Background: The purpose of this investigation is to evaluate the effect of prone ventilation for 16 hours or greater in potential lung donors with death by neurological criteria on lung transplantation outcomes.

Methods: Data was derived from the Midwest Transplant Network from January 2005 to November 2020. Prolonged proning began in January 2019. The primary endpoints were change in PAO2:FiO2 ratio, lungs transplanted per year, and percentage of lungs transplanted. Patients were divided into three groups: not prone, 360-degree rotational positioning, and prone for 16 hours or greater.

Results: The change in PFR was significantly higher (p-value < 0.001) with rotational positioning. Despite this, the average number of total lungs transplanted per year was significantly higher (p-value < 0.000) with a 16 hour or more prone position. A statistically significant increase was seen in lung transplantations after implementing a 16-plus hour prone ventilation protocol. Despite the greatest change in PFR seen in the rotational group, more lungs were transplanted in the 16-plus hour prone ventilation group.

Conclusion: These findings suggest that prone ventilation for 16 hours or more may improve lung transplantation rates despite smaller changes in oxygenation indices compared to rotational positioning. This protocol may offer a valuable strategy to expand the donor pool and increase the number of lungs successfully transplanted.

• Brain Death

• Lung Function

• Organ Donation

• Quality And Patient Safety

• Transplantation

Atluri S, Bly JD, Terrill DM, Mendez M, Ott M, et al. (2026) Effects of 16-Plus-Hour Prone Ventilation on Lung Donation Outcomes in Organ Donors with Death by Neurologic Criteria. J Surg Transplant Sci 13(1): 1092.

ABG: Arterial Blood Gas; ARDS: Acute Respiratory Distress Syndrome; ATS: American Thoracic Society; CCS: Critical Care Society; CI: Cardiac Index; CPAP: Continuous Positive Airway Pressure; DCD: Donation after Circulatory Death; FiO2: Fraction of Inspired Oxygen; ICU: Intensive Care Unit; IRB: Institutional Review Board; ISHLT: International Society for Heart and Lung Transplantation; MAP: Mean Arterial Pressure; MTN: Midwest Transplant Network; O2: Oxygen; OPO: Organ Procurement Organization; OPC: Organ Procurement Coordinator; PAO2: Partial Pressure of Oxygen in Alveoli; PFR: PaO2 FiO2 Ratio; PEEP: Positive End-Expiratory Pressure; RRT: Registered Respiratory Therapist; UNOS: United Network for Organ Sharing

The need for solid organ donation and transplantation continues to outpace transplant availability. It is estimated that a new recipient is added to the transplant waitlist every ten minutes [1]. In 2017 alone, 6,500 candidates died either on the waitlist or within 30 days of leaving the waitlist without receiving an organ transplant [2]. As of April 2023, there are 104,234 people in need of a life-saving organ transplant. Of these patients, 960 require a lung transplant [2]. Lung transplantation is a well-established treatment choice for patients with end-stage lung disease utilized after all other medical and surgical therapies have been exhausted.

To donate an organ, a patient must first qualify as an eligible donor. In the 1990s, a standardized criterion for lung donation was drafted with the following recommendations9:

- Age 20 to 45

- ABO compatibility

- PaO2:FiO2 ratio (PFR) of >350MmHg

- Clear chest radiograph without evidence of cardiopulmonary disease

Once these initial criteria are met, donors will then undergo a second series of criteria, which include:

- Donor management

-  Minimal ischemic time of the organ planned for donation

- Tobacco history less than 20 pack-years

- Absence of chest trauma

- Laboratory data suggesting no evidence of aspiration or sepsis

- History and physical exam showing no prior cardiopulmonary surgery

- A sputum gram stain without any organisms

- An absence of purulent secretions during a bronchoscopy [3].

Though the above criteria seem ideal, the stringent requirements outlined may have unnecessarily limited the number of suitable candidates. Thus, over the years, advances have been created to liberalize some of the criteria to allow for the transplantation of organs that may have been previously discarded. Once identified as a potential lung donor, a patient will undergo critical care measures to achieve donor management guidelines, which at our Organ Procurement Organization (OPO) includes: mean arterial pressure (MAP) > 60 mmHg, target urine output of 0.5-3.0 cc/kg/hr, cardiac index (CI) > 2.5 L/min/ m2, pH between 7.30-7.45, maintaining adequate oxygen (O2) saturation on minimal supplementation fraction of inspired oxygen (FiO2), aggressive pulmonary hygiene, and antibiotics if indicated. These goals are used to create optimal organ function for transplantation.

In recent years, prone positioning has been linked to improved outcomes and increased survival for patients with acute respiratory distress syndrome and avoiding ventilator-induced lung injury by decreasing overdistension and atelectasis [4]. Proning a patient improves oxygenation to the lungs by 70-80% compared to when they are supine and creates a homogenized pleural pressure gradient to improve aeration and blood flow to the dorsal region of the lungs [4]. Additionally, prone positioning has also shown to decrease atelectasis in donors and increase successful lung transplantation rates by Marklin and colleagues [5]. When patients are placed prone, there is a direct correlation with increasing the patients’ PaO2 level and reducing over-inflation of lung tissues while promoting alveolar recruitment [4]. It should also be of note that although maximal benefit from prone positioning is achieved after 17 hours of proning per day, better outcomes and survival have been recorded with the prevention of ventilator- associated lung injury and increased oxygenation [4].

Even though there is a need for increased lung transplantations and prone ventilation has shown promising results, only a few studies show a correlation between prone positioning and a change in lung transplantation outcomes. Our study group recently showed that donors with death by neurological criteria had increased lung transplantation rates when rotated in a 360-degree rotational protocol. This protocol required manually turning donors every four hours, between the supine, prone, and lateral position, with each donor prone approximately 10 hours each day. This study showed a correlation between rotational positioning and increased PAO2:FiO2 ratio (PFR) while also significantly increasing the number of lungs transplanted from 18% to 28% in our donor population [6]. After transplantation, immediate lung function in the 360- degree turning protocol group increased from 68% to 99.5% [6]. Due to similar research over the last couple of years, a consortium of the American and European Thoracic and Critical Care Societies recommended in 2017 that patients with ARDS be prone for 12 hours or more each day to reach full potential benefit. Of note, not all lung donors meet the criteria for an ARDS diagnosis but do undergo neurogenic lung changes for which prone positioning may offer benefit. The purpose of our study is to determine whether prone ventilation for 16 hours or greater in organ donors with death by neurologic criteria may improve the number of lungs available for donation. We hypothesize that proning donors with death by neurological criteria for 16 hours or greater will result in a higher PFR and an increased number of lungs transplanted.

The study design is a longitudinal quality improvement project. The study protocol was reviewed by the University of Missouri-Kansas City’s Institutional Review Board and approved (IRB#: 18-253). A retrospective and prospective chart review was completed using de-identified donor data collected by the Midwest Transplant Network (MTN). MTN serves 5.5 million people in their demographic area and includes 247 hospital partners and five transplant centers. Respectively, the states of Missouri and Kansas have an 84% and 85% first-person authorization rate in which the individual elected to be an organ donor before their donation circumstance.

Data was collected from January 2005 to November 2020. The 16-plus hour prone ventilation began in January 2019. Data measurements compared included: donor demographics, change in PFR, the total number of lung donors per year, and percentage of lungs transplanted. Potential lung donors were divided into three periods based on proning practices at that time. Group 1 spanned 2005-2007 in which donors underwent supine ventilation with standard side to side turning only. Group 2 spanned 2008-2018 in which donors underwent 360-degree rotational positioning. Group 3 spanned 2019-2020 in which donors underwent prone ventilation for 16 hours or greater. These three groups were compared using Kruskal Wallis test, Chi-square, and independent Welch ANOVA given non-normally distributed data. P-values of <0.05 were deemed statistically significant. Data analysis on de identified data was performed on SPSS with the assistance of a biostatistician. To adequately track this study, donor data collection sheets were completed every month. This tool included all variables and measurable factors. Once data entry was complete, the chart was monitored for accuracy by the examiner, de-identified, and sent to the biostatistician for analysis.

All donors consisted of patients who had been declared dead by neurological criteria. Transplant surgery teams decided whether or not to utilize the lungs based on inclusion and exclusion criteria, among other factors.

Inclusion criteria for potential lung donors include:

- A diagnosis of death by neurological criteria 

- PFR greater than 300 mmHg Exclusion criteria included:

- Active cancer diagnosis

- A cause of death related to a respiratory condition

- Dependence on home inhaled corticosteroids

- Dependence on home oxygen

- Inability to prone patients for any reason

- Donation after circulatory death (DCD)

Individual demographics obtained on each donor were: age, sex, race, past medical history, cause of death, tests performed for declaration of brain death, time of death, and if first-person authorization was present.

The Organ Procurement Organization (OPO) identified donors with death by neurological criteria for donor potential and study candidacy. Authorization for organ donation was obtained either via the state registry or the donor’s next of kin. The evaluation looked at individual demographics. Once the organ donor was identified as a potential lung donation candidate, the proning protocol was implemented. The proning protocol involved manually turning the donors to prone position as soon as possible following authorization and leaving donors proned for as long as possible and only turning them supine as needed for procedures after 16 hours or greater. No specialized beds were used. Instead, MTN and hospital staff manually lifted and rotated all patients. No adverse effects or events were reported as a result of proning interventions in group.

Donor families were made aware of the protocol and were given what to expect from prone ventilation. Intensivists and the OPO have a standardized set of Donor Management Goals to meet within 12 hours of authorization if possible, which include: a Mean Arterial Pressure (MAP) of > 60 mmHg, a Cardiac Index (CI) > 2.5 L/ min/m2, Urine Output of 0.5-3 cc/kg/hr, pH of 7.30-7.45, and a PFR of >350 mmHg if the donor is less than 60 years old and >300 mmHg if the donor is older than 60 years old.

By protocol, all donors received 500 mg solumedrol, 10 mg vecuronium, and 8 mg Narcan at the beginning of their care. Protocol interventions used include lung recruitment procedures (such as an O2 washout), increased levels of Positive End Expiratory Pressure (PEEP) (8-12 cm H2O on average), an initial arterial blood gas (ABG), bronchoscopy evaluation and pulmonary hygiene interventions, sputum cultures for surveillance of treatment, and proning the donor. ABGs reoccurred every four - six hours to monitor the patient’s PaO2 levels throughout the study (of note,all PAO2:FiO2 analyses were performed at each recurring ABG). Every patient underwent lung recruitment every 1-2 hours with 40 cm H2O of PEEP in CPAP mode administered for 40 seconds.

The donor’s position was documented every hour by each Organ Procurement Coordinator (OPC) on-site and monitored using the Vigileo FloTrac system (Edwards Lifesciences, Irvine, CA, USA) to assist with fluid management. Patients were resuscitated with fluid until no longer fluid responsive. In addition, education was provided to all OPCs at MTN about each donor needing to be placed prone for a goal of 20 hours each day. Once MTN implemented the protocol, a chart check on each donor was completed to ensure the proning protocol was implemented, the number of hours prone, and lung transplantation outcomes.

A total of 1,470 subjects were analyzed. Only one adverse effect was reported: the dislodgement of one arterial line in the 360-degree rotational protocol. There were no inadvertent extubations. There was no significant difference found between the groups for gender and race (Table 1).

Table 1: Donor Demographics by Group

Age was significantly different among the groups, which was found to increase between the groups with the oldest age in group 3 with a mean age of 43.75 years old. The cause of death was significantly different and varied substantially across the three groups. Anoxia was the most significantly different cause of death, which increased as years passed.

The change in PFR from when the patient first arrived at the hospital to organ recovery was found to be significantly different among the three groups (Table 2).

Table 2: Change in PFR by Donor Group

In group 1 the difference in PFR was 35.73 mmHg ± 116.39 the difference was small (as expected). In group 2 the difference in PFR was 92.68 mmHg ± 144.98, significantly higher (p-value = 0.000) than the other two groups. In group 3, the difference in PFR was 77.59 mmHg ± 154.30. The average number of successful lung transplants per year was significantly higher in the 16-plus hour group (group 3): 145.5 lungs per year (p-value <0.000), whereas group 1 had 34.68 lungs per year, and group 2 had 94.3 lungs per year (Figure 1). The percent of lungs donated before 2008 (group 1) was 18%. Between 2008-2018 (group 2), the proportion of lungs donated increased to 23.8% with 360-degree rotational positioning. In 2019 2020 (group 3), the implementation of 16-plus hour prone ventilation led to a significantly higher increase of 28.5% (p-value <0.000) (Figure 2).

Figure 1: Percentage of Lungs Transplanted per Donor Group. This figure demonstrates the three positioning groups: Group 1 (2005-2007) represents the non-prone patient group, Group 2 (2008-2018) represents the 360-degree rotational position group, and Group 3 (2019-2020) represents the prone group. As seen in the figure, prone positioning resulted in the highest percentage of successful lung transplants.

Figure 2: Average Number of Lungs Successfully Transplanted Per Year. This figure demonstrates the three positioning groups: Group 1 (2005- 2007) represents the non-prone patient group, Group 2 (2008-2018) represents the 360-degree rotational position group, and Group 3 (2019-2020) represents the prone group. As seen in the figure, prone positioning resulted in the highest number of successful lung transplants.

The average total time patients were proned in the 360-degree rotational group was 10.81 hours. The average total time patients were proned in the 16-plus hour group was 30.68 hours.

Lung transplantation is often the last resort option for patients with end-stage lung disease and can prolong life. Stringent guidelines allow for successful transplantation and limit acute and chronic rejection via pathological processes such as graft versus host disease. Unfortunately, these stringent guidelines also contribute to the limited number of lungs available despite growing demand. Allowing for ease of guidelines can further open up the organ donor pool without necessarily risking organ efficacy.

Other studies have also been taking place recently that look at liberalizing criteria such as allowing a smoking history, allowing pathologic chest radiographs instead of only clear chest radiographs, or allowing prolonged ischemic time [7]. In efforts to find other techniques, the Midwest Transplant Network has also taken steps to improve organ care, as showcased in Table 3.

Table 3: Changes made in Donor Care over the Years by The Midwest Transplant Network

One such action is the formation of the MTN Critical Care Taskforce. In 2004, the United States Department of Health and Human Services formed the Organ Donation and Transplantation Collaborative in an attempt to increase the overall organs available for transplant. Following this initiative, the MTN Critical Care Taskforce was formed in 2005, from which several evidence-based strategies were employed in donor care that further increased organ transplantation. In 2006, MTN was the first institution to implement a call schedule to ensure an intensivist would be on call 24/7 to assist in the management of all organ donors with death by neurological criteria. This initiative further led to an additive effect of strategies utilized in donor care. Since then, other changes have been made as the result of the task force and intensivist-led management. These strategies include ventilator management guidelines, 360-degree rotational protocol and lung recruitment, intra-abdominal hypertension interventions and potential infectious process strategies.

Our study explored factors such as increasing donor age and using organs previously considered marginal and nurturing them to viability. By nurturing previously marginal and older donor organs to procurement, we could increase lung transplantations, potentially expanding the donor pool. At the conclusion of the 360-degree rotational protocol study, a 28% lung transplant rate was seen. By the initiation of the proning study in 2019, the lung transplant rate in this group decreased to 23.5%, which can be explained by an increased number of donors.

While demographics remained roughly the same, there was a significant increase in age noticed between the study groups. The significant increase in donor age following prolonged proning may be evidence that intensivists were able to coordinate with ICU and OPO teams to salvage organs for transplantation that may have been previously discarded from older donors. The cause of death between the groups was also significantly different. A significant increase in anoxic death over the years in our donor population was primarily due to cardiovascular reasons. Other leading factors include drug/intoxication and asphyxiation which contributed to anoxic deaths seen as well. The difference in PFRs being highest in group 2 could indicate higher quality and function in lungs, however in group 3, it could indicate a greater efficiency in reaching the threshold, allowing for a greater increase in lung transplants and contributing to the average number of successful lung transplants per year.

Looking towards the future of solid organ transplantation, specifically lung transplantation, organ procurement organizations and critical care specialists have taken innovative approaches. One such initiative includes genetic engineering. A study conducted in Toronto explored the concept of targeting cytokine production within the lung graft utilizing gene therapy. By employing genetic engineering of the donor and decreasing cytokine reactivity in the recipient, lung transplant survival can be longer [8]. Another push has included the discussion of machine perfusion. Machine lung perfusion has been studied in both normothermic and more recently, hypothermic circumstances.

The apparatus is composed of two parts: one is a ventilator providing oxygen to the lung and the other is a circuit that drives and filters the perfusate once deoxygenated. The normothermic circumstances mimic normal body temperature and thus help to facilitate the recovery. The hypothermic cooling helps to maintain function while being stored in preparation for the transplant to occur [9,10]. This process has not only improved lung function but also increased successful transplantations. This process can be used not only on lungs but on kidneys and liver as well. Surprisingly, it was also found that storage of these organs for prolonged periods of time (such as 7 days) showed preserved synthetic function without evidence of histological or cellular level damage [11]. To maximize the use of as many lungs as possible, there has also been an increase in the utilization of DCD lungs in which several studies have shown success [12-17]. All such initiatives look to increase the organ pool by transforming what are considered marginal organs by previously set stringent guidelines and nurturing these organs to procurement and successful transplantation.

Potential shortcomings of our study include not having level 1 data. Our study includes retrospective data in group 1 and group 2 with prospective data in group 3. Also, intensivists were involved with all cases but may not be responsible for the sole management of a single case. This made it difficult to identify specific management strategies employed in each individual case. The donation process as a whole is dependent not only on nurturing organs to procurement but acceptance of organs by transplant surgeons as well. We cannot rule out the fact that lung transplant surgeons may have adopted more liberal guidelines which may also have contributed to the increase seen in lung transplantations. Our data documents one OPO’s experience and does not represent the experience of OPOs across the nation. Changing management strategies over the years may have also contributed to the increases in lung transplantation seen in data over time.

Our study suggests a potential method to increase the number of lungs available for transplantation via utilization of a prone ventilation protocol for 16 hours or greater. This study is retrospective in nature, and this increase was seen in the setting of aggressive fluid management strategies, lung recruitment maneuvers, and management of intra-abdominal hypertension. These strategies could have also had an additive effect and contributed to the increase seen. Despite the greatest difference in PFR seen in the 360-degree rotational proning group, more lungs transplanted in the 16-plus hour prone ventilation group may be evidence that lungs were salvaged for transplantation, which may have previously been discarded. A randomized prospective multi-institution trial comparing conventional to 360-degree rotational proning to 16-plus hour proning may further validate this concept. Meanwhile, the authors suggest that prone ventilation for 16-hours or greater be considered in the critical care management of organ donors across the nation in efforts to increase solid organ transplantation.

The data that support the findings of this study are available from the Midwest Transplant Network. Restrictions apply to the availability of these data, which were used under license for this study. Data are available with the permission of the Midwest Transplant Network and Dr. Sahaja Atluri.

Sahaja Atluri, MD: Led the study design, coordinated data collection with the Midwest Transplant Network, and contributed significantly to data interpretation and manuscript writing. Played a central role in drafting and revising all versions of the manuscript.

Jacob D. Bly, MD: Assisted with data analysis, contributed to manuscript development, and provided critical feedback throughout the writing process.

Danielle M. Terrill, MD: Participated in study planning and interpretation of results. Helped with manuscript revisions and provided feedback during the drafting stages.

Marissa Mendez, MD: Contributed to data review, writing early manuscript drafts, and editing later versions for clarity and flow.

Melissa Ott, ARNP: Supported clinical data acquisition, reviewed manuscript drafts, and provided valuable insights on the clinical aspects of the study.

Lori Markham, RN, MSN: Assisted with protocol implementation and data organization. Reviewed and edited the manuscript for clinical clarity.

Scott Sander, RRT: Played a key role in operationalizing the prone ventilation protocol and assisted in data documentation. Contributed to reviewing manuscript.

Dustin R. Neel, MD: Participated in data interpretation, reviewed drafts, and offered important clinical context during revisions.

Scott S. Johnson, MD: Provided input on data relevance from a transplant perspective and contributed to reviewing and shaping the final manuscript.

Donald G. Vasquez, DO: Contributed to interpretation of clinical findings and manuscript editing with a focus on transplant medicine.

Stevan P. Whitt, MD: Offered guidance on research design and donor management approaches. Reviewed the manuscript and helped refine key clinical points.

Jody Olson, MD: Assisted in manuscript review and contributed edits related to donor management and clinical care.

Joseph R. Nold, MD: Provided feedback on clinical methodology and reviewed manuscript drafts for accuracy and relevance.

An-Lin Cheng, PhD: Performed statistical analysis and contributed to interpretation of results. Assisted in writing and revising the methods and results sections.

Anirudh Atluri: Helped with data entry and organization, and assisted in reviewing early drafts of the manuscript.

Anshal Vyas: Contributed to manuscript formatting, citation management, and finalization of abstract. Aided in figure development and final edits.

Ellie Choi: Supported manuscript formatting, figure development, and reference checking. Reviewed drafts to ensure consistency and clarity.

Safal Sapkota: Contributed to manuscript formatting, editing, reviewing drafts, and assisted with managing submission logistics and figure development.

Samuel Kim: Managed submission logistics, coordinated author revisions, and contributed to editing and formatting of the final manuscript.

Michael Moncure, MD: Provided oversight for the entire project, guided research direction, and critically reviewed all manuscript drafts.

1. United Network of Organ Sharing (UNOS). Data. 2020a.
2. United Network of Organ Sharing (UNOS). Transplant Trends. 2020c.
3. Chaney J, Suzuki Y, Cantu E 3rd, van Berkel V. Lung donor selection criteria. J Thorac Dis. 2014; 6: 1032-1038.
4. Guérin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013; 368: 2159-2168.
5. Marklin GF, O’Sullivan C, Dhar R. Ventilation in the prone position improves oxygenation and results in more lungs being transplanted from organ donors with hypoxemia and atelectasis. J Heart Lung Transplant. 2021; 40: 120-127.
6. Mendez MA, Fesmire AJ, Johnson SS, Neel DR, Markham LE, Olson JC, et al. A 360° Rotational Positioning Protocol of Organ Donors May Increase Lungs Available for Transplantation. Crit Care Med. 2019; 47: 1058-1064.
7. Mulvihill MS, Gulack BC, Ganapathi AM, Speicher PJ, Englum BR, Hirji SA, et al. The association of donor age and survival is independent of ischemic time following deceased donor lung transplantation. Clin Transplant. 2017; 31: 10.
8. Mohamed MS. Translational Insights on Lung Transplantation: Learning from Immunology. Iran J Immunol. 2015; 12: 156-165.
9. Tatum R, O’Malley TJ, Bodzin AS, Tchantchaleishvili V. Machine perfusion of donor organs for transplantation. Artif Organs. 2021; 45: 682-695.
10. Haywood N, Byler MR, Zhang A, Roeser ME, Kron IL, Laubach VE. Isolated Lung Perfusion in the Management of Acute Respiratory Distress Syndrome. Int J Mol Sci. 2020; 21: 6820.
11. Resch T, Cardini B, Oberhuber R, Weissenbacher A, Dumfarth J, Krapf C, et al. Transplanting Marginal Organs in the Era of Modern Machine Perfusion and Advanced Organ Monitoring. Front Immunol. 2020 May 12; 11: 631.
12. Erasmus ME, van Raemdonck D, Akhtar MZ, Neyrinck A, de Antonio DG, Varela A, et al. DCD lung donation: donor criteria, procedural criteria, pulmonary graft function validation, and preservation. Transpl Int. 2016; 29: 790-797.
13. Garrity E, Bag R. Lung transplantation: Deceased donor evaluation. 2018.
14. United Network of Organ Sharing (UNOS). News. 2020b.
15. Maurer JR, Frost AE, Estenne M, Higenbottam T, Glanville AR. International guidelines for the selection of lung transplant candidates. The International Society for Heart and Lung Transplantation, the American Thoracic Society, the American Society of Transplant Physicians, the European Respiratory Society. Transplantation. 1998; 66: 951-956.
16. Mohite PN, Sabashnikov A, Patil NP, Garcia-Saez D, Zych B, Zeriouh M, et al. The role of cardiopulmonary bypass in lung transplantation. Clin Transplant. 2016; 30: 202-209.
17. Dong L, Mizota T, Tanaka T, Chen-Yoshikawa TF, Date H, Fukuda K. Off-Pump Bilateral Cadaveric Lung Transplantation Is Associated With Profound Intraoperative Hypothermia. J Cardiothorac Vasc Anesth. 2016; 30: 924-929.