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Elevated Arterial Lactate Concentrations Early After Coronary Artery Bypass Grafting Are Associated With Increased Anaerobic Metabolism in Skeletal Muscle
Elevated Arterial Lactate Concentrations Early After Coronary Artery Bypass Grafting Are Associated With Increased Anaerobic Metabolism in Skeletal Muscle Hans Henrik Dedichen, MD,*† Jonny Hisdal, PhD,‡ Petter Aadahl, MD, PhD,* Dag Nordhaug, MD, PhD,*¶ Per Olav Olsen, MD,§ and Idar Kirkeby-Garstad, MD, PhD§ Objective: To assess the effect of coronary artery bypass grafting with cardiopulmonary bypass on muscle perfusion, oxygen extraction, and lactate release during postoperative rest and exercise. Design: Prospective observational study. Setting: University hospital. Participants: Patients undergoing planned coronary artery bypass grafting. Intervention: Knee-extensor exercise before and after coronary artery bypass grafting. Measurements and Main Results: Femoral artery blood flow was measured with ultrasound. Femoral vein blood and arterial blood were sampled at rest and during light exercise and were analyzed for hemoglobin, lactate, oxygen saturation, and oxygen partial pressure. Fourteen patients were tested before and after surgery. The arterial lactate concentrations were increased after surgery, both at rest and during light exercise. Resting arterial lactate increased from 0.65 (0.5-0.8) to 1.0 (0.9-1.3) mmol/L (p ¼ 0.01) (median and interquartile range).
Furthermore, lactate was released from the leg even during postoperative rest, and the release of lactate was increased during postoperative exercise. There were no significant differences between the preoperative and postoperative femoral artery blood flow. Femoral vein oxygen partial pressure was reduced significantly after surgery, indicating reduced muscle cell oxygen partial pressure. Conclusions: The patients had elevated anaerobic metabolism in skeletal muscle after surgery to compensate for anemia. Lactate was released from the leg into the general circulation during postoperative rest and exercise. The postoperatively reduced hemoglobin concentration of 11.4 mg/dL (10.6-12.3) resulted in increased anaerobic metabolism and release of lactate from skeletal muscle. The authors concluded that coronary artery bypass grafting patients are susceptible to anaerobic metabolism even with maintained peripheral blood flow. & 2015 Elsevier Inc. All rights reserved.
T
To test the hypothesis that the skeletal muscle’s ability to extract oxygen is preserved after CABG with CPB, CABG patients were examined during one-legged knee-extensor exercises before and the day after surgery.
EMPORARY IMPAIRED FUNCTION is common in several organ systems after cardiac surgery with the use of cardiopulmonary bypass (CPB).1–3 Mandak et al used microdialysis to compare the metabolism and perfusion of skeletal muscle in coronary artery bypass grafting (CABG) patients who underwent surgery with and without CPB.4 They reported increased skeletal muscle aerobic metabolism in patients who did not undergo CPB. The difference in aerobic metabolism did not arise from differences in tissue perfusion, which was similar in both groups. Mandak et al suggested that cardiopulmonary bypass compromises skeletal muscle energy metabolism. Other investigators have suggested that cardiac surgery with CPB decreases the extraction of oxygen from blood, implying either a cytotoxic effect or a microcirculatory mismatch.5,6 In patients with impaired oxygen extraction, increased blood lactate concentrations and relatively high venous oxygen levels may occur simultaneously. Reduced oxygen extraction often is referred to as “dysoxia”, and the resulting lactatemia is classified as type B. The authors previously observed increased arterial lactate concentrations in CABG patients during early postoperative leg exercise even when cardiac output was increased and global oxygen consumption was maintained.7 Other investigators have reported results supporting increased regional anaerobic metabolism in the gut after cardiac surgery with CPB.8 Therefore, a study of blood flow and metabolism of one region of the body was considered valuable to extend the knowledge from studies of cardiac output and whole body oxygen consumption. The aim of the present study was to illuminate the effect of cardiac surgery with CPB on the perfusion, oxygen extraction, and metabolism of skeletal muscle. Knee-extensor exercises were used—an exercise model that is suitable for the study of skeletal muscle and has limited effects on systemic hemodynamics,9 such as cardiac output and systemic vascular resistance, which were not aims of the present study.
KEY WORDS: cardiac surgery, postoperative care, lactate, oxygen consumption
METHODS Patients who were admitted to the authors’ institution for planned CABG without concomitant procedures between January 2009 and June 2010 were included. The inclusion criteria were stable angina pectoris without severe activity limitations (Canadian Cardiovascular Society grade 2 or 3) and consent to participate in the study. All of the patients showed evidence of severe coronary artery disease with wellpreserved systolic function of the left ventricle and no significant valve disease. The exclusion criteria were unstable coronary artery disease, heart failure, chronic obstructive pulmonary disease more severe than stage 2 of the Global Initiative for Chronic Obstructive Lung Disease classification, renal disease, hepatic failure, or impaired mobility. The study was approved by the Regional Committee for Medical and
From the *Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; †K. G. Jebsen Center for Exercise in Medicine, Norwegian University of Science and Technology, Trondheim, Norway; ‡Section for Vascular Investigations, Oslo Vascular Centre, Oslo University Hospital Aker, Oslo, Norway; §Department of Cardiothoracic Anesthesiology and Intensive Care, St. Olav’s Hospital, Trondheim, Norway; and ¶Department of Cardiothoracic Surgery; St. Olav’s Hospital, Trondheim, Norway. Address reprint requests to Hans Henrik Dedichen, Department of Circulation and Medical Imaging, St. Olav’s Hospital, Prinsesse Kristinas Gate 3, Akutten og Hjertelungesenteret, 7006 Trondheim, Norway. E-mail: [email protected] © 2015 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.08.001
Journal of Cardiothoracic and Vascular Anesthesia, Vol 29, No 2 (April), 2015: pp 367–373
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Healthcare Research Ethics, Mid-Norway (approval no. 4.2008.1614). All of the patients gave written consent and were allowed to withdraw from the study at any time. The study was conducted in accordance with the Helsinki Declaration. The patients received the standard treatment at the authors’ institution. Anesthesia was induced with diazepam, thiopental, fentanyl, and pancuronium, and maintained with isoflurane and fentanyl. During CPB, the patients were sedated with propofol. The CPB circuit consisted of a roller pump and a microporous polypropylene hollow-fiber oxygenator (Medtronic Affinity NT, Medtronic, Minneapolis, MN) with an open reservoir (Medtronic Affinity CRV). The oxygenator and tubings were all heparin coated, and the circuit was primed with 1,700 mL of Ringer’s acetate containing 7,500 U of heparin. Nonpulsatile flow at a rate of 2.4 L/min/m2, alpha-stat blood gas control, and cooling to 34 1C in venous blood were used. Activated clotting time was kept above 480 s, with the initial administration of heparin (Leo, Copenhagen, Denmark), 300 U/kg, and additional doses as indicated. Cardiotomy suction was used when activated clotting time was above 480 seconds. After CPB, heparinization was reversed with protamine sulfate at a 1:1 ratio. The heart was arrested with aortic cross-clamping and the infusion of cold St. Thomas Hospital cardioplegia solution. Revascularization was performed by anastomosing the left internal mammary artery to the left anterior descending artery and placing saphenous vein grafts from the ascending aorta to the circumflex and the right coronary arteries. The vein grafts were harvested from the left leg. In this study, preoperative test results were compared with postoperative results. The same test protocol was used in both tests. The preoperative test took place on the day of surgery, with the patients fasted and prepared for surgery. The postoperative test took place on the first morning after surgery. The patients breathed room air preoperatively and were given 3-5 L O2/min postoperatively. Inotropic and vasoactive infusions were terminated before the postoperative test. Preparations for the postoperative test did not begin until the patients were circulatorystable without vasoactive or inotropic support. Postoperative chest x-rays were examined and approved, and drains were removed before testing. One-leg knee extensor exercise was used because it enables the exercise of a small muscle group with reproducible intensity and limited effect on cardiac output and hemodynamics. This exercise model permits assessment of quadriceps blood flow through the measurement of the femoral artery blood flow and quadriceps metabolism trough analysis of arterial blood and femoral vein blood.10 The patient sat in a comfortable armchair with the left leg on a footstool (Fig 1). The right foot was connected to the cycle pedal with a boot and a light aluminum rod. The ergometer automatically adjusts braking to pedaling frequency to maintain a constant level of exercise intensity and allow workload adjustments in 1-watt increments (Monarc Ergomedic 828E, Monark, Sweden). The ergometer was zeroed and calibrated according to the manufacturer’s instructions. To minimize the increases in cardiac output, the exercise intensity was very low. The first measurements were taken before the exercise
Fig 1. Knee extensor exercise. A schematic drawing of the set-up of the knee-extensor test. The left leg was positioned on a footstool, and the right leg was connected to the pedal of the cycle ergometer.
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Fig 2. Measurement of femoral artery blood flow. Example of measurement of femoral artery blood flow at rest (A) and during light exercise (B). Note that the blood flow is reversed in diastole at rest.
began while the foot was connected to the ergometer. At the lowest intensity level, no ergometer resistance was set (unloaded pedaling). Thereafter, the load was increased gradually to 1, 2, and 5 watts with 2 minutes of rest between each 3-minute session. The pedaling frequency was 50-60 kicks/minutes.
Measurements Heart rate was measured continuously with a 5-lead electrocardiogram. The heart rate readings from the last 30 seconds of each 3-minute session of cycling for each workload were averaged and used in the analysis. Arterial pressure was measured via a catheter inserted into the left radial artery connected to a pressure transducer (Edwards Lifesciences, pressure monitoring transducers, Irvine, CA). Leg blood flow was measured in the common femoral artery using ultrasound Doppler in the first 10 seconds immediately after each 3minute session (Fig 2). The ultrasound probe was held by hand over the femoral artery with the smallest possible insonation angle. A constant angle of insonation was maintained by supporting the hand at the patient’s leg. The sample volume was adjusted to achieve pulsed Doppler signals from the entire lumen of the artery below the inguinal ligament and above the bifurcation of the superficial femoral artery and the profunda artery using a 12-MHz linear array probe connected to a Vivid 7 ultrasound scanner (Vingmed Horten, Norway). The recordings were postprocessed with automatic tracing of the velocity signals and angle correction. The vessel diameter was measured during end-diastole. Femoral vein blood was sampled from a catheter with an outer diameter of 2.1 mm inserted below the inguinal ligament and approximately 5 cm into the femoral vein (Certofix Mono S315, Braun, Melsungen, Germany).
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RESULTS
Table 1. Patient Characteristics Characteristics
Age (years) Male sex Height (cm) Weight (kg) Hypertension Diabetes mellitus CCS class III EF angiography (%) EF echocardiography (%) Three-vessel disease or left main stenosis CPB time (min) Aorta cross-clamp time (min) Number of bypasses Patients receiving transfusion
62 13 178 83 5 4 11 62 50 10 61 41 4 1
(13) [93] (8) (14) [36] [29] [79] (11) (8) [71] (23) (15) (1) [7]
Seventeen patients were included in the study. Three patients were not tested postoperatively because of nausea (2) and bleeding (1). The clinical characteristics of the 14 patients who were tested preoperatively and postoperatively are
NOTE. Values are median (interquartile range) and number [%]. Abbreviations: CCS, Canadian Cardiovascular Society; CPB, cardiopulmonary bypass; EF, ejection fraction.
Arterial blood was sampled from a radial artery catheter and used as a substitute for femoral artery blood. The catheters were placed using a local anesthetic cream and infiltration anesthesia. Arterial and venous blood samples were drawn during the last 15 seconds of each cycling session, and blood gases and lactate concentrations were analyzed immediately (ABL 800 Radiometer, Copenhagen, Denmark). With this apparatus, the coefficients of variation are 6.2% for lactate and 3.9% for oxygen partial pressure in the actual measurement areas.11 Central venous lines and bladder catheters were inserted after the preoperative test. Finger pulse oximetry was used continuously in the intensive care unit. The data were analyzed using the statistical software package Stata IC 12 (Stata Corp, Lakeway Drive, College Station, TX). Because a normal distribution for all of the variables could not be confirmed, the results are presented as medians with 25th and 75th percentiles. The resting data were analyzed using the Wilcoxon signed-rank test. A linear relationship was assumed between exercise intensity and the variables measured during exercise. The exercise data were analyzed in a mixed linear regression model to analyze changes in measured variables before and after surgery and differences in the response to exercise before and after surgery. The observations were clustered in patients, with exercise intensity as a continuous covariate and surgery as an indicator covariate. The p values indicated the differences between the preoperative values and the postoperative values. The residuals from the linear model were displayed on histograms and showed normal distribution when inspected graphically. Pilot tests indicated an increased release of lactate and the extraction of a large fraction of oxygen at low intensities. Sample size calculations estimated that significant differences were demonstrable with as few as 10 patients with paired t test (significance level: 0.05; power: 0.8). Table 2. Resting Heart Rate, Hemoglobin, Arterial Saturation, and Oxygen Content Preoperative
Postoperative
p Value
Hemoglobin (mg/dL) 14.0 (13.4-14.7) 11.4 (10.6-12.3) o0.001 Arterial oxygen saturation 97.4 (96.1-98.4) 97.9 (97.3-98.7) 0.15 (%) Arterial oxygen content 18.3 (16.8-19.4) 14.8 (13.6-16.5) o0.001 (mL/dL) Serum glucose (mmol/L) 6.2 (5.9-6.9) 7.1 (6.6-8.0) 0.03 Alanine transaminase (U/L) 33 (23-42) 24 (18-29) 0.01 NOTE. Values are median (interquartile range). The p value was calculated with the Wilcoxon signed rank test.
Fig 3. Leg blood flow, oxygen extraction rate, and oxygen partial pressure in femoral vein blood. (A) Leg blood flow measured in the femoral artery with pulsed-wave Doppler in mL/min. (B) Oxygen extraction rate calculated from arterial blood oxygen content and femoral vein blood oxygen content (%). (C) Femoral vein oxygen partial pressure, reflecting femoral muscle cell oxygen partial pressure. Values are median, before surgery (circles), and after surgery (filled squares). Error bars indicate 25th percentiles and 75th percentiles. The p values for difference between preoperative and postoperative measurements are given for rest and exercise, respectively. Wilcoxon signed-rank test was used for resting data and mixed model linear regression for exercise data.
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summarized in Table 1. None of the patients experienced atrial fibrillation, significant hypotension, or other adverse events during or after testing. One patient received 1 unit of packed red cells after surgery. All of the patients recovered well and were alive 3 months later. All 14 patients completed the postoperative test at the lowest resistance; 12 completed the 1-watt test, 10 completed the 2-watt test, and 7 completed the 5-watt test. The hemoglobin concentration was reduced after surgery (p o 0.01) while arterial oxygen saturation was maintained (p ¼ 0.15; Table 2). Statistically significant differences between preoperative and postoperative leg blood flow could not be detected at rest (p ¼ 0.06) or during exercise (p ¼ 0.08; Fig 3A). Light exercise caused the leg blood flow to increase markedly. This marked increase in leg blood flow also was present after surgery (Fig 3). The oxygen extraction rate at rest was increased significantly after surgery (p ¼ 0.03) from 58% (54%-63%) to 66% (58%-70%). This increase was sustained during exercise (p o 0.001; Fig 3B). The femoral vein oxygen partial pressure (pO2) was reduced after surgery, indicating lower oxygen pressure in the femoral muscle cells (Fig 3C). At rest, the venous pO2 was 24.0 mmHg (21.8-27.0) before and 21.8 mmHg (19.5-24.8) after surgery (p ¼ 0.03). The venous pO2 also was reduced significantly during postoperative exercise (p o 0.01). The arterial lactate concentration was increased after surgery; at rest, it increased from 0.65 mmol/L (0.5-0.8) to 1.0 mmol/L (0.9-1.3) (p ¼ 0.01; Fig 4A). An increased difference between arterial and venous lactate concentrations was observed at postoperative rest, indicating an increased release of lactate: 0.1 mmol/L (0-0.3) v 0.6 mmol/L (0.4-0.7; p o 0.01). A similar increase also was found during postoperative exercise (p o 0.01; Fig 4B). During CPB, the maximal arterial lactate was 1.15 mmol/L (1.0-1.45). On arrival at the intensive care unit, the median arterial lactate concentration was 1.1 mmol/L (0.9-1.3). Heart rates and blood pressures are shown in Fig 5. Before CABG, there was no association between femoral vein pO2 and the venoarterial lactate difference. However, venous pO2 was reduced significantly after surgery; furthermore, linear regression analysis confirmed a
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negative correlation between venous pO2 and the difference between arterial and venous lactate concentrations (p ¼ 0.03; Fig 6). DISCUSSION
The most important finding in the present study was that circulatory stable, low-risk CABG patients with normal arterial oxygen saturation and a postoperative hemoglobin concentration of 11.4 g/dL had a significant efflux of lactate from the skeletal muscles during postoperative rest and exercise, as determined by the venoarterial difference in lactate concentrations. At preoperative rest, the venous lactate concentration was only slightly higher than the arterial lactate concentration; whereas during postoperative rest, the venous lactate concentration was almost twice as high as the arterial lactate concentration. Comparable findings were observed during exercise. Results indicated that skeletal muscle metabolism was shifted toward more anaerobic metabolism after surgery and that lactate was released from the large muscle groups in the legs. The results further indicated that the lactate released from skeletal muscles contributed to increasing the arterial lactate concentration on the first postoperative day. Another important finding was that increased anaerobic metabolism was associated with increased oxygen extraction rate in the leg, indicating that increased anaerobic metabolism was caused by reduced oxygen delivery and not by reduced oxygen extraction ability in skeletal muscle. Linear regression showed that there was a negative correlation between femoral vein pO2 and veno-arterial differences in lactate concentration during postoperative exercise; this finding indicated that anaerobic metabolism was indeed associated with reduced intramuscular oxygen partial pressure. Before surgery, there was no association between femoral vein pO2 and the veno-arterial lactate difference. It is also of note that a marked increase in leg blood flow occured during very light exercise and that this response was not attenuated after surgery. The maintained postoperative response indicated that the local regulation of blood flow was not blunted after cardiac surgery with CPB.
Fig 4. Concentrations of lactate in arterial blood and in femoral vein blood. (A) Arterial lactate concentrations before surgery (circles) and after surgery (filled squares). (B) Venous lactate concentrations before surgery (circles) and after surgery (filled squares). Values are median, error bars indicate 25th percentiles, and 75th percentiles. The p values for difference between preoperative and postoperative measurements are given for rest and exercise, respectively. Wilcoxon signed-rank test was used for resting data and mixed model linear regression for exercise data.
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enough to prevent significant reductions in venous pO2 after surgery. Results showed that lactate was transported away from the skeletal muscles on the day after CABG. The release of lactate from the skeletal muscles may be seen as a “lactate shuttle,” a term first introduced by Brooks et al.12 This means that the release of lactate from skeletal muscle is normal, even during exercise of moderate intensity. Released lactate is transported to better-oxygenated tissues, mainly the myocardium, for oxidative metabolism. Results showed that after surgery, lactate was released from skeletal muscle even before exercise began. In other words, anaerobic metabolism was needed for energy production, most likely because postoperative anemia resulted in intramuscular oxygen partial pressures that were too low for sufficient energy production by aerobic metabolism alone. The term “critical hemoglobin concentration” may be used to describe the lowest hemoglobin concentration that does not result in increased anaerobic metabolism. The critical hemoglobin concentration varies among individuals and exercise intensities and also is different in different tissues.13 Results show, that even 11.4 g/dL was below the critical hemoglobin concentration for leg muscle. Weisskopf et al reported that resting, healthy, and young individuals were able to compensate for anemia as low as 4.5 g/dL with increased cardiac index and increased oxygen extraction without any increase in lactate levels,14 illustrating the wide difference in critical hemoglobin level between healthy and diseased persons. A well-performed study by Koskolou et al studied the effect of acute anemia on leg metabolism and blood flow in healthy young men during knee extensor exercise.15 In that study, the withdrawal of blood and substitution of the removed blood volume with an albumin solution reduced hemoglobin from 14.4 g/dL ⫾ 3.8 g/dL (mean ⫾ standard error) to 11.5 g/dL ⫾ 1.9 g/dL, values almost identical to the
Fig 5. Heart rate, systolic blood pressure, and diastolic blood pressure. (A). Heart rate. (B) Systolic blood pressure measured in radial artery catheter. (C) Diastolic blood pressure measured in radial artery catheter. Values are median, before surgery (circles), and after surgery (filled squares). Error bars indicate 25th percentiles and 75th percentiles. The p values for difference between preoperative and postoperative measurements are given for rest and exercise, respectively. Wilcoxon signed-rank test was used for resting data and mixed model linear regression for exercise data.
va Lactate difference (mmol/L)
2.5
2.0
1.5
1.0
0.5
0.0 12
14
16
18
20
22
24
26
28
Venous oxygen pressure (mmHg)
The large natural variations in blood flow in the femoral artery and a possible lack of statistical power may explain why no statistical difference between preoperative and postoperative leg blood flow was observed. However, the possible postoperative increase in blood flow was not large
Fig 6. Postoperative venoarterial lactate difference/femoral vein oxygen pressure. Postoperative oxygen partial pressure plotted against the corresponding difference between femoral vein lactate concentration and arterial lactate concentration. Lines are linear regression line (middle) and 95% CI of regression line (upper and lower lines).
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preoperative and postoperative hemoglobin concentrations in the present study. Neither the present study nor the study by Koskolou et al found any increase in resting leg blood flow during acute anemia. The most striking difference between patients in the present study and the young healthy people in the previous study was that young healthy individuals compensated for acute anemia solely by increasing oxygen extraction, and CABG patients also relied on increased anaerobic metabolism. At rest, the young men in the Koskolou et al study increased their oxygen extraction rate from 50% to 56% after blood withdrawal and volume substitution, and the anemic resting venous pO2 was 25.0 ⫾ (0.7) mmHg. Anaerobic metabolism was not increased during light exercise in acute anemia; there were no differences between the arterial and venous lactate concentrations at rest or during 30 watts of exercise. The CABG patients in the present study had an oxygen extraction rate of 58% (54%-63%) at preoperative rest and 67% (58%70%) at postoperative rest, and the postoperative resting venous pO2 was 21.8 (19.5-24.8) mmHg. The authors hypothesized that the difference in venous pO2 during anemia was why CABG patients had increased anaerobic metabolism at a hemoglobin concentration that did not increase anaerobic metabolism in healthy young men. Comparably high oxygen extraction rates and low venous pO2 previously has been shown in patients with chronic heart failure16 and may result from reduced muscle capillary density and sympathetically mediated vasoconstriction.17 The use of beta-blockers also may contribute to reduced muscle perfusion. Ades et al studied the effects of a training program in coronary patients and reported that the increase in peak aerobic capacity was associated almost exclusively with peripheral skeletal muscle adaptions with no discernible improvement in cardiac output or calf blood flow.18 Reduced muscular capillarity and other muscular changes secondary to inactivity are an attractive explanation of why the present patients had anaerobic metabolism with hemoglobin levels of 11.4 g/dL.
The results of the present study did not indicate any dysfunction in the extraction or utilization of oxygen in skeletal muscle after CABG with CPB. The patients in the present study were not in oxygen debt after the operation, as judged by the lactate levels during CPB and on arrival to the intensive care unit. This means that lactate levels measured during the test reflected the oxygenation and metabolism at the time of testing. The authors suspected that elevated intraoperative and postoperative arterial lactate levels, as reported by Shinde et al, may depend on different CPB management, which may cause metabolic derangement and possible tissue dysfunction.19 This was a study of low-risk patients and may not provide valid conclusions for all cardiac surgery patients. More complicated surgery on high-risk patients may have a larger impact on postoperative cardiac and vascular function that may result in altered muscle perfusion. The exercise intensity was very low in the present study, and it is possible that more intense exercise may have resulted in significant differences in preoperative and postoperative leg blood flow. However, the study did not aim to test cardiac function; therefore, low exercise intensities were used to minimize possible confounding by reduced myocardial function. The present study found an increased release of lactate from skeletal muscle to the general circulation on the first day after cardiac surgery, both at rest and during light exercise. The leg blood flow was similar before and after surgery, resulting in reduced oxygen delivery because of postoperative anemia. The oxygen extraction rate was increased after surgery, and the suspicion of impaired oxygen extraction was not supported. The main clinical implication of this study was that uncomplicated CABG patients who maintain tissue perfusion and have hemoglobin concentrations that are common in the postoperative situation are susceptible to increased anaerobic metabolism in peripheral tissues. Early postoperative anaerobic metabolism in skeletal muscle may be reduced by minimizing perioperative blood loss.
CONCLUSIONS
A hemoglobin concentration of 11.4 g/dL was too low to maintain the preoperative balance between aerobic and anaerobic metabolism in this group of CABG patients.
ACKNOWLEDGMENTS The authors acknowledge the nurses of the cardiothoracic intensive care unit for participation in conducting the tests.
REFERENCES 1. Huen SC, Parikh CR: Predicting acute kidney injury after cardiac surgery: A systematic review. Ann Thorac Surg 93:337-347, 2012 2. Lombard FW, Mathew JP: Neurocognitive dysfunction following cardiac surgery. Semin Cardiothorac Vasc Anesth 14:102-110, 2010 3. Dong G, Liu C, Xu B, et al: Postoperative abdominal complications after cardiopulmonary bypass. J Cardiothorac Surg 7: 108, 2012 4. Mandak J, Pojar M, Cibicek N, et al: Impact of cardiopulmonary bypass on peripheral tissue metabolism and microvascular blood flow. Perfusion 23:339-346, 2008 5. Raper RF, Cameron G, Walker D, et al: Type B lactic acidosis following cardiopulmonary bypass. Crit Care Med 25:46-51, 1997 6. Inoue S, Kuro M, Furuya H: What factors are associated with hyperlactatemia after cardiac surgery characterized by well-maintained
oxygen delivery and a normal postoperative course? A retrospective study. Eur J Anaesthesiol 18:576-584, 2001 7. Kirkeby-Garstad I, Wisloff U, Skogvoll E, et al: The marked reduction in mixed venous oxygen saturation during early mobilization after cardiac surgery: The effect of posture or exercise? Anesth Analg 102:1609-1616, 2006 8. Solligard E, Wahba A, Skogvoll E, et al: Rectal lactate levels in endoluminal microdialysate during routine coronary surgery. Anaesthesia 62:250-258, 2007 9. Râdegran G: Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans. J Appl Physiol (1985) 83:1383-1388, 1997 10. Andersen P, Adams RP, Sjogaard G, et al: Dynamic knee extension as model for study of isolated exercising muscle in humans. J Appl Physiol 59:1647-1653, 1985
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11. De Koninck AS, De Decker K, Van Bocxlaer J, et al: Analytical performance evaluation of four cartridge-type blood gas analyzers. Clin Chem Lab Med 50:1083-1091, 2012 12. Brooks GA: Lactate production under fully aerobic conditions: the lactate shuttle during rest and exercise. Fed Proc 45:2924-2929, 1986 13. Tsui AK, Dattani ND, Marsden PA, et al: Reassessing the risk of hemodilutional anemia: Some new pieces to an old puzzle. Can J Anaesth 57:779-791, 2010 14. Weiskopf RB, Viele MK, Feiner J, et al: Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA 279:217-221, 1998 15. Koskolou MD, Roach RC, Calbet JA, et al: Cardiovascular responses to dynamic exercise with acute anemia in humans. Am J Physiol 273:H1787-H1793, 1997
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16. Katz SD, Maskin C, Jondeau G, et al: Near-maximal fractional oxygen extraction by active skeletal muscle in patients with chronic heart failure. J Appl Physiol (1985) 88:2138-2142, 2000 17. Poole DC, Hirai DM, Copp SW, et al: Muscle oxygen transport and utilization in heart failure: Implications for exercise (in)tolerance. Am J Physiol Heart Circ Physiol 302:H1050-H1063, 2012 18. Ades PA, Waldmann ML, Meyer WL, et al: Skeletal muscle and cardiovascular adaptations to exercise conditioning in older coronary patients. Circulation 94:323-330, 1996 19. Shinde SB, Golam KK, Kumar P, et al: Blood lactate levels during cardiopulmonary bypass for valvular heart surgery. Ann Card Anaesth 8:39-44, 2005
Furthermore, lactate was released from the leg even during postoperative rest, and the release of lactate was increased during postoperative exercise. There were no significant differences between the preoperative and postoperative femoral artery blood flow. Femoral vein oxygen partial pressure was reduced significantly after surgery, indicating reduced muscle cell oxygen partial pressure. Conclusions: The patients had elevated anaerobic metabolism in skeletal muscle after surgery to compensate for anemia. Lactate was released from the leg into the general circulation during postoperative rest and exercise. The postoperatively reduced hemoglobin concentration of 11.4 mg/dL (10.6-12.3) resulted in increased anaerobic metabolism and release of lactate from skeletal muscle. The authors concluded that coronary artery bypass grafting patients are susceptible to anaerobic metabolism even with maintained peripheral blood flow. & 2015 Elsevier Inc. All rights reserved.
T
To test the hypothesis that the skeletal muscle’s ability to extract oxygen is preserved after CABG with CPB, CABG patients were examined during one-legged knee-extensor exercises before and the day after surgery.
EMPORARY IMPAIRED FUNCTION is common in several organ systems after cardiac surgery with the use of cardiopulmonary bypass (CPB).1–3 Mandak et al used microdialysis to compare the metabolism and perfusion of skeletal muscle in coronary artery bypass grafting (CABG) patients who underwent surgery with and without CPB.4 They reported increased skeletal muscle aerobic metabolism in patients who did not undergo CPB. The difference in aerobic metabolism did not arise from differences in tissue perfusion, which was similar in both groups. Mandak et al suggested that cardiopulmonary bypass compromises skeletal muscle energy metabolism. Other investigators have suggested that cardiac surgery with CPB decreases the extraction of oxygen from blood, implying either a cytotoxic effect or a microcirculatory mismatch.5,6 In patients with impaired oxygen extraction, increased blood lactate concentrations and relatively high venous oxygen levels may occur simultaneously. Reduced oxygen extraction often is referred to as “dysoxia”, and the resulting lactatemia is classified as type B. The authors previously observed increased arterial lactate concentrations in CABG patients during early postoperative leg exercise even when cardiac output was increased and global oxygen consumption was maintained.7 Other investigators have reported results supporting increased regional anaerobic metabolism in the gut after cardiac surgery with CPB.8 Therefore, a study of blood flow and metabolism of one region of the body was considered valuable to extend the knowledge from studies of cardiac output and whole body oxygen consumption. The aim of the present study was to illuminate the effect of cardiac surgery with CPB on the perfusion, oxygen extraction, and metabolism of skeletal muscle. Knee-extensor exercises were used—an exercise model that is suitable for the study of skeletal muscle and has limited effects on systemic hemodynamics,9 such as cardiac output and systemic vascular resistance, which were not aims of the present study.
KEY WORDS: cardiac surgery, postoperative care, lactate, oxygen consumption
METHODS Patients who were admitted to the authors’ institution for planned CABG without concomitant procedures between January 2009 and June 2010 were included. The inclusion criteria were stable angina pectoris without severe activity limitations (Canadian Cardiovascular Society grade 2 or 3) and consent to participate in the study. All of the patients showed evidence of severe coronary artery disease with wellpreserved systolic function of the left ventricle and no significant valve disease. The exclusion criteria were unstable coronary artery disease, heart failure, chronic obstructive pulmonary disease more severe than stage 2 of the Global Initiative for Chronic Obstructive Lung Disease classification, renal disease, hepatic failure, or impaired mobility. The study was approved by the Regional Committee for Medical and
From the *Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; †K. G. Jebsen Center for Exercise in Medicine, Norwegian University of Science and Technology, Trondheim, Norway; ‡Section for Vascular Investigations, Oslo Vascular Centre, Oslo University Hospital Aker, Oslo, Norway; §Department of Cardiothoracic Anesthesiology and Intensive Care, St. Olav’s Hospital, Trondheim, Norway; and ¶Department of Cardiothoracic Surgery; St. Olav’s Hospital, Trondheim, Norway. Address reprint requests to Hans Henrik Dedichen, Department of Circulation and Medical Imaging, St. Olav’s Hospital, Prinsesse Kristinas Gate 3, Akutten og Hjertelungesenteret, 7006 Trondheim, Norway. E-mail: [email protected] © 2015 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.08.001
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Healthcare Research Ethics, Mid-Norway (approval no. 4.2008.1614). All of the patients gave written consent and were allowed to withdraw from the study at any time. The study was conducted in accordance with the Helsinki Declaration. The patients received the standard treatment at the authors’ institution. Anesthesia was induced with diazepam, thiopental, fentanyl, and pancuronium, and maintained with isoflurane and fentanyl. During CPB, the patients were sedated with propofol. The CPB circuit consisted of a roller pump and a microporous polypropylene hollow-fiber oxygenator (Medtronic Affinity NT, Medtronic, Minneapolis, MN) with an open reservoir (Medtronic Affinity CRV). The oxygenator and tubings were all heparin coated, and the circuit was primed with 1,700 mL of Ringer’s acetate containing 7,500 U of heparin. Nonpulsatile flow at a rate of 2.4 L/min/m2, alpha-stat blood gas control, and cooling to 34 1C in venous blood were used. Activated clotting time was kept above 480 s, with the initial administration of heparin (Leo, Copenhagen, Denmark), 300 U/kg, and additional doses as indicated. Cardiotomy suction was used when activated clotting time was above 480 seconds. After CPB, heparinization was reversed with protamine sulfate at a 1:1 ratio. The heart was arrested with aortic cross-clamping and the infusion of cold St. Thomas Hospital cardioplegia solution. Revascularization was performed by anastomosing the left internal mammary artery to the left anterior descending artery and placing saphenous vein grafts from the ascending aorta to the circumflex and the right coronary arteries. The vein grafts were harvested from the left leg. In this study, preoperative test results were compared with postoperative results. The same test protocol was used in both tests. The preoperative test took place on the day of surgery, with the patients fasted and prepared for surgery. The postoperative test took place on the first morning after surgery. The patients breathed room air preoperatively and were given 3-5 L O2/min postoperatively. Inotropic and vasoactive infusions were terminated before the postoperative test. Preparations for the postoperative test did not begin until the patients were circulatorystable without vasoactive or inotropic support. Postoperative chest x-rays were examined and approved, and drains were removed before testing. One-leg knee extensor exercise was used because it enables the exercise of a small muscle group with reproducible intensity and limited effect on cardiac output and hemodynamics. This exercise model permits assessment of quadriceps blood flow through the measurement of the femoral artery blood flow and quadriceps metabolism trough analysis of arterial blood and femoral vein blood.10 The patient sat in a comfortable armchair with the left leg on a footstool (Fig 1). The right foot was connected to the cycle pedal with a boot and a light aluminum rod. The ergometer automatically adjusts braking to pedaling frequency to maintain a constant level of exercise intensity and allow workload adjustments in 1-watt increments (Monarc Ergomedic 828E, Monark, Sweden). The ergometer was zeroed and calibrated according to the manufacturer’s instructions. To minimize the increases in cardiac output, the exercise intensity was very low. The first measurements were taken before the exercise
Fig 1. Knee extensor exercise. A schematic drawing of the set-up of the knee-extensor test. The left leg was positioned on a footstool, and the right leg was connected to the pedal of the cycle ergometer.
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Fig 2. Measurement of femoral artery blood flow. Example of measurement of femoral artery blood flow at rest (A) and during light exercise (B). Note that the blood flow is reversed in diastole at rest.
began while the foot was connected to the ergometer. At the lowest intensity level, no ergometer resistance was set (unloaded pedaling). Thereafter, the load was increased gradually to 1, 2, and 5 watts with 2 minutes of rest between each 3-minute session. The pedaling frequency was 50-60 kicks/minutes.
Measurements Heart rate was measured continuously with a 5-lead electrocardiogram. The heart rate readings from the last 30 seconds of each 3-minute session of cycling for each workload were averaged and used in the analysis. Arterial pressure was measured via a catheter inserted into the left radial artery connected to a pressure transducer (Edwards Lifesciences, pressure monitoring transducers, Irvine, CA). Leg blood flow was measured in the common femoral artery using ultrasound Doppler in the first 10 seconds immediately after each 3minute session (Fig 2). The ultrasound probe was held by hand over the femoral artery with the smallest possible insonation angle. A constant angle of insonation was maintained by supporting the hand at the patient’s leg. The sample volume was adjusted to achieve pulsed Doppler signals from the entire lumen of the artery below the inguinal ligament and above the bifurcation of the superficial femoral artery and the profunda artery using a 12-MHz linear array probe connected to a Vivid 7 ultrasound scanner (Vingmed Horten, Norway). The recordings were postprocessed with automatic tracing of the velocity signals and angle correction. The vessel diameter was measured during end-diastole. Femoral vein blood was sampled from a catheter with an outer diameter of 2.1 mm inserted below the inguinal ligament and approximately 5 cm into the femoral vein (Certofix Mono S315, Braun, Melsungen, Germany).
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RESULTS
Table 1. Patient Characteristics Characteristics
Age (years) Male sex Height (cm) Weight (kg) Hypertension Diabetes mellitus CCS class III EF angiography (%) EF echocardiography (%) Three-vessel disease or left main stenosis CPB time (min) Aorta cross-clamp time (min) Number of bypasses Patients receiving transfusion
62 13 178 83 5 4 11 62 50 10 61 41 4 1
(13) [93] (8) (14) [36] [29] [79] (11) (8) [71] (23) (15) (1) [7]
Seventeen patients were included in the study. Three patients were not tested postoperatively because of nausea (2) and bleeding (1). The clinical characteristics of the 14 patients who were tested preoperatively and postoperatively are
NOTE. Values are median (interquartile range) and number [%]. Abbreviations: CCS, Canadian Cardiovascular Society; CPB, cardiopulmonary bypass; EF, ejection fraction.
Arterial blood was sampled from a radial artery catheter and used as a substitute for femoral artery blood. The catheters were placed using a local anesthetic cream and infiltration anesthesia. Arterial and venous blood samples were drawn during the last 15 seconds of each cycling session, and blood gases and lactate concentrations were analyzed immediately (ABL 800 Radiometer, Copenhagen, Denmark). With this apparatus, the coefficients of variation are 6.2% for lactate and 3.9% for oxygen partial pressure in the actual measurement areas.11 Central venous lines and bladder catheters were inserted after the preoperative test. Finger pulse oximetry was used continuously in the intensive care unit. The data were analyzed using the statistical software package Stata IC 12 (Stata Corp, Lakeway Drive, College Station, TX). Because a normal distribution for all of the variables could not be confirmed, the results are presented as medians with 25th and 75th percentiles. The resting data were analyzed using the Wilcoxon signed-rank test. A linear relationship was assumed between exercise intensity and the variables measured during exercise. The exercise data were analyzed in a mixed linear regression model to analyze changes in measured variables before and after surgery and differences in the response to exercise before and after surgery. The observations were clustered in patients, with exercise intensity as a continuous covariate and surgery as an indicator covariate. The p values indicated the differences between the preoperative values and the postoperative values. The residuals from the linear model were displayed on histograms and showed normal distribution when inspected graphically. Pilot tests indicated an increased release of lactate and the extraction of a large fraction of oxygen at low intensities. Sample size calculations estimated that significant differences were demonstrable with as few as 10 patients with paired t test (significance level: 0.05; power: 0.8). Table 2. Resting Heart Rate, Hemoglobin, Arterial Saturation, and Oxygen Content Preoperative
Postoperative
p Value
Hemoglobin (mg/dL) 14.0 (13.4-14.7) 11.4 (10.6-12.3) o0.001 Arterial oxygen saturation 97.4 (96.1-98.4) 97.9 (97.3-98.7) 0.15 (%) Arterial oxygen content 18.3 (16.8-19.4) 14.8 (13.6-16.5) o0.001 (mL/dL) Serum glucose (mmol/L) 6.2 (5.9-6.9) 7.1 (6.6-8.0) 0.03 Alanine transaminase (U/L) 33 (23-42) 24 (18-29) 0.01 NOTE. Values are median (interquartile range). The p value was calculated with the Wilcoxon signed rank test.
Fig 3. Leg blood flow, oxygen extraction rate, and oxygen partial pressure in femoral vein blood. (A) Leg blood flow measured in the femoral artery with pulsed-wave Doppler in mL/min. (B) Oxygen extraction rate calculated from arterial blood oxygen content and femoral vein blood oxygen content (%). (C) Femoral vein oxygen partial pressure, reflecting femoral muscle cell oxygen partial pressure. Values are median, before surgery (circles), and after surgery (filled squares). Error bars indicate 25th percentiles and 75th percentiles. The p values for difference between preoperative and postoperative measurements are given for rest and exercise, respectively. Wilcoxon signed-rank test was used for resting data and mixed model linear regression for exercise data.
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summarized in Table 1. None of the patients experienced atrial fibrillation, significant hypotension, or other adverse events during or after testing. One patient received 1 unit of packed red cells after surgery. All of the patients recovered well and were alive 3 months later. All 14 patients completed the postoperative test at the lowest resistance; 12 completed the 1-watt test, 10 completed the 2-watt test, and 7 completed the 5-watt test. The hemoglobin concentration was reduced after surgery (p o 0.01) while arterial oxygen saturation was maintained (p ¼ 0.15; Table 2). Statistically significant differences between preoperative and postoperative leg blood flow could not be detected at rest (p ¼ 0.06) or during exercise (p ¼ 0.08; Fig 3A). Light exercise caused the leg blood flow to increase markedly. This marked increase in leg blood flow also was present after surgery (Fig 3). The oxygen extraction rate at rest was increased significantly after surgery (p ¼ 0.03) from 58% (54%-63%) to 66% (58%-70%). This increase was sustained during exercise (p o 0.001; Fig 3B). The femoral vein oxygen partial pressure (pO2) was reduced after surgery, indicating lower oxygen pressure in the femoral muscle cells (Fig 3C). At rest, the venous pO2 was 24.0 mmHg (21.8-27.0) before and 21.8 mmHg (19.5-24.8) after surgery (p ¼ 0.03). The venous pO2 also was reduced significantly during postoperative exercise (p o 0.01). The arterial lactate concentration was increased after surgery; at rest, it increased from 0.65 mmol/L (0.5-0.8) to 1.0 mmol/L (0.9-1.3) (p ¼ 0.01; Fig 4A). An increased difference between arterial and venous lactate concentrations was observed at postoperative rest, indicating an increased release of lactate: 0.1 mmol/L (0-0.3) v 0.6 mmol/L (0.4-0.7; p o 0.01). A similar increase also was found during postoperative exercise (p o 0.01; Fig 4B). During CPB, the maximal arterial lactate was 1.15 mmol/L (1.0-1.45). On arrival at the intensive care unit, the median arterial lactate concentration was 1.1 mmol/L (0.9-1.3). Heart rates and blood pressures are shown in Fig 5. Before CABG, there was no association between femoral vein pO2 and the venoarterial lactate difference. However, venous pO2 was reduced significantly after surgery; furthermore, linear regression analysis confirmed a
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negative correlation between venous pO2 and the difference between arterial and venous lactate concentrations (p ¼ 0.03; Fig 6). DISCUSSION
The most important finding in the present study was that circulatory stable, low-risk CABG patients with normal arterial oxygen saturation and a postoperative hemoglobin concentration of 11.4 g/dL had a significant efflux of lactate from the skeletal muscles during postoperative rest and exercise, as determined by the venoarterial difference in lactate concentrations. At preoperative rest, the venous lactate concentration was only slightly higher than the arterial lactate concentration; whereas during postoperative rest, the venous lactate concentration was almost twice as high as the arterial lactate concentration. Comparable findings were observed during exercise. Results indicated that skeletal muscle metabolism was shifted toward more anaerobic metabolism after surgery and that lactate was released from the large muscle groups in the legs. The results further indicated that the lactate released from skeletal muscles contributed to increasing the arterial lactate concentration on the first postoperative day. Another important finding was that increased anaerobic metabolism was associated with increased oxygen extraction rate in the leg, indicating that increased anaerobic metabolism was caused by reduced oxygen delivery and not by reduced oxygen extraction ability in skeletal muscle. Linear regression showed that there was a negative correlation between femoral vein pO2 and veno-arterial differences in lactate concentration during postoperative exercise; this finding indicated that anaerobic metabolism was indeed associated with reduced intramuscular oxygen partial pressure. Before surgery, there was no association between femoral vein pO2 and the veno-arterial lactate difference. It is also of note that a marked increase in leg blood flow occured during very light exercise and that this response was not attenuated after surgery. The maintained postoperative response indicated that the local regulation of blood flow was not blunted after cardiac surgery with CPB.
Fig 4. Concentrations of lactate in arterial blood and in femoral vein blood. (A) Arterial lactate concentrations before surgery (circles) and after surgery (filled squares). (B) Venous lactate concentrations before surgery (circles) and after surgery (filled squares). Values are median, error bars indicate 25th percentiles, and 75th percentiles. The p values for difference between preoperative and postoperative measurements are given for rest and exercise, respectively. Wilcoxon signed-rank test was used for resting data and mixed model linear regression for exercise data.
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enough to prevent significant reductions in venous pO2 after surgery. Results showed that lactate was transported away from the skeletal muscles on the day after CABG. The release of lactate from the skeletal muscles may be seen as a “lactate shuttle,” a term first introduced by Brooks et al.12 This means that the release of lactate from skeletal muscle is normal, even during exercise of moderate intensity. Released lactate is transported to better-oxygenated tissues, mainly the myocardium, for oxidative metabolism. Results showed that after surgery, lactate was released from skeletal muscle even before exercise began. In other words, anaerobic metabolism was needed for energy production, most likely because postoperative anemia resulted in intramuscular oxygen partial pressures that were too low for sufficient energy production by aerobic metabolism alone. The term “critical hemoglobin concentration” may be used to describe the lowest hemoglobin concentration that does not result in increased anaerobic metabolism. The critical hemoglobin concentration varies among individuals and exercise intensities and also is different in different tissues.13 Results show, that even 11.4 g/dL was below the critical hemoglobin concentration for leg muscle. Weisskopf et al reported that resting, healthy, and young individuals were able to compensate for anemia as low as 4.5 g/dL with increased cardiac index and increased oxygen extraction without any increase in lactate levels,14 illustrating the wide difference in critical hemoglobin level between healthy and diseased persons. A well-performed study by Koskolou et al studied the effect of acute anemia on leg metabolism and blood flow in healthy young men during knee extensor exercise.15 In that study, the withdrawal of blood and substitution of the removed blood volume with an albumin solution reduced hemoglobin from 14.4 g/dL ⫾ 3.8 g/dL (mean ⫾ standard error) to 11.5 g/dL ⫾ 1.9 g/dL, values almost identical to the
Fig 5. Heart rate, systolic blood pressure, and diastolic blood pressure. (A). Heart rate. (B) Systolic blood pressure measured in radial artery catheter. (C) Diastolic blood pressure measured in radial artery catheter. Values are median, before surgery (circles), and after surgery (filled squares). Error bars indicate 25th percentiles and 75th percentiles. The p values for difference between preoperative and postoperative measurements are given for rest and exercise, respectively. Wilcoxon signed-rank test was used for resting data and mixed model linear regression for exercise data.
va Lactate difference (mmol/L)
2.5
2.0
1.5
1.0
0.5
0.0 12
14
16
18
20
22
24
26
28
Venous oxygen pressure (mmHg)
The large natural variations in blood flow in the femoral artery and a possible lack of statistical power may explain why no statistical difference between preoperative and postoperative leg blood flow was observed. However, the possible postoperative increase in blood flow was not large
Fig 6. Postoperative venoarterial lactate difference/femoral vein oxygen pressure. Postoperative oxygen partial pressure plotted against the corresponding difference between femoral vein lactate concentration and arterial lactate concentration. Lines are linear regression line (middle) and 95% CI of regression line (upper and lower lines).
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preoperative and postoperative hemoglobin concentrations in the present study. Neither the present study nor the study by Koskolou et al found any increase in resting leg blood flow during acute anemia. The most striking difference between patients in the present study and the young healthy people in the previous study was that young healthy individuals compensated for acute anemia solely by increasing oxygen extraction, and CABG patients also relied on increased anaerobic metabolism. At rest, the young men in the Koskolou et al study increased their oxygen extraction rate from 50% to 56% after blood withdrawal and volume substitution, and the anemic resting venous pO2 was 25.0 ⫾ (0.7) mmHg. Anaerobic metabolism was not increased during light exercise in acute anemia; there were no differences between the arterial and venous lactate concentrations at rest or during 30 watts of exercise. The CABG patients in the present study had an oxygen extraction rate of 58% (54%-63%) at preoperative rest and 67% (58%70%) at postoperative rest, and the postoperative resting venous pO2 was 21.8 (19.5-24.8) mmHg. The authors hypothesized that the difference in venous pO2 during anemia was why CABG patients had increased anaerobic metabolism at a hemoglobin concentration that did not increase anaerobic metabolism in healthy young men. Comparably high oxygen extraction rates and low venous pO2 previously has been shown in patients with chronic heart failure16 and may result from reduced muscle capillary density and sympathetically mediated vasoconstriction.17 The use of beta-blockers also may contribute to reduced muscle perfusion. Ades et al studied the effects of a training program in coronary patients and reported that the increase in peak aerobic capacity was associated almost exclusively with peripheral skeletal muscle adaptions with no discernible improvement in cardiac output or calf blood flow.18 Reduced muscular capillarity and other muscular changes secondary to inactivity are an attractive explanation of why the present patients had anaerobic metabolism with hemoglobin levels of 11.4 g/dL.
The results of the present study did not indicate any dysfunction in the extraction or utilization of oxygen in skeletal muscle after CABG with CPB. The patients in the present study were not in oxygen debt after the operation, as judged by the lactate levels during CPB and on arrival to the intensive care unit. This means that lactate levels measured during the test reflected the oxygenation and metabolism at the time of testing. The authors suspected that elevated intraoperative and postoperative arterial lactate levels, as reported by Shinde et al, may depend on different CPB management, which may cause metabolic derangement and possible tissue dysfunction.19 This was a study of low-risk patients and may not provide valid conclusions for all cardiac surgery patients. More complicated surgery on high-risk patients may have a larger impact on postoperative cardiac and vascular function that may result in altered muscle perfusion. The exercise intensity was very low in the present study, and it is possible that more intense exercise may have resulted in significant differences in preoperative and postoperative leg blood flow. However, the study did not aim to test cardiac function; therefore, low exercise intensities were used to minimize possible confounding by reduced myocardial function. The present study found an increased release of lactate from skeletal muscle to the general circulation on the first day after cardiac surgery, both at rest and during light exercise. The leg blood flow was similar before and after surgery, resulting in reduced oxygen delivery because of postoperative anemia. The oxygen extraction rate was increased after surgery, and the suspicion of impaired oxygen extraction was not supported. The main clinical implication of this study was that uncomplicated CABG patients who maintain tissue perfusion and have hemoglobin concentrations that are common in the postoperative situation are susceptible to increased anaerobic metabolism in peripheral tissues. Early postoperative anaerobic metabolism in skeletal muscle may be reduced by minimizing perioperative blood loss.
CONCLUSIONS
A hemoglobin concentration of 11.4 g/dL was too low to maintain the preoperative balance between aerobic and anaerobic metabolism in this group of CABG patients.
ACKNOWLEDGMENTS The authors acknowledge the nurses of the cardiothoracic intensive care unit for participation in conducting the tests.
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11. De Koninck AS, De Decker K, Van Bocxlaer J, et al: Analytical performance evaluation of four cartridge-type blood gas analyzers. Clin Chem Lab Med 50:1083-1091, 2012 12. Brooks GA: Lactate production under fully aerobic conditions: the lactate shuttle during rest and exercise. Fed Proc 45:2924-2929, 1986 13. Tsui AK, Dattani ND, Marsden PA, et al: Reassessing the risk of hemodilutional anemia: Some new pieces to an old puzzle. Can J Anaesth 57:779-791, 2010 14. Weiskopf RB, Viele MK, Feiner J, et al: Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA 279:217-221, 1998 15. Koskolou MD, Roach RC, Calbet JA, et al: Cardiovascular responses to dynamic exercise with acute anemia in humans. Am J Physiol 273:H1787-H1793, 1997
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