Sodium bicarbonate for the prevention of contrast induced nephropathy: A meta-analysis of published clinical trials

doi:10.1016/j.ejrad.2009.12.015

European Journal of Radiology

Volume 79, Issue 1, July 2011, Pages 48-55

https://doi.org/10.1016/j.ejrad.2009.12.015 Get rights and content

Abstract

Background

Contrast induced nephropathy (CIN) is a serious but rare complication following contrast based procedures. Sodium bicarbonate (NaHCO₃) has been postulated to prevent CIN by various mechanisms. However, the outcomes following sodium bicarbonate administration to prevent CIN have been inconsistent.

Methods

A meta-analysis of published randomized clinical trials to determine if the administration of sodium bicarbonate is superior to sodium chloride among patients with chronic renal failure undergoing catheterization and interventional procedures in preventing CIN was performed.

Results

Data were combined across seven published clinical trials consisting of 1734 patients. There were no significant differences in the baseline characteristics between the NaHCO₃ and NaCl groups except patients in the bicarbonate group were heavier (P = 0.04). The odds ratio (OR) for the development of contrast nephropathy for NaHCO₃ versus NaCl was 0.33 (95% confidence interval [CI] 0.16–0.69; P = 0.003). Heterogeneity and publication bias were detectable with P-values 0.01 and 0.0005 respectively. There was no difference between the NaHCO₃ group and the NaCl group in the occurrence of death [OR 0.6; 95% CI (0.26–1.41); P = 0.24], congestive heart failure [OR 0.85; 95% CI (0.32–2.24); P = 0.74] and the requirement for renal replacement therapy [OR 0.56; 95% CI (0.22–1.41); P = 0.22].

Conclusion

This meta-analysis demonstrates that based on currently available randomized trials, the administration of NaHCO₃ is superior to the administration of NaCl alone in the prevention of CIN among patients with moderate to severe chronic kidney disease. However, further controlled clinical trials are needed due to significant study heterogeneity and publication bias.

Introduction

Contrast induced nephropathy (CIN) is a serious complication following cardiac catheterization procedures which results in increased mortality and morbidity. It is also associated with increased health care costs and length of hospital stay [1], [2], [3]. The incidence of CIN varies from 2% among low risk patients to 50% among high risk patients [2], [4], [5]. Several risk markers such as chronic kidney disease, diabetes mellitus (type 1 or 2), volume depletion, nephrotoxic drugs (non-steroidal anti-inflammatory drugs—NSAIDS, cyclosporine, and aminoglycosides), preprocedural hemodynamic instability and other comorbidities (anaemia, congestive heart failure, and hypoalbuminemia) are associated with the development of CIN [2], [6]. Risk scoring schemes have been developed to predict the risk of CIN [2]. Sodium bicarbonate (NaHCO₃) has been postulated to prevent CIN through various mechanisms [7], [8]. However, the outcomes following sodium bicarbonate administration to prevent CIN have been inconsistent [9], [10], [11], [12], [13], [14], [15].

The goal of this study was to perform a meta-analysis of published randomized clinical trials to determine the effects of NaHCO₃ in preventing CIN among patients with chronic renal failure and undergoing cardiac catheterization and interventional procedures.

Section snippets

Methods

A computerized literature search was performed on PubMed using the search terms “contrast nephropathy”, “sodium bicarbonate”, “sodium chloride” and “renal failure”. Randomized clinical trials comparing NaHCO₃ versus placebo or sodium chloride (NaCl) during diagnostic and interventional procedures requiring contrast media administration published as of September 2008 were included in this meta-analysis. The trials included in the present meta-analysis consisted of data on CIN and consisted of

Data extraction

Baseline characteristics including age, gender, past medical history (myocardial infarction, diabetes, hypertension, and congestive heart failure), current medical therapy, type of catheterization procedure, contrast volume and outcome measures (contrast induced nephropathy, death, heart failure, and renal replacement therapy) were recorded from all studies where this information was available by two reviewers (WQ and VK).

Results

Seven published randomized clinical trials were identified and were included in this analysis (Table 1). Data were combined across seven clinical trials consisting of 1734 patients.

Discussion

The present meta-analysis based on currently available published randomized clinical trials demonstrates that the administration of sodium bicarbonate is superior to sodium chloride alone in preventing contrast induced nephropathy among patients with moderate to severe chronic kidney disease undergoing diagnostic and interventional procedures requiring contrast media. However, the beneficial effect of sodium bicarbonate over sodium chloride in preventing the development of CIN was attenuated

Limitations

The enrolment criteria varied across the different trials included in this meta-analysis, and the results observed here may not be applicable to all patients in clinical practice. The number of patients, the inclusion and the exclusion criteria, dose and duration of therapy with sodium bicarbonate varied across the trials. The present study remains subject to the inherent caveats of a meta-analysis including publication bias [47], [48], [49]. Patient level data was not available in this study

Conclusions

The present meta-analysis demonstrates that based on currently available randomized trials, the administration of sodium bicarbonate is superior to the administration of sodium chloride alone in the prevention of contrast induced nephropathy among patients with moderate to severe chronic kidney disease undergoing diagnostic and interventional procedures requiring contrast media. The use of sodium bicarbonate however, did not result in significant benefit in terms of reductions in death,

Conflict of interest

None of the authors have any conflict of interest to disclose.

Acknowledgement

Dr Zaman was supported by a Clinical Research Leave Fellowship from the British Heart Foundation (FS 07/033).

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The Pathogenesis, Outcomes, and Prevention of Contrast-Associated Acute Kidney Injury
2018, Comprehensive Toxicology: Third Edition
Acute kidney injury (AKI) following exposure to iodinated radiocontrast media used for multiple medical imaging procedures including contrast-enhanced computed tomography and coronary and noncoronary angiography represents one of the most common forms of iatrogenic AKI. Multiple mechanisms are believed to contribute to the nephrotoxicity of these agents, including intrarenal vasoconstriction, hyperosmolality, generation of reactive oxygen species, and direct cytotoxicity. The most important risk factor for development of contrast-associated AKI following contrast exposure is preexisting kidney dysfunction. Other patient-related risk factors include concomitant diabetes mellitus, congestive heart failure, volume depletion, and concomitant administration of other nephrotoxic agents, particularly nonsteroidal anti-inflammatory drugs. The toxicity of iodinated contrast media is related to their osmolality, with higher nephrotoxicity associated with higher osmolal contrast media as compared with low-osmolal contrast media and iso-osmolal contrast media. Other risk factors include the volume of contrast media infused, intra-arterial as compared with intravenous administration, and repeated exposure to contrast media over a short period of time. The primary strategy to mitigate the risk of contrast-associated AKI is periprocedural administration of isotonic crystalloid solutions, although the optimal rate of fluid administration is not known. It is also uncertain whether the use of isotonic sodium bicarbonate provides greater renal protection than isotonic saline. Although periprocedural administration of multiple pharmacological agents, including N-acetylcysteine, adenosine antagonists, statins, and ascorbic acid, have been proposed for prevention of contrast-associated AKI, the true effectiveness of these agents remains uncertain. Other pharmacological agents, including loop diuretics, mannitol, and dopamine, and other dopaminergic agonists, as well as prophylactic hemodialysis and hemofiltration, are not effective at reducing the risk of contrast-associated AKI.
Vitamin C + sodium bicarbonate versus sodium bicarbonate alone in preventing contrast-induced nephropathy
2017, Annales de Cardiologie et d'Angeiologie
La néphropathie, induite par les produits de contraste (NIPC), est une complication fréquente et grave en milieu de cardiologie interventionnelle.
Le but de notre étude était de comparer l’incidence de NIPC selon deux protocoles d’hydratation accélérés : le premier par du sérum bicarbonaté seul et le deuxième associant le sérum bicarbonaté à la vitamine C orale.
Il s’agit d’une étude multicentrique prospective, randomisée menée entre octobre 2012 et mai 2013, incluant 160 patients.
L’âge moyen de notre population d’étude était de 60,8 ± 9,3 ans (36 à 83 ans). Les deux groupes de l’étude étaient comparables à l’état de base en termes de facteurs de risques cardiovasculaires, de la médication concomitante, et du taux de créatinémie basale. La NIPC était estimée à 6,3 % dans le groupe vitamine C et à 10 % dans le groupe témoin, avec une différence non significative (p = 0,38). L’analyse de sous-groupes selon le protocole utilisé n’a pas montré de différence significative quant à l’incidence de NIPC. Cependant, une forte tendance à un moindre taux de NIPC a été notée dans le sous-groupe vitamine C en cas d’utilisation de dose toxique de produit de contraste. De même, aucune NIPC n’a été notée dans le sous-groupe de patients âgés de plus de 75 ans sous vitamine C.
Selon notre étude, l’acide ascorbique administré par voie orale dans le cadre d’un protocole de réhydratation accéléré ne permet pas de réduire l’incidence de NIPC.
Contrast-induced nephropathy (CIN) is a common and severe complication in interventional cardiology.
The aim of our study was to compare the incidence of contrast-induced nephropathy in two accelerated hydration protocols: the first one by the serum bicarbonate and the second combining the serum bicarbonate and oral vitamin C.
This is a multicenter prospective, randomized study conducted between October 2012 and May 2013, including 160 patients.
The mean age of our study population was 60.8 ± 9.3 years (36–83 years). The two study groups were comparable in terms of cardiovascular risk factors, concomitant medication, and baseline serum creatinine. The CIN incidence was 6.3% in the vitamin C group and 10% in the control group (P = 0.38). No significant difference was observed in terms of CIN incidence between the different subgroups analyzed.
According to our study, ascorbic acid administered orally as part of an accelerated hydration protocol does not reduce the incidence of CIN.
Meta-Analysis of Individual Patient Data of Sodium Bicarbonate and Sodium Chloride for All-Cause Mortality After Coronary Angiography
2016, American Journal of Cardiology
Citation Excerpt :
Second, their estimate is based on only 5 of 10 trials included in this study.10,13,15,16,18 In another meta-analyses, Kunadian et al19 also found no significant difference between all-cause mortality risk in participants randomized to sodium bicarbonate (9 [2%] of 511) versus sodium chloride (16 [3%] of 514): OR 0.60 (0.26 to 1.41) p = 0.24 (random-effects model). This estimate is subject to the same limitations of the analysis by Jang et al.
We sought to examine the relation between sodium bicarbonate prophylaxis for contrast-associated nephropathy (CAN) and mortality. We conducted an individual patient data meta-analysis from multiple randomized controlled trials. We obtained individual patient data sets for 7 of 10 eligible trials (2,292 of 2,764 participants). For the remaining 3 trials, time-to-event data were imputed based on follow-up periods described in their original reports. We included all trials that compared periprocedural intravenous sodium bicarbonate to periprocedural intravenous sodium chloride in patients undergoing coronary angiography or other intra-arterial interventions. Included trials were determined by consensus according to predefined eligibility criteria. The primary outcome was all-cause mortality hazard, defined as time from randomization to death. In 10 trials with a total of 2,764 participants, sodium bicarbonate was associated with lower mortality hazard than sodium chloride at 1 year (hazard ratio 0.61, 95% confidence interval [CI] 0.41 to 0.89, p = 0.011). Although periprocedural sodium bicarbonate was associated with a reduction in the incidence of CAN (relative risk 0.75, 95% CI 0.62 to 0.91, p = 0.003), there exists a statistically significant interaction between the effect on mortality and the occurrence of CAN (hazard ratio 5.65, 95% CI 3.58 to 8.92, p <0.001) for up to 1-year mortality. Periprocedural intravenous sodium bicarbonate seems to be associated with a reduction in long-term mortality in patients undergoing coronary angiography or other intra-arterial interventions.
Symptomatic renal artery stenosis and infra-renal AAA
2015, European Journal of Vascular and Endovascular Surgery
To identify evidence to guide the vascular surgeon as to the relevance of renal artery stenting in a patient with symptomatic renal artery stenosis undergoing elective endovascular aortic aneurysm repair (EVAR).
A comprehensive literature search of MEDLINE was performed without time limits. The following terms were used in the first instance: renal artery stenting and renal artery stenosis, and any other analogous terms identified during the search. Selection criteria were set to randomised control trials.
Despite several large, randomised controlled trials investigating renal artery stenting against medical treatment alone in symptomatic renal artery stenosis, there has been no significant benefit identified in terms of improvement in renal function, control of blood pressure, or need for dialysis. The stented populations were also more likely to suffer from complications caused by the procedure such as bleeding, cholesterol embolisation and flash pulmonary oedema.
There is no evidence for the use of renal artery stenting over optimal medical management in the treatment of patients with symptomatic atherosclerotic renal artery stenosis, irrelevant of the degree of stenosis. In the setting of EVAR, prevention of deterioration of renal function should be with involvement of the renal physicians, adequate hydration, and use of minimal contrast agent. Repair should be undertaken in centres with access to 24-hour haemofiltration services.
Intravascular ultrasound guidance to minimize the use of iodine contrast in percutaneous coronary intervention the MOZART (minimizing contrast utilization with IVUS guidance in coronary angioplasty) randomized controlled trial
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The aim of this study was to evaluate the impact of intravascular ultrasound (IVUS) guidance on the final volume of contrast agent used in patients undergoing percutaneous coronary intervention (PCI).
To date, few approaches have been described to reduce the final dose of contrast agent in PCIs. We hypothesized that IVUS might serve as an alternative imaging tool to angiography in many steps during PCI, thereby reducing the use of iodine contrast.
A total of 83 patients were randomized to angiography-guided PCI or IVUS-guided PCI; both groups were treated according to a pre-defined meticulous procedural strategy. The primary endpoint was the total volume contrast agent used during PCI. Patients were followed clinically for an average of 4 months.
The median total volume of contrast was 64.5 ml (interquartile range [IQR]: 42.8 to 97.0 ml; minimum, 19 ml; maximum, 170 ml) in the angiography-guided group versus 20.0 ml (IQR: 12.5 to 30.0 ml; minimum, 3 ml; maximum, 54 ml) in the IVUS-guided group (p < 0.001). Similarly, the median volume of contrast/creatinine clearance ratio was significantly lower among patients treated with IVUS-guided PCI (1.0 [IQR: 0.6 to 1.9] vs. 0.4 [IQR: 0.2 to 0.6, respectively; p < 0.001). In-hospital and 4-month outcomes were not different between patients randomized to angiography-guided and IVUS-guided PCI.
Thoughtful and extensive use of IVUS as the primary imaging tool to guide PCI is safe and markedly reduces the volume of iodine contrast compared with angiography-alone guidance. The use of IVUS should be considered for patients at high risk of contrast-induced acute kidney injury or volume overload undergoing coronary angioplasty. (Minimizing cOntrast utiliZation With IVUS Guidance in coRonary angioplasTy [MOZART]; NCT01947335)
Current concepts of contrast-induced nephropathy: A brief review
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Citation Excerpt :
Typically, patients should receive 154 mEq/L of NaHCO3, as a bolus of 3 mL/kg/h for 1 hour prior to CM administration, followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure.77 Recent large meta-analysis studies demonstrated that NaHCO3 had a greater benefit than sodium chloride (NaCl; OR = 0.33–0.57, CI = 0.16–0.85), but no significant difference in the occurrence of death (OR = 0.6, CI = 0.26–1.41, p = 0.24) and requirement for renal replacement therapy (OR = 0.56, CI = 0.22–1.41, p = 0.22).78,79 We suggest hydration with NaHCO3 prior to CM exposure instead of NaCl for prophylaxis of CIN in patients at risk and who are not contraindicated for NaHCO3 infusion.
Contrast-induced nephropathy (CIN) is a common hospital-acquired acute kidney injury. Published studies on this condition have dramatically increased in recent years. This article aims to provide a brief literature review. English articles published from 1983 to 2012 were retrieved from PubMed by searching using the term “contrast-induced nephropathy.” Patients with CIN were associated with increased resource utilization, prolonged hospital stay, and increased long-term mortality. CIN is defined as a ≥0.5 mg/dL rise in serum creatinine or a 25% increase, assessed within 48–72 hours after administration of contrast medium (CM). All patients receiving CM should be evaluated for their CIN risk, especially preexisting kidney disease. The CM should be prewarmed to 37 °C and injected at the lowest possible dose. Repeat injection within 72 hours should be avoided. Either iso-osmolar CM or low-osmolar CM, except ioxaglate or iohexol, can be used in all patients. Iso-osmolar CM iodixanol may be a better choice for high-risk patients with chronic kidney disease requiring intra-arterial administration. Nephrotoxic drugs should be stopped 2 days prior to when the patient undergoes a procedure. All patients receiving CM should be at an optimal volume status. Parenteral isotonic saline without any diuretic should be started 12 hours prior to CM at a rate of 1 mL/kg/h and continued for 24 hours if there is no contraindication. In patients who require shorter volume supplement periods or are at a higher risk, bicarbonate infusion (154 mEq/L, 3 mL/kg/h for 1 hour bolus prior to CM, followed by 1 mL/kg/h for 6 hours) may be used as an alternative to isotonic saline. Oral N-acetylcysteine (600 mg bid, starting on the day prior to the procedure) together with parenteral hydration is suggested for patients at risk. Hemodialysis/hemofiltration is only considered in chronic kidney disease stage 4/5 patients when an access is available. The other medications or techniques for reducing CIN risk are still unclear. CIN is a potentially preventable clinical condition. A careful review of published reports gives us a deeper understanding of CIN and a greater chance of decreasing its risk.

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Sodium bicarbonate for the prevention of contrast induced nephropathy: A meta-analysis of published clinical trials

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Data extraction

Results

Discussion

Limitations

Conclusions

Conflict of interest

Acknowledgement

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Am J Kidney Dis

J Am Coll Cardiol

Am J Cardiol

Am Heart J

J Am Coll Cardiol

Control Clin Trials

Kidney Int

Am Heart J

Am J Kidney Dis

Kidney Int

Am J Med

J Am Coll Cardiol

Am Heart J

Am J Kidney Dis

J Am Coll Cardiol

JACC Cardiovasc Interv

J Clin Epidemiol

Urol Oncol

The effect of acute renal failure on mortality. A cohort analysis

JAMA

Radiocontrast nephropathy: identifying the high-risk patient and the implications of exacerbating renal function

Rev Cardiovasc Med

Risk prediction of contrast-induced nephropathy

Am J Cardiol