A, Roosnek E, Gregory T, et al. T cells can present antigens such as HIV gp120 targeted to their own surface molecules.

7. Lanzavecctioa

Nature 1988; 334: 530-32. 8.

Smith DH, Byrn RA, Marsters SA, et al. Blocking of HIV-1 infectivity by a soluble, secreted form of the CD4 antigen. Science 1987; 228:

1704-07. 9. Fisher RA, Bertonis JM, Meier W, et al. HIV infection is blocked in vitro by recombinant soluble CD4. Nature 1988; 331: 76-78. 10. Hussey RE, Richardson NE, Kowalski M, et al. A soluble CD4 selectively inhibits HIV replication and syncytium formation. Nature 1988; 331: 78-81 11. Deen KC, McDougal JS, Macker R, et al. A soluble form of CD4 (T4) protein inhibits AIDS virus infection. Nature 1988; 331: 82-84. 12. Trannecker A, Luke W, Karjalian K. Soluble CD4 molecules neutralise human immunodeficiency virus type 1. Nature 1988; 331: 76-78. 13. Manca F, Habeshaw JA, Dalgleish AG. HIV envelope glycoprotein, antigen-specific T-cell responses, and soluble CD4. Lancet 1990; 335: 811-15. 14. Watanabe M, Reimann KA, De Long PA, et al. Effects of recombinant CD4 in rhesus monkeys infected with simian immunodeficiency virus of macaques. Nature 1989; 237: 267-70. 15. Schosley RT, Merigan TC, Gant P, et al. Recombinant soluble CD4 therapy in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A phase I-II escalating dosage trial. Ann Intern Med 1990; 112: 247-53. 16. Kalm JO, Allan JD, Hodges TL, et al. The safety and pharmacokinetics of recombinant soluble CD4 (rCD4) in subjects with the acquired

immunodeficiency syndrome (AIDS) and AIDS-related complex. A phase 1 study. Ann Intern Med 1990; 112: 254-61. 17. Lamarre D, Capon DJ, Karp DR, et at. Class II MHC molecules and the HIV gp120 envelope protein interact with functionally distinct regions of the CD4 molecule. EMBO J 1989; 8: 3271-77. 18. Bym RA, Mordenti J, Lucas C, et al. Biological properties of a CD4 immunoadhesin. Nature 1990; 344: 667-70. 19. Dalgleish AG, Thomson BJ, Chanh TC, Malkovsky M, Kennedy RC. Neutralisation of HIV isolates by anti-idiotypic antibodies which mimic the T4 (CD4) epitope: a potential AID S vaccine. Lancet 1987; ii: 1047-50. 20. Johnson VA, Barlow MA, Chanh TC, et al. Synergistic inhibition of human immunodeficiency virus type 1 (HIV-1) replication in vitro by recombinant soluble CD4 and 3’ azido-3’ deoxythymidine. J Infect Dis 1989; 159: 837-44.

THE TRUST IN PULSE OXIMETERS Pulse oximeters give a non-invasive continuous readout of the oxygen saturation of haemoglobin in arterial blood. They are widely accepted as sensitive and accurate instruments that produce clinically useful data and are used extensively in anaesthetic practice. Are we becoming too complacent about the accuracy of such monitors? These instruments rely on spectrophotometric analysis of light transmitted through tissues to measure haemoglobin oxygen saturations. A microprocessor is used to isolate the pulsatile component of the light signal, which is assumed to be solely of arterial origin. Two specific wavelengths of light suited to the detection of haemoglobin and oxyhaemoglobin are used to generate the sensor output. Haemoglobin saturation values are calculated by use of an inbuilt algorithm derived from human experimental data. Current models are unable to distinguish between chromophores other than haemoglobin and oxyhaemoglobin, so in practice all pulsatile signals are attributed to these two

compounds. Since the introduction of pulse oximetry there have been several clinical reports of erroneous data generation. Oximeters process complex data from highly amplified signals and are therefore subject to interference from the hostile electromagnetic environment in which they are used. Sensor movement,l infrared2 and theatre lighting,3 and surgical diathermy may produce such interference, which is usually transient. However, a permanent instrument

readout error following diathermy was lately reported4 The assumptions that underlie the calculation of saturation may give rise to difficulties. Thus it is assumed that the pulsatile component of the sensor output indicates only events in the arterial circulation, yet venous pulsationl or anything that causes slight rhythmical changes in optical conduction can give spurious readings. Use of oximeters with a waveform display may allow the operator to reject artifactual readings obtained from non-arterial sources. The assumption that all absorption signals at the two wavelengths used by the instrument arise from haemoglobin or oxyhaemoglobin is potentially a more serious source of error since any other substance in the arterial blood that absorbs light at the detection wavelengths will be reported as being one of these two compounds. Substances of this type include carboxyhaemoglobin,s5 methaemoglobin,6 and certain dyes such as methylene blue.7 Exclusive reliance on pulse oximeter readings in patients with raised blood concentrations of these interfering chromophores may be dangerous and therefore confirmatory investigations such as co-oximetry should be used if there is uncertainty. Skin dyes,8 dried blood,9 and nail polishlO have also affected the accuracy of readings, despite the fact that the absorbance they produce would be expected to be non-pulsatile. Pulse oximeters are widely thought to provide a measurement of oxygen saturation throughout the body. This generalisation may be true in the steady state, but under dynamic conditions oximetry gives an accurate assessment of arterial oxygen saturation only at the point of measurement-ie, simultaneous pulse oximeter readings taken from tissues with different perfusion rates show different saturation values after induced changes in arterial oxygen tension. Thus Severinghaus" induced decreases in arterial oxygen tension in normal subjects and found response lags of 50 s and 10 s for saturation readings obtained from pulse oximeter sensors placed on the finger and earlobe, respectively. Any factors that impair blood flow to the tissues onto which the sensor is placed may increase this response lag and further delay detection of arterial hypoxaemia. These effects will be greater in instruments with long averaging times. A computer model of the cardiorespiratory system has been used to assess the importance of time delays on the detection of hypoxic events. 12 Various causes of oxygen supply failure were examined and in most cases pulse oximetry, even with a 60 s delay, gave adequate warning of a fall in brain oxygen tension. However, when arterial oxygen saturation fell most rapidly-ie, during ventilation with a gas mixture containing no oxygen-severe brain hypoxia could occur before a pulse oximeter with finger sensor would alarm. If this computer simulation accurately represents human pathophysiology, over-reliance on finger pulse oximetry may, in this circumstance, result in an unacceptable risk of

hypoxic damage. Pulse oximetry undoubtedly represents an important advance in patient monitoring technology and its use is strongly recommended by the Association of Anaesthetists.13 A survey of insurance claims resulting from over a thousand anaesthetic mishaps concluded that its addition to a monitoring system could have prevented over a third of avoidable incidents.14 Nevertheless, the limitations of the technique suggest that unqualified reliance on the values produced might sometimes be dangerously misleading. Technological advances may overcome some of these limitations; meanwhile, the effect of different



sites on reducing the time desaturation warrants further study.



detection of

1. Taylor MB. Erroneous actuation of the pulse oximeter. Anaesthesia 1987; 42: 1116. 2. Brooks TD, Paulus DA, Winkle WE. Infrarad heat lamps interfere with pulse oximeters. Anesthesiology 1984; 61: 630. 3. Costarino AT, Davies DA, Keon TP. Falsely normal saturation reading with the pulse oximeter. Anesthesiology 1987; 67: 830-31. 4. Broome IJ. A dangerous failure of a pulse oximeter. Anaesthesia 1990; 45: 166. 5. Hodges MR, Preece LP, Downs JB. Clinical experience with pulse oximetry in the presence of elevated carboxyhemoglobin. Anesthesiology 1989; 71: A369. 6. Rieder HU, Frei FJ, Zbinden AM, Thomson DA. Pulse oximetry in methaemoglobinaemia. Anaesthesia 1989; 44: 326-27. 7. Gorman ES, Shnider MR. Effect of methylene blue on the absorbance of solutions of haemoglobin. Br J Anaesth 1988; 60: 439-44. 8. Goucke R. Hazards of henna. Anesth Analg 1989; 69: 416-17. 9. Hopkins PM. An erroneous pulse oximeter reading. Anaesthesia 1989; 44: 868. 10. Cote CJ, Goldstein EA, Fuchsman WH, Hoaglin DC. The effect of nail polish on pulse oximetry. Anesth Analg 1988; 67: 683-86. 11. Severinghaus JW, Naifeh KH. The accuracy of six pulse oximeters to profound hypoxia. Anesthesiology 1987; 67: 551-58. 12. Verhoeff F, Sykes MK. Delayed detection of hypoxic events by pulse oximeters: computer simulations. Anaesthesia 1990; 45: 103-09. 13. Recommendations for standards of monitoring during anaesthesia and recovery. London: Association of Anaesthetists of Great Britain and Ireland, 1988. 14. Dull DL, Tinker JH, Caplan RA, Ward RJ, Cheney FW. ASA closed claims study: can pulse oximetry and capnometry prevent anesthetic mishaps? Anesth Analg 1989; 68: S74.

RADIAL KERATOTOMY Patients with myopic (shortsighted) eyes can achieve clear distance vision reliably and safely with spectacles or contact lenses. Over the past decade radial keratotomy (the most widespread form of refractive surgery) has emerged as another way of correcting low to moderate myopia; the aim of the operation is to provide good unaided distance acuity. The sight-threatening consequences of myopia (risk of retinal detachment and macular degeneration), which are more common in moderate to high myopia, are not affected by refractive surgery. Radial keratotomy was developedl in the USSR and is becoming established in the USA but it is not widely available in the UK. The value of this technique is defined, as with any surgical procedure, by the balance between potential benefits and risks compared with the consequences of conservative treatment. Specifically, its results need to be assessed in relation to the accuracy, predictability, and stability of refractive correction; the proportion of patients who can subsequently do without spectacles; and the frequency and severity of postoperative complications. Deep radial cuts are made into the cornea (sparing an optical clear zone of 3-4 mm), which reduce the steepness of the corneal curvature and therefore the eye’s refractive power. The structure of the (healthy) cornea is irreversibly altered, so the operation cannot be undone if the patient finishes up worse off, and inevitably there are risks of infection and

perforation. The relation between refractive error and visual acuity alters after radial keratotomy, and both components must be assessed to measure success adequately. Four-year results from the PERK study3 show that although the myopic error is reduced in most patients and uncorrected visual acuity generally improves considerably, the

tends to be unpredictable. Uncorrected acuity better than 6/60 was found in 31% of eyes preoperatively and in 98% at 4 years. The percentage of eyes with uncorrected acuity of 6/12 or better (approximately the legal driving standard) increased from 0-25% to 76% at 4 years postoperatively, but 19% of eyes lost at least one line of best-corrected acuity. Between 16% and 40% of all eyes became hypermetropic by more than 05 D, indicating that improved distance acuity required accommodative effort in some cases; these patients will become presbyopic early and therefore require glasses once again, this time for reading, which they might have avoided without surgery. Astigmatism increased (36%) more often than it decreased (16%), and 36% of patients still wear a spectacle or contact lens before one or both eyes. "Starburst" glare (most troublesome when the central optical clear zone is small) is especially disabling in conditions such as night driving, which some patients have to discontinue after radial


keratotomy. Although the initial postoperative instability of refraction and acuity appears to settle in most patients at about 3-6 months, a proportion of eyes show a persistent reduction in myopia (or increase in hypermetropia): in 27% refraction changed by 1 D or more between 6 months and 4 years after surgery. Diurnal fluctuations in refraction also occur in some eyes. This fluctuation is greatest at about 2 weeks postoperatively (up to 4 D change from morning to evening), reducing to 1-5-2 D at 6 months.4 37% had diurnal variation of 05 D or more at 35 years,s associated with diurnal variation in uncorrected acuity of 2 or more Snellen lines in 21%. It was not possible to identify the factors responsible for the unpredictability and instability of postoperative refraction, except to confirm earlier indications that those whose initial myopia was lower generally do better. The reported complications of refractive corneal surgery occur early in the postoperative course, and include perforation, endophthalmitis," keratitis,7,8 persistent corneal epitheliopathy,9 ptosis,l° and cystoid macular oedema." Experience of long-term complications or tolerance of later surgery (eg, for cataract or glaucoma) is not yet available. Radial keratotomy is an irreversible surgical procedure carried out on the healthy cornea of a healthy eye to avoid the need to wear glasses. This aim was achieved in the PERK study in 64% of patients, while 36% had to continue to wear optical correction. At 1 year less than half (48%) the patients who had undergone keratotomy were "very satisfied" with the result, 42% were "moderately satisfied", and 10% were dissatisfied.l2 The "desire to see unaided may transcend reason",13 and patients contemplating refractive surgery must be fully informed of the risks of ocular and visual complications, as well as of the real possibility that they may still need glasses after surgery. Those with a compelling need for good unaided distance acuity, who are genuinely intolerant of contact lenses and are prepared to risk surgical and refractive complications, may entertain the procedure. In most low to moderate myopes, for whom the desire to do without glasses is largely a question of convenience or cosmesis, it would seem safer to keep them or to persevere with contact lenses rather than to choose a risky operation that offers only small gains. 1.

Fyodorov SN, Durnev VV. Operation of dosaged dissection of the corneal circular ligament in cases of myopia of mild degree. Ann Ophthalmol 1979; 11: 1885-90. 2. Santos VR, Waring GO, Lynn MJ, et al. Relationship between refractive

The trust in pulse oximeters.

1130 A, Roosnek E, Gregory T, et al. T cells can present antigens such as HIV gp120 targeted to their own surface molecules. 7. Lanzavecctioa Natur...
344KB Sizes 0 Downloads 0 Views