Asian Cardiovasc Thorac Ann 2004;12:193-197
© 2004 Asia Publishing EXchange Ltd
Capillary Leakage in Cardiac Surgery with Cardiopulmonary Bypass
Yoshihiro Hamada, MD,
Kanji Kawachi, MD,
Nobuo Tsunooka, MD,
Yoshitsugu Nakamura, MD,
Shinji Takano, MD,
Hiroshi Imagawa, MD
Second Department of Surgery, Ehime University School of Medicine, Shigenobu, Japan
For reprint information contact: Yoshihiro Hamada, MD Tel: 81 743 650 372 Fax: 81 743 651 976 Email: pag63886{at}mopera.ne.jp Department of Cardiac Surgery, Takai Hospital, 461-2 Kuranosyo, Tenri, Nara 632-0006, Japan.
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ABSTRACT
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Cardiopulmonary bypass causes a systemic inflammatory response, which can lead to capillary leak syndrome. In 15 adults undergoing elective cardiac surgery with cardiopulmonary bypass, we determined the volume and peak time of capillary leakage from the measurements of extracellular fluid volume and circulating blood volume taken preoperatively, at various intervals up to 24 hours after surgery, and on the 7th postoperative day. Extracellular fluid volume rose from 15.5 ± 2.7 Lpreoperatively to a peak 4 hours after surgery of 18.3 ± 3.2 L and remained elevated at 24 hours. Circulating blood volume fell from 4.10 ± 0.68 L preoperatively to 3.20 ± 0.58 L at the end of surgery. Fluid administered intraoperatively did not raise the circulating blood volume. Intraoperative fluid balance was positive at 2.62 ± 0.72 L but negative at all time points postoperatively. There was significant postoperative capillary leakage, increasing from 4.7% ± 2.3% of body weight at the end of surgery to a peak 4 hours later of 5.4% ± 2.0% and falling to 2.8% ± 3.3% at 24 hours. This knowledge of the pattern of change in capillary leakage after cardiac surgery with cardiopulmonary bypass might serve as a valuable guide for postoperative management.
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INTRODUCTION
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Despite refinement in technique and instrumentation, cardiopulmonary bypass (CPB) still causes a systemic inflammatory response,1 which can lead to capillary leak syndrome or postperfusion syndrome.2,3 This phenomenon has been attributed to complement activation caused by reperfusion injury or exposure of blood to the foreign surfaces of the CPB circuit. The pathophysiology of this response includes endothelial injury4 and increased microvascular permeability, which, if severe enough, may develop into organ dysfunction, particularly in the lung.5 The effect of microvascular leakage is most prominent at the end of surgery, when the circulating blood volume may decrease.6 These patients may have some degree of myocardial dysfunction as well and are likely to be hemodynamically unstable. Therefore, knowledge of the pattern of change in capillary leakage following cardiac surgery with CPB could be valuable for early postoperative management. To our knowledge, capillary leakage in patients undergoing cardiac surgery with CPB has not been measured before. This study investigates capillary leakage, calculated from measurements of circulating blood volume and extracellular fluid volume, in adults undergoing cardiac surgery.
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PATIENTS AND METHODS
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Fifteen adults (10 men and 5 women) scheduled for elective cardiac surgery with CPB were enrolled in this study. All operations were performed at the same institution by the same surgeon. The study protocol was approved by the ethics committee, and written informed consent was obtained from all patients before the operation.
CPB flow was initiated at a perfusion index of 2.4 L·min–1·m–2 and then reduced according to the perfusion pressure. Mild hypothermia (rectal temperature 32°C) was induced. Myocardial protection was initiated with antegrade crystalloid cardioplegia at 10 mL·kg–1 and then maintained with blood cardioplegia at 5 mL·kg–1 every 30 minutes. After releasing the aortic crossclamp for 30 minutes at the end of surgery, when the patient’s rectal temperature had risen to at least 34°C, weaning from CPB was begun. About 5 minutes before weaning, a continuous infusion of dopamine at 5 µg·kg–1·min–1 and nitroglycerin at 0.4 µg·kg–1·min–1 was administered routinely. Upon successful weaning, the patient was managed with diuretics, vasoactive drugs, and fluid restriction as necessary.
Mean arterial pressure, heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, and central venous pressure were recorded before and after CPB, at the end of surgery, and 2, 4, 6, 12, and 24 hours after surgery. Cardiac output was also measured at these time points with a Swan-Ganz catheter.
The volume of extravascular water is defined as the difference between extracellular fluid volume and circulating blood volume. The difference between preoperative and postoperative volume of extravascular water is capillary leakage.
Extracellular fluid volume was determined using a bioimpedance spectrum analyzer (4000C; Xitron Technologies, San Diego, CA, USA), based on the principle that all membranes are virtually nonconducting at low frequencies and become short-circuited at high frequencies because of dielectric currents. The patient was placed in a supine position, and electrodes were positioned in pairs 7.5 cm apart on a wrist and an ipsilateral ankle. The reliability of this method, expressed as the coefficient of correlation between the bioimpedance spectrum method and the isotope dilution technique, has been reported as 0.879 to 0.95.7,8 The method is noninvasive and can be performed easily as a part of routine clinical care. Measurements were taken continuously before and after surgery.
Circulating blood volume was determined by pulse dye densitometry (DDG-2001; Nihon Koden, Tokyo, Japan), which involves analyzing pulsatile changes in indocyanine green (ICG) concentrations in peripheral arterial blood without direct sampling.9,10 Probes were attached to the nostril or the index finger for measurement, and a solution containing 10 mg of ICG (Diagnogreen; Dai-ichi Pharmaceutical, Tokyo, Japan) dissolved in 2 mL of distilled water was injected as a bolus via an intravenous catheter placed in the forearm, followed by a flush of 20 mL of saline. The ICG concentration was plotted semilogarithmically and extrapolated back to the mean transit time point to determine the initial ICG concentration, from which blood volume was calculated.6 Blood volume was determined preoperatively, immediately after surgery, 2, 4, 6, 12, and 24 hours postoperatively, and on the 7th postoperative day.
Net fluid intake or output during and after the operation was calculated as total fluid balance = (infusion volume + transfusion volume) – (blood loss + urine output). It was correlated with circulating blood volume.
Data are expressed as mean ± standard deviation and were statistically analyzed in Stat View version 5.0 (SAS Institute, Cary, NC, USA). One-way analysis of variance of repeated measurements was computed to detect changes during the study period. Pairwise post-hoc comparison of means was made using Fisher’s least significant difference test. Values are considered statistically significant when p < 0.05.
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RESULTS
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The demographic and clinical characteristics of the patients along with operative details are summarized in Table 1
. The patients ranged in age from 22 to 81 years. No patient required intraaortic balloon pumping or reoperation. All were discharged with no postoperative complications. Changes in major hemodynamic variables are summarized in Table 2. Heart rate and cardiac output were significantly higher after CPB and postoperatively than preoperatively. And no other hemodynamic variable was lower than its pre-CPB value except for the mean arterial pressure.
Extracellular fluid volume, shown in Figure 1A, increased after surgery and remained elevated for 24 hours, peaking at 4 hours (18.3 ± 3.2 L versus 15.5 ± 2.7 L preoperatively). Circulating blood volume, shown in Figure 1B, reached the nadir at the end of surgery (3.20 ± 0.58 L versus 4.10 ± 0.68 L preoperatively) before gradually climbing to its preoperative level. The volume 24 hours after the operation was not significantly different from the preoperative level, but on the 7th postoperative day it was again decreased. Total fluid balance, shown in Figure 1C, was positive during CPB (0.65 ± 0.72 L) as well as intraoperatively (2.62 ± 0.72 L; range, 0.92 to 5.30 L). However, this fluid gain did not correlate with the change in blood volume between before and after surgery. Thus, fluid given during surgery did not produce an increase in the circulating blood volume. The overall fluid balance was negative at all the points measured after the operation. Capillary leakage, shown in Figure 1D, peaked between 2 and 6 hours after surgery in all patients. Leakage, expressed as a percentage of preoperative body weight, was significant throughout the 24-hour postoperative study period, increasing from 4.7% ± 2.3% at the end of surgery to a peak 4 hours later of 5.4% ± 2.0% and falling to 2.8% ± 3.3% at 24 hours. By the 7th postoperative day, it had diminished to reach almost the preoperative status.
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DISCUSSION
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Complement activation and the subsequent activation of leukocytes and their sequestration into target organs are considered the major cause of capillary leak and organ dysfunction associated with the use of CPB in cardiac surgery.1–4 It has been reported that histamine11 and interleukin-812 increase capillary permeability after CPB. However, it remains unclear how much capillary leakage occurs and how long leakage persists postoperatively. This information might be useful for postoperative management. Moreover, we have shown that the production of inflammatory mediators can be reduced by using a heparin-coated circuit equipped with leukocyte-depleting filters,13 and trials on preventing capillary leak using a selectin-antagonist14 or a C1 esterase inhibitor15 have been conducted. Exact measurement of capillary leakage is important in evaluating the effectiveness of these interventions.
Techniques for measuring capillary leakage in patients with sepsis or adult respiratory distress syndrome have been described,16,17 but a simpler and easier method is needed for routine use. The bioimpedance analysis method, which has been used to measure body fluid after CPB,18,19 allows extracellular fluid volume to be determined continuously and noninvasively. Although several methods exist for measuring circulating blood volume, using for example hydroxyethyl starch or a radioactive isotope,10,20 pulse dye densitometry is noninvasive and reliable.6 The combination of these 2 methods enables a simple and straightforward determination of capillary leakage.
Patients frequently develop marked hypovolemia after cardiac surgery with CPB, requiring intravascular volume replacement in the early postoperative period to restore hemodynamic stability. This hypovolemia is thought to be due to transient microvascular injury and extravascular fluid shifts during and after CPB. However, we found that intraoperative administration of fluid did not result in an increase in circulating blood volume. Rather, blood volume shrank by about 1 L at the end of surgery, despite an increase in cardiac output and central venous pressure. Therefore, hypovolemia can exist despite a strongly positive intraoperative fluid balance. Within hours after surgery, blood volume recovered gradually in spite of a negative fluid balance. Thus, in most cases, fluid administered intraoperatively does not remain in the vascular bed but is sequestrated interstitially. These findings agree with those of studies that hypothesize, based on postoperative fluid requirements, a blood volume deficit.20 We also found that circulating blood volume was lower on the 7th postoperative day than it was preoperatively. We believe that this represents a return to a normal blood volume secondary to recovery of cardiac function.
We found significant capillary leakage throughout the 24-hour postoperative study period with a peak at 5.4% of body weight at 4 hours, although circulating blood volume had gradually returned to its preoperative level. However, several limitations to the results have to be taken into account. First, we assumed that the volume of extravascular water equals extracellular fluid volume minus circulating blood volume. Strictly speaking, extravascular water does not always correspond to this derived value. Nevertheless, this formula provides an estimate of the general amount of capillary leakage that can be used in the perioperative management of patients undergoing cardiac surgery with CPB. Second, because hemodynamic stability was restored a few hours after surgery, we did not determine capillary leakage between 24 hours after surgery and the 7th postoperative day. More data points in between should be obtained. Third, the sample size was small. However, the finding that capillary leakage peaked between 2 and 6 hours postoperatively in all the patients lends support to the results. For future studies, capillary leakage in patients undergoing cardiac surgery without CPB should be investigated to isolate the effects of CPB. Furthermore, as preoperative fluid retention may be a consequence of heart failure in some cases, capillary leakage in different types of cardiac pathology may be worth studying.
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REFERENCES
|
|---|
- Cremer J, Martin M, Redl H, Bahrami S, Abraham C, Graeter T, et al. Systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg
1996;61:1714–20.[Abstract/Free Full Text]
- Seghaye MC, Grabitz RG, Duchateau J, Busse S, Däbritz S, Koch D, et al. Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations. J Thorac Cardiovasc Surg
1996;112:687–97.[Abstract/Free Full Text]
- Smith EE, Naftel DC, Blackstone EH, Kirklin JW. Microvascular permeability after cardiopulmonary bypass. An experimental study. J Thorac Cardiovasc Surg
1987;94:225–33.[Abstract]
- Moat NE, Rebuck N, Shore DF, Evans TW, Finn AH. Humoral and cellular activation in a simulated extracorporeal circuit. Ann Thorac Surg
1993;56:1509–14.[Abstract]
- Taggart DP, el-Fiky M, Carter R, Bowman A, Wheatley DJ. Respiratory dysfunction after uncomplicated cardiopulmonary bypass. Ann Thorac Surg
1993;56:1123–8.[Abstract]
- Hamada Y, Kawachi K, Nakata T, Tsunooka N, Takano S, Kohtani T. Effects of a phosphodiesterase III inhibitor on circulating blood volume after cardiopulmonary bypass. Heart Vessels
2000;15:70–3.[Medline]
- Marta D, Loan V, Withers P, Matthie J, Mayclin PL. Use of bioimpedance spectroscopy to determine extracellular fluid, intracellular fluid, total body water, and fat-free mass. In: Ellis KJ, Eastman JD, editors. Human body composition: in vivo methods, models, and assessment. New York: Plenum Press, 1993:67–70.
- van Marken Lichtenbelt WD, Westerterp KR, Wouters L, Luijendijk SC. Validation of bioelectrical-impedance measurements as a method to estimate body-water compartments. Am J Clin Nutr
1994;60:159–66.[Abstract/Free Full Text]
- He YL, Tanigami H, Ueyama H, Mashimo T, Yoshiya I. Measurement of blood volume using indocyanine green measured with pulse-spectrophotometry: its reproducibility and reliability. Crit Care Med
1998;26:1446–51.[Medline]
- Iijima T, Iwao Y, Sankawa H. Circulating blood volume measured by pulse dye-densitometry: comparison with 131I-HSA analysis. Anesthesiology
1998;89:1329–35.[Medline]
- Marath A, Man W, Taylor KM. Histamine release in paediatric cardiopulmonary bypass — a possible role in the capillary leak syndrome. Agents Actions
1987;20:299–302.[Medline]
- Finn A, Naik S, Klein N, Levinsky RJ, Strobel S, Elliott M. Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg
1993;105:234–41.[Abstract]
- Hamada Y, Kawachi K, Nakata T, Kohtani T, Takano S, Tsunooka N. Antiinflammatory effect of heparin-coated circuits with leukocyte-depleting filters in coronary bypass surgery. Artif Organs
2001;25:1004–8.[Medline]
- Cox CS Jr, Allen SJ, Sauer H, Frederick J. Effects of selectin-sialyl Lewis blockade on mesenteric microvascular permeability associated with cardiopulmonary bypass. J Thorac Cardiovasc Surg
2000;119:1255–61.[Abstract/Free Full Text]
- Stiller B, Sonntag J, Dähnert I, Alexi-Meskishvili V, Hetzer R, Fischer T, et al. Capillary leak syndrome in children who undergo cardiopulmonary bypass: clinical outcome in comparison with complement activation and C1 inhibitor. Intensive Care Med
2001;27:193–200.[Medline]
- Marx G, Vangerow B, Burczyk C, Gratz KF, Maassen N, Cobas Meyer M, et al. Evaluation of noninvasive determinants for capillary leakage syndrome in septic shock patients. Intensive Care Med
2000;26:1252–8.[Medline]
- Ishihara H, Matsui A, Muraoka M, Tanabe T, Tsubo T, Matsuki A. Detection of capillary protein leakage by indocyanine green and glucose dilutions in septic patients. Crit Care Med
2000;28:620–6.[Medline]
- Gonzalez J, Morrissey T, Byrne T, Rizzo R, Wilmore D. Bioelectric impedance detects fluid retention in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg
1995;110:111–8.[Abstract/Free Full Text]
- Maehara T, Novak I, Wyse RK, Elliot MJ. Perioperative monitoring of total body water by bio-electrical impedance in children undergoing open heart surgery. Eur J Cardio-thorac Surg
1991;5:258–64.[Abstract]
- Tschaikowsky K, Neddermeyer U, Pscheidl E, von der Emde J. Changes in circulating blood volume after cardiac surgery measured by a novel method using hydroxyethyl starch. Crit Care Med
2000;28:336–41.[Medline]
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ABSTRACT
INTRODUCTION
