INTRODUCTION
Acute kidney injury (AKI) is one of the serious postoperative complications in cardiac surgery as a result of hypoperfusion to renal tissues with subsequent ischemia.[1] The incidence of this complication ranges between 7% in patients with normal preoperative renal function to 40% in patients with preoperative renal impairment or those with risk factors for renal injury.[2–6]
Renal-dose dopamine has been shown to exert a renal protective effect in different experimental models.[7,8] These properties include but are not limited to dilatation of the renal afferent arterioles, increasing renal blood flow, and natriuresis.[9] These effects are independent of dopamine vasogenic effect on the circulation or its inotropic effect on the heart muscle.[8]
However, when used clinically, the use of low-dose dopamine in different studies and randomized clinical trials showed controversial results.[9–11] Some studies found a significant improvement in renal function with the use of prophylactic low-dose dopamine,[12,13] whereas others showed that administration of low-dose dopamine to critically ill patients at risk of renal failure was not effective as a protective prophylactic measure from renal dysfunction.[14,15]
Although many studies have investigated the prophylactic use of dopamine in cardiac or critically ill patients, there were only very few studies on the therapeutic use of low-dose dopamine in cardiac surgery patients after the development of AKI.[13,16] These studies showed favorable results toward better kidney function. However, more studies are needed to confirm these effects.
Therefore, the aim of our study was to investigate the effect of postoperative use of low-dose dopamine in patients who develop AKI postcardiac surgery on improvement in renal function and perioperative mortality.
METHODS
Study design
This is a retrospective cohort study that was conducted in a specialized cardiac center at a tertiary hospital and included 96 patients. The inclusion criteria were: (1) all adult patients, (2) who underwent cardiac surgery, (3) with the use of cardiopulmonary bypass, (4) between January 2017 and December 2020, and (5) who developed postoperative AKI. Exclusion criteria were: (1) all patients with preoperative renal dysfunction, (2) or patients with end-stage renal disease. AKI was defined according to AKI network criteria[17] as a more than 1.5-fold increase in postoperative serum creatinine from the preoperative value within 48 h. The study population was divided into two groups according to the use of renal-dose dopamine (3 mg/kg/min) as a therapeutic measure. The decision to start renal-dose dopamine was based on the discretion of the treating physician. The outcomes of interest were the improvement in renal function as indicated by the serum creatinine level, the requirement for dialysis, and the 30-day mortality. Our hypothesis is that therapeutic renal-dose dopamine may result in improvement in renal function and 30-day mortality in patients who develop AKI postcardiac surgery.
Data collection
Ninety-six patients were included in the study. Data were collected on patients’ demographics, operative, and postoperative data as well as perioperative complications from electronic medical records.
Ethical statement
The procedures followed in this study were in accordance with the ethical standards of the responsible committee on human experimentation (institutional or regional) and with the Helsinki Declaration of 1975, as revised in 2000 (available at https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles -for-medical-research-involving-human-subjects/). The study was approved by the Institutional Review Board at the College of Medicine (E-22-E-22-7017, July 26, 2022) and the need for consent was waived due to the retrospective nature of the study. There has been no duplicate publication or submission of this manuscript elsewhere. The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and each author believes that the manuscript represents honest work. Subject to acceptance, authors will transfer the copyright to the publisher. There is no ethical problem or conflict of interest to be declared for any of the coauthors.
Statistical analysis
Continuous variables were compared using the Wilcoxon rank-sum test. Categorical variables were compared using Fisher’s exact test. A P < 0.05 was considered statistically significant. Multivariate regression analysis was performed to determine the factors affecting the change in creatinine level using the random effects model. The statistical analysis was performed using Stata 16.1 software (Stata Corp, College Station, TX, USA).
RESULTS
A total of 159 patients met the inclusion criteria, out of whom 63 were excluded because they had either preoperative renal impairment or preexisting end-stage renal disease. Ninety-six patients were enrolled in the study and were divided into two groups; the first group who did not receive postoperative renal-dose dopamine (39 patients) and the second group who received dopamine (57 patients).
All preoperative characteristics were similar between the two groups [Table 1]. The dopamine group had a higher postoperative peak creatinine level (205 vs 164, P < 0.001) and higher requirement for dialysis (22.81% vs. 2.56%, P = 0.01) compared to the nondopamine group. In addition, the dopamine group had a longer duration of intubation (24 h vs. 21 h, P = 0.01), a longer requirement for inotropic support (4 days vs. 3 days, P < 0.001), and a higher rate of re-exploration for bleeding or tamponade (21.05% vs. 2.56%, P = 0.01). The use of an intra-aortic balloon pump and the mortality were both higher in the dopamine group. However, they did not reach statistical significance. The rest of the postoperative variables are described in Table 2.
;)
Table 1: Preoperative data
Table 2: Postoperative outcomes
We used the multivariate regression analysis to study the factors affecting the change in postoperative creatinine level [Table 3]. Time from surgery was the only factor associated with an increase in creatinine level, whereas dopamine use was not associated with an increase or decrease in postoperative creatinine level. Smoking history was inversely associated with the change in creatinine level. The relationship between time and change in postoperative creatinine level [Figure 1] shows a higher rate of change in the dopamine group compared to the nondopamine group.
Table 3: Factors affecting the change in creatinine level (random effects model): Regression results
Figure 1: Change in creatinin level [Median (Bar: Interquartile range)]
DISCUSSION
The protective effects of low dose have been demonstrated in multiple experimental models with normal kidney function.[7,8] However, these effects may or may not occur in patients with abnormal kidney function or at risk of renal injury. Many studies including randomized clinical trials focused on the prophylactic use of dopamine in critically ill patients or patients going for major procedures that carries a risk of AKI such as cardiac surgical procedures. However, the results of these studies were controversial and nonconclusive.[9–13] Some studies found a significant improvement in renal function with the use of prophylactic low-dose dopamine,[12,13] whereas others showed that administration of low-dose dopamine to critically ill patients at risk of renal failure was not effective as a protective tool from renal dysfunction.[14,15]
These differences in outcomes between normal patients in experimental models and patients with critical conditions could be explained by the abnormal hemodynamics and filling status in critically ill patients and postmajor procedures that could create a suboptimal environment for dopamine to exert its protective effects.
Some studies showed that the favorable effect of low-dose dopamine is related to other factors including the adequacy of perfusion pressure, filling status of the patient, combination with other infusions such as lasix and mannitol, and the use of inotropic drugs.[18]
Although many studies have investigated the prophylactic use of dopamine in cardiac or critically ill patients, there were only very few studies on the therapeutic use of low-dose dopamine in cardiac surgery patients after the development of AKI.[13,16] that showed favorable outcomes.
In this study, we used low-dose dopamine in a group of patients with a normal preoperative renal function who developed postoperative AKI as a therapeutic agent. We found that dopamine did not reverse the AKI and did not eliminate the need for dialysis in those patients compared to the group that did not receive dopamine. In addition, there was higher mortality in the dopamine group. These worse outcomes in the dopamine group are more likely related to selection bias since dopamine was started in a patient with higher creatinine levels, longer duration of intubation, higher use of inotropes, and higher rate of bleeding and re-exploration. This was confirmed using the multivariate regression analysis that showed dopamine use was not a predictor of the change in creatinine level.
Multiple factors have been suggested as an etiology for the lack of effectiveness of low-dose dopamine in critically ill patients.[19–33] The question that is still not answered is: “Is dopamine not effective as a therapeutic intervention after AKI” or “Should dopamine be used early after the occurrence of AKI before creatinine becomes higher indicating a more advanced stage of AKI.”
One of the secondary interesting findings in this study was the association between the higher rate of re-exploration for bleeding and the worsening postoperative renal function. This is a modifiable factor finding that needs further investigation in future studies.
Limitations
This is a nonrandomized study and included a small number of patients that shows some associations but do not provide strong evidence of causation. However, it provides some insight into the therapeutic use of postoperative renal dose dopamine on cardiac surgery patients who develop postoperative AKI.
CONCLUSION
The use of low-dose dopamine was not effective as a therapeutic agent in improving renal function or eliminating the need for dialysis in patients who develop AKI postcardiac surgery. Further studies are needed to clarify the optimal timing and conditions for using low-dose dopamine in those patients.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
This study was supported by the College of Medicine Research Center, Deanship of Scientific Research, King Saud University, Riyadh, Saudi Arabia.
REFERENCES
1. O'Neal JB, Shaw AD, Billings FT 4th. Acute kidney injury following cardiac surgery:Current understanding and future directions. Crit Care 2016;20:187.
2. Conlon PJ, Stafford-Smith M, White WD, Newman MF, King S, Winn MP, et al. Acute renal failure following cardiac surgery. Nephrol Dial Transplant 1999;14:1158–62.
3. Corwin HL, Sprague SM, DeLaria GA, Norusis MJ. Acute renal failure associated with cardiac operations. A case-control study. J Thorac Cardiovasc Surg 1989;98:1107–12.
4. Kuitunen A, Vento A, Suojaranta-Ylinen R, Pettilä V. Acute renal failure after cardiac surgery:Evaluation of the RIFLE classification. Ann Thorac Surg 2006;81:542–6.
5. Machado MN, Nakazone MA, Maia LN. Prognostic value of acute kidney injury after cardiac surgery according to kidney disease:Improving global outcomes definition and staging (KDIGO) criteria. PLoS One 2014;9:e98028.
6. Reents W, Hilker M, Börgermann J, Albert M, Plötze K, Zacher M, et al. Acute kidney injury after on-pump or off-pump coronary artery bypass grafting in elderly patients. Ann Thorac Surg 2014;98:9–14.
7. Sophasan S, Sanposn W, Kraisawekwisai S, Chatsudthipong V. The effects of dopamine on kidney function of rats. Arch Int Pharmacodyn Ther 1981;252:219–28.
8. Olsen NV. Effects of dopamine on renal haemodynamics tubular function and sodium excretion in normal humans. Dan Med Bull 1998;45:282–97.
9. Lee MR. Dopamine and the kidney:Ten years on. Clin Sci (Lond) 1993;84:357–75.
10. Tang AT, El-Gamel A, Keevil B, Yonan N, Deiraniya AK. The effect of 'renal-dose'dopamine on renal tubular function following cardiac surgery:Assessed by measuring retinol binding protein (RBP). Eur J Cardiothorac Surg 1999;15:717–21.
11. Myles PS, Buckland MR, Schenk NJ, Cannon GB, Langley M, Davis BB, et al. Effect of “renal-dose”dopamine on renal function following cardiac surgery. Anaesth Intensive Care 1993;21:56–61.
12. Gatot I, Abramov D, Tsodikov V, Yeshayahu M, Orman S, Gavriel A, et al. Should we give prophylactic renal-dose dopamine after coronary artery bypass surgery?. J Card Surg 2004;19:128–33.
13. Davis RF, Lappas DG, Kirklin JK, Buckley MJ, Lowenstein E. Acute oliguria after cardiopulmonary bypass:Renal functional improvement with low-dose dopamine infusion. Crit Care Med 1982;10:852–6.
14. Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal dysfunction:A placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000;356:2139–43.
15. Woo EB, Tang AT, el-Gamel A, Keevil B, Greenhalgh D, Patrick M, et al. Dopamine therapy for patients at risk of renal dysfunction following cardiac surgery:Science or fiction?Eur J Cardiothorac Surg 2002;22:106–11.
16. Sirivella S, Gielchinsky I, Parsonnet V. Mannitol, furosemide, and dopamine infusion in postoperative renal failure complicating cardiac surgery. Ann Thorac Surg 2000;69:501–6.
17. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network:Report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.
18. Carcoana OV, Hines RL. Is renal dose dopamine protective or therapeutic?Yes. Crit Care Clin 1996;12:677–85.
19. Juste RN, Moran L, Hooper J, Soni N. Dopamine clearance in critically ill patients. Intensive Care Med 1998;24:1217–20.
20. Ichai C, Passeron C, Carles M, Bouregba M, Grimaud D. Prolonged low-dose dopamine infusion induces a transient improvement in renal function in hemodynamically stable, critically ill patients:A single-blind, prospective, controlled study. Crit Care Med 2000;28:1329–35.
21. Heyman SN, Fuchs S, Brezis M. The role of medullary ischemia in acute renal failure. New Horiz 1995;3:597–607.
22. Heyman SN, Kaminski N, Brezis M. Dopamine increases renal medullary blood flow without improving regional hypoxia. Exp Nephrol 1995;3:331–7.
23. Kullmann R, Breull WR, Reinsberg J, Wassermann K, Konopatzki A. Dopamine produces vasodilation in specific regions and layers of the rabbit gastrointestinal tract. Life Sci 1983;32:2115–22.
24. Burns A, Gray PA, Park GR. Effects of dopaminergic stimulation on the splanchnic and renal vasculature. Clin Intensive Care 1991;2 Suppl 50–2.
25. Nevière R, Mathieu D, Chagnon JL, Lebleu N, Wattel F. The contrasting effects of dobutamine and dopamine on gastric mucosal perfusion in septic patients. Am J Respir Crit Care Med 1996;154:1684–8.
26. Van den Berghe G, de Zegher F, Wouters P, Schetz M, Verwaest C, Ferdinande P, et al. Dehydroepiandrosterone sulphate in critical illness:Effect of dopamine. Clin Endocrinol (Oxf) 1995;43:457–63.
27. Van den Berghe G, de Zegher F, Lauwers P. Dopamine and the sick euthyroid syndrome in critical illness. Clin Endocrinol (Oxf) 1994;41:731–7.
28. Van den Berghe G, de Zegher F, Lauwers P, Veldhuis JD. Luteinizing hormone secretion and hypoandrogenaemia in critically ill men:Effect of dopamine. Clin Endocrinol (Oxf) 1994;41:563–9.
29. Van den Berghe G, de Zegher F, Lauwers P, Veldhuis JD. Growth hormone secretion in critical illness:Effect of dopamine. J Clin Endocrinol Metab 1994;79:1141–6.
30. Devins SS, Miller A, Herndon BL, O'Toole L, Reisz G. Effects of dopamine on T-lymphocyte proliferative responses and serum prolactin concentrations in critically ill patients. Crit Care Med 1992;20:1644–9.
31. Kouassi E, Boukhris W, Descotes J, Zukervar P, Li YS, Revillard JP. Selective T cell defects induced by dopamine administration in mice. Immunopharmacol Immunotoxicol 1987;9:477–88.
32. Ward DS, Bellville JW. Effect of intravenous dopamine on hypercapnic ventilatory response in humans. J Appl Physiol Respir Environ Exerc Physiol 1983;55:1418–25.
33. Olson LG, Hensley MJ, Saunders NA. Ventilatory responsiveness to hypercapnic hypoxia during dopamine infusion in humans. Am Rev Respir Dis 1982;126:783–7.
