|Year : 2021 | Volume
| Issue : 3 | Page : 174-178
Effects of hemofiltration during cardiopulmonary bypass in children undergoing intracardiac repair for tetralogy of Fallot
Rahul Singh1, Praveen Nayak1, Archit Patel1, Srikanth Bhumana2
1 Department of CVTS, U.N. Mehta Institute of Cardiology and Research Centre, Civil Hospital Campus, Ahmadabad, Gujarat, India
2 Department of CVTS, Apollo Hospital, Trichy, Tamil Nadu, India
|Date of Submission||12-Oct-2021|
|Date of Decision||28-Oct-2021|
|Date of Acceptance||10-Nov-2021|
|Date of Web Publication||22-Dec-2021|
Dr. Srikanth Bhumana
Department of CVTS, Apollo Hospital, Trichy, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Introduction: This study was planned to compare postoperative hemodynamics, blood loss, platelet count, and coagulation parameters in patients undergoing intracardiac repair for tetralogy of Fallot with and without hemofiltration and, in addition, to determine whether hemofiltration during cardiopulmonary bypass (CPB) reduces cytokines in children undergoing intracardiac repair for tetralogy of Fallot.
Methods: Thirty children suffering from tetralogy of Fallot were enrolled in the study and randomly divided into two groups: one group had hemofiltration from beginning of rewarming till weaning off CPB, whereas in the other group, hemofiltration was not used during CPB. In the hemofiltration group, samples were taken for the comparison of tumor necrosis factor-α, interleukin-6 (IL-6), and IL-8 levels, before and after hemofiltration. Platelet count, coagulation parameters, postoperative blood loss, extubation time, hemodynamic parameters were recorded for hemofiltration as well as non-hemofiltration group and analysed.
Results: The extubation time in the hemofiltration group was 15.6 h (mean), whereas that in the control group was 28.6 h (mean), and the difference, when compared, was significant between the two groups (P = 0.05). The cumulative postoperative blood loss at 24 h was significantly less in the hemofiltration group compared to the control group, 97.4 ml (80–114 ml) versus 159 ml (100–210 ml), respectively, with P = 0.001. No other statistically significant difference could be appreciated in the parameters analyzed.
Conclusion: There was a significant reduction in postoperative blood loss and extubation time in the hemofiltration group. There was no significant reduction in cytokines. No significant difference was observed in requirement of inotropic agents, hemodynamic status, and intensive care unit stay between the two groups. Small sample size and shorter ultrafiltration time during rewarming phase were limitations of the study.
Keywords: Cardiopulmonary bypass, hemofiltration, tetralogy of Fallot
|How to cite this article:|
Singh R, Nayak P, Patel A, Bhumana S. Effects of hemofiltration during cardiopulmonary bypass in children undergoing intracardiac repair for tetralogy of Fallot. Heart India 2021;9:174-8
|How to cite this URL:|
Singh R, Nayak P, Patel A, Bhumana S. Effects of hemofiltration during cardiopulmonary bypass in children undergoing intracardiac repair for tetralogy of Fallot. Heart India [serial online] 2021 [cited 2022 Jan 28];9:174-8. Available from: https://www.heartindia.net/text.asp?2021/9/3/174/333299
| Introduction|| |
The systemic inflammatory response after cardiopulmonary bypass (CPB) results in capillary leak syndrome that remains a major cause of morbidity and mortality in children. This process can lead to fluid overload, impede pulmonary gas exchange, and delay separation from mechanical ventilation.
This problem is compounded by homologous blood components to prime the circuit to maintain the hematocrit and osmotic pressure during CPB in infants, neonates, and smaller children., Because of the disproportionately large priming volume of CPB circuit in neonates and infants, fluid overload is a major concern in CPB of long duration.
Hemofiltration occurs across a semi-permeable membrane filter and leads to separation of plasma water and low-molecular-weight solutes from the cells and the plasma proteins of blood. The hydrostatic pressure gradient across the membrane leads to ultrafiltration.
Ultrafiltration is commonly categorized by the timing of deployment and the techniques used in the ultrafiltration process.
- Conventional ultrafiltration is generally defined as the use of ultrafiltration during CPB for fluid management. Ultrafiltration is most often performed during rewarming although it takes place throughout CPB, albeit intermittently.
- Modified ultrafiltration refers to the use of ultrafiltration after separation from CPB. Most often, blood is pumped retrograde from the aortic cannula through a hemoconcentrator and returned to the systemic circulation by way of the venous cannula to the right atrium.
Several studies demonstrated significant improvements in hemodynamics that were unlikely to be explained solely by the control of water balance. Hence, it has been postulated that hemofiltration might remove some toxic substances and inflammatory mediators.
This study was planned to compare postoperative hemodynamics, blood loss, platelet count, and coagulation parameters in patients undergoing intracardiac repair for tetralogy of Fallot with and without hemofiltration and, in addition, to determine whether hemofiltration during CPB reduces cytokines in children undergoing intracardiac repair for tetralogy of Fallot.
| Methods|| |
This prospective study was conducted in the Department of Cardiothoracic and Vascular Surgery and Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, from October 2012 to December 2013.
Thirty patients undergoing intracardiac repair for tetralogy of Fallot were enrolled in the study. They were randomly divided into two groups (Hemofiltration and Non-Hemofiltration) of 15 patients each depending upon conduct of hemofiltration during rewarming phase. In order to curtail bias, attending perfusionist was blinded regarding likelihood of hemofiltration till actual initiation of hemofiltration during CPB.
All the patients received the same standard premedication, induction, and maintenance of anesthetic agents.
CPB was performed with a roller pump and an appropriately sized membrane oxygenator. PVC (polyvinylchloride) tubings were used for extracorporeal circuit. The circuit was primed with ringer lactate, 20% human albumin, calcium gluconate, and sodium bicarbonate. The CPB priming volume was 300 ml in patients with weight <7 kg and 500–600 ml in those weighing more than 7 kg.
The pump flow rate was linearly adjusted to provide a blood flow depending on body surface area (BSA) and temperature. Alpha stat blood gas management was used and sodium bicarbonate was administered when required.
Anticoagulation was achieved with heparin 3 mg/kg before cannulation. During bypass, supplemental heparin was administered to maintain ACT above 400 s. After CPB, protamine was administered to neutralize heparin at a ratio of 1:1.
Myocardial protection was achieved using cold blood cardioplegia in all patients with an initial dose of 30 ml/kg and repeated every 20 min. 15 ml/kg of warm blood cardioplegia was administered before removal of aortic cross-clamp.
Hemofiltration was connected between the arterial line and the reservoir. Hemofiltration started at the beginning of rewarming and continued till weaning off CPB.
Two milliliters of arterial blood samples were collected in ethylenediaminetetraacetic acid (EDTA) vials as follows:
- T1: After aortic cannulation
- T2: Before rewarming
- T3: After weaning off CPB
- T4: 24 h later in the postoperative period.
Blood samples for complement fragments and cytokines were drawn at T2 and T3 only. Blood samples were stored in EDTA vials at 4°C and sent to Immunopathology Lab, where the plasma was extracted from the samples at 4°C and stored at −20°C for analysis.
Inflammatory mediators were measured using enzyme-linked immunosorbent assay kits (Immunotech, Beckman Coulter, France, and Biocheck Inc., Foster City, CA, USA).
Baseline blood gas analysis was done after induction of anesthesia followed by repetition after weaning off CPB and during postoperative stay in the intensive care. Systemic arterial pressure, postoperative blood loss along with blood volume administered, and duration of mechanical ventilation were recorded.
| Results|| |
There was no significant difference between the hemofiltration group (n = 15) and the control group (n = 15) with respect to age and BSA, as the mean age of the hemofiltration group was 6.4 years, whereas in the control group it was 6.6 years. Similarly, mean BSA was 0.66 m2 for the hemofiltration group and it was 0.70 m2 for the control group.
The mean CPB time between the two groups was similar: in the control group, it was 157 min, whereas in the hemofiltration group, it was 161 min with no significant difference. The cross-clamp time showed no significant difference (115 vs. 120).
Although the mean arterial pressures in the hemofiltration group (mean: 82.6) increased compared to the control group (mean: 79.4), it was not statistically significant (P = 0.33). Mean central venous pressure in both the groups was almost similar with no significant difference (10.4 vs. 11.4).
The extubation time in the hemofiltration group was 15.6 h (mean), whereas that in the control group was 28.6 h (mean), and the difference when compared was significant between the two groups (P = 0.05). However, duration of total intensive care unit (ICU) stay, inotropic requirements, and postoperative urinary output did not reveal a significant difference.
The cumulative postoperative blood loss at 24 h was significantly less in the hemofiltration group comparatively to the control group, 97.4 ml (80–114 ml) versus 159 ml (100–210 ml), respectively, with P = 0.001. No significant difference was observed between the two groups with respect to blood or colloid transfusions received and postoperative fluid requirements.
There was no significant difference between the two groups in respect to platelet count (mean: 2.11 × 105 vs. 2.21 × 105) and clotting parameters (mean: 95.2 vs. 95.6 s) after 24 h in ICU.
The mean hemofiltration time in the hemofiltration group was 25 min.
In the hemofiltration group, the mean plasma concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL-6), and IL-8 were 5.2 pg/ml, 53.4 pg/ml, and 31.2 pg/ml, respectively, and after rewarming, the plasma concentrations of IL-6 were 50.4 pg/ml, IL-8 were 30.20 pg/ml, and TNF-alpha were 3.5 pg/ml. There was no significant difference between the plasma concentrations of IL-6, IL-8, and TNF-alpha in T2 and T3 samples of the hemofiltration group. Although the levels in T3 sample were reduced compared to the control group, it was not statistically significant.
| Discussion|| |
The results of tetralogy of Fallot repair have improved during recent times because of technical improvements in surgery, conduct of CPB, and postoperative care; however, capillary leak that occurs after CPB and fluid overload remains a major cause for morbidity and mortality in smaller children with prolonged duration of CPB.
Numerous postoperative strategies such as peritoneal dialysis, extensive use of diuretics, and administration of colloids or postoperative hemofiltration have been used to reduce the consequences of capillary leak and fluid overload.
Naik et al. performed the hemofiltration technique after CPB termination to reduce the amount of accumulated tissue water. They observed significant improvements in hemodynamics that were unlikely to be explained solely by the control of water balance.
Elliot et al. postulated in their study that hemofiltration might remove some toxic substances that promoted capillary leak.
Millar et al. investigated the effects of hemofiltration on plasma levels of cytokines, TNF, IL-6, and IL-8. They observed a remarkable decrease in TNF levels after hemofiltration, with no such reflection in the group without hemofiltration.
A similar difference was detected in the levels of IL-6 between the two groups after bypass, although this was largely due to changes in two subjects. IL-8 values were higher in the hemofiltration group although, in small number of subjects hence, it was not sufficient enough for statistical analysis.
In these abovementioned studies, the surgical populations were heterogeneous with respect to diagnosis, surgery, and hemofiltration duration. In our study, we examined the effects of hemofiltration in patients with the same diagnosis and the same surgical procedure.
Only patients with tetralogy of Fallot were studied to avoid any variability due to hemodynamics or water distribution that might have been associated with different congenital heart lesions.
Effect of hemofiltration on hemostasis
In our study, we observed a significant reduction in postoperative blood loss in the hemofiltration group (P < 0.001). The postoperative bleeding reduction by hemofiltration also was observed by Naik et al. They speculated that clotting factors and platelets are concentrated by hemofiltration leading to improved clotting conditions.
In our study, we did not find any difference in prothrombin time and platelet count. These results suggest that, when hemofiltration is performed during rewarming, its effects on postoperative bleeding are unlikely to be explained solely by hemoconcentration.
Our observations suggest that reduction in postoperative blood loss is because of less dilution of coagulation factors other than platelets.
Effects of hemofiltration on hemodynamics
In our study, the mean arterial pressures were increased in the hemofiltration group, but there is no significant difference observed between the two groups. Naik et al. reported a significant increase in mean arterial pressure in a similar study. They demonstrated that the overall effect of hemofiltration is an increase in cardiac index, blood pressure, and systemic vascular resistance associated with a decrease in heart rate and pulmonary vascular resistance. The mechanism by which blood pressure improves remains uncertain.
Journois et al. speculated that hemofiltration may improve the elimination of some toxic substances or reduce myocardial water content, thereby improving cardiac output. This latter hypothesis is supported by some recent findings demonstrating a reduction in myocardial wall volume associated with an improvement of the left ventricle diastolic function produced by hemofiltration.
Effects of hemofiltration on ventilation
The reduction in duration of mechanical ventilation justifies the use of hemofiltration during correction of tetralogy of Fallot. Nevertheless, these findings may have important implications for the CPB management of other children operated upon for congenital heart defects associated with impaired pulmonary function, especially in those patients with pulmonary artery hypertension.
In our study, there was a significant reduction in the time for extubation in the hemofiltration group. Removal of fluid by ultrafiltration improves pulmonary mechanisms in the postoperative period, thereby resulting in earlier extubation. Similar findings were reported by Meliones JN et al.
The significantly less extubation time is an important advantage; this is not because of better hemodynamic parameter or less requirement of inotropic support. This could be because of reduction in fluid overload, not by reduction in the inflammatory cytokines.
Hence, hemofiltration plays a major role in cyanotic children undergoing surgical repair when there is an anticipated fluid overload at the end of CPB.
Effects of hemofiltration on cytokines
Finn et al. demonstrated that IL-6, IL-8, and TNF-α release was stimulated by CPB in adults and even more in children. Hirthler et al. reported numerous similarities between post-CPB morbidity and sepsis syndrome. In another study done by Casey, the elimination of TNF-α and IL-1β by continuous hemofiltration was observed. Journois et al. reported that hemofiltration performed during the late phase of rewarming can reduce the concentrations of IL-6 and TNF-α.
In our study, although we observed decreased levels of IL-6, IL-8, and TNF-α in the group with hemofiltration compared to the control group, there is no significant difference between the two groups.
The study by Miller et al. revealed that the release of cytokines was pronounced during rewarming phase of CPB, which influenced our study, and we used hemofiltration from time of rewarming till weaning off CPB. The average time was 25 ± 4 min. Our results show that although there was a reduction in inflammatory cytokines (TNF-alpha, IL-6, and IL-8), it was not significant, suggesting that short period (mean: 25 min) of hemofiltration is not adequate for removing inflammatory cytokines released by CPB.
If hemofiltration aims for reduction in release of inflammatory cytokines, hemofiltration for a long duration needs to be evaluated. However, there are drawbacks of doing hemofiltration routinely during CPB for a longer period such as subjecting patient blood to more extracorporeal circulation, addition of more priming volume from time to time which might cause electrolyte imbalance and low hematocrit, which demands the accurate balance of added fluid during CPB and removal by hemofiltration. This is further complicated by blood loss during surgery and cold saline requirement for myocardial protection.
Our study suggests that cytokines were poorly eliminated by hemofiltration with the membrane used, following their release during rewarming. Shorter ultrafiltration time could be the reason behind the reduced elimination of inflammatory markers during hemofiltration.
| Conclusions|| |
The conclusions of this study are as follows:
- There was a significant reduction in postoperative blood loss and extubation time in the hemofiltration group
- No significant reduction in cytokines in 30 min rewarming phase of CPB
- No significant difference in requirement of inotropic agents, hemodynamic status, and ICU stay between the two groups.
Limitations of the study
- Small sample size
- Shorter ultrafiltration time during rewarming
The study involves human participants; the study has been approved by the appropriate Institutional Ethics Committee from PGIMER, Chandigarh and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki. This article does not contain study performed on animals by any of the authors.
Dr. Rahul Singh - Design, Aquisition, Dr. Praveen Nayak- Analysis, Interpretation, Drafting Dr. Archit Patel - Aquisition,Analysis, Drafting Dr. Srikanth Bhumana,- Conceptualization,Design, Interpretation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Perry LW, Neill CA, Ferencz C. EUROCAT working party on congenital heart disease: Perspective in pediatric cardiology. Epidemiology of congenital heart disease, the Baltimore-Washington Infant Study (1981-1989),N.Y, Futura Publishing Co Inc. 1993.
Fallot E. Contribution to the pathological anatomy of the disease blue (cardiac cyanotic). Marseille Med 1888;25:77-138.
Lillehei CW, Varco RL, Cohen M, Warden HE, Gott VL, DeWall RA, et al
. The first open heart corrections of tetralogy of Fallot. A 26-31 year follow-up of 106 patients. Ann Surg 1986;204:490-502.
Kirklin JK, Blackstone EH, Kirklin JW. Cardiopulmonary bypass: Studies on its damaging effects. Blood Purif 1987;5:168-78.
Zobel G, Stein JI, Kuttnig M, Beitzke A, Metzler H, Rigler B. Continuous extracorporeal fluid removal in children with low cardiac output after cardiac operations. J Thorac Cardiovasc Surg 1991;101:593-7.
Naik SK, Knight A, Elliott M. A prospective randomized study of a modified technique of ultrafiltration during pediatric open-heart surgery. Circulation 1991;84:I422-31.
Elliott MJ. Ultrafiltration and modified ultrafiltration in pediatric open heart operations. Ann Thorac Surg 1993;56:1518-22.
Millar AB, Armstrong L, van der Linden J, Moat N, Ekroth R, Westwick J, et al. Cytokine production and hemofiltration in children undergoing cardiopulmonary bypass. Ann Thorac Surg 1993;56:1499-502.
Journois D, Pouard P, Greeley WJ, Mauriat P, Vouhé P, Safran D. Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Effects on hemostasis, cytokines, and complement components. Anesthesiology 1994;81:1181-9.
Naik SK, Balaji S, Elliott MJ. Modified ultrafiltration improves hemodynamics after cardiopulmonary bypass in children. J Am Coll Cardiol 1993;19:37.
Meliones JN, Gaynor JW, Wilson BG, Kern FH, Schulman SR, Shearer IR, et al. 762-3 Modified ultrafiltration reduces airway pressures and improves lung compliance after congenital heart surgery. Journal of the American College of Cardiology. 1995;25(2):271A.
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.
Hirthler M, Simoni J, Dickson M. Elevated levels of endotoxin, oxygen-derived free radicals, and cytokines during extracorporeal membrane oxygenation. J Pediatr Surg 1992;27:1199-202.
Casey LC. Role of cytokines in the pathogenesis of cardiopulmonary-induced multisystem organ failure. Ann Thorac Surg 1993;56:S92-6.