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Cochrane Database of Systematic Reviews Protocol - Intervention

Bicarbonate versus lactate solutions for acute haemodialysis

Authors' declarations of interest

Version published: 17 October 2007 Version history

https://doi.org/10.1002/14651858.CD006819

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view the current version 05 March 2015
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Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

This review aims to look at the benefits and harms of bicarbonate versus lactate‐buffered haemodialysis solutions for treating ARF.

Background

Acute renal failure (ARF) is an acute loss of kidney function that occurs over days to weeks and results in an inability to appropriately excrete nitrogenous wastes and creatinine. Electrolyte disturbances and loss of fluid homeostasis may occur. Commonly accepted diagnostic criteria include an increase in the serum creatinine level of 0.5 mg/dL (44.2 mmol/L) or a 50% increase in the creatinine level above the baseline value, a 50% decrease in the baseline‐calculated glomerular filtration rate (GFR) (Albright 2001; Needham 2005; Singri 2003; Thadhani 1996). Causes of ARF can be broadly divided into three categories: prerenal, postrenal and intrinsic renal (Lamiere 2005). Prerenal ARF is results from decreased blood supply to the kidneys (Santacruz 1996). Postrenal ARF caused by obstruction in the urinary tract (Liano 1996). Intrarenal ARF is as a result of direct injury to the kidneys (Needham 2005). ARF is present in 1% to 5% of patients at hospital admission (Kaufman 1991). The condition affects 15% to 20% of patients in intensive care units (ICUs); reported mortality rates range from 50% to 70% in these patients (Albright 2001; Singri 2003; Thadhani 1996).

Infection and cardiorespiratory complications are the most common causes of death in patients with ARF (Needham 2005). Mortality rates have changed little over the past few decades despite significant advances in supportive care, however, this lack of improvement may be more apparent than real because patients nowadays are older and have more pre‐existing chronic health problems (Jaber 2004).The long‐term effects of ARF are unclear and controversial because of the diverse (and in many cases multiple) causes of the disorder and the paucity of long‐term follow‐up studies. However, the view that renal recovery is complete is simplistic, and progressive renal dysfunction after severe ARF is commonly observed. ARF is irreversible in 5% of patients, but in elderly people this proportion is as high as 16%. Recent reports on children suggest that residual damage after ARF develops into progressive renal failure by adolescence or early adulthood (Bhandari 1996; Lamiere 2005; Polito 1998).

When ARF is diagnosed, the cause(s) must be identified and treated. Critical measures include maintaining adequate intravascular volume and mean arterial pressure, discontinuing all nephrotoxic drugs, and eliminating exposure to any other nephrotoxins (Agrawal 2000). Many drugs have been used to treat or prevent ARF, however trials of these drugs are inconclusive. Therefore, the current treatment for ARF patients is essentially supportive, renal replacement therapy (RRT) is the supportive therapy for patients with diminished renal function (Uchino 2005). Modalities of RRT include haemodialysis, peritoneal dialysis, haemofiltration and haemodiafiltration. Among these various forms of RRT haemodialysis appears to have a significant and variable impact on the concentration of several electrolytes and on acid‐base balance (Heering 1999). Some of this effect is likely to depend on the composition of the replacement fluid. Haemofiltration solutions are used as the buffer to correct acidosis (Macias 1996). In Europe and Australia the dominant commercially available replacement fluids are either lactate‐buffered or bicarbonate‐buffered (Tan 2004). Bicarbonate‐buffered solutions have only recently become possible as a result of the development of a two‐chambered bag system to separate calcium and magnesium from the bicarbonate which have been shown to improve peritoneal cell function (Dratwa 2003); the lactate solution has been the standard dialysate solution for more than 15 years. It can be converted to bicarbonate by using a pyruvate dehydrogenase enzyme in the tissues of mainly the liver and muscles (Uchino 2005).

These fluids are not only likely to have a different effect on acid‐base physiology, they are also likely to have a different effect on several electrolytes because of their different composition. Such differences might affect electrolyte mass balance (Tan 2004). Appreciation of such differences might be important for clinicians faced with unexplained changes in serum electrolyte concentrations over time during continuous renal replacement therapy (CRRT) and might help them avoid unnecessary investigations or interventions. The effectiveness and safety of lactate‐buffered or bicarbonate‐buffered solutions needs to be reviewed and appraised critically to inform current practice.

Objectives

This review aims to look at the benefits and harms of bicarbonate versus lactate‐buffered haemodialysis solutions for treating ARF.

Methods

Criteria for considering studies for this review

Types of studies

All randomised controlled trials (RCTs) and quasi‐RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at the use of bicarbonate‐buffered and lactate buffered haemodialysis solutions in patients with ARF. Randomised cross‐over studies shall also be included. There will be no language restriction.

Types of participants

Patients (adults or children) with ARF, as estimated by either serum creatinine, creatinine clearance or GFR measurement.

For the purpose of this review ARF will be defined as an increase in the serum creatinine of 44.2 mmol/L over the base‐line value, an increase of more than 50% over the base‐line value, a reduction in the calculated creatinine clearance of more than 50%, or a decrease in renal function that results in the need for renal replacement therapy (RRT).

Types of interventions

  • Bicarbonate‐buffered replacement fluid versus lactate‐buffered replacement fluid.

Types of outcome measures

  • Mortality: death prior to ICU discharge; death prior to hospital discharge.

  • Length of time in ICU.

  • Total length of hospital stay.

  • Relapse.

  • Renal function measures (creatinine clearance, serum creatinine, proteinuria, dialysis, GFR).

  • Clinical and biochemical parameters (e.g. blood pressure, CVP cm H2O, pH, pCO2, blood sodium, blood potassium, blood chloride, blood magnesium, blood phosphate).

  • Adverse events (e.g. hyperkalaemia).

  • Economic outcomes.

Search methods for identification of studies

1). The Cochrane Renal Groups specialised register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, (most recent) which will be searched using the following terms:‐
#1 MeSH descriptor Bicarbonates explode all trees
#2 MeSH descriptor Sodium Lactate explode all trees
#3 (bicarbonate*):ti,ab,kw
#4 MeSH descriptor Lactates explode all trees
#5 MeSH descriptor Lactic Acid explode all trees
#6 (Lactic Acid):ti,ab,kw
#7 MeSH descriptor Sodium Lactate explode all trees
#8 OR/1‐7
#9 MeSH descriptor Dialysis explode all trees
#10 MeSH descriptor Hemodialysis Solutions explode all trees
#11 MeSH descriptor Hemodiafiltration explode all trees
#12 MeSH descriptor Hemofiltration explode all trees
#13 (dialysis):ti,ab,kw
#14 (hemodialysis solutions):ti,ab,kw
#15 (hemodiafiltration):ti,ab,kw
#16 (hemofiltration):ti,ab,kw
#17 (diafiltration):ti,ab,kw
#18 or/9‐17
#19 MeSH descriptor Renal Insufficiency, Acute explode all trees
#20 MeSH descriptor Kidney Failure, Acute explode all trees
#21 MeSH descriptor Kidney Tubular Necrosis, Acute explode all trees
#22 (acute kidney failure):ti,ab,kw
#23 (acute renal failure):ti,ab,kw
#24 (acute kidney tubular necrosis):ti,ab,kw
#25 (acute tubular necrosis):ti,ab,kw
#26(acute renal insufficiency):ti,ab,kw
#27 (acute kidney insufficiency):ti,ab,kw
#28 (ARF or AKF or ATN):ti,ab,kw
#29 OR/19‐29
#30 #8 AND #18 AND #29

CENTRAL and the Renal Groups specialised register contain the handsearched results of conference proceedings from general and speciality meetings. This is an ongoing activity across the Cochrane Collaboration and is both retrospective and prospective (Master List 2007). Therefore we will not specifically search conference proceedings. Please refer to The Cochrane Renal Review Group's Module in The Cochrane Library for the most up‐to‐date list of conference proceedings.

2). MEDLINE (1966 to most recent) using the optimally sensitive strategy developed for the Cochrane Collaboration for the identification of RCTs (Dickersin 1994) with a specific search strategy developed with input from the Cochrane Renal Groups Trial Search Co‐ordinator.
1. randomized controlled trial.pt.
2. controlled clinical trial.pt.
3. randomized controlled trials/
4. random allocation/
5. double blind method/
6. single blind method/
7. or/1‐7
8. animals/ not (animals/ and human/)
9.7 not 8
10. clinical trial.pt.
11. exp clinical trials/
12.(clinic$ adj25 trial$).ti,ab.
13. cross‐over studies/
14.(crossover or cross‐over or cross over).tw.
15.((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$)).tw.
16. placebos/
17. placebo$.ti,ab.
18. random$.ti,ab.
19. research design/
20. or/10‐19
21.20 not 8
22.9 or 21
23. exp bicarbonates/
24. exp sodium bicarbonate/
25. bicarbonate$.tw.
26. exp lactates/
27. exp lactic acid/
28. exp sodium lactate/
29. lactate$.tw.
30. lactic acid.tw.
31. or/23‐30
32. exp dialysis/
33. exp hemodialysis solutions/
34. exp hemodiafiltration/
35. exp hemofiltration/
36. dialysis.tw.
37. hemodialysis solutions.tw.
38. hemodiafiltration.tw.
39. hemofiltration.tw.
40. diafiltration.tw.
41. or/32‐40
42. exp renal insufficiency, acute/
43. exp kidney failure, acute/
44. exp kidney tubular necrosis, acute/
45. acute kidney failure.tw.
46. acute renal failure.tw.
47. acute renal insufficiency.tw.
48. acute kidney insufficiency.tw.
49. acute tubular necrosis.tw.
50. acute kidney tubular necrosis.tw.
51. (ARF or AKF or ATN).tw.
52. or/42‐51
53.22 and 31 and 41 and 52

3). EMBASE (1980 to most recent) using a search strategy adapted from that developed for the Cochrane Collaboration for the identification of RCTs (Lefebvre 1996) together with a specific search strategy developed with input from the Cochrane Renal Groups Trial Search Co‐ordinator.
1. exp clinical trial/
2. comparative study/
3. drug comparison/
4. major clinical study/
5. randomization/
6. crossover procedure/
7. double blind procedure/
8. single blind procedure/
9. placebo/
10. prospective study/
11. ((clinical or controlled or comparative or placebo or prospective or randomi#ed) adj3 (trial or study)).ti,ab.
12. (random$ adj7 (allocat$ or allot$ or assign$ or basis$ or divid$ or order$)).ti,ab.
13. ((singl$ or doubl$ or trebl$ or tripl$) adj7 (blind$ or mask$)).ti,ab.
14. (cross?over$ or (cross adj1 over$)).ti,ab.
15. ((allocat$ or allot$ or assign$ or divid$) adj3 (condition$ or experiment$ or intervention$ or treatment$ or therap$ or control$ or group$)).ti,ab.
16. or/1‐10
17. or/11‐15
18. (16 or 17)
19. exp bicarbonates/
20. bicarbonate$.tw.
22. exp lactic acid/
23. exp lactate sodium/
24. lactate$.tw.
25. lactic acid.tw.
26. or/19‐25
27. exp dialysis/
28. exp hemodialysis fluid/
29. exp hemodiafiltration/
30. exp hemofiltration/
31. exp diafiltration/
32. dialysis.tw.
33. hemodialysis solutions.tw.
34. hemodiafiltration.tw.
35. hemofiltration.tw.
36. diafiltration.tw.
37. or/27‐36
38. exp acute kidney failure/
39. exp acute kidney tubule necrosis/
40. acute kidney failure.tw.
41. acute renal failure.tw.
42. acute renal insufficiency.tw.
43. acute kidney insufficiency.tw.
44. acute tubular necrosis.tw.
45. acute kidney tubular necrosis.tw.
46. (ARF or AKF or ATN).tw.
47. or/38‐46
48.(18 and 26 and 37 and 47)

4). Reference lists of nephrology textbooks, review articles and relevant trials.
5). Letters seeking information about unpublished or incomplete trials to investigators known to be involved in previous trials.

Data collection and analysis

Included and excluded studies

The review will be undertaken by six authors (JHT, KHY, JYT, BM, YlL, TXL). The search strategy described will be used to obtain titles and abstracts of studies that may be relevant to the review. The titles and abstracts will be screened independently by JHT and JYT, who will discard studies that are not applicable, however studies and reviews that might include relevant data or information on trials will be retained initially. Authors JHT and BM will independently assess retrieved abstracts and, if necessary the full text, of these studies to determine which studies satisfy the inclusion criteria. Data extraction will be carried out independently by the same authors using standard data extraction forms. Studies reported in non‐English language journals will be translated before assessment. Where more than one publication of one trial exists, reports will be grouped together and the most recent or most complete dataset will be used. Any discrepancy between published versions will be highlighted. Any further information required from the original author will be requested by written correspondence and any relevant information obtained in this manner will be included in the review. Disagreements will be resolved in consultation with KHY and TXL.

Study quality

The quality of studies to be included will be assessed independently by JHT and YlL without blinding to authorship or journal using the checklist developed for the Cochrane Renal Group. Discrepancies will be resolved by discussion with KHY. The quality items to be assessed are allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention‐to‐treat analysis and completeness of follow‐up.

Quality checklist

Allocation concealment

  • Adequate (A): Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study

  • Unclear (B): Randomisation stated but no information on method used is available

  • Inadequate (C): Method of randomisation used such as alternate medical record numbers or unsealed envelopes; any information in the study that indicated that investigators or participants could influence intervention group

Blinding

  • Blinding of investigators: Yes/No/not stated

  • Blinding of participants: Yes/No/not stated

  • Blinding of outcome assessor: Yes/No/not stated

  • Blinding of data analysis: Yes/No/not stated

  • The above are considered not blinded if the treatment group can be identified in > 20% of participants because of the side effects of treatment.

Intention‐to‐treat

  • Yes: Specifically reported by authors that intention‐to‐treat analysis was undertaken and this was confirmed on study assessment.

  • Yes: Not stated but confirmed on study assessment

  • No: Not reported and lack of intention‐to‐treat analysis confirmed on study assessment. (Patients who were randomised were not included in the analysis because they did not receive the study intervention, they withdrew from the study or were not included because of protocol violation)

  • No: Stated but not confirmed upon study assessment

  • Not stated

Completeness of follow‐up

Per cent of participants excluded or lost to follow‐up.

Statistical assessment

For dichotomous outcomes (e.g. mortality, adverse events) results will be expressed as risk ratio (RR) with 95% confidence intervals (CI). Data will be pooled using the random‐effects model but the fixed‐effect model will also be analysed to ensure robustness of the model chosen and susceptibility to outliers. Where continuous scales of measurement are used to assess the effects of treatment (e.g. serum creatinine, length of hospital stay), the mean difference (MD) will be used, or the standardised mean difference (SMD) if different scales have been used. Heterogeneity will be analysed using a chi squared test on N‐1 degrees of freedom, with an alpha of 0.05 used for statistical significance and with the I² test (Higgins 2003). ). I² values of 25%, 50% and 75% correspond to low, medium and high levels of heterogeneity.

Subgroup analysis will be used to explore possible sources of heterogeneity (e.g. participants, interventions, ICU and study quality). Heterogeneity among participants could be related to age and renal pathology. Heterogeneity in treatments could be related to prior agent(s) used and the agent, dose and duration of therapy. Adverse effects will be tabulated and assessed with descriptive techniques, as they are likely to be different for the various agents used. Where possible, the risk difference with 95% CI will be calculated for each adverse effect, either compared to no treatment or to another agent.