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Did the oxygen upregulate oxidative phosphorylation by reducing pH?
- Richard G Fiddian-Green (15 September 2006)
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REGIONAL CEREBRAL OXIMETRY FOLLOWING OXYGE ADNINISTRATION
- Anis S. Baraka, Maud Nawfal, Mohamad El-Khatib, Sania Haroun-Bizri (8 August 2005)
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Is neurological assessment during awake surgery an adequate form of cerebral monitoring?
- Richard G Fiddian-Green (11 April 2005)
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Richard G Fiddian-Green, FRCS, FACS None
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This Swedish study (1), which I had missed, might well have the answer to the reversal by oxygen of the neurological defects induced by cross clamping the carotid reported in this study. "The effect of different fractions of inspired oxygen on subcutaneous oxygen tension, carbon dioxide tension and pH in relation to arterial and mixed venous blood gases and pH and hemodynamic variables was evaluated in 13 domestic pigs. A minor increase in subcutaneous carbon dioxide tension was noted during hyperoxia (p < 0.05) and a minor decrease in subcutaneous pH (p < 0.05). Had a minor decrease in pH been achieved by increasing the FiO2 in this study it might have induced its beneficial effects by upregulating oxidative phosphorylation by increasing the protonmotive force driving ATP resynthesis. Upregulation could also explain the benefical effects of hypercarbia induced by 10% FiCO2 following traumatic brain injury in another animal model (2). Increasing FiCO2 is, not, however, to be undertaken lightly for it has the potential to down-regulate and even inhibit oxidative phosphorylation by mass action. Indeed when the interstitial pH becomes abnormally low in the heart apoptosis of myocytes occurs in proportion with the degree of acidosis induced (3). What is more, as observed in a recent issue of Nature, hypercarbia is the preferred mode of euthanasia in many small animal models presumably because it inhibits oxphos by mass action. Increasing FiCO2 has been used in cardiac surgery to address the rise in pH that occurs with cooling. This pH-stat protocol was superceded by an alpha-stat protocol that allowed the pH to rise (4). Recent data favours the pH stat protocol (5), the inference being that the lower pH prevents the down-regulation of oxidative phosphorylation that appears to occur with an abnormal rise in pH (6). Given the opposing forces acting upon oxidative phosphorylation outlined in this eLetter it is not surprisng that conflicting data have been obtained. Knowing what the interstital pH is would certainly help in the management of cooling during cardiac surgery in addition to helping in the management of carotid artery surgery. Increasing the FiO2 is known to promote free radical production (7). Cultured enterocytes exposed to proinflammatory cytokines consume less oxygen due to NAD(+)/NADH depletion secondary to activation of PARP by free radicals (8). This may be a cytoprotective action intended to limit free radical injury rather than a cytopathic one as proposed by these investigators. Indeed inhibiting oxygen uptake when inhaled in low concentrations carbon monoxide is cytoprotective and may prevent ischaemia/reperfusion injury as observed in my earlier. If then the increase in FiO2 in the patients reported in this study release free radicals might oxygen have exerted its beneficial effect upon the neurological defects caused by cross clamping the carotid artery? If so did the free radicals do so by these means or by shifting mitochondrial consumption from glucose to fatty acids as suggested in my original eLetter? Alternatively might it have been a rise in interstitial pCO2 and fall in pH that induced a lipid shift and in so doing decreased cellular dependence upon the rate of blood flow? 1. Å. Mellströma, M. Hartmanna, Barbara Jedlinskaa, K. Jönssonb. Effect of Hyperoxia and Hypoxia on Subcutaneous Tissue Gases and pH. An Experimental Study in Pigs. European Surgical Research 1999;31:333-339 2. Glass TF, Fabian MJ, Schweitzer JB, Weinberg JA, Proctor KG. The impact of hypercarbia on the evolution of brain injury in a porcine model of traumatic brain injury and systemic hemorrhage. J Neurotrauma. 2001 Jan;18(1):57-71. 3. Thatte HS, Rhee JH, Zagarins SE, Treanor PR, Birjiniuk V, Crittenden MD, Khuri SF. Acidosis-induced apoptosis in human and porcine heart. Ann Thorac Surg. 2004 Apr;77(4):1376-83. 4. When Science Discovers that an Old Technique Is Better than the New focus.hms.harvard.edu/1998/Sept4_1998/cardio.html 5. Should the target in the pH-stat protocol be a lower pH? Richard G Fiddian-Green (4 March 2004) eLetter re: Vipin Zamvar, David Williams, Judith Hall, Nicola Payne, Clare Cann, Karen Young, S Karthikeyan, and John Dunne Assessment of neurocognitive impairment after off-pump and on-pump techniques for coronary artery bypass graft surgery: prospective randomised controlled trial BMJ 2002; 325: 1268 6. Cain SM. pH effects on lactate and excess lactate in relation to O2 deficit in hypoxic dogs. J Appl Physiol. 1977 Jan;42(1):44-9. 7. Doppenberg EM, Rice MR, Di X, Young HF, Woodward JJ, Bullock R. Increased free radical production due to subdural hematoma in the rat: effect of increased inspired oxygen fraction. J Neurotrauma. 1998 May;15(5):337-47. 8. Khan AU, Delude RL, Han YY, Sappington PL, Han X, Carcillo JA, Fink MP. Liposomal NAD(+) prevents diminished O(2) consumption by immunostimulated Caco-2 cells. Am J Physiol Lung Cell Mol Physiol. 2002 May;282(5):L1082-91. Conflict of Interest:None declared |
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Anis S. Baraka, Professor & Chairman Department of Anesthesiology, American University of Beirut, Maud Nawfal, Mohamad El-Khatib, Sania Haroun-Bizri
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We read with interest the report of Stoneham and Martin showing that the administration of oxygen 100% can reverse the neurological deficits following carotid cross-clamping(1). This was attributed to an increase of the blood oxygen content which could be enough to raise the mitochondrial PO2 above the critical level so that oxidative phosphorylation in ischemic cerebral neurons could restart. Near infra-red spectroscopy has been recently used to monitor regional cerebral oxymetry (RsO2) during carotid endarterectomy(2). Cerebral spectroscopy, whilst having limitations in terms of absolute measurement(3), may give continuous non-invasive assessments of the cerebral oxygen supply-demand balance(4). We investigated the effect of administration of oxygen 100% with a tight-fitting anaesthetic face-mask in 6 awake patients who were scheduled for coronary artery bypass grafting. The mean RsO2 in the awake patients during breathing room air was 62±9.5% which increased significantly to 67.8±10.6% after oxygenation. Following subsequent induction of general anaesthesia using thiopental, fentanyl and rocuronium, there was a further significant increase of RsO2 up to 80.2±9.7%. The 8% increase of RsO2 following 100% oxygenation matches the increase of the total oxygen content as calculated by Stoneham and Martin(1). The subsequent induction of general anaesthesia resulted in a further increase in RsO2 by about 20%. The combination of oxygenation which increases the oxygen delivery and general anaesthesia which decreases the cerebral oxygen consumption has an additive or even a synergistic effect which could have a significant impact on the neurons close to their ischemic threshold. Our results suggest that breathing oxygen 100% by the awake patients or induction of general anaesthesia using a high FiO2, while monitoring the cerebral oxygen supply-demand by cerebral oximetry can enhance the cerebral oxygen-supply demand balance, and may decrease the need for shunting in patients who are liable to develop neurologic deficits during carotid endarterectomy. References 1- Stoneham MD, Martin T. Increased oxygen administration during awake carotid surgery can reverse neurological deficit following carotid cross-clamping. Br J Anaesthesia 94(5):582-5, 2005 2- Ohnishi Y, Hayashi Y, Shimizu J, Koyama Y, Kuro M. Brain monitoring with near infrared spectroscopy during carotid endarterectomy. Masui 45:1420-3, 1996 3- Pattinson K, Clutton-Brock T, Imray C. Validity of near-infrared cerebral spectroscopy. Anaesthesia 59:507-8, 2004 4- Imray CH, Thacker AJ, Mead MK. Oxygen administration can reverse neurological deficit following carotid cross-clamping. Br J Anaesthesia 95(2):274-5, 2005 Conflict of Interest:None declared |
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Richard G Fiddian-Green, N/A
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As the increase in oxygen carrying capacity achieved by the administration of oxygen 100% with a close-fitting anaesthetic facemask in a patient with a normal haemoglobin and who is not desaturated, [delta PaO2 x 0.0031)], is miniscule how might these neurological deficits have been reversed (1)? By inducing an acute lipid shift? If so what was the trigger? Free radicals? If so might adverse effects have been detected had a prospective study been performed in which the neurocognitive tests used in an earlier study in your institution (2) were conducted preoperatively and three months later? "Detailed cognitive assessment, using a battery of tests, shows some impairment in as many as 80% of patients [having open heart surgery] at the time they are discharged from hospital, which persists in around a quarter of them at six months"(2). As neurocognitive impairment in patients undergoing conventional and off-pump coronary artery bypass grafting in your institution were similar it was "speculated that the effects of surgical injury and anaesthesia might be as important as the use of cardiopulmonary bypass in causing impairment". Hyperoxia might be a cause despite these two case reports (3). In a patient who develops an extradural haematoma after a head injury mild concussion may be followed by a lucid interval after which neurological symptoms and even death from coma may develop many hours later. I would be very wary of accepting these two case reports as evidence in support of the view that increasing FiO2 to 1.0 during carotid artery surgery is universally beneficial. There are many possible causes of secondary brain injury in these circumstances. "The introduction of routine intraoperative shunting and patch closure [in your institution], as well as allowing surgical trainees to perform supervised CEAs, has not affected perioperative morbidity and mortality rates or long-term outcome"(3). Your results (4) appear, however, to fall far short of those routinely achieved in the US (5). This difference, if real, could be technical. If so using awake carotid surgery to reduce the need for shunts is unlikely to be a satisfactory solution. The difference might alternatively or additionally be a reflection of differences in the standards of anaesthetic practicces in the UK and US Is mental functioning during awake neurosurgery, including intracranial revascularization, a reliable proxy for metabolic monitoring (6)? I suspect not because it has required detailed cognitive assessment to reveal the extent of the impairment after cardiac surgery and many neurocognitive disturbances appearing after head injuries and brain surgery might have been avoidable events(7). 1. M. D. Stoneham and T. Martin Increased oxygen administration during awake carotid surgery can reverse neurological deficit following carotid cross-clamping Br. J. Anaesth. 2005; 94: 582-585 2. Re: Preventing closed minds Richard G Fiddian-Green, Formerly Professor and Chair General Surgery, University of Massachusetts. (2 December 2002) eLetter re: David Taggart About impaired minds and closed hearts BMJ 2002; 325: 1255-1256 3. Is increasing FiO2 above 0.2 always harmful? Richard G Fiddian-Green (23 March 2005) eLetter re: K. S. Khaw, C. C. Wang, W. D. Ngan Kee, C. P. Pang, and M. S. Rogers Effects of high inspired oxygen fraction during elective Caesarean section under spinal anaesthesia on maternal and fetal oxygenation and lipid peroxidation Br. J. Anaesth. 2002; 88: 18-23 4. Hussain T, Senaratine JW, Green FR, Collin J, Hands L, Morris PJ. Vascular surgical society of great britain and ireland: twenty-three years of experience of carotid endarterectomy Br J Surg. 1999 May;86(5):690. 5. Cowan JA Jr, Dimick JB, Thompson BG, Stanley JC, Upchurch GR Jr Surgeon volume as an indicator of outcomes after carotid endarterectomy: an effect independent of specialty practice and hospital volume. J Am Coll Surg. 2002 Dec;195(6):814-21. 6. Fiddian-Green RG. eLetters re: M Czosnyka and J D Pickard Monitoring and interpretation of intracranial pressure J Neurol Neurosurg Psychiatry 2004; 75: 813-821 7. Neurocritical care of head injuries: an unsatisfactory state of affairs. Richard G Fiddian-Green (30 March 2005) eLetter re: M. Smith Editorial I: Neurocritical care: has it come of age? Br. J. Anaesth. 2004; 93: 753-755 Conflict of Interest:Patents issued in my name |
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