Oxygen

(BAN, USAN, rINN)

💊 Chemical information

Deguonis; E948; Happi; Kyslík; Ossigeno; Oxigén; Oxígeno; Oxygène; Oxygenium; Oxygenum; Sauerstoff; Tlen.
Chemical formula: O2 = 31.9988.
CAS — 7782-44-7.
ATC — V03AN01.
ATC Vet — QV03AN01.

Pharmacopoeias.

In Chin., Eur., Int., Jpn, US, and Viet.

Ph. Eur. 6.2 (Oxygen). A colourless, odourless gas. Soluble 1 in about 32 of water by volume at 20° and at a pressure of 101 kPa. Store as a compressed gas or liquid in appropriate containers. The BP 2008 directs that oxygen should be kept in approved metal cylinders, the shoulders of which are painted white and the remainder black. The cylinder should carry a label stating ‘Oxygen’. In addition, ‘Oxygen’ or the symbol ‘O 2 ’ should be stencilled in paint on the shoulder of the cylinder.

Ph. Eur. 6.2 (Air, Medicinal; Aer Medicinalis; Medical Air BP 2008). It is compressed ambient air containing not less than 20.4% and not more than 21.4% of oxygen. A colourless, odourless gas. Soluble 1 in about 50 of water by volume at 20° and at a pressure of 101 kPa. Store as a gas in suitable containers.

Ph. Eur. 6.2 (Air, Synthetic Medicinal; Aer Medicinalis Artificiosus; Synthetic Air BP 2008). It is a mixture of nitrogen and oxygen containing between 21.0% and 22.5% of oxygen. A colourless, odourless gas. Soluble 1 in about 50 of water by volume at 20° and at a pressure of 101 kPa. Store as a compressed gas in suitable containers.

USP 31 (Oxygen). A colourless, odourless, tasteless gas that supports combustion more energetically than does air. Soluble 1 in about 32 of water v/v and 1 in about 7 of alcohol v/v at 20° and at a pressure of 760 mmHg. Store in cylinders or in a pressurised storage tank.

USP 31 (Medical Air). A natural or synthetic mixture of gases consisting largely of nitrogen and oxygen. It contains not less than 19.5% and not more than 23.5% of oxygen. Store in cylinders or in a low pressure collecting tank.

USP 31 (Oxygen 93 Percent). It contains not less than 90% v/v and not more than 96% v/v of oxygen, the remainder consisting mostly of argon and nitrogen. Store in cylinders or in a low-pressure collecting tank.

💊 Adverse Effects

Oxygen toxicity depends upon both the inspired pressure (a function of concentration and barometric pressure) and the duration of exposure, the safe duration decreasing as the pressure increases. At lower pressures of up to 2 atmospheres absolute, pulmonary toxicity occurs before CNS toxicity; at higher pressures, the reverse applies. Symptoms of pulmonary toxicity include a decrease in vital capacity, cough, and substernal distress. Symptoms of CNS toxicity include nausea, mood changes, vertigo, twitching, convulsions, and loss of consciousness.

Hyperbaric oxygen therapy.

In a review of hyperbaric oxygen therapy1 the following were mentioned as potential complications: barotrauma (ear or sinus trauma, tympanic membrane rupture, or rarely pneumothorax or air embolism); oxygen toxicity (CNS toxicity or pulmonary toxicity); and reversible visual changes.
1. Grim PS, et al. Hyperbaric oxygen therapy. JAMA 1990; 263: 2216–20.

Retinopathy of prematurity.

In the 1940s and 1950s an epidemic of retinopathy of prematurity, affecting perhaps 10 000 babies, was attributed to excessive use of oxygen in neonates. This resulted in the use of oxygen being reduced or curtailed and the incidence of the condition fell dramatically. However, in the 1970s and later an unexpected resurgence of retinopathy of prematurity occurred (probably not due to excessive oxygen use). It was suggested1,2 that oxygen plays only a minor part and that retinopathy of prematurity is a multifactorial condition that affects the most immature and sick children; the increased incidence may reflect the improved survival of these very premature neonates. A study3 of supplemental oxygen in infants with prethreshold retinopathy of prematurity suggested that therapy was safe, but a beneficial effect could not be confirmed. However, a retrospective study4 in premature neonates given supplemental oxygen found that retinopathy of prematurity was more common in those maintained at higher oxygen saturations.
1. Anonymous. Retinopathy of prematurity. Lancet 1991; 337: 83–4
2. Holmström G. Retinopathy of prematurity. BMJ 1993; 307: 694–5
3. The STOP-ROP Multicenter Study Group. Supplemental therapeutic oxygen for prethreshold retinopathy of prematurity (STOP-ROP), a randomized, controlled trial. I: Primary outcomes. Pediatrics 2000; 105: 295–310
4. Tin W, et al. Pulse oximetry, severe retinopathy, and outcome at one year in babies of less than 28 weeks gestation. Arch Dis Child Fetal Neonatal Ed 2001; 84: F106–F110.

💊 Precautions

Any fire or spark is highly dangerous in the presence of increased oxygen concentrations especially when oxygen is used under pressure. Metal cylinders containing oxygen should be fitted with a reducing valve by which the rate of flow can be controlled. It is important that the reducing valve should be free from all traces of oil or grease, as otherwise a violent explosion may occur. Combustible material soaked in liquid oxygen is potentially explosive and the low temperature of liquid oxygen may cause unsuitable equipment to become brittle and crack. Liquid oxygen should not be allowed to come into contact with the skin as it produces severe ‘cold burns’. Oxygen intended for aviation or mountain rescue must have a sufficiently low moisture content to avoid blocking of valves by ice on freezing. High concentrations of oxygen should be avoided in patients whose respiration is dependent upon hypoxic drive, otherwise carbon dioxide retention and respiratory depression may ensue.

Neonates.

The use of supplemental oxygen in neonates is controversial.1 Although the use of 100% oxygen for the resuscitation of asphyxiated term neonates has been standard, there is some evidence that the use of room air (21% oxygen) is equally effective and possibly safer than 100% oxygen although a systematic review2 concluded that there was insufficient evidence for recommendations to be made. Guidelines3,4 for neonatal resuscitation state that the use of less concentrated oxygen or room air in preference to 100% oxygen is reasonable, but that supplemental oxygen should be available if room air is used initially. Use of supplemental oxygen in preterm neonates has been associated with an increased risk of retinopathy of prematurity, although other factors are probably also involved (see under Adverse Effects, above). However, another study5 has reported that supplemental oxygen has beneficial effects on sleep patterns in premature neonates. Although there is some evidence for a link between neonatal oxygen therapy and childhood cancer, this remains to be confirmed.6
1. Higgins RD, et al. Executive summary of the workshop on oxygen in neonatal therapies: controversies and opportunities for research. Pediatrics 2007; 119: 790–6
2. Tan A, et al. Air versus oxygen for resuscitation of infants at birth. Available in The Cochrane Database of Systematic Reviews; Issu
2. Chichester: John Wiley; 2005 (accessed 07/06/06)
3. Resuscitation Council (UK). Resuscitation Guidelines 2005: newborn life support. Available at: http://www.resus.org.uk/ pages/nls.pdf (accessed 07/06/06
4. The American Heart 1585, respectively. Radiation therapy can damage normal adjacent tissue resulting in tissue hypoxia and eventual cell death. Hyperbaric oxygen therapy appears to aid in salvaging such tissue by stimulating angioneogenesis in marginally viable tissue and has been demonstrated to be beneficial in osteoradionecrosis, radiation-induced haemorrhagic cystitis, and other radiation-damaged soft tissue.7 There has been interest in the use of hyperbaric oxygen in children with cerebral palsy, although a randomised study8 found that it was no better than pressurised air. However, improved neurological outcomes have been reported with hyperbaric oxygen therapy in neonates with hypoxic-ischaemic encephalopathy.9
1. Grim PS, et al. Hyperbaric oxygen therapy. JAMA 1990; 263: 2216–20
2. Tibbles PM, Edelsberg JS. Hyperbaric-oxygen therapy. N Engl J Med 1996; 334: 1642–8
3. Leach RM, et al. ABC of oxygen: hyperbaric oxygen therapy. BMJ 1998; 317: 1140–3
4. Wang C, et al. Hyperbaric oxygen for treating wounds: a systematic review of the literature. Arch Surg 2003; 138: 272–9
5. Roeckl-Wiedmann I, et al. Systematic review of hyperbaric oxygen in the management of chronic wounds. Br J Surg 2005; 92: 24–32
6. Juan W-H, et al. Livedoid vasculopathy: long-term follow-up results following hyperbaric oxygen therapy. Br J Dermatol 2006; 154: 251–5
7. Pasquier D, et al. Hyperbaric oxygen therapy in the treatment of radio-induced lesions in normal tissues: a literature review. Radiother Oncol 2004; 72: 1–13
8. Collet J-P, et al. Hyperbaric oxygen for children with cerebral palsy: a randomised multicentre trial. Lancet 2001; 357: 582–6
9. Liu Z, et al. Clinical effectiveness of treatment with hyperbaric oxygen for neonatal hypoxic-ischaemic encephalopathy: systematic review of Chinese literature. BMJ 2006; 333: 374–6.

Respiratory failure.

Respiratory failure occurs when the arterial plasma partial pressure of oxygen (PaO2) and of carbon dioxide (PaCO2) cannot be maintained within normal physiological limits.1 Respiratory failure can be classified into 2 types, both of which are characterised by a low PaO2 (hypoxaemia). However, in type I the PaCO2 is normal or low whereas in type II, referred to as ventilatory failure, PaCO2 is raised (hypercapnia). Some conditions, for example asthma, can produce either type of respiratory failure. Management of respiratory failure mainly involves giving oxygen to reverse hypoxaemia, and specific therapy for any underlying condition. Respiratory stimulants may be considered in some situations. In type I respiratory failure oxygen is used in high concentrations. Nasal prongs and certain face masks can provide concentrations of up to 60% but if concentrations higher than this are needed then tight-fitting anaesthetic-type masks or methods of delivery such as endotracheal intubation have to be used. In type II respiratory failure both high and low concentrations are used according to need. Patients with acute severe asthma should usually be given oxygen at high concentrations of 40 to 60%. In patients with exacerbations of chronic respiratory disorders such as chronic obstructive pulmonary disease the aim is to improve hypoxaemia without increasing hypercapnia and respiratory acidosis.2 The initial concentration of oxygen to give in COPD exacerbations is controversial. During the transfer to hospital, UK guidelines3 recommend starting at 40% and titrating upwards if the oxygen saturation falls below 90% and downwards if the patient becomes drowsy or if the saturation exceeds 93 to 94%. Special care is needed for patients with known type II respiratory failure, especially if they require a long ambulance journey or receive oxygen at home for a prolonged period before an ambulance arrives, as uncontrolled oxygen therapy can result in suppression of respiratory drive, carbon dioxide narcosis, and respiratory arrest. In hospital, arterial blood gases should be used to guide treatment. Other guidelines4 consider that lower initial oxygen concentrations of 24 to 28% are usually sufficient. Patients with exacerbations of chronic ventilatory failure already have an increased central drive to the respiratory muscles and therefore respiratory stimulants such as doxapram have a limited role but may be indicated for short-term use if hypercapnia worsens as a result of oxygen. For most patients with chronic obstructive pulmonary disease, non-invasive ventilation is the initial treatment of choice for hypercapnic ventilatory failure during exacerbations.3 Respiratory stimulants may be considered in the management of postanaesthetic hypoventilation. Although naloxone can reverse respiratory depression caused by opioid analgesics careful dosage adjustment is required as it can also abolish analgesia. Specific antagonists such as naloxone and flumazenil are also used to treat hypoventilation associated with opioid and benzodiazepine overdosage, respectively. If oxygen therapy fails to raise PaO2 in respiratory failure and there is worsening hypercapnia and respiratory acidosis the use of artificial ventilation should be considered. Severe respiratory failure in neonates may result from various disorders. Use of surfactant or inhaled nitric oxide may be of benefit in some cases but extracorporeal membrane oxygenation (ECMO), where blood is removed from the neonate, oxygenated, and re-injected in a continuous circuit that also removes carbon dioxide, may be required.5 ECMO has also been used in older children and in adults,6 but is less well established.
1. Gribbin HR. Management of respiratory failure. Br J Hosp Med 1993; 49: 461–77
2. Plant PK, Elliott MW. Chronic obstructive pulmonary disease 9: management of ventilatory failure in COPD. Thorax 2003; 58: 537–42
3. National Collaborating Centre for Chronic Conditions. Chronic obstructive pulmonary disease: national clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care. Thorax 2004; 59 (suppl 1): 1–232. Also available at: http://thorax.bmj.com/content/vol59/ suppl_1/ (accessed 18/12/07
4. McKenzie DK, et al. The COPDX plan: Australian and New Zealand guidelines for the management of chronic obstructive pulmonary disease 2007. Available at: http://www.copdx.org.au/ guidelines/documents/COPDX_Sep28_2007.pdf (accessed 18/12/07
5. Barrington KJ, Finer NN. Care of near term infants with respiratory failure. BMJ 1997; 315: 1215–18
6. Peek GJ, et al. Extracorporeal membrane oxygenation: potential for adults and children? Hosp Med 1998; 59: 304–8.

Wounds.

Hyperbaric oxygen therapy may have a role in the management of infected and problem wounds (see above). Supplemental normobaric oxygen has been tried in the prevention of postoperative wound infections, but results of controlled studies1-3 have been contradictory and its role is not established.
1. Greif R, et al. Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. N Engl J Med 2000; 342: 161–7
2. Pryor KO, et al. Surgical site infection and the routine use of perioperative hyperoxia in a general surgical population: a randomized controlled trial. JAMA 2004; 291: 79–87
3. Belda FJ, et al. Supplemental perioperative oxygen and the risk of surgical wound infection: a randomized controlled trial. JAMA 2005; 294: 2035–42.

💊 Preparations

Proprietary Preparations

Multi-ingredient: Fr.: Kalinox; Medimix; S.Afr.: Entonox; UK: Entonox; Equanox.
Published October 31, 2018.