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Oxygen delivery and consumption in critically ill pregnant patients: Association with ophthalmic artery diastolic velocity
Belfort and Saade
Volume 171, Number I Am J Obstet Gynecol
6, Fihn S, Johnson C, Pinkstaff C, Stamm W. Diaphragm use
and urinary tract infections: analysis of urodynamic and microbiologic factors. J Urol 1986;136:853-6. 7. Suarez G, Baum N, Jacobs J. Use of standard contraceptive diaphragm in management of stress urinary incontinence. Urology 1991;28:119-22. 8. Realini J, Walters M. Vaginal diaphragm rings in the treatment of stress urinary incontinence. J Am Board Fam Pract 1990;3:99-103. 9. Marshall S. Conservative management of stress incontinence. Urology 1991;28:204.
10. Bhatia N, Bergman A, GunningJ. Urodynamic effects of a vaginal pessary in women with stress urinary incontinence. AM J OBSTET GYNECOL 1983; 147: 8 76-84. 11. Bergman A, Bhatia N. Pessary test: simple prognostic test in women with stress urinary incontinence. Urology 1984; 24: 109-12. 12. Bhatia N, Bergman A. Pessary test in women with urinary incontinence. Obstet Gynecol 1985;65:220-6. 13. Schraub S, Sun X, Maingon P, et al. Cervical and vaginal cancer associated with pessary use. Cancer 1992;69: 2505-9.
Oxygen delivery and consumption in critically ill pregnant patients: Association with ophthalmic artery diastolic velocity Michael A. Belfort, MD, and George R. Saade, MD Houston, Texas OBJECTIVES: We aimed to investigate the relation between orbital vessel flow velocity and ~xygen delivery, oxygen consumption, cardiac index, and systemic vascular resistance index in critically ill pregnant patients. STUDY DESIGN: Eighteen pregnant or early postpartum patients requiring invasive monitoring were prospectively studied with Doppler ultrasonography. The blood flow velocity and resistance index from the central retinal and ophthalmic arteries were plotted against the oxygen delivery index, oxygen consumption index, cardiac index, and systemic vascular resistance index. Linear and polynomial regression analysis and receiver-operator characteristic curves were used to examine the data. RESULTS: The ophthalmic artery resistance index correlated with oxygen consumption, oxygen delivery index, and cardiac index. Only the cardiac index was independently related to the the ophthalmic artery resistance index. The ophthalmic artery diastolic velocity correlated with oxygen consumption index, oxygen delivery index, and cardiac index. The ophthalmic artery diastolic velocity correlated independently with mixed venous oxygen content and arteriovenous oxygen content difference. The central retinal artery Doppler index did not correlate with any of the invasively measured parameters. An ophthalmic artery diastolic velocity of > 7.12 cm/sec identified 75% of patients with an oxygen consumption index of < 140 ml/min per square meter and 91 % of patients with an oxygen delivery index of < 600 ml/min per square meter. CONCLUSIONS: These data suggest that the ophthalmic artery flow velocity is correlated with systemic oxygen delivery and consumption. This relationship may have potential research applications in the noninvasive assessment of oxygen delivery index and oxygen consumption index in critically ill pregnant patients. (AM J OBSTET GVNECOL 1994;171:211-7.)
Key words: Ophthalmic artery, Doppler, oxygen consumption, monitoring, noninvasive
From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine. Supported by a Grant-in-Aid from the American Heart Association. Received for publication September 29, 1993; revised November 17, 1993; accepted December 10, 1993. Reprint requests: Michael A. Belfort, MD, Division ofMaternal-Fetal Medicine, Department of Obstetrics and Gynecology, One Baylor Plaza, Houston, TX 77030. Copyright © 1994 by Mosby-Year Book, inc. 0002-9378/94 $3.00 + 0 6/1/53596
Oxygen consumption and delivery are important indicators of respiratory function in criticallly ill patients. " 2 Preeclampsia and adult respiratory distress syndrome (ARDS) are associated with very low levels of both these parameters."' 4 This may be partially explained by the increased pulmonary shunt fraction,5, 6 leftward shift of the oxyhemoglobin dissociation curve,7 and abnormal oxygen extraction ratio 3 frequently noted 211
212
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July 1994 Am J Obstet Gynecol
Table I. Demographic data of 18 patients Patient No. 1 2 3 4 5 6 7 8 9 lO
11 12 13 14 15 16 17 18
25 23 24 25 18 17 20 23 21 18 19 30 24 31 31 31 15 32
0 1 1 0 0 0 0 0 1 0 0 2 1 4 9 4 0 2
Gestational age (wk)
Timing of scan
Diagnosis
37.0 29.6 25.4 36.4 35.8 38.3 34.4 37.6 36.3 24.4 38.3 35.3 36.6 37.2 41.1 31.0 38.3 35.0
Antepartum Mter cesarean section Antepartum Mter cesarean section Antepartum Antepartum Antepartum Mter cesarean section Antepartum Antepartum Antepartum Mter cesarean section Antepartum Mter cesarean section Mter cesarean hysterectomy Antepartum Antepartum Mter cesarean section
Preeclampsia Chorioamnionitis, ARDS Pyelonephritis, sepsis Preeclampsia Preeclampsia Pyelonephritis, sepsis Preeclampsia Preeclampsia Preeclampsia Pyelonephritis, ARDS Aortic stenosis Preeclampsia Preeclampsia Preeclampsia Hemorrhage Preeclampsia Preeclampsia Preeclampsia
in such patients. Many of these patients are known to exhibit a low oxygen consumption and delivery despite having hyperdynamic cardiac function, 8 and the echocardiographic measurement of cardiac output alone is often not sufficient to gauge the severity of the disease state or to monitor the" effects of therapy. This uncertainty may lead to the insertion of a pulmonary artery catheter to determine the respiratory parameters. A noninvasive method of assessing oxygen consumption and delivery may provide a means of screening potential patients for invasive monitoring and may reduce the need for central catheterization. Tissue oxygenation is related to perfusion. The assessment of blood velocity in a vessel may provide useful information about oxygen delivery and consumption in that particular vascular bed. The cerebral circulation is easily accessible through the orbit with color Doppler ultrasonography and both small (central retinal artery)9 and larger (ophthalmic artery)lO resistance vessels may be studied. Therefore we designed a study to examine the usefulness of orbital color flow Doppler ultrasonography in the prediction of oxygen delivery and consumption in critically ill pregnant patients admitted to our intensive care area. Material and methods
The protocol was approved by the Baylor College of Medicine Institutional Review Board. All women gave informed consent. Eighteen pregnant or recently delivered patients who had received a pulmonary artery catheter as part of their management were included in this study. Patients were considered for the study only if they already had the invasive monitoring device in place, and inclusion in this study in no way influenced any of the management decisions. Indications for pulmonary artery catheteriza-
tion included oliguria, hypertension unresponsive to two intravenous bolus doses (10 mg) of hydralazine, pulmonary edema, ARDS, status eclampticus, cardiac valve disease, pyelonephritis complicated by septic shock or ARDS, and intraoperative hemorrhage. All patients with preeclampsia were receiving magnesium sulfate intravenously at a maintenance dosage of 2 gmlhr unless they had oliguria, in which case the dosage was titrated according to the blood magnesium level. None of these patients were being mechanically ventilated during the examination. Women in' active labor were not entered into the study. Of the 18 patients, 11 were scanned before delivery and 7 in the immediate postpartum period. Demographic data from these patients are shown in Table I. Patients with essential hypertension, chronic renal disease, epilepsy, diabetes mellitus, autoimmune disease, and any preexisting condition perceived to have had a long-term effect on the cerebral or the orbital vasculature were excluded. The patients were positioned in a Fowler position with a IS-degree left lateral tilt. The person performing the ultrasonographic examination was unaware of any of the hemodynamic and respiratory parameters previously obtained during the patient'S hospitalization. Specimens of mixed venous blood and peripheral arterial blood were drawn during the Doppler examination, and the hemodynamic parameters (cardiac output and pulmonary wedge capillary pressure) were determined at the completion of the ultrasonographic study to prevent observer bias. Five consecutive 10 ml injections of physiologic saline solution at room temperature were used. The high and low values were discarded, and the mean of the remaining three values were ~ecorded. Pulmonary capillary wedge pressure determinations were made at end expiration. The arterial blood pres-
Belfort and Saade
Volume 171, Number 1 Am J Obstet Gynecol
sure, central venous pressure, and heart rate were recorded continuously by the monitoring equipment (model MIOI2A; Hewlett-Packard, Waltham, Mass.). The respiratory parameters were calculated with the onboard software in the monitoring system. The following formulas were used for calculating the oxygen consumption and delivery data: Vo 2I (mVmin/m2) = avDo 2 * CO * IO/BSA avDo 2(mVdl) = Cao 2 - CV02 Cao2 = (1.34 * HGB * Sao2 /100) + (Pao2 * 0.0031) Cvo 2 = (1.34 * HGB * Svo2/IOO) + (Pv02 * 0.0031) where Vo 2I is oxygen consumption index, avDo 2 is arteriaVvenous oxygen difference, CO is cardiac output, BSA is body surface area, Cao2 is arterial oxygen concentration, Cvo 2 is mixed venous oxygen concentration, HGB is hemoglobin, Sao 2 is percent arterial oxyhemoglobin saturation, Svo 2 is percent venous oxyhemoglobin saturation, Pao 2 is arterial partial pressure of oxygen, and Pv0 2 is venous partial pressure of oxygen. Do 2 I = Cao 2
* CO * 10/BSA
where Do 2I is oxygen delivery index. A Siemens-Quantum 2000 color flow Doppler system (Siemens-Quantum Medical Systems, Issaquah, Wash.) was used for the Doppler studies. A 7.5 MHz lineararray transducer with a 0.2 mm x 0.2 mm sample volume was used to image ea,ch eye. The estimated in situ peak temporal average (SPTA) intensity at a depth of 4.2 cm in the color imaging mode is 7 mW/cm2 for the 7.5 MHz transducer (data provided by Quantum Medical Systems). During color flow Doppler spectrum analysis the SPTA intensity is approximately 71 mW/cm2. In this mode the SPTA intensity is within the safety limits set by the American Institute for Ultrasound in Medicine. 11 Spectrum analysis was limited to approximately 1 minute in each eye, and .the total examination was limited to approximately 5 minutes for each eye. The maximum power setting used was - 10 dB (i.e., 10 dB less than the maximum power setting allowed under Food and Drug Administration restrictions), and power output was continuously displayed on the screen. The technique for orbital Doppler examination has been described previously.12 The software package of the Siemens-Quantum 2000 system provided anglecorrected systolic and diastolic velocity measurements, as well as the Pourcelot resistance index. 13 The velocity and resistance index data from a minimum of three waveforms were averaged at each measurement. Because both the left and right central retinal and ophthalmic arteries were insonated, the average value was calculated and used for analysis purposes. No differences have been noted between measurements from right and left eyes in previous studies.1O Lieb et al. 10
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=0.80 R2 =0.64 P =0.0003 N =18 R
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have also shown this technique to have minimal interobservation variation in a group of normal subjects with paired observations on two separate occasions on the same day. All waveforms and calculated index values were recorded on thermal paper. Data were analyzed with the Epistat Statistical program (Epistat Services, Richardson, Tex.) and the Origin graphics program (Microcal Inc., Northampton, Mass.). Linear and polynomial regression plots were used to examine the data (from allIS patients and from the preeclamptic patients [n = 12] alone), and lines of best fit were derived. Stepwise multiple linear regression analysis was used to identifY the individual contribution of each invasively measured variable to the Doppler parameters. Normal probability plots were used to check for normal distribution of the residuals. The data were further analyzed to control for magnesium sulfate effect. The patients were separated into two groups: those who received magnesium sulfate and those who did not. Receiver-operator characteristic curves were used to evaluate the performance of the ophthalmic artery diastolic velocity in predicting a critically low oxygen delivery index « 600 mVmin per square meter), oxygen consumption index « 140 mVmin per square meter), and cardiac index
214
Belfort and Saade
July 1994 Am J Obstet Gynecol
R =0.81 R2 =0.65 P =0.0002 N = 18
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Fig. 2. Regression plot Qf ophthalmic artery diastolic velocity versus oxygen delivery index. Each point represents a baseline observation from a single patient. Preeclamptic patients are represented by solid squares. Other patients are represented by open triangles.
Fig. 3. Regression plot of ophthalmic artery diastolic velocity versus cardiac index. Each point represents a baseline observation from a single patient. Preeclamptic patients are represented by solid squares. Other patients are represented by open triangles.
«4 Umin per square meter) for pregnancy. A value of
(Fig. 3; Y = 20 - 2.6x; r = -0.53; R2 = 0.28; P = 0.02). This correlation persisted despite separation of the patients into two groups (a group of magnesium sulfate-treated patients and a group who did not receive magnesium sulfate). When data from the preeclamptic patients (n = 12), were separated from the heterogeneous group (n = 18) and examined separately, the relation described for the whole group persisted in the preeclamptic patients. The ophthalmic artery diastolic velocity correlated with oxygen consumption index (r = 0.78; R2 = 0.62; p = 0.0003), oxygen delivery index (r = -0.83; R2 = 0.69; P = 0.0002), and cardiac index (r = - 0.56; R2 = 0.31; P = 0.02). There were no statistically significant correlations noted when the other central retinal or ophthalmic vessel Doppler indexes were plotted against the respiratory or hemodynamic data. With the use of receiver-operator characteristic curves the ophthalmic artery diastolic velocity performed significantly better than chance in predicting critical levels of oxygen delivery index (p < 0.0001), oxygen consumption index (p < 0.001), an.d cardiac index (p < 0.0001). Table II shows the sensitivity and specificity of an ophthalmic artery diastolic velocity of
p < 0.05 was regarded as statistically significant. Results
Eighteen consecutive patients were included in this prospective descriptive study. Table I shows the demographic data of these women. The ophthalmic artery resistance index showed a positive correlation with oxygen consumption index (y = 0.65 - 0.002x; r = 0.50; R2 = 0.26; P = 0.04), oxygen delivery index (y = 0.42 + 0.0004x; r = 0.58; R2 = 0.34; P = 0.01), and cardiac index (y = 0.27 + 0.09x; r = 0.63; P = 0.005). Only the cardiac index was independently related to the ophthalmic artery resistance index when the data were subjected to stepwise multiple linear regression analysis. When the correlation between ophthalmic artery systolic and diastolic blood velocity and the respiratory and hemodynamic parameters were examined, only the diastolic velocity correlated with the invasively measured parameters. The ophthalmic artery diastolic velocity correlated with oxygen consumption index (Fig. 1; Y = 48 - 0.5x; r = 0.80; R2 = 0.64; P = 0.0003), oxygen delivery index (Fig. 2; Y = 32 - 0.06x; r = - 0.81; R2 = 0.65; P = 0.0002), and cardiac index
Belfort and Saade 215
Volume 171, Number 1 Am J Obstet Gynecol
Table II. Sensitivity and specificity of ophthalmic artery diastolic velocity > 7.12 cm/sec in predicting oxygen delivery index <600 mVmin per square meter,.oxygen consumption index < 140 mVmin per square meter, and cardiac index < 4 Vmin per square meter Sensitivity Oxygen delivery index < 600 mVmin/m2 Oxygen consumption index < 140 mVmin/m2 Cardiac index < 4 Umin/m2
> 7.12 cm/sec in predicting a critically low oxygen delivery index « 600 mVmin per square meter), oxygen consumption index « 140 mVmin per square meter), and cardiac index ( < 4 Vmin per square meter) for pregnancy.
Comment This study reports a novel application of orbital Doppler ultrasonography and notes a correlation between ophthalmic artery blood velocity and systemic respiratory parameters in pregnant patients. Preeclampsia-eclampsia and its complications are still a major cause of maternal morbidity and mortality in the United States. Oxygen delivery and consumption are known to be critically low in untreated severe preeclampsia and in ARDS.2. '. 8 These parameters are of great importance in the management of critically ill patients, I. 2 both as prognostic indicators and as a method of monitoring the effects of therapy. However, obtaining these data frequently requires invasive monitoring, and the availability of a noninvasive technique would add significantly to the clinician's methods. The ophthalmic artery diastolic velocity may be useful in the assessment of oxygen delivery and consumption in critically ill pregnant patients. A high ophthalmic artery diastolic velocity indicates low systemic oxygen delivery and consumption, and a low diastolic velocity is compatible with normal respiratory parameters. Although this association has not previously been demonstrated, there are good circumstantial data in the literature to explain our findings. The ophthalmic and retinal arteries are end-arterial branches of the internal carotid artery and are physiologically and morphologically similar to other intracranial cerebral arteries. 14 Similar vasodilatory responses to magnesium sulfate have been demonstrated in the middle cerebral artery and the orbital arteries in patients with preeclampsia.15. 16 . The brain is capable of sustaining cerebral oxygen consumption within normal limits despite extreme reductions in Pa0 2 and at times is able to increase cerebral blood flow by .as much as 600%.17 The exact mechanisms of this are not defined, but cerebral ischemia and low tissue oxygen tension are known to result in an increased production of adenosine (potent vasodi-
91%
75%
100%
I
Specificity 86% 67% 64%
lator) by the perivascular astrocytes. 18 Thus low cerebral oxygen delivery is countered by cerebral vasodilatation and increased cerebral blood flow to maintain oxygen consumption within the normal range. Cerebral oxygen delivery depends on the cardic output and the oxygen content of the arterial blood leaving the heart (i.e., the systemic oxygen delivery), and it is maintained within an error range by autoregulatory mechanisms that respond to the arterial oxgyen content. Changes in arterial oxygen content are accompanied by reciprocal changes in cerebral blood flow to maintain constant cerebral oxygen delivery.19 Data among species with differing cerebral oxygen consumption show that cerebral oxygen delivery is regulated according to cerebral oxgyen consumption.""o End-diastolic velocity has been demonstrated to be the optimal noninvasive measurement for the assessment of brain blood flow because of its independence from myocardial contractility." I In addition, end-diastolic cerebral artery blood flow velocity has been shown to be predominantly affected by blood gas changes, whereas cardiac output appears to be more responsible for alterations in peak systolic flow velocity."2 Van Bel et al."1 showed that the peak systolic velocity (or indices containing peak systolic velocity with mean velocity or end-diastolic velocity) of arteries supplying the brain had a strong correlation with the myocardial contractile state. Similarly, our data suggest that the relation between the ophthalmic artery Doppler index and the oxygen consumption index, oxygen delivery index, and cardiac index is dependent on diastolic velocity rather than systolic velocity. When stepwise multiple linear regression analysis was performed to identify the individual contribution of each invasively measured parameter, the ophthalmic artery diastolic velocity was noted to be independently related only to the mixed venous oxygen content (r = 0.62) and the arteriovenous oxygen content difference (r = 0.3). This supports the hypothesis that changes in the ophthalmic artery diastolic velocity are better related to changes in blood oxygen content than to changes in cardiac index. Duplex and color flow Doppler ultrasonography has been found to be useful as a method of estimating changes in absolute brain blood flow 2' and cerebrovascular resistance, given that cardiac output, heart rate,
216
Belfort and Saade
and vessel wall diameter remain constant. The cerebrovascular resistance is largely controlled by the cerebral arterioles situated distal to the larger diameter vessels (i.e., the middle cerebral artery, anterior cerebral artery, and ophthalmic artery, which have a diameter of approximately 2 mm). These larger vessels (;;:: 2 mm) have little capacity to actively alter their internal diameter. 24 The smaller vessels distal to the ophthalmic artery (central retinal artery) are more susceptible to segmental vasospasm and vessel wall diameter changes, which significantly alter velocity measurements. The wide variation in the Doppler measurements may explain the poor relation between the respiratory parameters and the central retinal artery velocity measurements. A further explanation for this finding is that the ophthalmic artery is a high-velocityhigh-resistance vessel (high peak systolic velocity and low end-diastolic velocity) and the central retinal artery is a low-velocity-low-resistance vessel during conditions of normal cerebral oxygen delivery.1O Ritchie and Erskine 25 demonstrated that a vessel diameter change is best evidenced by a change in the diastolic flow component in the time velocity waveform. ""'hen conditions of low oxygen delivery supervene, cerebral arterial dilatation occurs with a corresponding increase in diastolic velocity. In this situation the vessel most likely to show the greatest percentage change in diastolic velocity will be the high-resistance vessel with a low initial diastolic velocity. Fractional cerebral oxygen extraction increases as oxygen content decreases. This may complicate attempts to predict oxygen consumption and delivery on the basis of cerebral blood flow velocity measurements because oxygen consumption may increase without any appreciable change in cerebral blood flow until oxygen extraction is maximal. This mechanism depends on normal oxygen extraction and a normal oxyhemoglobin dissociation curve. However, the oxygen extraction ratio in preeclampsia" and ARDS 4 is not normal, and there is good evidence indicating a low or fixed oxygen extraction in these two conditions. In addition, both of these conditions exhibit leftward deviation of the oxyhemoglobin dissociation curve. These findings have special significance for pregnant patients with preeclampsia and ARDS because, if oxygen extraction is low or fixed, a major mechanism for the maintenance of cerebral oxygen consumption is ineffective, and cerebral oxygen consumption becomes much more dependent on cerebral blood flow. The ophthalmic artery diastolic velocity measurement may be a useful noninvasive method to identity those patients with critically low levels of oxygen delivery and consumption. An ophthalmic artery diastolic velocity of > 7 .l2 cm/sec identified 91 % of patients with an oxygen delivery index of < 600 ml/min per square
July 1994 Am J Obstet Gynecol
meter and 75% of patients with an oxygen consumption index of < 140 ml/min per square meter. In a clinical setting a noninvasive test that allows identification of those patients with critically low oxygen parameters would be invaluable and would help the clinician in deciding which patients would most benefit from invasive monitoring. A prospective study with a larger sample of patients is underway to confirm these findings. In terms of the reproducibility of these results, the technique has been well studied. Lieb et al. IO showed that color flow Doppler ultrasonographic examination of the eye had minimal interobservation variation in a group of normal subjects with paired observations on two separate occasions on the same day. In addition, there were no significant differences noted between the right and left eyes. Interobserver variation in our laboratory is < lO%. In summary, our data suggest that the ophthalmic artery diastolic velocity may be a useful, noninvasively acquired parameter in the management of critically ill patients where knowledge of oxygen consumption and delivery is important. This technique may serve as a noninvasive screening tool with which to select those patients who will need invasive monitoring. Further study is required before clinical use can be recommended. REFERENCES 1. Shoemaker WC. Relation of oxygen transport patterns to the pathophysiology and therapy of shock states. Intensive Care Med 1987;13:230-43. 2. Mohsenifar Z, Goldbach P, Tashkin DP, Campisi DJ. Relationship between 02 delivery and 02 consumption in the adult respiratory distress syndrome. Chest 1983;84: 267-71. 3. Belfort MA, Anthony J, Saade GR, et al. The oxygen consumption/oxygen delivery curve in severe preeclampsia: evidence for a fixed oxygen extraction state. AM J OBSTET GYNECOL 1993;169:1448-55. 4. Danek SJ, Lynch JP, Weg JG, Dantzker DR. The dependence of oxygen uptake on oxygen delivery in the adult respiratory distress syndrome. Am Rev Respir Dis 1980; 122:387-95. 5. Templeton A, Kelman GR. Maternal blood-gases (PA 02Pa 02), physiological shunt and VdTT in normal pregnancy. Br J Anaesth 1976;48:1001-4. 6. Templeton AA, Kelman GR. Arterial blood gases in preeclampsia. Br J Obstet Gynaecol 1977;84:290-3. 7. Kambam JR, Handte RE, Brown WU, Smith BE. Effect of normal and preeclamptic pregnancies on the oxyhemoglobin dissociation curve. Anesthesiology 1986;65:426-7. 8. Belfort MA, Anthony J, Kirshon B. Respiratory function in severe gestational proteinuric hypertension-the effects of rapid volume expansion and subsequent vasodilatation with verapamil. Br J Obstet Gynaecol 1991;98:964-72. 9. Belfort MA, Saade GR, Moise KJ. The effect of magnesium sulfate on maternal retinal blood flow in preeclampsia: a randomized placebo-controlled study. AM J OBSTET GYNECOL 1992;167:1548-53. 10. Lieb WE, Cohen SM, Merton DA, Shields JA, Mitchell DG, Goldberg Bn. Color Doppler imaging of the eye and orbit. Arch Ophthalmol 1991;109:527-31. 11. Lizzi FL, Mortimer AJ. Bioeffects considerations for the
Volume 171, Number 1 Am J Obstet Gynecol
safety of diagnostic ultrasound. J Ultrasound Med 1988; 7(suppl): 1-38. 12. Belfort MA. Effect of magnesium sulphate on blood flow velocity in the maternal retina in mild preeclampsia: a preliminary colour flow Doppler study. Br J Obstet Gynaeol 1992;99:641-5. 13. Gosling RG, King DH. Ultrasonographic angiography. In: Hascus AW, Adamson L, eds. Arteries and veins. Edinburgh: Churchill Livingstone, 1975:61. 14. Bill A. Blood circulation and fluid dynamics in the eye. Physiol Rev 1975;55:383-417. 15. Belfort MA, Moise KJ. The effect of magnesium sulfate on maternal brain blood flow in mild preeclampsia: a randomized placebo-controlled study. AM J OBSTET GYNECOL 1992;167:661-6. 16. Belfort MA, Carpenter RJ, Moise KJ, Saade GR. The use of nimodipine in a patient with eclampsia: color Doppler demonstration of retinal artery relaxation. AM J OBSTET GYNECOL 1993;169:204-6. 17. Borgstrom L, J ohannsson H, Siesjo BK. The influence of acute normovolemic anemia in cerebral blood flow and oxygen consumption of anesthesized rats. Acta Physiol Scand 1975;93:505-14. 18. Keutzberg Gw, Barron KD, Schubert P. Cytochemical localization of 5' -nucleotidase in glial plasma membranes. Brain Res 1978;158:247-57. 19. Jones MD, Traytsman RJ, Simmons MA, Molteni A. Effects of changes in arterial 02 content on cerebral blood flow in
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the lamb. Am J Physiol 1981;240(Heart Circ Physiol 9): H209-15. Jones MD, Sheldon RE, Peetes LL, Meschia G, Battaglia FC, Makowski EL. Fetal cerebral oxygen consumption at different levels of oxygenation. J Appl Physiol Respir Environ Exerc Physiol 1977;43:1080-7. Van Bel F, Steendijk P, Teitel DF, De Winter JP, Van Der Velde ET, Baan J. Cerebral blood flow velocity: the influence of myocardial contractility on the velocity waveform of brain supplying arteries. Ultrasound Med Bioi 1992;18: 441-9. Van Bel F, van de Bor M, Baan J, Ruys JH, Stijnen T. The influence of abnormal blood gases on cerebral blood flow velocity in the preterm newborn. Neuropediatrics 1988; 19:27-32. Sorteberg W, Lindegaard K-F, Rootwelt K, et al. Blood velocity and regional blood flow in defined cerebral artery systems. Acta Neurochir 1989;97:47-52. Kontos HA, Wei EP, Navari RM, Levasseur JE, Rosenblum WI, Patterson JL. Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol 1978;234:H371-83. Ritchie JWK, Erskine RLA. Background to Doppler blood flow and velocity investigation. In: Maulik D, McNellis D, eds. Doppler ultrasound measurement of maternal-fetal hemodynamics. Ithaca, New York: Perinatology Press, 1987:121-32.
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Volume 171, Number I Am J Obstet Gynecol
6, Fihn S, Johnson C, Pinkstaff C, Stamm W. Diaphragm use
and urinary tract infections: analysis of urodynamic and microbiologic factors. J Urol 1986;136:853-6. 7. Suarez G, Baum N, Jacobs J. Use of standard contraceptive diaphragm in management of stress urinary incontinence. Urology 1991;28:119-22. 8. Realini J, Walters M. Vaginal diaphragm rings in the treatment of stress urinary incontinence. J Am Board Fam Pract 1990;3:99-103. 9. Marshall S. Conservative management of stress incontinence. Urology 1991;28:204.
10. Bhatia N, Bergman A, GunningJ. Urodynamic effects of a vaginal pessary in women with stress urinary incontinence. AM J OBSTET GYNECOL 1983; 147: 8 76-84. 11. Bergman A, Bhatia N. Pessary test: simple prognostic test in women with stress urinary incontinence. Urology 1984; 24: 109-12. 12. Bhatia N, Bergman A. Pessary test in women with urinary incontinence. Obstet Gynecol 1985;65:220-6. 13. Schraub S, Sun X, Maingon P, et al. Cervical and vaginal cancer associated with pessary use. Cancer 1992;69: 2505-9.
Oxygen delivery and consumption in critically ill pregnant patients: Association with ophthalmic artery diastolic velocity Michael A. Belfort, MD, and George R. Saade, MD Houston, Texas OBJECTIVES: We aimed to investigate the relation between orbital vessel flow velocity and ~xygen delivery, oxygen consumption, cardiac index, and systemic vascular resistance index in critically ill pregnant patients. STUDY DESIGN: Eighteen pregnant or early postpartum patients requiring invasive monitoring were prospectively studied with Doppler ultrasonography. The blood flow velocity and resistance index from the central retinal and ophthalmic arteries were plotted against the oxygen delivery index, oxygen consumption index, cardiac index, and systemic vascular resistance index. Linear and polynomial regression analysis and receiver-operator characteristic curves were used to examine the data. RESULTS: The ophthalmic artery resistance index correlated with oxygen consumption, oxygen delivery index, and cardiac index. Only the cardiac index was independently related to the the ophthalmic artery resistance index. The ophthalmic artery diastolic velocity correlated with oxygen consumption index, oxygen delivery index, and cardiac index. The ophthalmic artery diastolic velocity correlated independently with mixed venous oxygen content and arteriovenous oxygen content difference. The central retinal artery Doppler index did not correlate with any of the invasively measured parameters. An ophthalmic artery diastolic velocity of > 7.12 cm/sec identified 75% of patients with an oxygen consumption index of < 140 ml/min per square meter and 91 % of patients with an oxygen delivery index of < 600 ml/min per square meter. CONCLUSIONS: These data suggest that the ophthalmic artery flow velocity is correlated with systemic oxygen delivery and consumption. This relationship may have potential research applications in the noninvasive assessment of oxygen delivery index and oxygen consumption index in critically ill pregnant patients. (AM J OBSTET GVNECOL 1994;171:211-7.)
Key words: Ophthalmic artery, Doppler, oxygen consumption, monitoring, noninvasive
From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine. Supported by a Grant-in-Aid from the American Heart Association. Received for publication September 29, 1993; revised November 17, 1993; accepted December 10, 1993. Reprint requests: Michael A. Belfort, MD, Division ofMaternal-Fetal Medicine, Department of Obstetrics and Gynecology, One Baylor Plaza, Houston, TX 77030. Copyright © 1994 by Mosby-Year Book, inc. 0002-9378/94 $3.00 + 0 6/1/53596
Oxygen consumption and delivery are important indicators of respiratory function in criticallly ill patients. " 2 Preeclampsia and adult respiratory distress syndrome (ARDS) are associated with very low levels of both these parameters."' 4 This may be partially explained by the increased pulmonary shunt fraction,5, 6 leftward shift of the oxyhemoglobin dissociation curve,7 and abnormal oxygen extraction ratio 3 frequently noted 211
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Table I. Demographic data of 18 patients Patient No. 1 2 3 4 5 6 7 8 9 lO
11 12 13 14 15 16 17 18
25 23 24 25 18 17 20 23 21 18 19 30 24 31 31 31 15 32
0 1 1 0 0 0 0 0 1 0 0 2 1 4 9 4 0 2
Gestational age (wk)
Timing of scan
Diagnosis
37.0 29.6 25.4 36.4 35.8 38.3 34.4 37.6 36.3 24.4 38.3 35.3 36.6 37.2 41.1 31.0 38.3 35.0
Antepartum Mter cesarean section Antepartum Mter cesarean section Antepartum Antepartum Antepartum Mter cesarean section Antepartum Antepartum Antepartum Mter cesarean section Antepartum Mter cesarean section Mter cesarean hysterectomy Antepartum Antepartum Mter cesarean section
Preeclampsia Chorioamnionitis, ARDS Pyelonephritis, sepsis Preeclampsia Preeclampsia Pyelonephritis, sepsis Preeclampsia Preeclampsia Preeclampsia Pyelonephritis, ARDS Aortic stenosis Preeclampsia Preeclampsia Preeclampsia Hemorrhage Preeclampsia Preeclampsia Preeclampsia
in such patients. Many of these patients are known to exhibit a low oxygen consumption and delivery despite having hyperdynamic cardiac function, 8 and the echocardiographic measurement of cardiac output alone is often not sufficient to gauge the severity of the disease state or to monitor the" effects of therapy. This uncertainty may lead to the insertion of a pulmonary artery catheter to determine the respiratory parameters. A noninvasive method of assessing oxygen consumption and delivery may provide a means of screening potential patients for invasive monitoring and may reduce the need for central catheterization. Tissue oxygenation is related to perfusion. The assessment of blood velocity in a vessel may provide useful information about oxygen delivery and consumption in that particular vascular bed. The cerebral circulation is easily accessible through the orbit with color Doppler ultrasonography and both small (central retinal artery)9 and larger (ophthalmic artery)lO resistance vessels may be studied. Therefore we designed a study to examine the usefulness of orbital color flow Doppler ultrasonography in the prediction of oxygen delivery and consumption in critically ill pregnant patients admitted to our intensive care area. Material and methods
The protocol was approved by the Baylor College of Medicine Institutional Review Board. All women gave informed consent. Eighteen pregnant or recently delivered patients who had received a pulmonary artery catheter as part of their management were included in this study. Patients were considered for the study only if they already had the invasive monitoring device in place, and inclusion in this study in no way influenced any of the management decisions. Indications for pulmonary artery catheteriza-
tion included oliguria, hypertension unresponsive to two intravenous bolus doses (10 mg) of hydralazine, pulmonary edema, ARDS, status eclampticus, cardiac valve disease, pyelonephritis complicated by septic shock or ARDS, and intraoperative hemorrhage. All patients with preeclampsia were receiving magnesium sulfate intravenously at a maintenance dosage of 2 gmlhr unless they had oliguria, in which case the dosage was titrated according to the blood magnesium level. None of these patients were being mechanically ventilated during the examination. Women in' active labor were not entered into the study. Of the 18 patients, 11 were scanned before delivery and 7 in the immediate postpartum period. Demographic data from these patients are shown in Table I. Patients with essential hypertension, chronic renal disease, epilepsy, diabetes mellitus, autoimmune disease, and any preexisting condition perceived to have had a long-term effect on the cerebral or the orbital vasculature were excluded. The patients were positioned in a Fowler position with a IS-degree left lateral tilt. The person performing the ultrasonographic examination was unaware of any of the hemodynamic and respiratory parameters previously obtained during the patient'S hospitalization. Specimens of mixed venous blood and peripheral arterial blood were drawn during the Doppler examination, and the hemodynamic parameters (cardiac output and pulmonary wedge capillary pressure) were determined at the completion of the ultrasonographic study to prevent observer bias. Five consecutive 10 ml injections of physiologic saline solution at room temperature were used. The high and low values were discarded, and the mean of the remaining three values were ~ecorded. Pulmonary capillary wedge pressure determinations were made at end expiration. The arterial blood pres-
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sure, central venous pressure, and heart rate were recorded continuously by the monitoring equipment (model MIOI2A; Hewlett-Packard, Waltham, Mass.). The respiratory parameters were calculated with the onboard software in the monitoring system. The following formulas were used for calculating the oxygen consumption and delivery data: Vo 2I (mVmin/m2) = avDo 2 * CO * IO/BSA avDo 2(mVdl) = Cao 2 - CV02 Cao2 = (1.34 * HGB * Sao2 /100) + (Pao2 * 0.0031) Cvo 2 = (1.34 * HGB * Svo2/IOO) + (Pv02 * 0.0031) where Vo 2I is oxygen consumption index, avDo 2 is arteriaVvenous oxygen difference, CO is cardiac output, BSA is body surface area, Cao2 is arterial oxygen concentration, Cvo 2 is mixed venous oxygen concentration, HGB is hemoglobin, Sao 2 is percent arterial oxyhemoglobin saturation, Svo 2 is percent venous oxyhemoglobin saturation, Pao 2 is arterial partial pressure of oxygen, and Pv0 2 is venous partial pressure of oxygen. Do 2 I = Cao 2
* CO * 10/BSA
where Do 2I is oxygen delivery index. A Siemens-Quantum 2000 color flow Doppler system (Siemens-Quantum Medical Systems, Issaquah, Wash.) was used for the Doppler studies. A 7.5 MHz lineararray transducer with a 0.2 mm x 0.2 mm sample volume was used to image ea,ch eye. The estimated in situ peak temporal average (SPTA) intensity at a depth of 4.2 cm in the color imaging mode is 7 mW/cm2 for the 7.5 MHz transducer (data provided by Quantum Medical Systems). During color flow Doppler spectrum analysis the SPTA intensity is approximately 71 mW/cm2. In this mode the SPTA intensity is within the safety limits set by the American Institute for Ultrasound in Medicine. 11 Spectrum analysis was limited to approximately 1 minute in each eye, and .the total examination was limited to approximately 5 minutes for each eye. The maximum power setting used was - 10 dB (i.e., 10 dB less than the maximum power setting allowed under Food and Drug Administration restrictions), and power output was continuously displayed on the screen. The technique for orbital Doppler examination has been described previously.12 The software package of the Siemens-Quantum 2000 system provided anglecorrected systolic and diastolic velocity measurements, as well as the Pourcelot resistance index. 13 The velocity and resistance index data from a minimum of three waveforms were averaged at each measurement. Because both the left and right central retinal and ophthalmic arteries were insonated, the average value was calculated and used for analysis purposes. No differences have been noted between measurements from right and left eyes in previous studies.1O Lieb et al. 10
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=0.80 R2 =0.64 P =0.0003 N =18 R
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Oxygen Consumption Index (mllmin/m 2) Fig. 1. Regression plot of ophthalmic artery diastolic velocity versus oxygen consumption index. Each point represents a baseline observation from a single patient. Preeclamptic patients are represented by solid squares. Other patients are represented by open triangles.
have also shown this technique to have minimal interobservation variation in a group of normal subjects with paired observations on two separate occasions on the same day. All waveforms and calculated index values were recorded on thermal paper. Data were analyzed with the Epistat Statistical program (Epistat Services, Richardson, Tex.) and the Origin graphics program (Microcal Inc., Northampton, Mass.). Linear and polynomial regression plots were used to examine the data (from allIS patients and from the preeclamptic patients [n = 12] alone), and lines of best fit were derived. Stepwise multiple linear regression analysis was used to identifY the individual contribution of each invasively measured variable to the Doppler parameters. Normal probability plots were used to check for normal distribution of the residuals. The data were further analyzed to control for magnesium sulfate effect. The patients were separated into two groups: those who received magnesium sulfate and those who did not. Receiver-operator characteristic curves were used to evaluate the performance of the ophthalmic artery diastolic velocity in predicting a critically low oxygen delivery index « 600 mVmin per square meter), oxygen consumption index « 140 mVmin per square meter), and cardiac index
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July 1994 Am J Obstet Gynecol
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Fig. 2. Regression plot Qf ophthalmic artery diastolic velocity versus oxygen delivery index. Each point represents a baseline observation from a single patient. Preeclamptic patients are represented by solid squares. Other patients are represented by open triangles.
Fig. 3. Regression plot of ophthalmic artery diastolic velocity versus cardiac index. Each point represents a baseline observation from a single patient. Preeclamptic patients are represented by solid squares. Other patients are represented by open triangles.
«4 Umin per square meter) for pregnancy. A value of
(Fig. 3; Y = 20 - 2.6x; r = -0.53; R2 = 0.28; P = 0.02). This correlation persisted despite separation of the patients into two groups (a group of magnesium sulfate-treated patients and a group who did not receive magnesium sulfate). When data from the preeclamptic patients (n = 12), were separated from the heterogeneous group (n = 18) and examined separately, the relation described for the whole group persisted in the preeclamptic patients. The ophthalmic artery diastolic velocity correlated with oxygen consumption index (r = 0.78; R2 = 0.62; p = 0.0003), oxygen delivery index (r = -0.83; R2 = 0.69; P = 0.0002), and cardiac index (r = - 0.56; R2 = 0.31; P = 0.02). There were no statistically significant correlations noted when the other central retinal or ophthalmic vessel Doppler indexes were plotted against the respiratory or hemodynamic data. With the use of receiver-operator characteristic curves the ophthalmic artery diastolic velocity performed significantly better than chance in predicting critical levels of oxygen delivery index (p < 0.0001), oxygen consumption index (p < 0.001), an.d cardiac index (p < 0.0001). Table II shows the sensitivity and specificity of an ophthalmic artery diastolic velocity of
p < 0.05 was regarded as statistically significant. Results
Eighteen consecutive patients were included in this prospective descriptive study. Table I shows the demographic data of these women. The ophthalmic artery resistance index showed a positive correlation with oxygen consumption index (y = 0.65 - 0.002x; r = 0.50; R2 = 0.26; P = 0.04), oxygen delivery index (y = 0.42 + 0.0004x; r = 0.58; R2 = 0.34; P = 0.01), and cardiac index (y = 0.27 + 0.09x; r = 0.63; P = 0.005). Only the cardiac index was independently related to the ophthalmic artery resistance index when the data were subjected to stepwise multiple linear regression analysis. When the correlation between ophthalmic artery systolic and diastolic blood velocity and the respiratory and hemodynamic parameters were examined, only the diastolic velocity correlated with the invasively measured parameters. The ophthalmic artery diastolic velocity correlated with oxygen consumption index (Fig. 1; Y = 48 - 0.5x; r = 0.80; R2 = 0.64; P = 0.0003), oxygen delivery index (Fig. 2; Y = 32 - 0.06x; r = - 0.81; R2 = 0.65; P = 0.0002), and cardiac index
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Table II. Sensitivity and specificity of ophthalmic artery diastolic velocity > 7.12 cm/sec in predicting oxygen delivery index <600 mVmin per square meter,.oxygen consumption index < 140 mVmin per square meter, and cardiac index < 4 Vmin per square meter Sensitivity Oxygen delivery index < 600 mVmin/m2 Oxygen consumption index < 140 mVmin/m2 Cardiac index < 4 Umin/m2
> 7.12 cm/sec in predicting a critically low oxygen delivery index « 600 mVmin per square meter), oxygen consumption index « 140 mVmin per square meter), and cardiac index ( < 4 Vmin per square meter) for pregnancy.
Comment This study reports a novel application of orbital Doppler ultrasonography and notes a correlation between ophthalmic artery blood velocity and systemic respiratory parameters in pregnant patients. Preeclampsia-eclampsia and its complications are still a major cause of maternal morbidity and mortality in the United States. Oxygen delivery and consumption are known to be critically low in untreated severe preeclampsia and in ARDS.2. '. 8 These parameters are of great importance in the management of critically ill patients, I. 2 both as prognostic indicators and as a method of monitoring the effects of therapy. However, obtaining these data frequently requires invasive monitoring, and the availability of a noninvasive technique would add significantly to the clinician's methods. The ophthalmic artery diastolic velocity may be useful in the assessment of oxygen delivery and consumption in critically ill pregnant patients. A high ophthalmic artery diastolic velocity indicates low systemic oxygen delivery and consumption, and a low diastolic velocity is compatible with normal respiratory parameters. Although this association has not previously been demonstrated, there are good circumstantial data in the literature to explain our findings. The ophthalmic and retinal arteries are end-arterial branches of the internal carotid artery and are physiologically and morphologically similar to other intracranial cerebral arteries. 14 Similar vasodilatory responses to magnesium sulfate have been demonstrated in the middle cerebral artery and the orbital arteries in patients with preeclampsia.15. 16 . The brain is capable of sustaining cerebral oxygen consumption within normal limits despite extreme reductions in Pa0 2 and at times is able to increase cerebral blood flow by .as much as 600%.17 The exact mechanisms of this are not defined, but cerebral ischemia and low tissue oxygen tension are known to result in an increased production of adenosine (potent vasodi-
91%
75%
100%
I
Specificity 86% 67% 64%
lator) by the perivascular astrocytes. 18 Thus low cerebral oxygen delivery is countered by cerebral vasodilatation and increased cerebral blood flow to maintain oxygen consumption within the normal range. Cerebral oxygen delivery depends on the cardic output and the oxygen content of the arterial blood leaving the heart (i.e., the systemic oxygen delivery), and it is maintained within an error range by autoregulatory mechanisms that respond to the arterial oxgyen content. Changes in arterial oxygen content are accompanied by reciprocal changes in cerebral blood flow to maintain constant cerebral oxygen delivery.19 Data among species with differing cerebral oxygen consumption show that cerebral oxygen delivery is regulated according to cerebral oxgyen consumption.""o End-diastolic velocity has been demonstrated to be the optimal noninvasive measurement for the assessment of brain blood flow because of its independence from myocardial contractility." I In addition, end-diastolic cerebral artery blood flow velocity has been shown to be predominantly affected by blood gas changes, whereas cardiac output appears to be more responsible for alterations in peak systolic flow velocity."2 Van Bel et al."1 showed that the peak systolic velocity (or indices containing peak systolic velocity with mean velocity or end-diastolic velocity) of arteries supplying the brain had a strong correlation with the myocardial contractile state. Similarly, our data suggest that the relation between the ophthalmic artery Doppler index and the oxygen consumption index, oxygen delivery index, and cardiac index is dependent on diastolic velocity rather than systolic velocity. When stepwise multiple linear regression analysis was performed to identify the individual contribution of each invasively measured parameter, the ophthalmic artery diastolic velocity was noted to be independently related only to the mixed venous oxygen content (r = 0.62) and the arteriovenous oxygen content difference (r = 0.3). This supports the hypothesis that changes in the ophthalmic artery diastolic velocity are better related to changes in blood oxygen content than to changes in cardiac index. Duplex and color flow Doppler ultrasonography has been found to be useful as a method of estimating changes in absolute brain blood flow 2' and cerebrovascular resistance, given that cardiac output, heart rate,
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and vessel wall diameter remain constant. The cerebrovascular resistance is largely controlled by the cerebral arterioles situated distal to the larger diameter vessels (i.e., the middle cerebral artery, anterior cerebral artery, and ophthalmic artery, which have a diameter of approximately 2 mm). These larger vessels (;;:: 2 mm) have little capacity to actively alter their internal diameter. 24 The smaller vessels distal to the ophthalmic artery (central retinal artery) are more susceptible to segmental vasospasm and vessel wall diameter changes, which significantly alter velocity measurements. The wide variation in the Doppler measurements may explain the poor relation between the respiratory parameters and the central retinal artery velocity measurements. A further explanation for this finding is that the ophthalmic artery is a high-velocityhigh-resistance vessel (high peak systolic velocity and low end-diastolic velocity) and the central retinal artery is a low-velocity-low-resistance vessel during conditions of normal cerebral oxygen delivery.1O Ritchie and Erskine 25 demonstrated that a vessel diameter change is best evidenced by a change in the diastolic flow component in the time velocity waveform. ""'hen conditions of low oxygen delivery supervene, cerebral arterial dilatation occurs with a corresponding increase in diastolic velocity. In this situation the vessel most likely to show the greatest percentage change in diastolic velocity will be the high-resistance vessel with a low initial diastolic velocity. Fractional cerebral oxygen extraction increases as oxygen content decreases. This may complicate attempts to predict oxygen consumption and delivery on the basis of cerebral blood flow velocity measurements because oxygen consumption may increase without any appreciable change in cerebral blood flow until oxygen extraction is maximal. This mechanism depends on normal oxygen extraction and a normal oxyhemoglobin dissociation curve. However, the oxygen extraction ratio in preeclampsia" and ARDS 4 is not normal, and there is good evidence indicating a low or fixed oxygen extraction in these two conditions. In addition, both of these conditions exhibit leftward deviation of the oxyhemoglobin dissociation curve. These findings have special significance for pregnant patients with preeclampsia and ARDS because, if oxygen extraction is low or fixed, a major mechanism for the maintenance of cerebral oxygen consumption is ineffective, and cerebral oxygen consumption becomes much more dependent on cerebral blood flow. The ophthalmic artery diastolic velocity measurement may be a useful noninvasive method to identity those patients with critically low levels of oxygen delivery and consumption. An ophthalmic artery diastolic velocity of > 7 .l2 cm/sec identified 91 % of patients with an oxygen delivery index of < 600 ml/min per square
July 1994 Am J Obstet Gynecol
meter and 75% of patients with an oxygen consumption index of < 140 ml/min per square meter. In a clinical setting a noninvasive test that allows identification of those patients with critically low oxygen parameters would be invaluable and would help the clinician in deciding which patients would most benefit from invasive monitoring. A prospective study with a larger sample of patients is underway to confirm these findings. In terms of the reproducibility of these results, the technique has been well studied. Lieb et al. IO showed that color flow Doppler ultrasonographic examination of the eye had minimal interobservation variation in a group of normal subjects with paired observations on two separate occasions on the same day. In addition, there were no significant differences noted between the right and left eyes. Interobserver variation in our laboratory is < lO%. In summary, our data suggest that the ophthalmic artery diastolic velocity may be a useful, noninvasively acquired parameter in the management of critically ill patients where knowledge of oxygen consumption and delivery is important. This technique may serve as a noninvasive screening tool with which to select those patients who will need invasive monitoring. Further study is required before clinical use can be recommended. REFERENCES 1. Shoemaker WC. Relation of oxygen transport patterns to the pathophysiology and therapy of shock states. Intensive Care Med 1987;13:230-43. 2. Mohsenifar Z, Goldbach P, Tashkin DP, Campisi DJ. Relationship between 02 delivery and 02 consumption in the adult respiratory distress syndrome. Chest 1983;84: 267-71. 3. Belfort MA, Anthony J, Saade GR, et al. The oxygen consumption/oxygen delivery curve in severe preeclampsia: evidence for a fixed oxygen extraction state. AM J OBSTET GYNECOL 1993;169:1448-55. 4. Danek SJ, Lynch JP, Weg JG, Dantzker DR. The dependence of oxygen uptake on oxygen delivery in the adult respiratory distress syndrome. Am Rev Respir Dis 1980; 122:387-95. 5. Templeton A, Kelman GR. Maternal blood-gases (PA 02Pa 02), physiological shunt and VdTT in normal pregnancy. Br J Anaesth 1976;48:1001-4. 6. Templeton AA, Kelman GR. Arterial blood gases in preeclampsia. Br J Obstet Gynaecol 1977;84:290-3. 7. Kambam JR, Handte RE, Brown WU, Smith BE. Effect of normal and preeclamptic pregnancies on the oxyhemoglobin dissociation curve. Anesthesiology 1986;65:426-7. 8. Belfort MA, Anthony J, Kirshon B. Respiratory function in severe gestational proteinuric hypertension-the effects of rapid volume expansion and subsequent vasodilatation with verapamil. Br J Obstet Gynaecol 1991;98:964-72. 9. Belfort MA, Saade GR, Moise KJ. The effect of magnesium sulfate on maternal retinal blood flow in preeclampsia: a randomized placebo-controlled study. AM J OBSTET GYNECOL 1992;167:1548-53. 10. Lieb WE, Cohen SM, Merton DA, Shields JA, Mitchell DG, Goldberg Bn. Color Doppler imaging of the eye and orbit. Arch Ophthalmol 1991;109:527-31. 11. Lizzi FL, Mortimer AJ. Bioeffects considerations for the
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safety of diagnostic ultrasound. J Ultrasound Med 1988; 7(suppl): 1-38. 12. Belfort MA. Effect of magnesium sulphate on blood flow velocity in the maternal retina in mild preeclampsia: a preliminary colour flow Doppler study. Br J Obstet Gynaeol 1992;99:641-5. 13. Gosling RG, King DH. Ultrasonographic angiography. In: Hascus AW, Adamson L, eds. Arteries and veins. Edinburgh: Churchill Livingstone, 1975:61. 14. Bill A. Blood circulation and fluid dynamics in the eye. Physiol Rev 1975;55:383-417. 15. Belfort MA, Moise KJ. The effect of magnesium sulfate on maternal brain blood flow in mild preeclampsia: a randomized placebo-controlled study. AM J OBSTET GYNECOL 1992;167:661-6. 16. Belfort MA, Carpenter RJ, Moise KJ, Saade GR. The use of nimodipine in a patient with eclampsia: color Doppler demonstration of retinal artery relaxation. AM J OBSTET GYNECOL 1993;169:204-6. 17. Borgstrom L, J ohannsson H, Siesjo BK. The influence of acute normovolemic anemia in cerebral blood flow and oxygen consumption of anesthesized rats. Acta Physiol Scand 1975;93:505-14. 18. Keutzberg Gw, Barron KD, Schubert P. Cytochemical localization of 5' -nucleotidase in glial plasma membranes. Brain Res 1978;158:247-57. 19. Jones MD, Traytsman RJ, Simmons MA, Molteni A. Effects of changes in arterial 02 content on cerebral blood flow in
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the lamb. Am J Physiol 1981;240(Heart Circ Physiol 9): H209-15. Jones MD, Sheldon RE, Peetes LL, Meschia G, Battaglia FC, Makowski EL. Fetal cerebral oxygen consumption at different levels of oxygenation. J Appl Physiol Respir Environ Exerc Physiol 1977;43:1080-7. Van Bel F, Steendijk P, Teitel DF, De Winter JP, Van Der Velde ET, Baan J. Cerebral blood flow velocity: the influence of myocardial contractility on the velocity waveform of brain supplying arteries. Ultrasound Med Bioi 1992;18: 441-9. Van Bel F, van de Bor M, Baan J, Ruys JH, Stijnen T. The influence of abnormal blood gases on cerebral blood flow velocity in the preterm newborn. Neuropediatrics 1988; 19:27-32. Sorteberg W, Lindegaard K-F, Rootwelt K, et al. Blood velocity and regional blood flow in defined cerebral artery systems. Acta Neurochir 1989;97:47-52. Kontos HA, Wei EP, Navari RM, Levasseur JE, Rosenblum WI, Patterson JL. Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol 1978;234:H371-83. Ritchie JWK, Erskine RLA. Background to Doppler blood flow and velocity investigation. In: Maulik D, McNellis D, eds. Doppler ultrasound measurement of maternal-fetal hemodynamics. Ithaca, New York: Perinatology Press, 1987:121-32.
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