- Email: [email protected]
Limitation of pulse oximetry
1092
subcutaneous sumatriptan. Twelve hours later, she developed a right hemiparesis (power 3 out of 5). Her erythrocyte sedimentation rate, autoantibody screen, immunoglobulins, and lipids were normal. A brain CT scan with intravenous contrast was normal. One week later, she completely regained her power. Sumatriptan binds to a particular subpopulation of 5hydroxytryptamine (5-HTi) receptors in pial and dural vessels causing vasoconstriction.2 It is believed that sumatriptan acts mainly on extracerebral vascular sites,3although experimental studies of possible binding sites in intracerebral vessels and neurons have yet to be done.4 The elimination serum half-life of sumatriptan is two hours. It might therefore be argued that the intervals between drug administration and cerebral infarction of one week in the first case and twelve hours in the second exonerate sumatriptan. However, no other risk factor for vascular disease was identified in our patients. Furthermore, the possibility of sumatriptan binding to cerebral vascular receptors after frequently repeated doses has yet to be explored. In addition, the hemiparesis in the second case was on the opposite cortical side from her migraine-associated hypoaesthesia. We suggest that caution should be exercised with the repeated prescription of sumatriptan and that further studies are needed on specific binding sites of sumatriptan in intracerebral vessels. Gastrointestinal Unit, Western General Hospital, Edinburgh EH4 2XU, UK
W. LUMAN
Department of Medicine, St Johns Hospital, Livingston
R. S. GRAY
McCarthy BG, Peroutka SJ. Comparative neuropharmacology of dihydroergotamine and sumatriptan Headache 1989; 29: 420-22. 2. Pearce JMS. Sumatriptan in migraine. BMJ 1991; 303: 1491. 3. Raskin N. Serotonin receptors and headache. N Engl J Med 1991; 325: 353-54. 4. Willett F, Curzen N, Adams J, Armitage M. Coronary vasospasm induced by subcutaneous sumatriptan. BMJ 1992; 304: 1415. 1.
SiR,—There is an anomaly between case reports of myocardial ischaemia and infarction (ref 1 and Dr Ottervanger and colleagues) after the administration of sumatriptan to patients with no history of coronary artery disease, and the in-vitro findings that the drug is only a weak constrictor of healthy human coronary vessels.2,3 We propose that this anomaly may be explained by an interaction between sumatriptan and nitric oxide (NO) from the endothelium, and that coronary vasospasm after sumatriptan may be caused by occult endothelial dysfunction. The role of endothelial dysfunction in coronary artery disease is well recognised.4 Moreover, recent reports have described endothelial dysfunction in groups at increased risk of coronary artery disease, such as smokers and children with familial hypercholesterolaemia.5 It has also been shown that diseased coronary vessels are less sensitive to stimuli such as potassium and a-methyl derivative of 5-hydroxytryptamine (5-HT), a selective 5-HT2 receptor agonist, whereas the response to sumatriptan, a 5-HTId receptor agonist, is preserved and, indeed, enhanced near atheromatous lesions. 5-HT does not relax pre-contracted human coronary vessels that exhibit endothelium-dependent relaxation to substance P.3 The authors of this study conclude that no interaction between 5-HT and the endothelium in the human coronary vessel occurred. However, these data do not exclude a modulatory role for NO in the contractile response of the vessel to 5-HT or selective agonists, because basal release of NO can inhibit the response of vessels to agonists without the agonist itself stimulating endothelium-dependent relaxation. We have looked at the effect of inhibiting the basal release of NO with the NO synthase inhibitor N-nitro-L-arginine methylester (L-NAME) on the response of the isolated human pulmonary artery to sumatriptan. We found that L-NAME increased the sensitivity of the artery to sumatriptan (figure) although sumatriptan did not relax the vessel pre-contracted with the stable thromboxane mimetic U46619. Endogenous NO production in the healthy coronary artery may inhibit the vessel’s response to sumatriptan and explain the increased sensitivity of the diseased coronary vessel to the drug.3 The occult loss of endothelial function seen in smokers5 would,
therefore, potentiate constriction of coronary vessels induced by sumatriptan, which might explain the isolated cases of myocardial ischaemia described. This suggests that exogenous nitrate, such as glyceryl trinitrate, might be particularly effective in the treatment of these incidents. It might also help to identify subgroups such as
might be at risk of myocardial ischaemia after sumatriptan. The role of endothelium in modulating the response to 5-HT receptor agonists in healthy and diseased coronary vessels smokers who
needs
to
be clarified. M. R. MACLEAN G. C. S. SMITH A. G. B. TEMPLETON
Institute of Physiology, University of Glasgow,
Glasgow G12 8QQ,
UK
1. Stricker BHC. Coronary vasospasm and sumatriptan BMJ 1992; 305: 118. 2. Connor HE, Feniuk W, Humphrey PPH. 5-hydroxytryptamine contracts human coronary arteries predominantly via 5HT2 receptor activation. Eur J Pharmacol 1989; 161: 91-94. 3. Chester AH, Martin GT, Bodelsson M, et al. 5-hydroxytryptamine receptor profile in healthy and diseased human epicardial coronary arteries. Cardiovasc Res 1990; 24: 932-37. 4. Healy B. Endothelial cell dysfunction: an emerging endocrinopathy linked to coronary disease. J Am Coll Cardiol 1990; 16: 357-58. 5. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111-15.
SIR,-We are aware of the case that Dr Ottervanger and colleagues report which was published in Dutch (Ned Tijschr Geneesk, 1993; 137: 141). We have reported this case to regulatory authorities worldwide with Ottervanger and colleagues’ evaluation of the event as being probably related to the use of sumatriptan. Although chest pain has been reported in association with coronary vasospasm after sumatriptan in four cases, this report suggesting myocardial infarction represents a very rare event, in view of an estimated population of over 6 million migraine attacks treated. Sumatriptan is contraindicated in patients with ischaemic heart disease, prinzmetal angina, uncontrolled hypertension, coronary vasospasm, or previous myocardial infarction, or with concomitant use of ergotamine. The rare, but possible, occurrence of coronary vasospasm or myocardial infarction is made clear in our international prescribing information, including the USA and Germany, where licences have most recently been granted. Glaxo takes very seriously the need to collect, evaluate, and report all available details of significant adverse events with all new drugs. Close scrutiny of the evolving safety profile of sumatriptan is important, and relies upon good cooperation with the prescribing and reporting physician. It is in the interests of the prescriber, the patient, and the company that an accurate view of the safety profile of the drug should be obtained, to ensure appropriate use in clinical practice. Department of Cardiovascular and Metabolic Medicine, International Medical Affairs, Glaxo Group Research Limited, Uxbridge, Middlesex UB11 1 BT, UK
D. K. LLOYD V. SIMMONS
Limitation of pulse oximetry SIR,-Pulse oximetry has been recommended as essential during anaesthesial-3 and postoperative recovery, but there are some limitations.4-ó We describe three postoperative cases in which pulse oximetry was being used to monitor ventilation. Doctors and nurses failed to recognise that normal peripheral oxygen saturation (Sp02) can occur in the presence of severe hypoventilation when supplemental oxygen is administered, which may result in severe hypercarbia with clinical consequences. The first case was a 71-year-old woman who was receiving oxygen at 4
L/min
via
a
Hudson mask in the recovery ward
post-laparotomy. Sp02 was 96% and the patient was pink, but on closer inspection she had upper airway obstruction and was deeply unconscious. After endotracheal intubation, without additional anaesthesia, mechanical ventilation was started. Arterial blood gases taken soon after intubation, on 100% oxygen, showed p02 56 kPa
andpC016kPa. The second case was a 53-year-old woman who had undergone cervical laminectomy for excision of suboccipital meningioma. On the ward, she had difficulty breathing and limb weakness. Oxygen was being administered via a Hudson mask and upper
1093
Sp02 was 95-97%. Blood gas measurements showed a p02 12 kPa a pC02 15 kPa. Endotracheal intubation and mechanical
and
ventilation were performed, and the patient then required tracheostomy. The third case was a 69-year-old man in the anaesthetic recovery after anterior cervical spinal fusion to relieve spinal cord compression. He was receiving oxygen via a Hudson mask, with Sp02 96%. The nurses were concerned when he became sleepy and called for medical assistance. The patient was found to be deeply unconscious, with no gag reflex and little ventilatory effort. Endotracheal intubation was done under general anaesthesia and mechanical ventilation was started. Naloxone administration roused the patient, but he was quadriplegic; he was electively sedated and ventilated. Blood gas measurements were not done until the patient was settled in the intensive care unit but there was clinical evidence of hypoventilation before intubation. Power had returned to normal after 12 h of mechanical ventilation. Nunn’ showed that only small increments in inspired oxygen concentration are required to correct hypoxaemia resulting from hypoventilation, by contrast with that resulting from ventilationperfusion mismatch. With the alveolar minute ventilation reduced to 1 L/min, alveolar pC02 may rise to about 20 kPa, while the administration of 40% oxygen can return alveolar p02 to normal. As a result, no conclusion should be made from Sp02 values about the adequacy of ventilation during supplemental oxygen administration. Staff need to understand that pulse oximetry can be used as an assessment of oxygenation and circulation but not as an alternative to clinical observation of ventilation or blood gas analysis. Department of Anaesthetics, R. E. JOHN Royal Hallamshire Hospital, Sheffield S10 2RX, UK J. E. PEACOCK area
1. Eichhom JH, Cooper JB, Cullen DJ, Maier WR, Philip JH, Seeman RG. Standards for patient monitoring during anaesthesia at Harvard Medical School. JAMA 1986; 256: 1017-20. 2. Sykes MK. Essential monitoring. Br J Anaesth 1987; 59: 901-12. 3. Aorab JSM. Who needs pulse oximetry? BMJ 1988; 296: 658-59. 4. Tremper KK, Barker SJ. Pulse oximetry. Anesthesiology 1989; 70: 98-108. 5. Kidd JF, Vickers MD. Pulse oximeters: essential monitors with limitations. Br J Anaesth 1989; 62: 355-57. 6. Editorial. The trust in pulse oximeters. Lancet 1990; 335: 1130-31. 7. Nunn JF. Applied respiratory physiology. 3rd ed. London: Butterworth, 1987: 389.
Trans fatty acids and
dieting
SIR,-Professor Willett and colleagues (March 6, p 581) show that there is a very good correlation between consumption of the trans fatty acids produced by partial hydrogenation of polyunsaturated vegetable oils and the occurrence of coronary heart disease (CHD). Scientists in essential fatty acid (EFA) research have long been aware of the negative effects of trans fatty acids on EFA metabolism,l,2 and more recently attention has been drawn to deleterious effects in adults3 and in infants.4 Warnings about health hazards of trans fatty acids have hitherto gone unheeded. That situation may now change, and the public should become aware that the partially hydrogenated domestic oils are, in fact, greater health hazards than dairy products and natural saturated fats. Trans fatty acids disturb the balance between synthesis of eicosanoids of the PGl’ PG2, and PG3 families by inhibiting the enzyme delta-6-desaturase, which is responsible for the initial further desaturation of the parent fatty acids of both omega-6 and omega-3 families, linoleic acid (LA), and ct-linolenic acid (ALA). Thus availability of the immediate precursors for eicosanoids of the PG1 and PG3 families, dihomo-gamma-linolenic acid (DGLA), and eicosapentanoic acid (EPA), respectively, is reduced. Where vegetable oils are the sole source of EFAs, the availability of arachidonic acid (AA), precursor for eicosanoids of the PGfamily, would also be reduced, but since the conventional human diet contains substantial amounts of meat, a considerable proportion of the AA used for prostaglandin synthesis is dietary and not endogenous in origin. It is also noteworthy that the presence of stearidonic acid (an omega-3 EFA from the action of delta-6desaturase on ALA) in the substrate pool competitively inhibits delta-5-desaturase, the enzyme responsible for converting DGLA to AA, and this is believed to be part of the regulatory mechanism for ensuring balance in prostaglandin synthesis.
When so-called normal food intake includes dietary sources of both trans fatty acids and AA, prostaglandin synthesis is not only quantitatively diminished, but also distorted into an unnatural equilibrium, since eicosanoids of the PG2 family will continue to be formed, but producton of the eicosanoids from the other families is reduced. Theoretically, this reduction can have considerable consequences for homoeostasis. For example, the production of thromboxane A2 could continue as normal, but in the absence of counterparts from the PG1 and PG3 families, the resultant imbalance could increase the risk of thrombosis. The practical verification of this prediction has been reported by Lands,s who noted that feeding AA to volunteers in fairly small amounts increased thrombogenic potential such that the study had to be abandoned. Patients on energy-restricted diets, if they have previously been consuming a normal western diet, will have stores of both AA and trans fatty acids in their adipose tissue; thus, when they are obliged to mobilise and eliminate these fat reserves in a weight reduction programme, free trans fatty acids and AA will be released into the circulation. Considerable increases in blood AA concentrations occur on low calorie diets,6,7 and patients on such diets may have increased EFA requirements.8 Conversion of the primary EFAs into the immediate precursors of the eicosanoids is therefore probably reduced in such patients. Recent findings9 indicate that the gall bladder contracts significantly less frequently in the dieting than in the non-dieting patient, and that the bile in patients on low-calorie diets contains increased amounts ofAA, which increases synthesis of the glycoprotein that stimulates cholesterol nucleation;’O and these are both prostaglandin-dependent factors in gallstone formation. Thus whether or not the dieting patient continues to consume foods containing AA and trans fatty acids, they remain exposed to the risk. In practice, most commercial diet programmes promote the use of light margarines and lean red meat, which aggravates the situation, and some diet programmes condone use of partially hydrogenated domestic oils, condemning use of other, more natural, alternatives. Banatrix International, Lachine, Quebec, Canada H8T 3J9
DENNIS
JONES
Fats and Oils in Human Nutrition; report of an expert consultation. Rome: Food and Agriculture Organization of the United Nations, 1980. 2. Hill EG, Johnson SB, Lawson LD, Mahfouz MM, Holman RT. Perturbation of the metabolism of essential fatty acids by dietary partially hydrogenated vegetable oil. Proc Natl Acad Sci 1982; 79: 953-57. 3. Mensink RP, Katan MB. Effect of dietary trans fatty acids on high density lipoprotein cholesterol levels in healthy subjects. N Engl J Med 1990; 323: 439-45. 4. Koletzko B. Trans fatty acids may impair biosynthesis of long-chain polyunsaturates and growth in man. Acta Paediatr Int J Paediatr 1992; 81: 302-06. 5. Lands WEM. Renewed questions about essential fatty acids. Nutr Rev 1986; 44: 189-95. 6. Rossner S, Walldius G, Bjorvell H. Fatty acid composition in serum lipids and adipose tissue in severe obesity before and after six weeks of weight loss. Int J Obesity 1989; 13: 603-12. 7. Phinney SD, Davis PG, Johnson SB, Holman RT. Obesity and weight loss alter serum polyunsaturated lipids in humans. Am J Clin Nutr 1991; 53: 831-38. 8. Jones D. Neglected nutrients in dietary weight reduction programmes: the essential fatty acids! The Bariatrician Am J Bar Med 1990 (fall); 11-15. 9. Marzio L, Capone F, Neri M, Mezzetti A, De Angelis K, Cuccurullo F. Gallbladder kinetics in obese patients. Effect ofa regular meal and low-calorie meal. Dig Dis Sci 1988; 33: 4-9. 10. Marks JW, Bonorris GG, Albers G, Schoenfield LJ. The sequence of biliary events preceding the formation of gallstones in humans. Gastroenterology 1992; 103: 566-67.
1. FAO/WHO, Dietary
SiR,—There seem to be three possible explanations for Professor Willet and colleagues findings. First, trans fatty acids, as previously shown, result in an increase in total or low-density-lipoprotein cholesterol, or possibly, a small decrease in high-densitylipoprotein (HDL) cholesterol similar to saturated fatty acids;’ second, they have an independent effect on the risk of cardiovascular disease; and third, trans fatty acid intake is a marker for other nutrients or behavioural characteristics that are associated with the risk of coronary heart disease. The Nurses Study provides no independent measurements of blood lipoprotein concentrations, blood pressure, or other risk factors. Thus, the relation between the trans fatty acids and risk factors related to cardiovascular disease could not be measured.
subcutaneous sumatriptan. Twelve hours later, she developed a right hemiparesis (power 3 out of 5). Her erythrocyte sedimentation rate, autoantibody screen, immunoglobulins, and lipids were normal. A brain CT scan with intravenous contrast was normal. One week later, she completely regained her power. Sumatriptan binds to a particular subpopulation of 5hydroxytryptamine (5-HTi) receptors in pial and dural vessels causing vasoconstriction.2 It is believed that sumatriptan acts mainly on extracerebral vascular sites,3although experimental studies of possible binding sites in intracerebral vessels and neurons have yet to be done.4 The elimination serum half-life of sumatriptan is two hours. It might therefore be argued that the intervals between drug administration and cerebral infarction of one week in the first case and twelve hours in the second exonerate sumatriptan. However, no other risk factor for vascular disease was identified in our patients. Furthermore, the possibility of sumatriptan binding to cerebral vascular receptors after frequently repeated doses has yet to be explored. In addition, the hemiparesis in the second case was on the opposite cortical side from her migraine-associated hypoaesthesia. We suggest that caution should be exercised with the repeated prescription of sumatriptan and that further studies are needed on specific binding sites of sumatriptan in intracerebral vessels. Gastrointestinal Unit, Western General Hospital, Edinburgh EH4 2XU, UK
W. LUMAN
Department of Medicine, St Johns Hospital, Livingston
R. S. GRAY
McCarthy BG, Peroutka SJ. Comparative neuropharmacology of dihydroergotamine and sumatriptan Headache 1989; 29: 420-22. 2. Pearce JMS. Sumatriptan in migraine. BMJ 1991; 303: 1491. 3. Raskin N. Serotonin receptors and headache. N Engl J Med 1991; 325: 353-54. 4. Willett F, Curzen N, Adams J, Armitage M. Coronary vasospasm induced by subcutaneous sumatriptan. BMJ 1992; 304: 1415. 1.
SiR,—There is an anomaly between case reports of myocardial ischaemia and infarction (ref 1 and Dr Ottervanger and colleagues) after the administration of sumatriptan to patients with no history of coronary artery disease, and the in-vitro findings that the drug is only a weak constrictor of healthy human coronary vessels.2,3 We propose that this anomaly may be explained by an interaction between sumatriptan and nitric oxide (NO) from the endothelium, and that coronary vasospasm after sumatriptan may be caused by occult endothelial dysfunction. The role of endothelial dysfunction in coronary artery disease is well recognised.4 Moreover, recent reports have described endothelial dysfunction in groups at increased risk of coronary artery disease, such as smokers and children with familial hypercholesterolaemia.5 It has also been shown that diseased coronary vessels are less sensitive to stimuli such as potassium and a-methyl derivative of 5-hydroxytryptamine (5-HT), a selective 5-HT2 receptor agonist, whereas the response to sumatriptan, a 5-HTId receptor agonist, is preserved and, indeed, enhanced near atheromatous lesions. 5-HT does not relax pre-contracted human coronary vessels that exhibit endothelium-dependent relaxation to substance P.3 The authors of this study conclude that no interaction between 5-HT and the endothelium in the human coronary vessel occurred. However, these data do not exclude a modulatory role for NO in the contractile response of the vessel to 5-HT or selective agonists, because basal release of NO can inhibit the response of vessels to agonists without the agonist itself stimulating endothelium-dependent relaxation. We have looked at the effect of inhibiting the basal release of NO with the NO synthase inhibitor N-nitro-L-arginine methylester (L-NAME) on the response of the isolated human pulmonary artery to sumatriptan. We found that L-NAME increased the sensitivity of the artery to sumatriptan (figure) although sumatriptan did not relax the vessel pre-contracted with the stable thromboxane mimetic U46619. Endogenous NO production in the healthy coronary artery may inhibit the vessel’s response to sumatriptan and explain the increased sensitivity of the diseased coronary vessel to the drug.3 The occult loss of endothelial function seen in smokers5 would,
therefore, potentiate constriction of coronary vessels induced by sumatriptan, which might explain the isolated cases of myocardial ischaemia described. This suggests that exogenous nitrate, such as glyceryl trinitrate, might be particularly effective in the treatment of these incidents. It might also help to identify subgroups such as
might be at risk of myocardial ischaemia after sumatriptan. The role of endothelium in modulating the response to 5-HT receptor agonists in healthy and diseased coronary vessels smokers who
needs
to
be clarified. M. R. MACLEAN G. C. S. SMITH A. G. B. TEMPLETON
Institute of Physiology, University of Glasgow,
Glasgow G12 8QQ,
UK
1. Stricker BHC. Coronary vasospasm and sumatriptan BMJ 1992; 305: 118. 2. Connor HE, Feniuk W, Humphrey PPH. 5-hydroxytryptamine contracts human coronary arteries predominantly via 5HT2 receptor activation. Eur J Pharmacol 1989; 161: 91-94. 3. Chester AH, Martin GT, Bodelsson M, et al. 5-hydroxytryptamine receptor profile in healthy and diseased human epicardial coronary arteries. Cardiovasc Res 1990; 24: 932-37. 4. Healy B. Endothelial cell dysfunction: an emerging endocrinopathy linked to coronary disease. J Am Coll Cardiol 1990; 16: 357-58. 5. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111-15.
SIR,-We are aware of the case that Dr Ottervanger and colleagues report which was published in Dutch (Ned Tijschr Geneesk, 1993; 137: 141). We have reported this case to regulatory authorities worldwide with Ottervanger and colleagues’ evaluation of the event as being probably related to the use of sumatriptan. Although chest pain has been reported in association with coronary vasospasm after sumatriptan in four cases, this report suggesting myocardial infarction represents a very rare event, in view of an estimated population of over 6 million migraine attacks treated. Sumatriptan is contraindicated in patients with ischaemic heart disease, prinzmetal angina, uncontrolled hypertension, coronary vasospasm, or previous myocardial infarction, or with concomitant use of ergotamine. The rare, but possible, occurrence of coronary vasospasm or myocardial infarction is made clear in our international prescribing information, including the USA and Germany, where licences have most recently been granted. Glaxo takes very seriously the need to collect, evaluate, and report all available details of significant adverse events with all new drugs. Close scrutiny of the evolving safety profile of sumatriptan is important, and relies upon good cooperation with the prescribing and reporting physician. It is in the interests of the prescriber, the patient, and the company that an accurate view of the safety profile of the drug should be obtained, to ensure appropriate use in clinical practice. Department of Cardiovascular and Metabolic Medicine, International Medical Affairs, Glaxo Group Research Limited, Uxbridge, Middlesex UB11 1 BT, UK
D. K. LLOYD V. SIMMONS
Limitation of pulse oximetry SIR,-Pulse oximetry has been recommended as essential during anaesthesial-3 and postoperative recovery, but there are some limitations.4-ó We describe three postoperative cases in which pulse oximetry was being used to monitor ventilation. Doctors and nurses failed to recognise that normal peripheral oxygen saturation (Sp02) can occur in the presence of severe hypoventilation when supplemental oxygen is administered, which may result in severe hypercarbia with clinical consequences. The first case was a 71-year-old woman who was receiving oxygen at 4
L/min
via
a
Hudson mask in the recovery ward
post-laparotomy. Sp02 was 96% and the patient was pink, but on closer inspection she had upper airway obstruction and was deeply unconscious. After endotracheal intubation, without additional anaesthesia, mechanical ventilation was started. Arterial blood gases taken soon after intubation, on 100% oxygen, showed p02 56 kPa
andpC016kPa. The second case was a 53-year-old woman who had undergone cervical laminectomy for excision of suboccipital meningioma. On the ward, she had difficulty breathing and limb weakness. Oxygen was being administered via a Hudson mask and upper
1093
Sp02 was 95-97%. Blood gas measurements showed a p02 12 kPa a pC02 15 kPa. Endotracheal intubation and mechanical
and
ventilation were performed, and the patient then required tracheostomy. The third case was a 69-year-old man in the anaesthetic recovery after anterior cervical spinal fusion to relieve spinal cord compression. He was receiving oxygen via a Hudson mask, with Sp02 96%. The nurses were concerned when he became sleepy and called for medical assistance. The patient was found to be deeply unconscious, with no gag reflex and little ventilatory effort. Endotracheal intubation was done under general anaesthesia and mechanical ventilation was started. Naloxone administration roused the patient, but he was quadriplegic; he was electively sedated and ventilated. Blood gas measurements were not done until the patient was settled in the intensive care unit but there was clinical evidence of hypoventilation before intubation. Power had returned to normal after 12 h of mechanical ventilation. Nunn’ showed that only small increments in inspired oxygen concentration are required to correct hypoxaemia resulting from hypoventilation, by contrast with that resulting from ventilationperfusion mismatch. With the alveolar minute ventilation reduced to 1 L/min, alveolar pC02 may rise to about 20 kPa, while the administration of 40% oxygen can return alveolar p02 to normal. As a result, no conclusion should be made from Sp02 values about the adequacy of ventilation during supplemental oxygen administration. Staff need to understand that pulse oximetry can be used as an assessment of oxygenation and circulation but not as an alternative to clinical observation of ventilation or blood gas analysis. Department of Anaesthetics, R. E. JOHN Royal Hallamshire Hospital, Sheffield S10 2RX, UK J. E. PEACOCK area
1. Eichhom JH, Cooper JB, Cullen DJ, Maier WR, Philip JH, Seeman RG. Standards for patient monitoring during anaesthesia at Harvard Medical School. JAMA 1986; 256: 1017-20. 2. Sykes MK. Essential monitoring. Br J Anaesth 1987; 59: 901-12. 3. Aorab JSM. Who needs pulse oximetry? BMJ 1988; 296: 658-59. 4. Tremper KK, Barker SJ. Pulse oximetry. Anesthesiology 1989; 70: 98-108. 5. Kidd JF, Vickers MD. Pulse oximeters: essential monitors with limitations. Br J Anaesth 1989; 62: 355-57. 6. Editorial. The trust in pulse oximeters. Lancet 1990; 335: 1130-31. 7. Nunn JF. Applied respiratory physiology. 3rd ed. London: Butterworth, 1987: 389.
Trans fatty acids and
dieting
SIR,-Professor Willett and colleagues (March 6, p 581) show that there is a very good correlation between consumption of the trans fatty acids produced by partial hydrogenation of polyunsaturated vegetable oils and the occurrence of coronary heart disease (CHD). Scientists in essential fatty acid (EFA) research have long been aware of the negative effects of trans fatty acids on EFA metabolism,l,2 and more recently attention has been drawn to deleterious effects in adults3 and in infants.4 Warnings about health hazards of trans fatty acids have hitherto gone unheeded. That situation may now change, and the public should become aware that the partially hydrogenated domestic oils are, in fact, greater health hazards than dairy products and natural saturated fats. Trans fatty acids disturb the balance between synthesis of eicosanoids of the PGl’ PG2, and PG3 families by inhibiting the enzyme delta-6-desaturase, which is responsible for the initial further desaturation of the parent fatty acids of both omega-6 and omega-3 families, linoleic acid (LA), and ct-linolenic acid (ALA). Thus availability of the immediate precursors for eicosanoids of the PG1 and PG3 families, dihomo-gamma-linolenic acid (DGLA), and eicosapentanoic acid (EPA), respectively, is reduced. Where vegetable oils are the sole source of EFAs, the availability of arachidonic acid (AA), precursor for eicosanoids of the PGfamily, would also be reduced, but since the conventional human diet contains substantial amounts of meat, a considerable proportion of the AA used for prostaglandin synthesis is dietary and not endogenous in origin. It is also noteworthy that the presence of stearidonic acid (an omega-3 EFA from the action of delta-6desaturase on ALA) in the substrate pool competitively inhibits delta-5-desaturase, the enzyme responsible for converting DGLA to AA, and this is believed to be part of the regulatory mechanism for ensuring balance in prostaglandin synthesis.
When so-called normal food intake includes dietary sources of both trans fatty acids and AA, prostaglandin synthesis is not only quantitatively diminished, but also distorted into an unnatural equilibrium, since eicosanoids of the PG2 family will continue to be formed, but producton of the eicosanoids from the other families is reduced. Theoretically, this reduction can have considerable consequences for homoeostasis. For example, the production of thromboxane A2 could continue as normal, but in the absence of counterparts from the PG1 and PG3 families, the resultant imbalance could increase the risk of thrombosis. The practical verification of this prediction has been reported by Lands,s who noted that feeding AA to volunteers in fairly small amounts increased thrombogenic potential such that the study had to be abandoned. Patients on energy-restricted diets, if they have previously been consuming a normal western diet, will have stores of both AA and trans fatty acids in their adipose tissue; thus, when they are obliged to mobilise and eliminate these fat reserves in a weight reduction programme, free trans fatty acids and AA will be released into the circulation. Considerable increases in blood AA concentrations occur on low calorie diets,6,7 and patients on such diets may have increased EFA requirements.8 Conversion of the primary EFAs into the immediate precursors of the eicosanoids is therefore probably reduced in such patients. Recent findings9 indicate that the gall bladder contracts significantly less frequently in the dieting than in the non-dieting patient, and that the bile in patients on low-calorie diets contains increased amounts ofAA, which increases synthesis of the glycoprotein that stimulates cholesterol nucleation;’O and these are both prostaglandin-dependent factors in gallstone formation. Thus whether or not the dieting patient continues to consume foods containing AA and trans fatty acids, they remain exposed to the risk. In practice, most commercial diet programmes promote the use of light margarines and lean red meat, which aggravates the situation, and some diet programmes condone use of partially hydrogenated domestic oils, condemning use of other, more natural, alternatives. Banatrix International, Lachine, Quebec, Canada H8T 3J9
DENNIS
JONES
Fats and Oils in Human Nutrition; report of an expert consultation. Rome: Food and Agriculture Organization of the United Nations, 1980. 2. Hill EG, Johnson SB, Lawson LD, Mahfouz MM, Holman RT. Perturbation of the metabolism of essential fatty acids by dietary partially hydrogenated vegetable oil. Proc Natl Acad Sci 1982; 79: 953-57. 3. Mensink RP, Katan MB. Effect of dietary trans fatty acids on high density lipoprotein cholesterol levels in healthy subjects. N Engl J Med 1990; 323: 439-45. 4. Koletzko B. Trans fatty acids may impair biosynthesis of long-chain polyunsaturates and growth in man. Acta Paediatr Int J Paediatr 1992; 81: 302-06. 5. Lands WEM. Renewed questions about essential fatty acids. Nutr Rev 1986; 44: 189-95. 6. Rossner S, Walldius G, Bjorvell H. Fatty acid composition in serum lipids and adipose tissue in severe obesity before and after six weeks of weight loss. Int J Obesity 1989; 13: 603-12. 7. Phinney SD, Davis PG, Johnson SB, Holman RT. Obesity and weight loss alter serum polyunsaturated lipids in humans. Am J Clin Nutr 1991; 53: 831-38. 8. Jones D. Neglected nutrients in dietary weight reduction programmes: the essential fatty acids! The Bariatrician Am J Bar Med 1990 (fall); 11-15. 9. Marzio L, Capone F, Neri M, Mezzetti A, De Angelis K, Cuccurullo F. Gallbladder kinetics in obese patients. Effect ofa regular meal and low-calorie meal. Dig Dis Sci 1988; 33: 4-9. 10. Marks JW, Bonorris GG, Albers G, Schoenfield LJ. The sequence of biliary events preceding the formation of gallstones in humans. Gastroenterology 1992; 103: 566-67.
1. FAO/WHO, Dietary
SiR,—There seem to be three possible explanations for Professor Willet and colleagues findings. First, trans fatty acids, as previously shown, result in an increase in total or low-density-lipoprotein cholesterol, or possibly, a small decrease in high-densitylipoprotein (HDL) cholesterol similar to saturated fatty acids;’ second, they have an independent effect on the risk of cardiovascular disease; and third, trans fatty acid intake is a marker for other nutrients or behavioural characteristics that are associated with the risk of coronary heart disease. The Nurses Study provides no independent measurements of blood lipoprotein concentrations, blood pressure, or other risk factors. Thus, the relation between the trans fatty acids and risk factors related to cardiovascular disease could not be measured.