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Estimation of cerebral blood flow with near infrared spectroscopy and indocyanine green
ion-exchange chromatography is uncertain and often unstated. The calibrators provided with different kits may not have any fixed relation to a "gold standard". In his review of the US Diabetes Control and Complications Trial, one of the participating physicians highlighted the problem of different assay techniques.3 He is rightly concerned about the "HbA1c mess" and asks for a common gold standard assay. We have been using an ELI SA kit, the protocol for which has been modified by the manufacturer. We have found a small but definite rise in the results obtained with the altered protocol. Normal monthly mean HbAc on about 500 samples rose from 6 57% to 7-32% between August and October, 1993. This is a major difference in terms of clinical management. This rise might not be noticeable in a laboratory analysing small numbers of samples on patients who have infrequent blood tests. With larger numbers and more frequent tests a clear difference is evident. Fluctuations of this type and magnitude will persist until a gold standard is agreed and used by the manufacturers of diagnostic kits. David R Hadden, Geraldine A G Elizabeth Elder
Savage, T R J Lappin,
Diabetic Clinic and Haematology Laboratory, Royal Victoria Hospital, Belfast BT12 6BA, UK
Trivelli LA, Ranney HM, Lai H-T. Hemoglobin components in patients with diabetes mellitus. N Engl J Med 1971; 284: 353-57. 2 Kennedy AL, Lappin TRJ, Lavery TD, Hadden DR, Weaver JA, Montgomery DAD. Relation of high-density lipoprotein cholesterol concentration to type of diabetes and its control. BMJ 1978; ii: 1191-94. 3 Santiago JV. Perspectives in diabetes: lessons from the Diabetes Control and Complications Trial. Diabetes 1993; 42: 1549-54. 1
Estimation of cerebral blood flow with near infrared spectroscopy and indocyanine green SiR-Neurological impairment after open heart surgery1 may to perioperative derangements of cerebral blood flow (CBF). However, clinicians lack a practical method for measuring CBF during cardiopulmonary bypass rapidly and repeatedly. We report the use of near infrared spectroscopy (NIRS) for this purpose. The method is a development of a modification of Fick’s equationthat has been validated by studies in adults3 and infants4,s Indocyanine green (IG) absorbs near-infrared light and is strongly protein-bound in blood. We measured absorption coefficients at near-infrared wavelengths for albumin-bound IG that allow quantitation of changes in IG concentration in vivo by NIRS. 27 CBF measurements were made in six children aged 18 days to 12 years (median 27 months) undergoing hypothermic cardiopulmonary bypass (body temperature 18-36°C, median 25) during surgery for congenital heart disease. 1-8 (median 4-5) measurements were made in each child every 2-28 (10) min. IG (01mg/kg) was injected into the cardiopulmonary bypass circuit just proximal to its insertion into the aorta. The arterial concentration of tracer (Pa) was quantified optically (Model IVH4, Pulsion Medizintechnik). Optodes placed on
be due
the head at least 35 cm apart allowed the change in cerebral IG concentration to be measured by NIRS (NIRO 500, Hammamatsu Photonics KK), and thus the accumulation of tracer in the brain (Q) was recorded. Data were rapidly collected after the appearance of dye in the optical field (figure), and because measurements were taken over a period less than the cerebral vascular transit time (mean transit time was greater than 10 s), the dye in the cerebral veins was assumed to be zero. CBF was calculated from the Fick equation modified for zero venous concentration,2 where k is a constant reflecting cerebral
Time
(seconds)
Figure: Change In arterial and cerebral IG after the cardiopulmonary bypass circuit.
Injection Into
CBF calculated by relating increase in cerebral tG (Q) to time integral of arterial concentration over first 5 s after appearance of dye in each optical field.
(oft(Pa)dt)
tissue density and the molecular weight of IG: thus CBF= k Mean CBF ranged from 6 to 19 (median 12) mL/100 g per min, and the SD of repeated measures in individuals ranged from 1 to 4 (1). Measurement took about 10 s, and could be repeated within 2 min. The technique was simple, rapid, precise, and avoided assumptions required by previous methods.2 Very small quantities of IG were required, so that some 50 estimations of CBF could be made before the maximum permitted dose is reached. Advances in the understanding of light propagation through tissue would improve accuracy (especially in studies of adult patients) and would make regional flow estimations possible. Cerebral blood volume, and blood flow to other organs, may be measured simultaneously. The technique should allow investigation of potential neuroprotective strategies and improve decision-making during surgery.
(Q(t)/(JBPa)dt).
Supported by the British Heart Foundation. CC is an MRC Training Fellow. We thank M Cope and C Elwell for valuable discussions, and Hammamatsu Photonics and Pulsion Medizintechnik. I Roberts, P Fallon, FJ Kirkham, A R Maynard, M Elliot, A D Edwards
Lloyd-Thomas, C Cooper,
Neurosciences Unit, Institute of Child Health; Departments of Cardiothoracic Surgery and Anaesthetics, Hospital for Sick Children; Department of Paediatrics, University College London Medical School; and Department of Paediatrics and Neonatal Medicine, Royal Postgraduate Medical School, London, UK
1
2
3
4
5
Govier A. Central nervous system complications after cardiopulmonary bypass. In: Tinker JH, ed. Cardiopulmonary bypass: current concepts and controversies. Philadelphia: W B Saunders Co, 1989. Edwards AD, Wyatt JS, Richardson C, et al. Cotside measurement of cerebral blood flow in ill newborn infants by near infrared spectroscopy. Lancet 1988; 2: 770-71. Edwards AD, Richardson C, Elwell CE, et al. Measurement of hemoglobin flow and blood flow by near infrared spectroscopy. J Appl
Physiol (in press). Skov L, Pryds O, Greisen G. Estimating cerebral flow in newborn infants: comparison of near infrared spectroscopy and 133xenon clearance. Pediatr Res 1991; 30: 570-73. Bucher HU, Edwards AD, Lipp AE, Duc G. Comparison between near infrared spectroscopy and xenon clearance for estimation of cerebral blood flow in critically ill preterm infants. Pediatr Res 1993; 33: 56-60.
1425
Savage, T R J Lappin,
Diabetic Clinic and Haematology Laboratory, Royal Victoria Hospital, Belfast BT12 6BA, UK
Trivelli LA, Ranney HM, Lai H-T. Hemoglobin components in patients with diabetes mellitus. N Engl J Med 1971; 284: 353-57. 2 Kennedy AL, Lappin TRJ, Lavery TD, Hadden DR, Weaver JA, Montgomery DAD. Relation of high-density lipoprotein cholesterol concentration to type of diabetes and its control. BMJ 1978; ii: 1191-94. 3 Santiago JV. Perspectives in diabetes: lessons from the Diabetes Control and Complications Trial. Diabetes 1993; 42: 1549-54. 1
Estimation of cerebral blood flow with near infrared spectroscopy and indocyanine green SiR-Neurological impairment after open heart surgery1 may to perioperative derangements of cerebral blood flow (CBF). However, clinicians lack a practical method for measuring CBF during cardiopulmonary bypass rapidly and repeatedly. We report the use of near infrared spectroscopy (NIRS) for this purpose. The method is a development of a modification of Fick’s equationthat has been validated by studies in adults3 and infants4,s Indocyanine green (IG) absorbs near-infrared light and is strongly protein-bound in blood. We measured absorption coefficients at near-infrared wavelengths for albumin-bound IG that allow quantitation of changes in IG concentration in vivo by NIRS. 27 CBF measurements were made in six children aged 18 days to 12 years (median 27 months) undergoing hypothermic cardiopulmonary bypass (body temperature 18-36°C, median 25) during surgery for congenital heart disease. 1-8 (median 4-5) measurements were made in each child every 2-28 (10) min. IG (01mg/kg) was injected into the cardiopulmonary bypass circuit just proximal to its insertion into the aorta. The arterial concentration of tracer (Pa) was quantified optically (Model IVH4, Pulsion Medizintechnik). Optodes placed on
be due
the head at least 35 cm apart allowed the change in cerebral IG concentration to be measured by NIRS (NIRO 500, Hammamatsu Photonics KK), and thus the accumulation of tracer in the brain (Q) was recorded. Data were rapidly collected after the appearance of dye in the optical field (figure), and because measurements were taken over a period less than the cerebral vascular transit time (mean transit time was greater than 10 s), the dye in the cerebral veins was assumed to be zero. CBF was calculated from the Fick equation modified for zero venous concentration,2 where k is a constant reflecting cerebral
Time
(seconds)
Figure: Change In arterial and cerebral IG after the cardiopulmonary bypass circuit.
Injection Into
CBF calculated by relating increase in cerebral tG (Q) to time integral of arterial concentration over first 5 s after appearance of dye in each optical field.
(oft(Pa)dt)
tissue density and the molecular weight of IG: thus CBF= k Mean CBF ranged from 6 to 19 (median 12) mL/100 g per min, and the SD of repeated measures in individuals ranged from 1 to 4 (1). Measurement took about 10 s, and could be repeated within 2 min. The technique was simple, rapid, precise, and avoided assumptions required by previous methods.2 Very small quantities of IG were required, so that some 50 estimations of CBF could be made before the maximum permitted dose is reached. Advances in the understanding of light propagation through tissue would improve accuracy (especially in studies of adult patients) and would make regional flow estimations possible. Cerebral blood volume, and blood flow to other organs, may be measured simultaneously. The technique should allow investigation of potential neuroprotective strategies and improve decision-making during surgery.
(Q(t)/(JBPa)dt).
Supported by the British Heart Foundation. CC is an MRC Training Fellow. We thank M Cope and C Elwell for valuable discussions, and Hammamatsu Photonics and Pulsion Medizintechnik. I Roberts, P Fallon, FJ Kirkham, A R Maynard, M Elliot, A D Edwards
Lloyd-Thomas, C Cooper,
Neurosciences Unit, Institute of Child Health; Departments of Cardiothoracic Surgery and Anaesthetics, Hospital for Sick Children; Department of Paediatrics, University College London Medical School; and Department of Paediatrics and Neonatal Medicine, Royal Postgraduate Medical School, London, UK
1
2
3
4
5
Govier A. Central nervous system complications after cardiopulmonary bypass. In: Tinker JH, ed. Cardiopulmonary bypass: current concepts and controversies. Philadelphia: W B Saunders Co, 1989. Edwards AD, Wyatt JS, Richardson C, et al. Cotside measurement of cerebral blood flow in ill newborn infants by near infrared spectroscopy. Lancet 1988; 2: 770-71. Edwards AD, Richardson C, Elwell CE, et al. Measurement of hemoglobin flow and blood flow by near infrared spectroscopy. J Appl
Physiol (in press). Skov L, Pryds O, Greisen G. Estimating cerebral flow in newborn infants: comparison of near infrared spectroscopy and 133xenon clearance. Pediatr Res 1991; 30: 570-73. Bucher HU, Edwards AD, Lipp AE, Duc G. Comparison between near infrared spectroscopy and xenon clearance for estimation of cerebral blood flow in critically ill preterm infants. Pediatr Res 1993; 33: 56-60.
1425