical appraisal of the support, and typically, HFNO may consume the entire content available literature and personal clinical experiences of of a large oxygen cylinder within 2–3 hours, rapidly depleting healthcare workers in various settings around the world. We oxygen supply. cannot exclude selection and information bias. Close monitoring and clear escalation criteria are needed with awake proning, also in resource-limited settings. In LMICs, pulse oximeters are often not available, but recent CONCLUSION initiatives have been set up to provide them on a larger scale.54 Pulse oximetry together with monitoring of clinical and vital Awake proning is an attractive and safe adjunctive treat- signs might help timely identification of those patients who ment for hypoxemia refractory to supplemental oxygen in need escalation of care.55 In settings where blood gas ana- patients with COVID-19 acute respiratory failure, especially in lyzers are unavailable, SpO2 relative to inspiratory oxygen con- settings where there is shortage or absolute lack of ventilators. centration, or SpO2/FiO2 ratio, can be used for continuous Here, this could be the only option to improve oxygenation. It monitoring, decision-making, and prognostication.56–58 The ROX may even prevent the need for invasive ventilation; although index is likely to be useful because it requires simple input (SpO2/ randomized trial evidence remains lacking, randomized clini- FiO2 and respiratory rate) and is easy to calculate at the bedside.59 cal trials are urgently needed. During the supine periods between awake proning, oral in- take is to be encouraged to maintain normovolemia in Received November 9, 2020. Accepted for publication February 28, resource-limited settings, as other resources for fluid intake 2021. are usually limited. The risk of aspiration, however, should be Published online March 11, 2021. highlighted, especially in obese patients. The suggestion of Acknowledgments: The American Society of Tropical Medicine and using low-dose benzodiazepines or morphine to enhance Hygiene has waived the Open Access fee for this article due to the awake proning should be conducted with care in environ- ongoing COVID-19 pandemic. ments with limited or absent patient monitoring. Financial support: This study received funding from the Amsterdam University Medical Center, location “AMC”; Center of Expertise Urban DISCUSSION Vitality, Faculty of Health, Amsterdam University of Applied Science. Disclosure: All authors contributed to the drafting of this manuscript. A rapidly growing number of observational studies describe Paul Dark was supported by the NIHR Manchester Biomedical Re- the use of awake proning in patients with COVID-19 acute search Centre. For the purpose of open access, the author has applied respiratory failure in whom hypoxemia is refractory to simple a CC BY public copyright license to any author-accepted manuscript version arising from this submission. This research was funded in supplementary oxygen. Awake proning improves oxygenation whole, or in part, by the Wellcome Trust [Grant number 220211] (au- within minutes, and the effects are maintained for up to one thors T. B., C. C., R. McG., and F. N.). hour after turning back to supine and disappear mostly after SUBGROUP CHAIRS AND MEMBERS 6–12 hours. Awake proning is associated with few complica- tions. Because no particular technological resources are re- Group 1: Evidence for benefit of awake proning quired, it is particularly applicable in settings where resources Chairs: Willemke Stilma and Marcus J. Schultz; members (in alpha- are limited, or even absent. A set of pragmatic recommenda- betic order): Andrew Bentley, Hendrik de Bruin, Gregg Chesney, tions were formulated on awake proning in relation to indica- Domenico L. Grieco, Giovanni Landoni, Diego de Mendoza, Luis Morales-Quinteros, Gianluca Paternoster, Oriol Roca, Chiara Sartini, tions and contraindications, oxygen supply, position, nutrition, Vittorio Scaravilli, Chaisit Sivakorn, Peter E. Spronk, Jaques Sztajn- monitoring, and risk management based on the available evi- bok, and Youssef Trigui. dence and experiences of healthcare workers in LMICs. Group 2: Practical application of awake proning It is important to notice that so far there is no randomized trial evidence for the effect of awake proning in patients with Chairs: Frederique Paulus and Lieuwe D. Bos; members (in alphabetic order): Eva Åkerman, Thomas J.C. Bosman, Laura A. Buiteman- COVID-19 acute respiratory failure. Current evidence comes Kruizinga, Gregg Chesney, Cindy Chu, Paul Dark, Harm J.H. Gijsbers, from few studies, mostly case reports and single-center ob- Weihua Lu, Lisa M.N. Maduro, Bairbre McNicholas, Eloi Prud’homme, servations. None of these originated in LMICs. The available and Margaretha C.E. van der Woude. results, however, suggest that awake proning could be ef- Group 3: Specific recommendations for use of awake proning in fective adjunctive therapy that is also safe and tolerable. The LMICs suggestion that it may prevent the need for invasive ventilation Chairs: Luigi Pisani and Marcus J. Schultz; members (in alphabetic or increased need of oxygen makes this intervention worth a order): Eva Åkerman, Antonio Artigas, Andrew Bentley, Tobias try, certainly in settings where there is a shortage of ventilators Brummaier, Francesco Carcò, Cindy Chu, Arjen M. Dondorp, Mary or where ventilators are absent20,22 or health care is un- Ellen Gilder, Rebecca Inglis, John G. Laffey, Rose McGready, François affordable for patients. Nosten, Gianluca Paternoster, Alfred Papali, Jean-Damien Ricard, Oriol Roca, Chaisith Sivakorn, Peter E. Spronk, and Kathleen M. One strength of this guidance on awake proning is the Vollman. cooperation of a set of healthcare workers from resource- Authors’ addresses: Willemke Stilma and Frederique Paulus, De- rich settings in high-income countries and from resource- partment of Intensive Care, Amsterdam University Medical Cen- limited settings in LMICs. There was a large expertise in ters, Location ‘AMC’, Amsterdam, The Netherlands, and Faculty of proning, and a deep understanding of the challenges in Health, Center of Expertise Urban Vitality, Amsterdam University of 1684 STILMA AND OTHERS Applied Science, Amsterdam, The Netherlands, E-mail: w.stilma@ quironsalud.es. Luis Morales-Quinteros, Intensive Care Depart- amsterdamumc.nl and f.paulus@amsterdamumc.nl. Eva Åkerman, ment, Hospital Universitari Sagrat Cor. Grupo Quironsalud, Barce- Division of Nursing, Department of Neurobiology, Care Sciences and lona, Spain, and Institut d’ Investigacio I Innovacio Parc Taulı́ I3PT, Society, Karolinska Institute, Stockholm, Sweden, and Function of Universidad Autonoma de Barcelona, Barcelona, Spain, E-mail: Perioperative Medicine and Intensive Care, Department of Intensive luchomq2077@gmail.com. Alfred Papali, Division of Pulmonary and Care, Karolinska University Hospital, Stockholm, Sweden, E-mail: Critical Medicine, Atrium Health, Charlotte, NC, and School of Medi- eva.akerman@gmail.com. Antonio Artigas, Department of Intensive cine, University of Maryland, Baltimore, MD, E-mail: alfred. Care, Hospital de Sabadell, CIBER Enfermedades Respiratorias, papali@atriumhealth.org. Gianluca Paternoster, Department of Car- Sabadell, Barcelona, Spain, and Autonomous University of Barcelona, diovascular Anaesthesia and ICU, San Carlo Hospital, Potenza, Italy, Sabadell, Barcelona, Spain, E-mail: aartigas@tauli.cat. Andrew E-mail: paternostergianluca@gmail.com. Luigi Pisani, Department of Bentley, Acute Intensive Care Unit, Manchester University NHS Intensive Care, Amsterdam University Medical Centers, Location Foundation, Manchester, United Kingdom, and Faculty of Biology, ‘AMC’, Amsterdam, The Netherlands, Faculty of Tropical Medicine, Medicine and Health, Manchester Academic Health Science Centre, Mahidol–Oxford Tropical Medicine Research Unit (MORU), Mahidol University of Manchester, Manchester, United Kingdom, E-mail: University, Bangkok, Thailand, and Section of Operational Research, andrew.bentley@manchester.ac.uk. Lieuwe D. Bos, Thomas J. C. Doctors with Africa CUAMM, Padova, Italy, E-mail: luigipisani@ Bosman, and Hendrik de Bruin, Department of Intensive Care, gmail.com. Eloi Prud’homme, Intensive Care Unit, Détresse Respira- Amsterdam University Medical Centers, Location ‘AMC’, Amsterdam, toire Infections Sévères, Assistance Publique Hôpitaux de Marseille, The Netherlands, E-mails: l.d.bos@amsterdamumc.nl, t.j.bosman@ Marseille, France, E-mail: eloiprudhomme@gmail.com. Jean-Damien amsterdamumc.nl, and h.debruin2@amsterdamumc.nl. Tobias Ricard, DMU ESPRIT-Enseignements et Soins de Proximité, Brummaier, Cindy Chu, Rose McGready, Francois Nosten, Shoklo Recherche, Innovation et Territoires, Université de Paris, Paris, Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research France, Infection, Antimicrobiens, Modélisation, Evolution (IAME), Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Université de Paris, Paris, France, and Service de Médecine Intensive Thailand, and Centre for Tropical Medicine and Global Health, Nuffield Réanimation, Hôpital Louis Mourier, Assistance Publique – Hôpitaux Department of Medicine, University of Oxford, Oxford, United King- de Paris, Colombes, France, E-mail: jean-damien.ricard@aphp.fr. dom, E-mails: tobias.brummaier@gmx.at, cindy@tropmedres.ac, Oriol Roca, Servei de Medicina Intensiva, Hospital Vall d’Hebron, rose@shoklo-unit.com, and francois@tropmedres.ac. Laura A. Barcelona, Spain, E-mail: oroca@vhebron.net. Chiara Sartini, De- Buiteman-Kruizinga, Department of Intensive Care, Amsterdam Uni- partment of Anesthesia and Intensive Care, IRCCS San Raffaele versity Medical Centers, Location ‘AMC’, Amsterdam, The Nether- Scientific Institute, Milan, Italy, E-mail: doc.chiara.sartini@gmail.com. lands, and Department of Intensive Care, Reinier de Graaf Hospital, Vittorio Scaravilli, Department of Anesthesia, Critical Care and Delft, The Netherlands, E-mail: l.kruizinga@rdgg.nl. Francesco Carcò, Emergency, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Department of Anesthesia and Intensive Care, IRCCS San Raffaele Policlinico, Milan, Italy, E-mail: vittorio.scaravilli@gmail.com. Marcus Scientific Institute, Milan, Italy, E-mail: carco.fn@gmail.com. Gregg J. Schultz, Department of Intensive Care, Amsterdam University Chesney, Division of Emergency Medicine-Critical Care, Department Medical Centers, Location ‘AMC’, Amsterdam, The Netherlands, of Emergency Medicine, NYU Grossman School of Medicine, New Centre for Tropical Medicine and Global Health, Nuffield Department York, NY, E-mail: gregg.chesney@nyulangone.org. Paul Dark, Critical of Medicine, University of Oxford, Oxford, United Kingdom, and Care Medicine, NIHR Manchester Biomedical Research Centre, Uni- Faculty of Tropical Medicine, Mahidol–Oxford Tropical Medicine Re- versity of Manchester, Manchester, United Kingdom, Division of In- search Unit (MORU), Mahidol University, Bangkok, Thailand, E-mail: fection, Immunity and Respiratory Medicine, NIHR Manchester marcus.j.schultz@gmail.com. Chaisith Sivakorn, Department of Clin- Biomedical Research Centre, University of Manchester, Manchester, ical Tropical Medicine, Mahidol University, Bangkok, Thailand, E-mail: United Kingdom, and Humanitarian and Conflict Response Institute, chaisith.siv@mahidol.edu. Peter E. Spronk, Expertise Center for In- University of Manchester, Manchester, United Kingdom, E-mail: tensive Care Rehabilitation Apeldoorn, Gelre Hospitals Apeldoorn, paul.m.dark@manchester.ac.uk. Arjen M. Dondorp, Faculty of Tropi- Apeldoorn, The Netherlands, E-mail: p.spronk@gelre.nl. Jaques cal Medicine, Mahidol–Oxford Tropical Medicine Research Unit Sztajnbok, Intensive Care Unit, Instituto de Infectologia Emilio Ribas, (MORU), Mahidol University, Bangkok, Thailand, E-mail: arjen@ São Paulo, Brazil, E-mail: jaques.sztajnbok@hc.fm.usp.br. Youssef tropmedres.ac. Harm J. H. Gijsbers and Lisa M. N. Maduro, De- Trigui, Service des Maladies Respiratoires, Centre Hospitalier D’Aix- partment of Rehabilitation Medicine, Amsterdam University Medical en-Provence, Aix-en-Provence, France, E-mail: youssef.trigui@ Centers, Location ‘AMC’, Amsterdam, The Netherlands, E-mails: gmail.com. Kathleen M. Vollman, Clinical Nurse Specialist/Critical h.j.gijsbers@amsterdamumc.nl and l.m.maduro@amsterdamumc.nl. Care Consultant, Advancing Nursing LLC, Northville, MI, E-mail: Mary Ellen Gilder, Department of Family Medicine, Faculty of Medi- kvollman@comcast.net. Margaretha C. E. van der Woude, Intensive cine, Chiang Mai University, Chiang Mai, Thailand, E-mail: Care Unit, Zuyderland Medisch Centrum, Location ‘Heerlen’, Heerlen, mellietyros@gmail.com. Domenico L. Grieco, Department of Emer- The Netherlands, E-mail: m.vanderwoude@zuyderland.nl. gency, Intensive Care Medicine and Anesthesia, Fondazione Policli- nico Universitario A. Gemelli IRCCS, Rome, Italy, and Department of This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) License, which permits un- Anesthesiology and Intensive Care Medicine, Catholic University of restricted use, distribution, and reproduction in any medium, provided the Sacred Heart, Rome, Italy, E-mail: dlgrieco@outlook.it. Rebecca Inglis, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit the original author and source are credited. (LOMWRU), Mahosot Hospital, University of Oxford, Vientiane, Lao People’s Democratic Republic, E-mail: rebecca.i@tropmedres.ac. REFERENCES John G. Laffey, Department of Anaesthesia and Intensive Care, MedicineGalway University Hospitals, Galway, Ireland, and School of 1. Wiersinga WJ, Prescott HC, 2020. What is COVID-19? JAMA 324: Medicine, Disciplines of Anaesthesia and Intensive Care Medicine, 816. National University of Ireland, Galway, Ireland, E-mail: john.laffey@ 2. 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