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• Never?
  Richard G Fiddian-Green
  Published on: 30 March 2009

• Published on: 30 March 2009

  Never?

  • Richard G Fiddian-Green, FRCS, FACS

  Subhi et al have asked when oxygen should be given to children at high altitude observing that hypoxaemia is the most common fatal complication in deaths occurring from pneumonia in children in developing countries (1). Might the answer be never?

  Supplementary oxygen appears to be harmful in climbers on Everest possibly because it eliminates the up-regulation of oxidative phosphorylation by mass action by hypoc...

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  Subhi et al have asked when oxygen should be given to children at high altitude observing that hypoxaemia is the most common fatal complication in deaths occurring from pneumonia in children in developing countries (1). Might the answer be never?

  Supplementary oxygen appears to be harmful in climbers on Everest possibly because it eliminates the up-regulation of oxidative phosphorylation by mass action by hypocarbia (2) but the benefical effects of this up-regulation could be concealed by the adverse effects of hypothermia at this altitude. A more relevant question might be should supplementary oxygen be given to children with pneumonia or even asthma at low altitude for in these circumstances hypothermia is unlikely to be a confounding factor.

  Supplementary oxygen was not a significant factor in the non- traumatic deaths that occurred in descent from the summit of Everest. Nevertheless the putative beneficial effects of hypocarbia on oxidative phosphorylation can be expected to be far greater at sea level, than on Everest, for they will not be concealed by the adverse effects of hypothermia. Asthmatics, for example, might be better off not receiving oxygen. The same applies to patients with sepsis. In the latter progressive adjustments to the ventilator settings designed to achieve as low PaCO2 as safely possible might not only up-regulate oxidative phosphorylation but also limit the severity of the metabolic acidosis that can develop in these patients. In so doing the associated development of cellular apoptosis and necrosis, the local inflammatory response induced by cellular necrosis, and organ dysfunctions and deaths might also be prevented.

  Two variables would seem to be particular important in the regulation of oxidative phosphorylation: the PaCO2 and the pH, the protonmotive force increasing as the extracellular, or more specifically the extramitochondrial, pH falls. The effects appear to be independent of one another. In the first place "the mammalian central chemoreceptor for respiratory control is responsive independently to H+ and CO2 and that H+ and CO2 exert differential effects on the respiratory centre in terms of frequency and magnitude" (3). Secondly lactate is a linear function of tissue PCO2 in rats (4). Thirdly in patients with sepsis those with a high lactate paradoxically appear to have a higher tissue pH than those with a low lactate (5) presumably because up-regulation of oxidative phosphorylation decreases the likelihood of developing a "lactic acidosis".

  Hypoxia exerts its effects upon respiration through peripheral chemoreceptors. In our study of ventilated dogs progressive decreases in FiO2 failed to induce oxygen supply-dependency before death from cardiac arrest (6). In retrospect this demonstrated the remarkable capacity to deliver adequate amounts of oxygen to tissues in the face of hypoxic stress, a finding confirmed by the studies on Everest. There was another study, conducted by Canadian investigators, that followed DO2 and VO2 in dying patients and found that oxygen supply-dependency failed to develop until the DO2 was so abnormally low that the findings were difficult to believe at the time. Regretably I have been unable to locate the reference. If, however, my recollection is accurate these studies add to the weight of evidence demonstrating that DO2 may not be the limiting factor in the acutely ill. More importantly, perhaps, is the hypothetical risk of ischaemia/ reperfusion or hyopoxia/reoxygenation injury if acute hypoxia is reversed with oxygen.

  To prevent reprfusion/reoxygenation injury, which must be a primary objective during resuscitation, it would seem desirable to withold supplementary oxygen in all circumstances and possibly even to reduce FiO2 to abnormally low levels or give supplementary carbon monoxide during the initial phases of resuscitation. To optimize ATP resynthesis in a child who is critically ill it might be best to reduce the PaCO2 as low as possible, and that might be as low as 10 mmHg, and/or to reduce the arterial bicarbonate concentration so that the pH is clamped at normal or slightly lower (7,8). Clamping of the pH at the derisred level could in theory be achieved using the pH-stat technique using two auto-burettes, one filled with a suitable acid and the other a suitable alkali (9).

  Giving supplementary oxygen to children with acute respiratory infections and even asthma might never be advisable. If oxygen is to be given it might be better to give it intraperitoneally for giving it into the lumen of the gut appears to be cardioprotective in hypoxaemia. There are good grounds for doing so (10, 11,12). The risk/benefit of such an approach has, however, not been established except in the case of ECMO.

  1. Rami Subhi, Katherine Smith, Trevor Duke When should oxygen be given to children at high altitude? A systematic review to define altitude -specific hypoxaemia. Archives of Disease in Childhood 2009;94:6-10

  2. Dexamethasone and hepatic energetics in climbers attempting Everest. Richard G Fiddian-Green (17 January 2009). eLetter re: Matiram Pun. Important points in analysing deaths on Mount Everest BMJ 2009; 338: b41.

  3. Y Harada, M Kuno, and Y Z Wang. Differential effects of carbon dioxide and pH on central chemoreceptors in the rat in vitro. J Physiol. 1985 November; 368: 679–693

  4. Nakagawa Y, Weil MH, Tang W, Sun S, Yamaguchi H, Jin X, Bisera J. Sublingual capnometry for diagnosis and quantitation of circulatory shock. Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1838-43.

  5. Effect of dobutamine on oxygen consumption and gastric mucosal pH in septic patients. Gutierrez G, Clark C, Brown SD, Price K, Ortiz L, Nelson C. Am J Respir Crit Care Med. 1994 Aug;150(2):324-9.

  6. Grum CM, Fiddian-Green RG, Pittenger GL, Grant BJ, Rothman ED, Dantzker DR. Adequacy of tissue oxygenation in intact dog intestine. J Appl Physiol. 1984 Apr;56(4):1065-9.

  7. Gastric intramucosal pH, tissue oxygenation and acid-base balance. Fiddian-Green RG. Br J Anaesth. 1995 May;74(5):591-606.

  8. Monitoring of tissue pH: the critical measurement. Fiddian-Green RG. Chest. 1999 Dec;116(6):1839-41.

  9. Mechanisms of disposal of acid and alkali in rabbit duodenum. Fiddian-Green RG, Silen W. Am J Physiol. 1975 Dec;229(6):1641-8.

  10. The intestinal factor in irreversible hemorrhagic shock. LILLEHEI RC. Surgery. 1957 Dec;42(6):1043-54.

  11. The intestinal factor in irreversible endotoxin shock. LILLEHEI RC, MACLEAN LD. Ann Surg. 1958 Oct;148(4):513-24

  12. Supplemental systemic oxygen support using an intestinal intraluminal membrane oxygenator. Gross BD, Sacristán E, Peura RA, Shahnarian A, Devereaux D, Wang HL, Fiddian-Green R. Artif Organs. 2000 Nov;24(11):864-9.

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  Conflict of Interest:
  None declared.

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