Portable Oxygen Concentrator Technology

Existing methods for generating medical grade oxygen depend on physicochemical processes where oxygen is either created through chemical reaction or extracted from existing gas mixtures. While chemical reactions can reliably generate oxygen, they are usually limited, inefficient, or rely upon strongly exothermic reactions. ^{Reference Arnold11,Reference Pollock and Natoli12} By contrast, POCs do not generate oxygen but instead concentrate oxygen that is freely available in ambient air (∼78% nitrogen and ∼21% oxygen). They compress air through a molecular sieve, usually of a zeolite composition, which selectively absorbs nitrogen. The remaining nitrogen-free air is highly concentrated oxygen (>95%) and argon (<5%), which can be routed directly to a patient or a storage tank for consumption. ^{Reference Litch and Bishop13} Most POCs incorporate a sieve-flushing process which returns the filtered nitrogen to the ambient air, clearing the sieve for recurring filtering. With a constant power supply and minor maintenance, POCs can produce oxygen continuously for thousands of hours. ^{Reference La Vincente, Peel and Carai14}

There are two main modes of POC operation: continuous and pulsed dose. During the continuous mode, a POC provides steady oxygen flow, typically at concentrations greater than 90%. Although dependent upon the model and manufacturer, most POCs provide continuous flow rates between 1-5L/minute. However, some larger, non-mobile models can provide flow rates up to 10L/minute. ⁸ Pulsed dose flow, by contrast, delivers a “pulse” of low-volume, highly concentrated oxygen in sync with the patient’s respiratory cycle. This timing allows the oxygen pulse to reach a patient’s alveoli during inspiration, using ambient air to fill respiratory dead space. Pulsed dose mode, in theory, maximizes the oxygen delivered to alveoli per inspiration.

Despite the efficiency of pulsed dose oxygen delivery, there is controversy regarding the definitive clinical outcomes of pulsed dose mode. ^{Reference Zhou and Chatburn15–Reference Chen, Katz and Pichelin17} Although pulsed dose mode often provides a lower fraction of inspired oxygen (FiO2) per breath, it may result in a higher partial pressure of oxygen (PaO2) by more efficiently utilizing the oxygen that is produced by a POC. ^{Reference Zhou and Chatburn15,Reference Gangidine, Blakeman, Branson and Johannigman16} Furthermore, there is no universally accepted conversion factor between continuous and pulsed dose modes, although manufacturers have provided conversions for individual POCs. ^{Reference Blakeman, Rodriquez and Gerlach18} One notable study compared the impact of continuous and pulsed dose modes in healthy subjects in simulated high-altitude settings. ^{Reference Blakeman, Rodriquez and Gerlach18} At an altitude of 14,000 feet, hypoxia was corrected in all patients using a minimum of 2L/minute of continuous flow. However, due to the impacts of gas laws at altitude and changes in subject tidal volumes, in order to overcome hypoxia, the manufacturer suggested equivalent pulsed dose settings had to be increased by 6%-37% in each subject. ^{Reference Zhou and Chatburn15}

The environment of many low-resource locations may impact POC performance despite their intended performance range. Due to Boyle’s Law, POC performance is impacted by lower atmospheric pressures at higher altitudes. It has previously been estimated that the output oxygen concentration decreases by approximately 10% for each 2000m gain in elevation. ^{Reference Litch and Bishop13} However, this appears dependent on a variety of factors including POC model, altitude, and temperature. ^{Reference Bunel, Shoukri and Choin19,Reference Blakeman, Rodriquez and Britton20} In a prospective cohort of ten healthy patients at an altitude of 3776m, oxygen concentrators performed within three percent of the manufacturers’ reported oxygen output. ^{Reference Sakaue, Suto and Kimura21} In laboratory testing of three POCs, oxygen concentrating ability was impacted by both temperature and altitude extremes, which is less likely with oxygen cylinders. ^{Reference Blakeman, Dario Rodriquez and Branson22} One POC was largely unaffected by altitude changes up to 6705m (22,000ft), one had progressively decreasing oxygen concentrations, and a third failed above 4876m (16,000ft). One-half of the models tested failed after being exposed to -35°C. ^{Reference Blakeman, Rodriquez and Britton20} Lastly, in areas with high humidity or wet conditions, care is needed with rubber seals and bacterial filters as they can impact POC function and lifespan if inappropriately exposed to moisture. ^{Reference Litch and Bishop13}

Austere Use

Oxygen is not readily available in many regions around the world, due to either financial or medical logistical limitations, and contributes to significant morbidity and mortality. ^{Reference Dobson5,Reference Dobson23–Reference Qazi, Aboubaker and MacLean25} Portable oxygen concentrators have been used in developing nations and austere locations for over 30 years. ^{Reference Dobson, Peel and Khallaf26,Reference Dobson27} They have become a critical component to providing oxygen in a variety of settings, including in both adult ^{Reference Dobson5} and pediatric care, ^{Reference Howie, Hill and Ebonyi28} during anesthesia and surgical procedures, ^{Reference McCormick and Eltringham29} and at extremes of both altitude and temperature. ^{Reference Sakaue, Suto and Kimura21,Reference Ritz and Previtera30} However, despite the prolonged use of POCs in austere locations, there are limited clinical data regarding patient outcomes available as most publications regarding austere use are cost assessments or feasibility reports. The most robust clinical data were reported by Shrestha, et al where a retrospective cohort of 378 patients received either standard oxygenation or oxygenation from a POC during a variety of surgical procedures in high altitude medical facilities in Nepal. The authors reported no cases of hypoxia, mortality, or morbidity associated with POC use. ^{Reference Shrestha, Singh, Gautam and Chand31}

Studies have shown that POCs are cost effective in low-resource areas, despite relatively high capital costs associated with initial equipment purchase. In assessments performed over 30 years ago, POCs were estimated to save small and large hospitals in remote settings between 25% and 75% of the annual cost of oxygen cylinders, respectively. ^{Reference Dobson27} Similarly, a hypothetical cost assessment in Gambia showed savings of up to 90% associated with POCs, but the savings were heavily dependent upon the cost and accessibility of power generation. ^{Reference Howie, Hill and Ebonyi28} These results have been confirmed in a retrospective cost comparison in Nepal with reported savings in excess of 75%. ^{Reference Litch and Bishop13} In a Nigerian neonatal ICU, the savings were similar with the annual cost of oxygen for a single ICU bed covering the cost of a POC. ^{Reference Mokuolu and Ajayi32} It has been suggested that POC cost could further be lowered by focusing on device development specific for austere locations. ^{Reference Ahmed, Bautista and Hasib33}

In austere settings, a single POC can provide low-flow oxygenation for multiple patients, especially in pediatrics. In a recommendation of the use of POCs for pediatric patients, the WHO recommended one POC for every 10-15 pediatric beds to ensure redundancy and adequacy of oxygen supply. ^{Reference Howie, Hill and Ebonyi28} No formal recommendation on the ratio of POCs to adult patients was identified during the review. However, given adult patient size and oxygen demand, a ratio closer to one POC to one patient is required. The number of POCs needed at any location is likely multifactorial, depending on medical setting, patient severity, available financial resources, and environmental conditions.

The POC electricity requirements may also be a challenge in remote or harsh environments. For example, 26% of health facilities in sub-Saharan report no access to electricity. In an assessment of the use of POCs in hospitals in Gambia in 2004, POCs were considered feasible and cost effective in only two of twelve medical facilities due to significant limitations in access to electricity. ^{Reference Howie, Hill and Ebonyi28} The authors concluded that the ten facilities without power would have more reliable and lower cost oxygen delivery with continued use of oxygen cylinders, despite complex logistics. ^{Reference Howie, Hill and Ebonyi28} Fortunately, POCs do not have robust electrical requirements, often being powered by mobile gasoline generators. ^{Reference Dobson27} However, POCs can be powered by solar panels, ^{Reference Pedersen and Nyrop34} wind turbines, and hydroelectric power. ^{Reference Litch and Bishop13} Although battery technology has been integrated into several POC models, the battery life remains limited, especially in man-packable lightweight models. It is clear that improvements in access to reliable electricity and extended battery life will be the primary improvements needed to drive clinical success of POCs in austere settings.

Despite these challenges, POCs have been used in a variety of developing nations, including Mongolia, ^{Reference La Vincente, Peel and Carai14} Malawi, ^{Reference Enarson, La Vincente and Gie24} Egypt, ^{Reference Dobson, Peel and Khallaf26} Nepal, ^{Reference Shrestha, Singh, Gautam and Chand31} New Guinea, ^{Reference Duke, Peel and Graham35} Gambia, ^{Reference Peel and Howie36} and Djibouti. ^{Reference Cungi, Mathais and D’Aranda37} Training programs prior to equipment deployment ensure medical providers have adequate knowledge for device operation and maintenance. ^{Reference Dobson, Peel and Khallaf26} Appropriate maintenance, such as changing filters and reloading zeolite cartridges, can ensure adequate lifespan of equipment, often functioning several years without failure. ^{Reference Litch and Bishop13,Reference Duke, Peel and Graham35} In an assessment of POCs after several years of use in Malawi and Mongolia, the majority of POCs were classified as either functioning “well” (>85% oxygen produced; 25/51 POCs) or “adequate” (75%-85% oxygen produced; 16/51 POCs) with some POCs operating for over 30,000 hours without maintenance. ^{Reference La Vincente, Peel and Carai14}

Military Use

During deployed military operations, oxygen is required throughout the medical evacuation continuity of care. Casualties’ care often starts with low-resource, mobile, combat medics, continues through isolated forward field hospitals, and ends with intra-continental critical care medical evacuation flights. ^{Reference Johannigman38} Unlike developing nations where cost may be the primary limiting factor for oxygen cylinder logistics, the distribution of oxygen to military settings has unique restraints. Military operations are often kinetic and unpredictable with changes in location and available resources. Additionally, compressed gas poses unique risks during combat, as explosive decompression can occur if oxygen tanks are struck by high-velocity projectiles. ^{Reference Rybak, Huffman and Nahouraii6} During care under fire and prolonged field care, accessing electricity can be difficult. For these reasons, the US Department of Defense (DoD; Virginia USA) and international militaries have invested in deployed POC technology to bridge gaps in oxygen logistics in combat and deployed environments. ^{Reference Blakeman, Rodriquez and Britton20,Reference Bouak39,40}

Portable oxygen concentrators were first suggested for military operations in the 1980s as POC technology was in its infancy. ^{Reference Carter, Baskett and The41} Design improvements for fighter aircraft oxygenation systems played a large role in the development of POC technology, including zeolite sieves. ^{Reference Arnold11} Robust pre-clinical data have been published confirming the effectiveness of ruggedized, compressor-driven, military ventilators in conjunction with deployed POCs. ^{Reference Rybak, Huffman and Nahouraii6,Reference Rodriquez, Blakeman and Dorlac42–Reference Cardinale, Cungi and Bordes46} By contrast, there is notable paucity of clinical data published involving military use of POCs. A retrospective cohort of patients treated by a Pakistani Military Mobile Surgical Team showed an improvement by a factor of 13 in the cylinder to patient ratio after introduction of POCs; ^{Reference Masroor, Iqbal, Buland and Kazi47} however, they treated routine surgical patients and reported no combat casualties. There were no manuscripts identified during the review involving the efficacy of POCs for combat casualties or clinical outcomes in combat.

Despite these limited data, POCs have been deployed with American, French, and Pakistani military units. ^{Reference Rybak, Huffman and Nahouraii6,Reference Bordes, d’Aranda and Savoie44,Reference d’Aranda, Bordes and Bourgeois45,Reference Masroor, Iqbal, Buland and Kazi47,Reference Nguyen, Montcriol and Janvier48} While often deployed with surgical teams, POCs have been integrated into combat vehicles, aeromedical evacuation aircraft, assault ships, and hand-carried by combat medics. ^{Reference Arnold11,Reference Blakeman, Dario Rodriquez and Branson22} This shows that POCs have traversed the entire battlespace, but the requirements of a POC deployed with a large surgical team are vastly different than one given to a special forces medic. For this reason, numerous models of POCs are deployed with US forces. Care by combat medics requires oxygen to be sufficiently mobile to carry equipment in rucks, requiring equipment to be “man-portable.” Unlike a forward surgical team where a 30kg unit may be ideal and provide higher oxygen flow, the DoD defines “man-portable” as equipment weighing less than 14kg. ⁴⁹ This limits the size, oxygen flow, and battery life of ruggedized POCs. The majority of man-portable POCs currently hand-carried by US forces are limited to 3L/minute or 96mL pulsed dose flow. ^{Reference Rybak, Huffman and Nahouraii6} However, the US Army has published plans to design the next generation of mobile POCs, including extended battery life, higher oxygen flows, and lighter weight equipment. ⁴⁰ Such improved equipment, in addition to increased clinical data involving the use of POCs in the treatment of combat casualties, is required to solidify POC’s value on the modern battlefield.

Austere Veterinary Use

Given the nature of veterinary care, medical evaluations and surgical procedures often occur outside or in low-resource field conditions. As such, POCs provide a mobile, low-cost source of oxygen to veterinarians who have limited access to oxygen. There is published evidence for the use of POCs in horses, ^{Reference Coutu, Caulkett, Pang and Boysen50} dogs, ^{Reference Burn, Caulkett and Gunn51} bears, sheep, and reindeer. ^{Reference Fahlman, Caulkett and Arnemo52} Veterinary medicine and animal studies have provided the most robust data on the physiological effectiveness of POCs. Multiple animal studies have reported real-time improvements in oxygenation with the use of POCs, including high-resource veterinary anesthesia settings, ^{Reference Burn, Caulkett and Gunn51} low-resource field conditions, ^{Reference Fahlman, Caulkett and Arnemo52} and in pathologic animal models of acute lung injury. ^{Reference Gustafson, Yang and Blakeman43}

In a notable case series of multiple species, oxygen from a POC was delivered by nasal cannula during field anesthesia. ^{Reference Fahlman, Caulkett and Arnemo52} Using the pulsed dose setting, the delivered oxygen volume was adjusted to compensate for animal respiratory rate and body size. In field conditions, animals had a marked improvement in arterial blood oxygenation. However, this effect was not universal across species. Bears had an improvement in PaO2 from a baseline of 73 (SD = 11) mmHg to 134 (SD = 29) mmHg after the POC was applied. By contrast, bighorn sheep remained hypoxic after application of a POC with a PaO2 only marginally improving from 40 (SD = 9) mmHg to 52 (SD = 11) mmHg. Furthermore, the authors reported that approximately one-half of bighorn sheep had a reduction in PaO2 with 16/18 animals remaining hypoxic throughout the surgical procedure. High baseline respiratory rate, differing nasopharynx structures, and veterinary operating conditions such as outdoor temperature may impact POCs performance in animals. These limitations should be considered for each species prior to field deployment, such as military working dogs, non-human primates, or mammals with atypical respiratory structures.

EMS and Disasters

During emergency medical transport on ambulances, helicopters, or fixed-wing aircraft, large oxygen tanks are often impractical due to weight and space restrictions within vehicles. While providing a limited flow of gas, POCs may help bridge oxygen requirements for EMS providers without routine access to equipment to refill oxygen cylinders. However, there is limited literature discussing the use of POCs in the EMS environment with no clinical outcome data identified during the review. Furthermore, there was no discussion identified regarding routine use of POCs across an entire fleet of ambulances or helicopters. Fixed-wing air medical evacuation is an exception. Due largely to the use of POCs for treatment of chronic respiratory conditions on commercial airlines, POCs have been evaluated for use during flight. ^{Reference Fischer, Wanka and Einhaeupl53} The Federal Aviation Administration (FAA; Washington, DC USA) regulates POC use on aircraft and requires POC manufacturers to comply with flight standards. They are commonly used during fixed-wing medical evacuation and during medical escort on commercial aircraft. ^{Reference Chapman, Tagore and Ariyaprakai54}

Portable oxygen concentrators may close a critical gap in oxygen supply during mass-casualty events or pandemics. ^{Reference Ritz and Previtera30,Reference Williams55} As seen during the coronavirus disease 2019 (COVID-19) pandemic, there was a critical shortage of oxygen in both developed and developing nations, particularly with compressed gas cylinders. ^{Reference Usher56,57} As astutely acknowledged by Williams several years prior to the COVID-19 pandemic, in the context of POCs, “there is market demand for a device capable of providing oxygen therapy during an emergency situation.” ^{Reference Williams55} They were used around the world to provide emergency oxygen to COVID-19 patients when oxygen cylinders or liquid oxygen was not available cylinders. ⁵⁷ Simple engineering solutions were developed to combine several POCs together to feed oxygen directly to a ventilator to provide flows up to 10L/minute for hypoxic, adult patients. ^{Reference Cheah, Steven and Ng58} The success of POCs during the COVID-19 pandemic highlight the potential for POCs during future mass-casualty events.

Future of POCs

Despite advancements in POC technology, POCs cannot fully replace high-pressure oxygen cylinders in low-resource settings. For example, if a patient is extremely hypoxic during intubation, a high-pressure cylinder may be the only source of sufficient oxygen to prevent respiratory arrest. However, POCs will continue to become smaller, more cost efficient, and will likely provide higher flows of oxygen. Furthermore, there is already technology available that combines a larger oxygen concentrator with a compressor system capable of refilling small oxygen cylinders within 60-90 minutes. ⁵⁹ Although proprietary adapters are required and the system is not portable, the ability to both provide continuous flows of oxygen and refill oxygen cylinders with one device would significantly reduce the logistical limitations of providing oxygen in low-resource settings. Such technology, if ruggedized and miniaturized, could transform oxygen delivery in austere environments and even be incorporated into alternative technologies such as supraglottic and endotracheal devices, portable suction units, and extracorporeal tissue preservation. ^{Reference Copeland, Zilevicius and Bedolla60–Reference Portillo, Bayliss and Rivas63} The ideal POC is one that can be carried by one individual, provide moderate to high flows of oxygen, has a battery backup, is low cost, and can refill oxygen cylinders, if required.