This action might not be possible to undo. Are you sure you want to continue?
David R. McIlroy,
MB, BS, FANZCA,
and Evan D. Kharasch,
Department of Anesthesiology, University of Washington Medical Center, Seattle
Although the distribution of various crystalloid and colloid solutions at equilibrium has been well established, the acute peak expansion of intravascular volume that can be achieved with the rapid administration of crystalloid or colloid is unknown. We studied eight healthy male subjects in a two-part crossover trial designed to assess the maximal increase in intravascular volume achieved with 1000 mL of lactated Ringer’s solution compared with the same volume of 6% Hetastarch. Subjects were made moderately hypovolemic by the withdrawal of 900 mL of blood, and then the crystalloid or colloid solution was rapidly infused over 5–7 min. Serial dilution of hematocrit was measured every 5 min for 30 min to determine
changes in blood volume. Peak expansion of intravascular volume with lactated Ringer’s solution was 630 Ϯ 127 mL, occurring immediately the rapid infusion was complete, whereas the peak expansion of intravascular volume with 6% Hetastarch was 1123 Ϯ 116 mL and occurred 5 min after the completion of the fluid infusion. The results were significantly different (P Ͻ 0.001). These results would suggest that even for very short periods of time, rapid infusion of colloid significantly more effectively increases blood volume and, by inference, cardiac output than the same volume of crystalloid, even if the crystalloid is administered very rapidly. (Anesth Analg 2003;96:1572–7)
V fluid resuscitation is an integral part of modern anesthesia practice. The goal is to increase intravascular volume as a means to augment cardiac output and organ perfusion. This may be attempted with a colloid or crystalloid solution. The benefits of each type of fluid have been widely debated for many years. Although the amount of each fluid that remains in the intravascular space at equilibrium has been well documented (1), the ability of a given fluid to acutely and temporarily expand the intravascular space when given rapidly to hypovolemic subjects has not been adequately investigated. Several complex and sophisticated mathematical models have predicted the rate of redistribution of these fluids and thus the increase in blood volume for differing rates and duration of crystalloid infusion (2). However, these models have used relatively slow fluid infusion rates (30 min) and rapidly administered fluid
Supported, in part, by the Department of Anesthesiology and NIH grant M01-RR-00037 of the University of Washington Clinical Research Center. Accepted for publication January 27, 2003. Address correspondence and reprint requests to David McIlroy, Department of Anesthesia and Pain Management, Alfred Hospital, Commercial Rd., Melbourne 3004, Victoria, Australia. Address e-mail to firstname.lastname@example.org. DOI: 10.1213/01.ANE.0000061460.59320.B0
(Ͼ100 mL/min) does not fit the constructed pharmacokinetic model (3,4). Other recent studies from the same group show that a larger proportion of crystalloid than expected is retained in the intravascular space at equilibrium in subjects who are made hypovolemic immediately before the fluid challenge (5,6). The aim of the present investigation was to compare the peak increase in intravascular volume achieved with crystalloid compared with colloid when administered IV rapidly to moderately hypovolemic subjects using a balanced crossover trial. The hypothesis was that equal volumes of crystalloid or colloid would provide the same initial increase in intravascular volume when administered rapidly to moderately hypovolemic subjects.
Materials and Methods
Eight healthy males 22–36 yr (mean, 29 yr) weighing 71–103 kg (84 Ϯ 11 kg) were studied. We performed a prospective two-part crossover trial designed to assess the maximal increase in intravascular volume achieved with 1000 mL of lactated Ringer’s solution compared with 1000 mL of 6% Hetastarch. Each subject was studied on two separate occasions at least
©2003 by the International Anesthesia Research Society 0003-2999/03
Anesth Analg 2003;96:1572–7
Increase in blood volume (mL) ϭ (baseline hematocrit/measured hematocrit) ϫ baseline blood volume Ϫ baseline blood volume. When the withdrawal of 900 mL of blood was complete. (8): Blood Volume (L) ϭ 0.3669 height3 (m) ϩ 0.96:1572–7 CARDIOVASCULAR ANESTHETIC MCILROY AND KHARASCH ACUTE INTRAVASCULAR VOLUME EXPANSION: COLLOID VERSUS CRYSTALLOID 1573 6 days apart. A 14-gauge IV catheter was then placed in each antecubital fossa. 273 mOsm/L) or 6% Hetastarch (Abbott Laboratories. Abott. Ca 2.03219 weight (kg) ϩ 0. The study was approved by the University of Washington’s IRB. Lactated Ringer’s solution 1000 mL was typically delivered in 4 –5 min.6041 We then subtracted 900 mL from this value as our postphlebotomy baseline blood volume. (7) the order of fluids was not randomized. the calculation of plasma volume requires the injection of indocyanine green. Rockland. and all volunteers gave written informed consent with the knowledge that they could withdraw from the trial at any time. and 900 mL of venous blood was drained by gravity over 15 min. a 4-mL blood sample was obtained for baseline hematocrit measurement. automated noninvasive blood pressure measurement. where the peak increase in intravascular volume was expected to occur within 5 min of completion of the fluid infusion. IL. At the time of each blood sample.9). an initial volume of 5 mL of venous blood was withdrawn to prevent any contamination of the sample with other fluid. Smiths Industries Medical System. MA) was attached to the other IV cannula and was primed with either lactated Ringer’s solution (Baxter Healthcare Corporation. On arrival. from which to calculate the increase in blood volume with fluid infusion. Subjects were admitted to the Clinical Research Center having been instructed to eat a light meal before their arrival. Subjects were monitored with 3-lead electrocardiography. The completion of the rapid infusion of fluid was designated time zero (0). Deerfield. Although traditional methods for measuring the amount of fluid remaining in the intravascular space involve indicator dye dilution or dilution of radiolabeled red blood cells.5. However. It was therefore deemed unsuitable for use in this setting. which. It has been shown that the ratio of large-vessel:whole-body hematocrit does not remain constant in the setting of volume loading with colloid. 308 mOsm/L). and pulse oximetry and remained supine throughout the procedure. . Previous studies indicate that the redistribution process of crystalloid is almost complete in euvolemic subjects 30 min after completion of the infusion (4. Corrections were not made for the blood samples removed (32 mL total) or the lactated Ringer’s solution used to flush the sampling line (24 mL total) because the small volumes were not felt to significantly affect the results.ANESTH ANALG 2003. their height and weight were checked and they were asked to void and then lay down in bed where baseline vital signs were obtained. electrolyte composition [mEq/L]: Na 154 and Cl 154. Although most of the published work in this area has used hemoglobin dilution to indicate changes in blood volume (2. Individual hematocrits are accurate to Ϯ2 hematocrit percentage points. After 30 min. A rapid fluid infusing device (Level 1. whereas 1000 mL of 6% Hetastarch took 7– 8 min to deliver. A blood sample was obtained from the IV cannula not used for fluid infusion. the sum of which provides blood volume. A citrated blood collection bag was attached to one of the IV cannula. An attending anesthesiologist was also present throughout the procedure with full resuscitation drugs and equipment available. followed by a rapid decline in those subjects given crystalloid. and each subject received the lactated Ringer’s solution on their first visit and then 6% Hetastarch at their second visit. the precision of this technique has been questioned (10). Sampling was repeated every 5 min for 30 min. We then began the rapid infusion of 1000 mL of fluid via the Level-1 device. and Lactate 28. and a more precise measure of blood volume change may be obtained with independent measures of erythrocyte volume and plasma volume. CA) by technicians blinded to which fluid had been given. IL. The hematocrit of each 4-mL sample of blood was measured in duplicate (Cell Dyne 3500. cannot be repeated more frequently than every 20 min. K 4. North Chicago.7. Cl 109. Santa Clara. these methods are unsuitable for studies of nonsteady-state conditions because they require an unchanged blood volume for a period of 30 – 40 min to be accurate (4). which warms the fluid close to body temperature and delivers it under 300 mm Hg of pressure. the 900 mL of collected blood was returned to the subject over 90 min. and the mean was used for further calculations. Because of the long and slightly uncertain elimination half-life of 6% Hetastarch. because of its clearance.4. Initial blood volume was calculated according to the formula of Nadler et al. This volume was subsequently returned to the patient. The study was jointly funded by an intra-departmental research grant and a National Institute of Health grant to the University of Washington Clinical Research Center. Changes in blood volume were calculated from serial dilutional changes in hematocrit.5). electrolyte composition [mEq/L]: Na 130.
whereas increasing only slightly in the 6% Hetastarch group. there was a large and statistically significant difference between lactated Ringer’s solution and 6% Hetastarch in their ability to increase the intravascular volume. The primary outcome measure was the difference in peak intravascular volume expansion between lactated Ringer’s solution and 6% Hetastarch after completion of the rapid infusion of fluid compared using Student’s t-test. Results The withdrawal of 900 mL of blood from subjects was generally well tolerated. At every time point from 0 to 30 min. Ϫ29 to ϩ17). The mean reduction in systolic and diastolic blood pressure was 9 and 4 mm Hg.001). the rapid infusion of 6% Hetastarch was associated with an increase in mean heart rate from 69 Ϯ 21 bpm to 79 Ϯ 17 bpm. Rapid infusion of lactated Ringer’s solution produced no significant change in mean heart rate or mean value of systolic blood pressure. the mean pulse pressure did increase from 51 Ϯ 12 mm Hg to 58 Ϯ 16 mm Hg. One subject became symptomatically bradycardic at the completion of blood withdrawal with a sinus bradycardia at 28 bpm but responded to atropine 1 mg IV and was happy to continue the study. Hetastarch actually occurred 5 min after completion of the infusion and was 1123 Ϯ 116 mL. after 900 mL of venesection. 593 mL. However. The measured hematocrit decreased with the rapid infusion of fluid to values ranging from 29. The rapid infusion of fluid via the Level 1 produced no symptoms.5 and then tended to increase steadily over 30 min in the lactated Ringer’s group. The secondary outcome was timespecific differences in intravascular volume expansion between lactated Ringer’s solution and 6% Hetastarch determined using two-way repeated-measures analyses of variance.5 to 39. Heart rate (bpm) at admission. The difference between the colloid and crystalloid was significant (P Ͻ 0. but grew larger with each 5-min time interval to 20 min. Previous studies (11) confirm that 6% Hetastarch does not significantly alter the rheological properties of blood independent of a simple dilutional effect. The peak increase in intravascular volume with the 6% Figure 2. and every 5 min for 30 min after the rapid infusion of either lactated Ringer’s solution or 6% Hetastarch 1000 mL. Time 0 represents immediately when the fluid infusion was complete. There was also an increase in the mean value of systolic blood pressure from 115 Ϯ 24 mm Hg to 128 Ϯ 19 mm Hg along with an increase in the mean value of pulse pressure from 51 Ϯ 12 mm Hg to 59 Ϯ 12 mm Hg (Fig. The difference between the two solutions was smallest immediately after completion of the infusion (time ϭ 0). By contrast. One other subject experienced some mild light headedness that settled with elevation of the legs. where the difference in intravascular volume expansion was 708 mL.1574 CARDIOVASCULAR ANESTHETIC MCILROY AND KHARASCH ACUTE INTRAVASCULAR VOLUME EXPANSION: COLLOID VERSUS CRYSTALLOID ANESTH ANALG 2003. 3 and 4). respectively. Group means for hematocrit and the corresponding calculated increase in intravascular volume (Ϯ sd) are shown in Table 1. after 900 mL of venesection. Time 0 represents immediately when the fluid infusion was complete. Pulse pressure (mm Hg) at admission. which was slightly larger than the actual volume infused. Figure 1. and every 5 min for 30 min after the rapid infusion of either lactated Ringer’s solution or 6% Hetastarch 1000 mL. 1 and 2). . the discrepancy between the two solutions did not increase further.96:1572–7 There was no need to include a correction factor for the standard ratio between large-vessel and wholebody hematocrit because the initial blood volume calculation was not based on a large-vessel hematocrit measure. Beyond 20 min. The mean change in heart rate was a reduction of 9 bpm (range. The peak increase in intravascular volume with lactated Ringer’s solution occurred immediately after completion of the rapid infusion of fluid (time ϭ 0) and was 630 Ϯ 127 mL (Figs.
8 32. . Not surprisingly. it has become apparent that IV infused crystalloid is distributed in an expandable space that is significantly smaller than the traditional extracellular volume (20% lean body mass). For lactated Ringer’s solution. For 6% Hetastarch. Also shown are mean Ϯ sd.6 32. Figure 4. In fact.2 35. There was no statistically significant reduction in the volume expansion until time ϭ 30 min.2 Increase in intravascular volume (mL)a 0 1008 (134) 1018 (110) 1017 (142) 990 (98) 986 (145) 957 (150) 917 (149) Increase in intravascular volume (mL)a 0 572 (113) 482 (86) 442 (72) 366 (77) 342 (113) 343 (103) 292 (67) 40. Figure 3. (2) particularly in the first 30 minutes after completion of the infusion. However. complex and sophisticated mathematical models have been developed that are able to predict the expansion in intravascular volume for a given volume of crystalloid infused over a set period of time. Time 0 represents the completion of the rapid infusion of fluid.2 36. where the reduction in mean volume expansion was a little over 100 mL compared with the volume expansion at time ϭ 5–10 min. the peak volume expansion occurred 5 min after completion of the infusion.9 36. Lines show the results for individual subjects. the intravascular volume expanding effect of lactated Ringer’s solution declined rapidly after its initial peak at time ϭ 0. The intravascular volume expanding effect of the 6% Hetastarch was well maintained throughout the study period. Discussion The expansion of intravascular volume by crystalloid and colloid after the process of redistribution has occurred is well documented in physiology texts (1).7 32. Peak increase in intravascular volume after rapid infusion of 1000 mL of lactated Ringer’s solution or 6% Hetastarch. Beyond 15 min.ANESTH ANALG 2003. By 15 min after completion of the infusion. Increase in intravascular volume (mean Ϯ sd) determined by hemodilution after the rapid infusion of 1000 mL of lactated Ringer’s solution or 6% Hetastarch. the mean increase in intravascular volume was only 403 Ϯ 88 mL.1 35.9). From these models. there was no further significant decline in intravascular volume.4 Group means are given in parentheses.6 32. complete redistribution to equilibrium takes significant time.96:1572–7 CARDIOVASCULAR ANESTHETIC MCILROY AND KHARASCH ACUTE INTRAVASCULAR VOLUME EXPANSION: COLLOID VERSUS CRYSTALLOID 1575 Table 1. Lactated Ringer’s Hematocrit Baseline Time 0 Time 5 Time 10 Time 15 Time 20 Time 25 Time 30 a 6% Hetastarch Hematocrit 40. and the studies on which they are based.9 33. the peak increase occurred immediately after completion of the fluid infusion. by examining the early distribution of these fluids. and more recent work has focused on the distribution of these fluids during and shortly after their infusion (2–5.5 32.5 32.8 37 37 37.
13). In the one study. This is unlikely to have had a significant impact on our primary outcome. and the rapid redistribution of lactated Ringer’s solution after the initial peak increase in intravascular volume. Most of the previous studies have infused the crystalloid into subjects over a period of 30 minutes. The intravascular volume expansion created by the crystalloid is only slightly larger than that achieved in a previous study where 900 mL of lactated Ringer’s solution was infused over 30 minutes to moderately hypovolemic volunteers or yet another study where 25 mL/kg of crystalloid was administered to normovolemic subjects over various time periods ranging from 15 minutes to 45 minutes.16). in which normovolemic volunteers received 1500 mL of lactated Ringer’s solution over 15 minutes. Despite the moderate hypovolemia and infusing the fluid rapidly. it might be expected that it would be able to reverse just as quickly with appropriate restoration of intravascular volume. the cardiac output than is the same volume of lactated Ringer’s solution. is also achieved with more rapid infusions (3. This result is consistent with the theory that at rapid infusion rates. In such a situation. the double label measurements of both plasma volume and erythrocyte volume (10) were not suitable for our study. Because of the time required for indocyanine green clearance (15. by inference. it more likely represents an effect of autotransfusion. Increased volume expansion. given the rapidity with which autotransfusion can occur. These results would suggest that for acute resuscitation. the magnitude of the change in large-vessel:whole-body hematocrit ratio with a colloid volume load similar to ours has been demonstrated to be approximately 10%. but we believe that any confounding . the compliance of the vasculature may be such that larger amounts of crystalloid can be retained within the intravascular space.1576 CARDIOVASCULAR ANESTHETIC MCILROY AND KHARASCH ACUTE INTRAVASCULAR VOLUME EXPANSION: COLLOID VERSUS CRYSTALLOID ANESTH ANALG 2003. However. However. Some have suggested increases in intravascular volume of up to 500 mL over 10 minutes because of autotransfusion. Our observation that the peak expansion of intravascular volume with 6% Hetastarch was more than the infused volume (1123 mL) and occurred 5 minutes after the completion of the infusion is not a new finding (14). Several studies have addressed this topic and found varying results (5. Typically. does it matter whether you infuse a colloid or a crystalloid to these patients while waiting for blood to arrive. The only two subjects who experienced symptomatic hypotension with the blood withdrawal had the largest increase in intravascular volume with the lactated Ringer’s solution (744 mL and 798 mL). Given that part of the mechanism of autotransfusion is believed to be a reduced capillary hydrostatic pressure operating as part of Starling’s forces. and much faster rates of crystalloid or colloid resuscitation must be used to temporize the situation. Our study may be criticized for having used the hemoglobin dilution method because of the inconstancy of the large-vessel:whole-body ratio for hematocrit. We may also be criticized for comparing two fluids of differing tonicity. the 6% Hetastarch solution is slightly hypertonic with respect to plasma (308 mOsm/L). This may represent increased amounts of autotransfusion in these subjects. so long as you do it quickly? We have demonstrated a significant difference in the ability of 6% Hetastarch and lactated Ringer’s solution to acutely expand the intravascular volume in moderately hypovolemic subjects in the period immediately after rapid infusion. The finding of a peak volume expansion that is larger than the volume administered may be explained by measurement error. the reality of anesthesia is that moderate or severe hypovolemia occurs often and when blood is not instantly available. Autotransfusion is a powerful homeostatic mechanism.9. even in the initial 5–10 minutes. at least temporarily. It may also represent an over estimation of the volume effect caused by an alteration of the large-vessel:whole-body hematocrit ratio. it seems logical that the two patients who started to decompensate from their hypovolemia may also have had the greatest degree of autotransfusion. whereas others have documented much smaller volumes. However. possibly suggesting that it was caused by the hypertonicity of the fluid in addition to a component of autotransfusion.96:1572–7 Hypovolemia also increases the amount of crystalloid retained in the intravascular space (5.9). and it may be that this is having a continuing effect of increasing intravascular volume in the time immediately after completion of the infusion. The increased intravascular volume in our subjects receiving colloid remained more than the 1000 mL infused throughout the entire 30-minute measurement period. the increase in intravascular volume did not fit the mathematical models (3). the compliance of the vasculature rapidly becomes less than the compliance of a portion of the interstitial space and so no further increase in intravascular volume occurs. with moderate hypovolemia. blood volume increases by approximately 50% of the administered volume of crystalloid. 6% Hetastarch is significantly more able to expand the intravascular volume and. there is no statistically significant difference between the increased intravascular volume measurements.12). 1000 mL of the lactated Ringer’s solution could only expand the intravascular volume by 630 Ϯ 127 mL compared with the 1123 mL Ϯ 116-mL expansion achieved by 6% Hetastarch under the same conditions. However. The delayed peak may simply represent imprecision of the measurement technique because between 0 and 25 minutes after completion of the infusion. but given that it was consistently present throughout all but one of the subjects. It may also suggest that at even more profound levels of hypovolemia.
11. In conclusion. Volume kinetics of Ringer’s solution in female volunteers. et al. 12. Iijima T. Audibert G. Prough D.96:1572–7 CARDIOVASCULAR ANESTHETIC MCILROY AND KHARASCH ACUTE INTRAVASCULAR VOLUME EXPANSION: COLLOID VERSUS CRYSTALLOID 1577 effect on the results is likely to have been small. Rheologic effects of plasma substitutes used for preoperative hemodilution. Hextend is a hydroxyethyl starch colloid in an electrolyte solution very similar to Ringer’s solution rather than normal saline. The dynamics of vascular volume and fluid shifts of lactated Ringer’s solution and hypertonic saline-dextran solutions infused in normovolemic sheep. We used healthy awake volunteers whose cardiovascular homeostatic defense mechanisms can be assumed to function optimally.25:635– 40. Sven’son C. Hahn RG. Plasma dilution and the rate of infusion of Ringer’s solution. Acta Physiol Scand 1989.90:81–91. The results of this controlled situation of moderate acute hypovolemia may.ANESTH ANALG 2003. 7th ed.13:81–9. Haruna M. rapid infusion of colloid is significantly more able to increase blood volume and. by inference. 4. v. Crit Care Med 1997. 15. the rapid infusion of lactated Ringer’s solution 1000 mL over four to five minutes can acutely expand the intravascular volume by approximately 600 mL. 16. Lundvall J. 8. Br J Anaesth 2001. Orth V. Bloch T. Hahn RG. 9. Klotz U. Our measurements did not allow us to calculate the magnitude of any autotransfusion. the same volume of 6% Hetastarch can expand intravascular volume by more than 1100 mL. By contrast. therefore. Drobin D. London: WB Saunders. Hahn RG. 3. 6.78:740 –5. Prough D. J Clin Monit 1997. Br J Anaesth 1997. Rehm M. 10. Lanne T. it will have operated equally across both colloid and crystalloid arms of the trial and is unlikely to have significantly affected the calculated difference between the two solutions in their ability to increase the intravascular volume under the conditions studied. Kroemer H. Current concepts in perioperative fluid management. Ideally. Prediction of blood volume in normal human adults. Blood volume measurement at the bedside using ICG pulse spectrophotometry. Anesthesiology 2001. these results would suggest that even for very short periods of time.92:70 –7. et al. et al. Volume kinetics of Ringer’s solution in hypovolemic volunteers.95:849 –56.12: 123–35.137:513–20. Central and regional hemodynamics during acute hypovolemia and volume substitution in volunteers. Kumon K. Nadler SB. Clinical pharmacokinetic considerations in the use of plasma expanders. Brismar B. 5. Riddez L. et al. we have demonstrated that under controlled conditions of moderate hypovolemia. Yahagi N. 2. Anesth Analg 2001. 7. Hahn RG. Nilsson A. Drobin D. Br J Anaesth 1997.93:823–31. Svensen C.78:144 – 8. . Ewaldsson CA. Anesth Analg 2001. fluid therapy. Lefevre JC.51:224 –32. et al. Textbook of physiology. cardiac output than is the same volume of crystalloid even when the crystalloid is given very rapidly.382–92. Donner M. Whereas this may potentially have affected our raw data for increase in intravascular volume. Modelling the volume of expandable body fluid spaces during i. 13. Anesthesiology 1998. Changes in blood volume and hematocrit during acute preoperative volume loading with 5% albumin or 6% hetastarch solutions in patients before radical hysterectomy. Guyton AC. Large capacity in man for effective plasma volume control in hypovolemia via fluid transfer from tissue to blood. Clin Pharmacokinet 1987. not be applicable to an anesthetized surgical population with more severe hypovolemia and shock superimposed on preexisting comorbidities.78:138 – 43. we would have used 6% Hextend as our colloid solution. Iwao Y. Within the limitations discussed. but it is not available in our institution.89:1322– 8. References 1. et al. Stahle L. Aoyagi T. Anesthesiology 1999. Hidalgo JU. Haller M. Cardiac output and circulating blood volume analysis by pulse dye-densitometry. 14.87:406 –14. Tollofsrud S. Stahle L. 1986.79:64 –7. Surgery 1962. Anesth Analg 1994. Hahn RG. Br J Anaesth 1997. The authors would like to acknowledge the efforts of Ms Christine Hoffer in the recruitment of subjects for this study. Elgjo G. Volume kinetics of Ringer’s solution during induction of spinal and general anaesthesia. Hahn RG.
This action might not be possible to undo. Are you sure you want to continue?
We've moved you to where you read on your other device.
Get the full title to continue reading from where you left off, or restart the preview.