e-ISSN : 2149-8156
Turkish Journal of Thoracic and Cardiovascular Surgery     
Effect of cardiopulmonary bypass on late-onset hyperlactatemia after pediatric cardiac surgery
Behzat Tüzün1, Servet Ergün1, Şerife Özalp2, Mehmet Akif Önalan1, Berra Zümrüt Tan Recep1, Eymen Recep1, İbrahim Cansaran Tanıdır3, Erkut Öztürk3, Ali Can Hatemi1
1Department of Pediatric Cardiovascular Surgery, Başakşehir Çam and Sakura City Hospital, İstanbul, Türkiye
2Department of Anesthesiology and Reanimation, Başakşehir Çam and Sakura City Hospital, İstanbul, Türkiye
3Department of Pediatric Cardiology, Başakşehir Çam and Sakura City Hospital, İstanbul, Türkiye
DOI : 10.5606/tgkdc.dergisi.2025.26627

Abstract

Background: This study aimed to investigate the effect of operative and postoperative parameters on late-onset hyperlactatemia (LOHL) after cardiac surgery in the pediatric patient population.

Methods: One hundred fifty-nine ventricular septal defect patients (77 males, 82 females; mean age: 8.0±8.6 years; range, 1 to 48 years) were retrospectively examined between August 2020 and February 2023. Patients with the highest lactate value measured between 6 to 12 h postoperatively <3 mmol/L were defined as Group 1, and those with lactate values ≥3 mmol/L (LOHL) were included in Group 2.

Results: Cardiopulmonary bypass (CPB) time, aortic cross-clamp time, and CPB flow did not differ between groups (p=0.916, p=0.729, and p=0.699, respectively). The difference between partial oxygen pressure (PaO2) in the first blood gas obtained after CPB was statistically significant (p=0.017). The lactate level measured in the first arterial blood gas obtained after CPB was 1.74±0.61 mmol/L in Group 1 and 3.01±1.63 mmol/L in Group 2 (p<0.001). The PaO2 in the arterial blood gas measured at 6 h postoperatively was 129.22±61.20 mmHg in Group 1 and 156.07±64.49 mmHg in Group 2 (p=0.046).

Conclusion: The development of hyperlactatemia due to ischemia in the early post-CPB period may affect the development of LOHL. Microcirculatory changes at the tissue level may play a role in the etiology of LOHL.

Late-onset hyperlactatemia (LOHL) is known to be a benign phenomenon developing approximately 6 to 12 h after cardiac surgery, and unlike early-onset hyperlactatemia (EOHL) (0-6 hours), it is not associated with low cardiac output and ischemia and does not cause mortality and morbidity.[1] It occurs in approximately 10 to 20% of patients after cardiac surgery despite adequate cardiac output.[2-5] There are various hypotheses regarding the factors that cause the development of LOHL, including hyperglycemia, bleeding, glucogenesis due to stress response, and exogenous epinephrine.[1,6-11] There is limited data in the literature regarding the relationship between changes in operative parameters, particularly during cardiopulmonary bypass (CPB) and LOHL,[12] and the etiology of LOHL is not fully understood. The present study aimed to investigate the effect of operative and postoperative parameters on LOHL and whether LOHL causes mortality and morbidity in a pediatric patient population undergoing cardiac surgery.

Methods

One hundred fifty-nine ventricular septal defect (VSD) patients (77 males, 82 females; mean age: 8.0±8.6 years; range, 1 to 48 years) operated at the Başakşehir Çam and Sakura City Hospital, Department of Pediatric Cardiovascular Surgery between August 2020 and February 2023 were retrospectively analyzed. Patients who underwent tricuspid valve repair, atrial septal defect (ASD) closure, and patent ductus arteriosus closure in addition to VSD closure were included in the study. Patients who underwent additional procedures apart from these procedures were excluded from the study. Patients with terminal intraoperative and early postoperative period (0 to 6 h) lactate values above 3 mmol/L were excluded. Patients with preoperative intubation, previous cardiopulmonary resuscitation, preoperative low cardiac output (need for preoperative inotropic support), known renal or hepatic insufficiency, diabetes mellitus, and history of preoperative catheterization due to delayed diagnosis were excluded. The study protocol was approved by the Başakşehir Çam and Sakura City Hospital Clinical Research Ethics Committee (date: 12.07.2023, no: 2023-286). Written informed consent was obtained from the parents of the patients included in the study. The study was conducted in accordance with the principles of the Declaration of Helsinki.

Late-onset hyperlactatemia was defined as 6 to 12 h from intensive care unit (ICU) admission in some studies.[1,3] In our study, we defined LOHL as hyperlactatemia (HL) occurring after the 6 h postoperatively. Patients with the highest lactate value measured between 6 to 12 hours postoperatively <3 mmol/L were defined as Group 1, and those ≥3 mmol/L (LOHL) were included in Group 2.[4,13]

The arithmetic mean of the total mean arterial pressure values measured during aortic cross-clamping (ACC) was accepted as the mean blood pressure during ACC.

Vasoactive inotropic score (VIS) was calculated with the following formula: dopamine (µg/kg/min) + dobutamine (µg/kg/min) + 100 × epinephrine (µg/kg/min) + 100 × norepinephrine (µg/kg/min) +10 × milrinone (µg/kg/min) + 10,000 × vasopressin (units/kg/min).[14]

Major adverse events (MAEs) included complete atrioventricular block requiring pacemaker implantation, renal failure, diaphragmatic paralysis, neurological deficit, unplanned reoperation due to residual lesions, sudden circulatory arrest, need for postoperative mechanical circulation support, or death.[15] Renal failure was considered temporary or permanent depending on dialysis need.

Surgical techniques
All patients underwent CPB with bicaval venous and aortic arterial cannulation following standard median sternotomy. The diastolic arrest was achieved by administering antegrade del Nido cardioplegia, and the VSD was closed using an autologous pericardial patch treated with glutaraldehyde in all patients.

The Cobe-Stockert S5 heart-lung machine (Sorin Group Italia, Mirandola, Italy) was used in all patients. Terumo Capiox FX05 (Terumo Cardiovascular Systems Corporation, Tokyo, Japan) oxygenator was used for patients with a calculated CPB flow of 0 to 1200 mL/kg/min, and Terumo Capiox FX15 (Terumo Cardiovascular Systems Corporation, Tokyo, Japan) oxygenator was used for patients with a CPB flow above 1200 mL/kg/min. All operations were performed under mild hypothermia (32 to 34º). During CPB, blood pH level was aimed to be 7.35 to 7.40, partial oxygen pressure (PaO2) >200 mmHg, partial carbon dioxide pressure 35 to 40 mmHg, and mixed venous oxygen saturation >75%. Sets were washed with the prime solution. The prime solution consisted of Isolyte S (Koçak Farma, İstanbul, Türkiye), erythrocyte suspension, fresh frozen plasma, sodium bicarbonate (1 mL/kg), heparin (250 IU/kg), prednisolone (10 mg/kg), cefazolin (25 mg/kg), and mannitol (250 mg/kg).

b>Postoperative treatment protocol
A one-third saline solution or normal saline solution was routinely used in the postoperative period. Ringer lactate solution was not used for maintenance fluid or volume replacement in any patient preoperatively, operatively, or postoperatively. We routinely used milrinone (0.5 mcg/kg/min), cefazolin (4¥20 mg/kg/dose), pantoprazole (1 mg/kg), paracetamol (4x10 mg/kg/dose), and acetylcysteine (20 mg/kg/day) in all patients. Morphine (0.1 mg/kg/dose) was administered as needed for pain control. In patients requiring inotropic support in addition to milrinone, norepinephrine was started at a dose of 0.03 mcg/kg/min as the first choice.

Statistical analysis
Statistical analyzes were performed using IBM SPSS version 22.0 software (IBM Corp., Armonk, NY, USA). The normal distribution of variables was evaluated visual (histogram and probability graphs) and analytical (Kolmogorov-Smirnov/Shapiro- Wilk tests) methods. Descriptive analysis was performed using frequency tables for categorical variables and mean ± standard deviations (SD) for normally distributed variables. Whether the obtained quantitative variables demonstrated significant differences according to the groups was analyzed by the independent samples t-test, and the relationship between categorical variables and study groups was analyzed by the chi-square test. Analyzes were performed with IBM SPSS version 20.0 software at a 95% confidence level. The level of statistical significance was set at p<0.05.

Results

Lactate levels measured between 6 to 12 h were ≥3 mmol/L in 33 (20.7%) patients. No statisticallysignificant difference was determined between thegroups in terms of age, weight, body surface area, sex,and genetic anomaly incidence (p=0.978, p=0.215,p=0.834, p=0.426, and p=0.499, respectively; Table 1).

Table 1. Demographic data

No statistically significant difference wasdetermined between the groups in terms of CPBflow, duration of ACC, CPB time, lowest bodytemperature, ultrafiltration volume, and themean arterial pressure during ACC (p=0.699,p=0.69, p=0.56, p=0.752, p=0.166, and p=0.272,respectively; Table 2, Figure 1). However, in thefirst blood gas after CPB, the PaO2 measuredin arterial blood gas was 131.67±81.10 mmHg inGroup 1 and 171.44±91.52 mmHg in Group 2, andthe difference between the groups was statisticallysignificant (p=0.017; Figure 2). The lactate levelmeasured in the first arterial blood gas followingCPB was 1.74±0.61 mmol/L in Group 1 and3.01±1.63 mmol/L in Group 2 (p<0.001). The highestlactate value measured between the 6 and 12 h was1.87±0.52 mmol/L in Group 1 and 4.45±1.93 mmol/Lin Group 2 (Table 2).

Table 2. Operative and postoperative parameters

Figure 1. Operative parameters.
ACC: Aortic cross-clamping; CPB: Cardiopulmonary bypass; UF: Ultrafiltration; TA: Arterial blood pressure; ES:Erythrocyte suspension; FFP: Fresh frozen plasma.

Figure 2. Postcardiopulmonary bypass blood gas parameters.CPB: Cardiopulmonary bypass;
ABG: Arterial blood gas; VBG: Venous blood gas; Hb: Hemoglobin; Htc: Hematocrit; PaO2: Partial oxygenpressure; SaO2: Saturation of oxygen; SmvO2: Mixed venous oxygen saturation; PmvOv: Partial mixed venousoxygen.

There was no statistically significant differencebetween the groups regarding PaO2, saturationof oxygen (SaO2), and glucose levels in the firstarterial blood gas obtained at 1 h postoperatively(p=0.270, p=0.253, and p=0.239, respectively;Table 2). The PaO2 in the arterial blood gas measuredat 6 h postoperatively was 129.22±61.20 mmHg in Group 1 and 156.07±64.49 mmHg in Group2 (p=0.046). Additionally, SaO2 in the arterialblood gas measured at the 6 h postoperativelywas 97.07±4.27 in Group 1 and 98.84±1.50 in Group 2 (p=0.036; Table 2, Figure 3). No statisticallysignificant difference was detected between thegroups regarding the amount of drainage at 6, 12, 24,and 48 h postoperatively (p=0.843, p=0.711, p=0.519, and p=0.402, respectively; Table 2). The mean VISwas 6.93±5.4 in Group 1 and 6.36±3.13 in Group 2(p=0.566).

Figure 3. Postoperative parameters.
VBG: Venous blood gas; SmvO2: Mixed venous oxygen saturation; PmvO2: Partial mixed venous oxygen; ABG:Arterial blood gas; PaO2: Partial oxygen pressure.

There was no statistically significant differencebetween the groups in terms of MAEs and mortality(p=0.148 and p=0.792, respectively; Table 3). Nostatistically significant difference was observed between the groups in terms of duration of mechanicalventilation and ICU or hospital stays (p=0.439,p=0.381, and p=0.743, respectively; Table 4).

Table 3. Postoperative complications

Table 4. Vasoactive inotropic score and durations

Discussion

This study examined the relationship between CPB and LOHL and whether LOHL causes mortality and morbidity. The study was designed with a patient group undergoing VSD closure, which is a more homogeneous patient group that causes relatively less mortality and morbidity. It was observed that high PaO2 levels and high lactate levels after CPB, high PaO2, and SaO2 values in arterial blood gas at 6 h postoperatively affected the development of LOHL, and LOHL was not associated with morbidity. Furthermore, CPB flow, CPB duration, and duration of ACC did not have an impact on LOHL.

The incidence of LOHL is reported to be approximately 14 to 25% after cardiac surgery and even higher in pediatric patients.[1,3-5,8,16] There are various hypotheses regarding the etiology of LOHL. However, the number of studies on the subject in the pediatric patient population is limited. In a study by Abraham et al.,[13] where 68 patients with isolated ASD closure were analyzed, all patients who developed early and late hyperlactatemia postoperatively between 0 to 12 h were defined as the high lactate group. In their results, they reported that 38% of patients developed HL, and they retrospectively found that lower CPB flows were used in the HL group leading to lower oxygen delivery during CPB and higher blood glucose values in the early postoperative period. They also reported that low CPB flows (<100 mL/kg/min) and mean arterial blood pressure values during CPB were risk factors for HL. Only patients with LOHL (6 to 12 h) were included in our study. None of our patients had a target CPB flow below 100 mL/kg/min. We did not observe a statistically significant difference between Groups 1 and 2 regarding CPB flows (140.04 mL/min/m2 vs. 140.4 mL/min/m2). However, the lactate level after CPB was higher in the LOHL group. Therefore, we believe that the development of HL due to ischemia in the early post-CPB period may have affected the development of LOHL. Klee et al.[12] reported in a more complex post- CPB pediatric patient group that lactate values measured at 4 hafter pediatric ICU admission were high (>2 mmol/L) in 62% of patients, but oxygen extraction was normal in 55% of these patients. They reported that HL at the 4 h postoperatively was associated with hyperglycemia and a high lactate-to-pyruvate ratio and was not associated with parameters such as oxygen extraction, patient body weight, severity of cardiac lesion, and CPB duration. They also indicated that HL at 12 h postoperatively was not associated with oxygen extraction but with hyperglycemia. In our study, no difference was observed between the groups in CPB duration, duration of ACC, CBP flows, and hematocrit levels after CPB and in the postoperative period. No difference was determined between the groups in terms o f m ixed venous oxygen s aturation (SmvO2) and partial mixed venous oxygen (PmvO2), both after CPB and in the early postoperative period. However, arterial PaO2 values after CPB and arterial PaO2 values at 6h postoperatively were higher in the LOHL group. Moreover, arterial SaO2 measured at the 6 h postoperatively was higher in the LOHL group. However, SmvO2 levels were similar in the two groups. SmvO2 is used as an indicator of adequate oxygen delivery. Although oxygen delivery was sufficient in both groups, the high PaO2 in the LOHL group means that the arteriovenous saturation range was higher in this group. This result may indicate a need for higher oxygen utilization at the tissue level in the LOHL group, or, as in septic shock, functional shunts may occur due to the deleterious effects of CPB on the microcirculation. Although oxygen delivery is sufficient and sometimes even higher than necessary, oxygenated blood may bypass the capillary bed and cause ischemia at the tissue level despite high SmvO2.[17-19] Klee et al.[12] reported that they did not observe a relationship between oxygen extraction and LOHL. However, some studies conducted in the adult patient population have shown that high oxygen levels during CPB are associated with increased systemic vascular resistance and increased microcirculatory perfusion heterogeneity.[20-22] We believe pathological oxygen use at the tissue level may play a role in the etiology of LOHL. However, further prospective studies are needed on this subject.

Hemodilution during CPB is considered to play a role in the etiology of LOHL. Nonetheless, in our study, no statistically significant difference was revealed between the groups in terms of ultrafiltration volumes and operative and postoperative hematocrit levels. Exogenous epinephrine is another cause of HL. Furthermore, stress-related endogenous epinephrine release has a role in the etiology of HL by increasing glucose uptake into the cell and causing increased glycolysis.[9,23,24] In a study comparing epinephrine and norepinephrine after cardiac surgery, the incidence of HL was reported to be lower in the norepinephrine group.[9] In our study, no statistical difference was detected between the groups in terms of VIS. However, since we conducted the study in a patient group with simple cardiac pathology, the incidence of inotrope use was quite low. Additionally, our inotrope strategy was to use norepinephrine in the first line in addition to milrinone. Therefore, the number of patients receiving epinephrine infusion was limited.

Another critical factor in the development of LOHL is glucogenesis due to hyperglycemia and stress response.[1,25,26] Palermo et al.[6] included 132 (10%) patients who developed HL despite adequate tissue perfusion in their pediatric patient population and examined the relationship between HL and hyperglycemia. The median time to development of HL after CPB was reported as 4.4 h, and the time to development of hyperglycemia was reported as 4.9 h. They reported that lactate and blood glucose levels rise and fall simultaneously. The present study demonstrated no statistically significant difference in terms of blood glucose levels measured after CPB and at 1 and 6 h postoperatively.

Various studies in the literature have examined factors related to the etiology of LOHL. In a study by Auborg et al.,[7] 432 adult patients were examined after cardiac surgery, and LOHL was detected in 8.5%. Bleeding amounts of >300 mL at the 6 h postoperatively and fluid loading >250 mL at the 6 h postoperatively were reported as risk factors for LOHL. The study did not report the fluid that was used for fluid loading. In our study, no statistical difference was observed between groups in terms of bleeding.

There are various studies in the literature regarding the effect of LOHL on mortality and morbidity. It was reported that LOHL generally has a benign course.[3,5] Maillet et al.,[4] in their study examining low lactate, EOHL, and LOHL reported that the mortality rate was 1.5% in the low lactate group, 3.6% in the LOHL group, and 14.9% in the EOHL group. However, Auborg et al.[7] observed that complications such as the need for mechanical ventilation for longer than 24 h, acute renal failure, blood transfusion, and postoperative bleeding were higher in the LOHL group and reported that LOHL may be related to inadequate tissue oxygenation. In the present study, we did not determine a statistically significant difference between the groups in terms of MAEs and mortality.

The major limitation of our study was that it was a single-center retrospective study. In addition, since our study was retrospective, parameters such as oxygen extraction ratio, indexed oxygen delivery, and oxygen consumption could not be calculated. Instead, values such as PaO2 and mixed venous SmvO2 were considered, and CPB flows calculated according to the routine CPB strategy applied in our clinic were investigated. Therefore, it was not possible to evaluate the effect of oxygen delivery and oxygen consumption on LOHL in our study.

In conclusion, the present study demonstrated that LOHL was not associated with mortality and MAEs, and LOHL was frequently observed following pediatric cardiac surgery. The lactate level after CPB was higher in the LOHL group. Therefore, we believe that the development of HL due to ischemia in the early post-CPB period may have affected the development of LOHL. In addition, higher arterial PaO2 levels were determined in the LOHL group despite normal mixed venous PmvO2 both in the early post-CPB period and the early postoperative period. Therefore, we believe that microcirculatory changes at the tissue level may play a role in the etiology of LOHL. Further prospective studies are needed.

Data Sharing Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Author Contributions: Idea/concept: B.T., S.E.; Design: S.Ergün.; C ontrol/supervision: A .C.H.; D ata c ollection a nd/ or processing: Ş.Ö.; Analysis and/or interpretation: M.A.Ö.; Literature review: E.R.; Writing the article: S.E., B.Z.T.R.; Critical review: E.Ö.; References and fundings: İ.C.T.; Materials: A.C.H.

Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding: The authors received no financial support for the research and/or authorship of this article.

References

1) Minton J, Sidebotham DA. Hyperlactatemia and cardiac surgery. J Extra Corpor Technol 2017;49:7-15.

2) Allen M. Lactate and acid base as a hemodynamic monitor and markers of cellular perfusion. Pediatr Crit Care Med 2011;12:S43-9. doi: 10.1097/PCC.0b013e3182211aed.

3) Raper RF, Cameron G, Walker D, Bowey CJ. Type B lactic acidosis following cardiopulmonary bypass. Crit Care Med 1997;25:46-51. doi: 10.1097/00003246-199701000-00011.

4) Maillet JM, Le Besnerais P, Cantoni M, Nataf P, Ruffenach A, Lessana A, et al. Frequency, risk factors, and outcome of hyperlactatemia after cardiac surgery. Chest 2003;123:1361-6. doi: 10.1378/chest.123.5.1361.

5) O'Connor E, Fraser JF. The interpretation of perioperative lactate abnormalities in patients undergoing cardiac surgery. Anaesth Intensive Care 2012;40:598-603. doi:10.1177/0310057X1204000404.

6) Palermo RA, Palac HL, Wald EL, Wainwright MS, Costello JM, Eltayeb OM, et al. Metabolic uncoupling following cardiopulmonary bypass. Congenit Heart Dis 2015;10:E250-7. doi: 10.1111/chd.12285.

7) Aubourg C, Collard A, Léger M, Gros A, Fouquet O, Sargentini C, et al. Risk factors and consequences of late-onset hyperlactatemia after cardiac surgery with cardiopulmonary bypass: A single-center retrospective study. J Cardiothorac Vasc Anesth 2022;36:4077-84. doi: 10.1053/j. jvca.2022.07.007.

8) Hosein RB, Morris KP, Brawn WJ, Barron DJ. Use of tissue microdialysis to investigate hyperlactataemia following paediatric cardiac surgery. Interact Cardiovasc Thorac Surg 2008;7:384-8. doi: 10.1510/icvts.2007.166264.

9) Totaro RJ, Raper RF. Epinephrine-induced lactic acidosis following cardiopulmonary bypass. Crit Care Med 1997;25:1693-9. doi: 10.1097/00003246-199710000-00019.

10) Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, et al. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: A randomised trial. Lancet 2007;370:676-84. doi: 10.1016/ S0140-6736(07)61344-0.

11) Myburgh JA, Higgins A, Jovanovska A, Lipman J, Ramakrishnan N, Santamaria J, et al. A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med 2008;34:2226-34. doi: 10.1007/s00134- 008-1219-0.

12) Klee P, Rimensberger PC, Karam O. Association between lactates, blood glucose, and systemic oxygen delivery in children after cardiopulmonary bypass. Front Pediatr 2020;8:332. doi: 10.3389/fped.2020.00332.

13) Abraham BP, Prodhan P, Jaquiss RD, Bhutta AT, Gossett JM, Imamura M, et al. Cardiopulmonary bypass flow rate: A risk factor for hyperlactatemia after surgical repair of secundum atrial septal defect in children. J Thorac Cardiovasc Surg 2010;139:170-3. doi: 10.1016/j.jtcvs.2009.04.060.

14) Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye RG, et al. Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med 2010;11:234-8. doi: 10.1097/ PCC.0b013e3181b806fc.

15) Mercer-Rosa L, Elci OU, DeCost G, Woyciechowski S, Edman SM, Ravishankar C, et al. Predictors of length of hospital stay after complete repair for tetralogy of fallot: A prospective cohort study. J Am Heart Assoc 2018;7:e008719. doi: 10.1161/JAHA.118.008719.

16) Jackman L, Shetty N, Davies P, Morris KP. Late-onset hyperlactataemia following paediatric cardiac surgery. Intensive Care Med 2009;35:537-45. doi: 10.1007/s00134- 008-1331-1.

17) Kanoore Edul VS, Ince C, Dubin A. What is microcirculatory shock? Curr Opin Crit Care 2015;21:245-52. doi: 10.1097/ MCC.0000000000000196.

18) Østergaard L, Granfeldt A, Secher N, Tietze A, Iversen NK, Jensen MS, et al. Microcirculatory dysfunction and tissue oxygenation in critical illness. Acta Anaesthesiol Scand 2015;59:1246-59. doi: 10.1111/aas.12581.

19) Koning NJ, Atasever B, Vonk AB, Boer C. Changes in microcirculatory perfusion and oxygenation during cardiac surgery with or without cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2014;28:1331-40. doi: 10.1053/j. jvca.2013.04.009.

20) Harten JM, Anderson KJ, Kinsella J, Higgins MJ. Normobaric hyperoxia reduces cardiac index in patients after coronary artery bypass surgery. J Cardiothorac Vasc Anesth 2005;19:173-5. doi: 10.1053/j.jvca.2004.11.053.

21) Inoue T, Ku K, Kaneda T, Zang Z, Otaki M, Oku H. Cardioprotective effects of lowering oxygen tension after aortic unclamping on cardiopulmonary bypass during coronary artery bypass grafting. Circ J 2002;66:718-22. doi:10.1253/circj.66.718.

22) Joachimsson PO, Sjöberg F, Forsman M, Johansson M, Ahn HC, Rutberg H. Adverse effects of hyperoxemia during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1996;112:812-9. doi: 10.1016/S0022-5223(96)70069-7.

23) Day NP, Phu NH, Bethell DP, Mai NT, Chau TT, Hien TT, et al. The effects of dopamine and adrenaline infusions on acid-base balance and systemic haemodynamics in severe infection. Lancet 1996;348:219-23. doi: 10.1016/s0140- 6736(96)09096-4.

24) Levy B, Perez P, Perny J, Thivilier C, Gerard A. Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study. Crit Care Med 2011;39:450-5. doi: 10.1097/ CCM.0b013e3181ffe0eb.

25) De Wever O, Nguyen QD, Van Hoorde L, Bracke M, Bruyneel E, Gespach C, et al. Tenascin-C and SF/HGF produced by myofibroblasts in vitro provide convergent pro-invasive signals to human colon cancer cells through RhoA and Rac. FASEB J 2004;18:1016-8. doi: 10.1096/fj.03-1110fje.

26) Chatham JC. Lactate -- the forgotten fuel! J Physiol 2002;542:333. doi: 10.1113/jphysiol.2002.020974.

Keywords : Late onset hyperlactatemia, pediatric cardiac surgery, ventricular septal defect
Viewed : 240
Downloaded : 74