Oxygen is an essential medicine: a call for international action

SUMMARY

HYPOXAEMIA is a major cause of morbidity and mortality associated with acute and chronic lung disease in children and adults. Hypoxaemia is a low level of oxygen in the arterial circulation and, in lung disease, results from impaired alveolar exchange of oxygen from inspired air into the pulmonary circulation. Tissue hypoxia is the consequence of arterial hypoxaemia. Hypoxaemia is a constant in the pathogenesis that leads to death due to lung disease ir respective of age, sex, aetiology, geographic region or clinical presentation of the patient. As we commemorate World Pneumonia Day this month, in 2010: Year of the Lung, it is timely and important to emphasise the potential of oxygen treatment to reduce deaths due to lung disease globally. Oxygen treatment is also critical for the effective management of many other diseases where the primary pathology is not in the lung (severe sepsis, severe malaria, status epilepticus), and oxygen treatment is an essential part of surgical (including trauma and obstetric) care and anaesthesia.

Oxygen was discovered by Joseph Priestley in 1774, and has been available as treatment for hypoxaemia and used with significant clinical benefit for over a century,1 predating antibiotics for pneumococcal pneumonia or pulmonary tuberculosis (TB). It is therefore remarkable that oxygen treatment is still not widely available in low- and middle-income settings that bear by far the greatest burden of death due to lung disease.^2-5 There are a number of common misperceptions as to why this is the case (see Table): the burden of hypoxaemia is small and does not justify its inclusion as a public health issue; oxygen therapy is too expensive or too complicated to implement; it is palliative and does not improve rates of cure; there is a lack of evidence of effectiveness; and it is not cost-effective. This paper aims to challenge such misperceptions. It will emphasise the importance of reliable and low-cost sources of oxygen to treat hypoxaemia and the use of pulse oximetry to detect hypoxaemia for effective care of lung disease and other conditions in health facilities. Like universally accepted and far-reaching treatments such as antibiotics, oxygen is a life-saving therapy in many critical serious illnesses that can and should be widely available.

DEFINITION OF HYPOXAEMIA AND WHEN TO GIVE OXYGEN

Definitions of hypoxaemia have been established from studies using pulse oximetry.¹⁴ The normal range for arterial oxygen pulsed saturation (SpO₂) at sea level is 94–100%. Because of the lower partial pressure of oxygen in arterial blood at higher altitudes, the normal range of SpO₂ is lower in populations living in mountainous regions.^14,15 However, the lower limit of the normal range for a population is not necessarily the optimal point at which supplemental oxygen therapy is indicated. Changing the level of SpO₂ at which oxygen is given will result in a major variation in the amount of oxygen used.¹⁶

In practice, most studies of hypoxaemia prevalence and oxygen effectiveness have adopted a threshold at which to give oxygen of SpO₂ < 90%.^6,17 An SpO₂ of 90% corresponds to the beginning of the steep part of the haemoglobin–oxygen dissociation curve and represents a safe margin for error where oxygen supplies are sufficient. Conditions such as severe anaemia, severe heart failure, severe sepsis, brain injury and postoperative care require oxygen therapy at thresholds of SpO₂ > 90%. In these conditions, oxygen delivery from the lungs to body tissues is seriously impaired, or vital organs may be particularly susceptible to low oxygen levels, and many clinicians recommend giving oxygen at SpO₂ < 94%. On the other hand, the therapeutic target range of SpO₂ in pre-term infants at risk of oxygen toxicity, particularly to the retina and lungs, should be lower, at 85–90%.¹⁸

ESTIMATING THE GLOBAL BURDEN OF HYPOXAEMIA

Every year, nearly 9 million children die mostly from preventable or treatable diseases, and more than 95% of these deaths occur in developing countries.¹⁹ Pneumonia is the leading cause of death in children aged <5 years, responsible for an estimated 18% of all deaths in this age category.20–22 Hypoxaemia is a major fatal complication of pneumonia, and the risk of death increases with increasing severity of hypoxaemia.^23,24 In a recent systematic review of more than 16 000 children with acute pneumonia or other lower respiratory tract infections, the median hypoxaemia prevalence of children with severe pneumonia requiring hospitalization was 13.3% (interquartile range of studies 9.3–37.5%).⁶ On the basis of an estimated 11–20 million children admitted to hospital with pneumonia each year,²¹ this corresponds to 1.5–2.7 million cases of hypoxaemic pneumonia presenting to health facilities; countless more do not make it to the health facilities.

Hypoxaemia also occurs in children with illnesses that are not primarily due to lower respiratory tract infection, such as acute sepsis, meningitis, severe malaria and acute asthma.⁶ For example, of 491 sick neonates and children presenting to a provincial hospital in the highlands (1600 m above sea level) of Papua New Guinea (PNG), 257 (52%) were hypoxaemic. Hypoxaemia was present in 73% of the neonates and children with pneumonia, and also in 32% of those with non-pneumonia illnesses, including meningitis, septicaemia, severe malnutrition, low birth weight, birth asphyxia and congenital syphilis.²⁵ Even conditions that are infrequently complicated by hypoxaemia, such as malaria (where 3–5% of all hospitalised cases have hypoxaemia), contribute substantially to the global hypoxaemia burden because they are so common.⁶ Of 13 183 children aged 60 days or more admitted to a district hospital in rural coastal Kenya, 5.3% were hypoxaemic; the most frequent final diagnoses among hypoxaemic children were malaria (35%), pneumonia (32%), malnutrition (10%) and gastroenteritis (7%).¹⁷ Hypoxaemia also occurs in acute asthma, an increasing problem in low- and middle-income settings.²⁶ One study found that 26% of 51 children presenting to an emergency department in India with asthma had hypoxaemia.²⁷

Among newborns, in addition to pneumonia, conditions such as respiratory distress syndrome, birth asphyxia, transient tachypnoea of the newborn and sepsis may lead to hypoxaemia.^25,28 Apnoea and hypo-ventilation occur in otherwise healthy premature babies (usually <32 weeks gestational age) due to immature respiratory drive, and in babies of any gestational age with sepsis, asphyxia, seizures or hypoglycaemia. Judicious oxygen therapy is often necessary for these common conditions that are the cause of a large proportion of the neonatal deaths occurring globally each year.²⁹ In the abovementioned Kenyan study, 8% of 991 children admitted aged 7–59 days were hypoxaemic, with the most frequent diagnoses being pneumonia (47%) and sepsis (32%).¹⁷ Of 1105 neonates admitted at <1 week of age, 19% were hypoxaemic, and the most common diagnoses were sepsis (54%), birth asphyxia (30%) and prematurity (24%). Hypoxaemia was strongly associated with in-patient mortality (age-adjusted risk ratio 4.5, 95% confidence interval [CI] 3.8–5.5) in all age groups.¹⁷

The predominant causes of hypoxaemia in adults are chronic obstructive pulmonary disease, acute asthma and pneumonia. Hypoxaemia also occurs in sepsis, shock, major trauma, anaphylaxis, acute heart failure, pulmonary embolism, pleural effusion, pneumothorax, lung fibrosis, carbon monoxide poisoning, obstetric and surgical emergencies and in sickle cell crises.⁷

Oxygen therapy should also be available for maternal care, especially for the management of complications associated with delivery. Obstetric emergencies associated with hypoxaemia include amniotic fluid embolus, eclampsia and antepartum or postpartum haemorrhage. Supplemental oxygen is also indicated for women with underlying hypoxaemic conditions, such as heart failure, during labour.⁷ Oxygen therapy is a core requirement for safe surgery and anaesthesia.⁷

The morbidity and substantial mortality associated with the outbreak of avian influenza in South-East Asia, and the more recent H1N1 influenza pandemic, have increased attention to deaths due to respiratory infections in adults. Part of pandemic preparedness is to ensure that health facilities have effective oxygen systems.²

OXYGEN IS AN ESSENTIAL MEDICINE

Oxygen is included on the World Health Organization (WHO) list of essential medicines.³⁰ Although it is listed under anaesthetic agents, oxygen has broad indications and should be in a class of its own, perhaps the only drug with no alternative agent. In its guidelines, the WHO emphasises the importance of oxygen within the necessary package of providing care for seriously ill children,³¹ and for emergency, anaesthesia and surgical services in district and provincial hospitals.^32,33 Administration of oxygen at the point of care requires a source, such as an oxygen concentrator or cylinder, and equipment for delivery, such as tubing, face mask or nasal prongs. Although it is a treatment that is a basic requirement to save the lives of seriously ill patients, oxygen is rarely available in primary care facilities and is often lacking in district hospitals.^2,34,35 Health authorities should ensure that oxygen equipment is available and included in their health planning budget for any health facility where seriously ill patients may present.

IMPROVED AND CHEAPER TECHNOLOGY FOR MEASURING HYPOXAEMIA

Hypoxaemia can be detected using clinical signs, blood gas analysis or pulse oximetry. Examining for more than one clinical sign is usually more sensitive for detecting hypoxaemia than a single sign, but increased sensitivity is at the price of lower specificity, so that misdiagnosis of the presence or absence of hypoxaemia using clinical signs is common.^17,23,36-38 Cyanosis has poor sensitivity: the lack of cyanosis despite severe significant central nervous system symptoms from hypoxaemia was recognised by J S Haldane in 1920.¹ Blood gas analysis is expensive, invasive and provides a single measure in time only. Pulse oximetry measures oxygen saturation of haemoglobin in the arterial blood by comparing absorbance of light of different wavelengths across an illuminable part of the body. When used correctly, pulse oximetry can provide reliable monitoring with little or no distress to the patient, and is the accepted standard for detecting hypoxaemia (Figure).³⁹ Pulse oximetry can correctly identify 20–30% more children with hypoxaemia than using clinical signs alone.^25,40,41

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Figure

Oxygen systems require a reliable method for detecting hypoxaemia and an uninterrupted supply of oxygen. Illustration by David Woodroffe, David Woodroffe Digital Illustration, UK.

Pulse oximetry can ensure the most efficient use of oxygen therapy, which is especially important in resource-limited settings. As not all patients with signs associated with hypoxaemia (such as the inability to drink in children) will have hypoxaemia, the use of oximetry can also reduce unnecessary oxygen use. A highly cost-effective intervention in hospitals that care for large numbers of children with acute respiratory disease,⁸ pulse oximetry technology is robust and becoming increasingly affordable as the price of oximeters decreases. The reliability, durability and replacement costs of oximeter sensors has been a limiting factor in pulse oximetry being sustained as a clinical tool in resource-poor health facilities, but there are now many examples of achieving sustainability and measuring effect on clinical outcomes.^8,40

Monitoring with pulse oximetry is included in the WHO Surgical Safety Checklist, launched in 2008 as part of the WHO project to improve safety in operating rooms worldwide.^32,42 The checklist is simple, and can be completed in less than 2 minutes. However, monitoring with pulse oximetry is not currently achievable in many operating rooms around the world.^43,44 The Global Pulse Oximetry Project, a partnership including the WHO and the World Federation of Societies of Anaesthesiologists, aims to address this by making available for purchase or donation low-cost pulse oximeters and replacement parts, including low-priced probes, to hospitals in low-income settings.⁴⁵

There is a wide range of oximeters on the market: from handheld, disposable battery-operated oximeters, costing about US$100, to desktop oximeters with re-chargeable batteries and technology to reduce movement artefact, costing about US$1000. Reusable sensors cost around $150–200, and should have a guaranteed life-span of at least 12 months. More detail on the technical aspects and use of pulse oximetry in paediatric care in developing countries can be found in a recent review.⁴¹

IMPROVED AND CHEAPER SYSTEMS FOR OXYGEN THERAPY

Oxygen supplies are limited in many health facilities. Oxygen cylinders—the standard storage form of oxygen in most poorly resourced or remote health facilities—are expensive, difficult to transport and require regular replenishment. Oxygen concentrators are a less expensive and more reliable alternative for providing oxygen treatment, as long as there is a reliable power supply (Figure). Oxygen concentrators take air from the environment and push it through a sieve bed that allows oxygen to pass freely through while retaining nitrogen. Bedside portable oxygen concentrators can provide a reliable source of oxygen at a maximum rate in the range of 5–10 l/min. Good quality machines cost between US$600 and $1200, and run for many years with minimal service and maintenance.^46,47 Concentrators can supply oxygen to multiple patients, depending on patient size and oxygen requirements, by using additional equipment to divide the flow of oxygen from the concentrator.⁴⁶

There is growing experience in the clinical, organisational, biomedical technology and training aspects of setting up and sustaining oxygen concentrators in hospitals and small health facilities in developing countries. Concentrators are now successfully supplying oxygen needs in hospitals in many developing countries, including Egypt, Malawi, PNG, The Gambia, Nigeria and Nepal.^{8,9,11,13,48-50} Concentrators have also been used successfully to supply oxygen to anaesthetic machines in Malawi and other African countries.^51,52 Oxygen concentrators have recently been reviewed, including up-to-date mod els, their specifications, use and effectiveness.^46,47

COST-EFFECTIVENESS OF OXYGEN THERAPY

There is strong evidence that the use of pulse oximetry and the availability of reliable oxygen sources in district and provincial hospitals can reduce death rates from pneumonia by one third.⁸ An implementation field trial of an improved system for detecting hypoxaemia and giving oxygen in five hospitals in PNG, which included more than 10 000 children with pneumonia, demonstrated a 35% overall reduction in case-fatality rate from pneumonia. This system for detection and treatment of hypoxaemia using pulse oximetry and oxygen concentrators cost just over US$1670 per additional life saved, and US$50 per disability adjusted life years (DALY) averted.⁸

The Malawi Child Lung Health project introduced a comprehensive strategy to improve case management of pneumonia in infants and children in district hospitals. This included the introduction of oxygen concentrators where they were not already available. The project followed over 40 000 children and reported a fall in pneumonia case-fatality rates from 18.6% to 8.4%, and estimated that the average cost of treatment for a hospitalised case of pneumonia was $136.⁵³ These cost-benefit data compare favourably with other interventions that are already accepted and recommended to be universally available to reduce mortality from pneumonia, such as pneumococcal conjugate vaccines (estimated at US$100 per DALY averted and US$4500 per life saved in moderate and high mortality countries).⁵⁴

BARRIERS TO GLOBAL OXYGEN THERAPY

The current barriers to achieving effective oxygen ther apy for sufferers of hypoxaemia exist on several levels. At the policy level, both internationally and locally, the aforementioned misperceptions that oxygen therapy is not a necessity, is too expensive, and does not improve rates of cure can be squarely refuted with evidence (Table). Such arguments against oxygen therapy would never be accepted in industrialised countries. The rich-poor disparity in the availability of this important treatment must be addressed by moving oxygen up the international health agenda. Pneumonia has been an overlooked disease, but the momentum exemplified through World Pneumonia Day shows that this is changing. The barrier of ineffective health systems may also be cited by sceptics, but this holds true with many other effective treatments, and country examples are now available that demonstrate the effectiveness and impact of oxygen systems in remote settings with limited resources.⁴⁶ Technological solutions to oxygen concentrators in settings without a reliable power source are being explored.⁴⁶ These include solar-powered systems (currently a capital-intensive option),¹² storing power in batteries to provide energy when mains power is unavailable, and more energy efficient concentrators that run on direct current.

IMPROVING QUALITY OF CARE AND STRENGTHENING HEALTH SYSTEMS

Improving access to oxygen treatment should already be a priority—we should not have to debate the provision of adequate oxygen in hospitals or any health facility with high workloads, and its benefits to the overall system should further boost support for broader availability. Programmes that emphasise the use of oxygen concentrators and pulse oximetry are an entry point for improving the overall quality of health care.^41,46 Benefits of a functioning oxygen system cut across various programmes involving several disciplines: internal medicine, paediatrics, obstetrics, anaesthesia, surgery, trauma and burns. To implement and maintain oxygen concentrators requires strengthening of health systems and building of capacity and collaboration among clinicians, administrators and technicians.

Training for clinicians and technicians is necessary for the implementation of an effective oxygen system. Clinical training includes indications for and how to give oxygen therapy, supportive care for seriously ill children, screening and monitoring using pulse oximetry, and simple maintenance and cleaning of oxygen equipment.^31,55 Such training was provided along with the installation of oxygen concentrators in Malawi and PNG, and reinforced with regular review of the oxygen systems by a National Oxygen Team.^8,9,46 The designation of a ‘high-dependency’ area for seriously ill children within the children's ward, close to the nurses' station, improved the recognition of hypoxaemia and other complications.³⁵ Building capacity among local biomedical engineers and technicians has resulted in timely servicing and maintenance of equipment, and reduced the sense of isolation felt by hospital technicians in rural hospitals.⁹

In scaling up oxygen systems, we urge that more prospective data on cost, challenges and patient outcomes from different settings be collected through implementation or operational research. These data will help to advance the argument for further improving oxygen therapy systems while also providing a unique opportunity to examine the integration of appropriate technology into patient care.

TECHNICAL RESOURCES

The Oxygen Systems Working Group of the International Union Against Tuberculosis and Lung Disease (The Union) has compiled a set of resources on the Union website that freely provides information relating to the identification and management of hypoxaemia: http://www.theunion.org/news/saving-lives-of-children-with-hypoxaemic-pneumonia.html (or http://www.rch.org.au/cich/links/index.cfm?doc_id–699). These resources include published literature as referred to in this article, and focus particularly on providing technical assistance for implementation of an effective oxygen system. The group aims to keep this set of resources updated as new, relevant information emerges. The WHO has produced a handbook, The Clinical Use of Oxygen,³⁵ a working draft of which is downloadable free from the websites. Free consultancy is available from members of the group with practical experience in the planning and provision of local and national oxygen systems.

CONCLUSION

The evidence is compelling that oxygen therapy is a highly effective intervention for positively impacting global mortality. We call for international health policy makers, funders and implementers to grasp the opportunity to ensure that it is available to all who need it.

Acknowledgements

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