Interventions for protecting renal function in the perioperative period

  • Review
  • Intervention

Authors


Abstract

Background

A number of methods have been used to try to protect kidney function in patients undergoing surgery. These include the administration of dopamine and its analogues, diuretics, calcium channel blockers, angiotensin converting enzyme inhibitors and hydration fluids.

Objectives

For this review, we selected randomized controlled trials which employed different methods to protect renal function during the perioperative period. In examining these trials, we looked at outcomes that included renal failure and mortality as well as changes in renal function tests, such as urine output, creatinine clearance, free water clearance, fractional excretion of sodium and renal plasma flow.

Search methods

We searched the Cochrane Central register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to June, 2007), and EMBASE (1988 to June, 2007); and handsearched six journals (Anesthesia and Analgesia, Anesthesiology, Annals of Surgery, British Journal of Anaesthesia, Journal of Thoracic and Cardiovascular Surgery, and Journal of Vascular Surgery).

Selection criteria

We selected all randomized controlled trials in adults undergoing surgery where a treatment measure was used for the purpose of renal protection in the perioperative period.

Data collection and analysis

We selected 53 studies for inclusion in this review. As well as data analysis from all the studies, we performed subgroup analysis for type of intervention, type of surgical procedure, and pre-existing renal dysfunction. We undertook sensitivity analysis on studies with high and moderately good methodological quality.

Main results

The review included data from 53 studies, comprising a total of 2327 participants. Of these, 1293 received some form of treatment and 1034 acted as controls. The interventions mostly consisted of different pharmaceutical agents, such as dopamine and its analogues, diuretics, calcium channel blockers, ACE inhibitors, or selected hydration fluids. The results indicated that certain interventions showed minimal benefits. All the results suffered from significant heterogeneity. Hence we cannot draw conclusions about the effectiveness of these interventions in protecting patients' kidneys during surgery.

Authors' conclusions

There is no reliable evidence from the available literature to suggest that interventions during surgery can protect the kidneys from damage. There is a need for more studies with high methodological quality. One particular area for further study may be patients with pre-existing renal dysfunction undergoing surgery.

摘要

背景

在手術期間保護病患腎功能的治療方式

過去曾使用很多方法保護接受手術的病人的腎功能。這些方式包括使用dopamine與其類似藥物, 利尿劑(diuretics), 鈣離子拮抗劑(calcium channel blockers), 血管張力素轉換脢抑制劑(angiotensin converting enzyme inhibitors)及輸液治療。

目標

此篇回顧性文章挑選了使用各種不同方法保護術中病患腎功能的隨機分配研究。我們檢視這些研究的最終結果包括腎衰竭(renal failure)、死亡率,以及腎功能相關實驗數據的變化, 如尿量、肌酐酸清除率(creatinine clearance)、水分清除(free water clearance)、鈉離子清除分率(fractional excretion of sodium)及腎臟血流量(renal plasma flow)。

搜尋策略

搜尋the Cochrane Central register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966to June, 2007), 及EMBASE (1988 to June,2007); 和手動檢索6份雜誌(Anesthesia and Analgesia, Anesthesiology, Annals of Surgery, British Journal of Anaesthesia, Journal of Thoracicand Cardiovascular Surgery, and Journal of Vascular Surgery)。

選擇標準

我們挑選成人在手術期間接受保護腎功能的治療的隨機分配研究。

資料收集與分析

此次回顧挑出53個符合條件的研究分析。分析所有資料的同時, 我們也進行子群體在不同治療方式、手術術式及本來就具有腎功能異常病患的各項分析。我們用高度到中等程度的方法品質要求進行各研究的敏感度的分析。

主要結論

此篇回顧收集了53篇研究, 比較了總共2327個病人。其中1293名病患接受了各種不同形式的治療,另外1034名病患為對照組。治療方法為使用不同的藥物,如dopamine及其類似藥物及其類似藥物、利尿劑, 鈣離子拮抗劑,血管張力素轉換脢抑制劑及輸液治療。結果指出某些治療顯示些微極少助益。但所有的結果因為明顯的異質性而無法形成共識。因此我們不能獲得這些治療能有效保護接受手術的病患之腎功能的結論。

作者結論

過去文獻中沒有可靠的證據建議手術中使用任何治療可保護腎臟功能不被破壞。所以仍需要使用高竿的方法學來進一步研究,尤其是已存在腎功能異常的病人接受手術時如何保護腎臟功能。

翻譯人

本摘要由慈濟醫院鄭偉君翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

手術中有很多治療方法被用來保護腎臟功能。此篇回顧文章探討這些方法的有效性。尚未有研究提供證據建議以下的治療方法對保護手術中病人的腎功能是有益的, 包括dopamine 利尿劑, 鈣離子拮抗劑,血管張力素轉換脢抑制劑或輸液治療。不管手術期間有無接受各項治療, 對產生併發症(腎衰竭)或死亡率是沒有差異的。針對此領域,尤其是已存在腎功能異常的病患來說,仍需要一個設計完整的隨機分配研究來提供有力證據。

Plain language summary

There is no evidence that any of the measures used to protect patients' kidneys during the perioperative period are beneficial

There is no evidence from available randomized controlled trials to suggest that any of the measures used to protect the kidneys during the perioperative period, including the use of dopamine and its analogues, diuretics, calcium channel blockers, ACE inhibitors or hydration fluids, are beneficial. There is no difference in morbidity (renal failure) or mortality following the various perioperative interventions. There is a need for well-designed randomized controlled trials in this field, particularly in patients with pre-existing renal dysfunction.

Background

Intraoperative changes in renal blood flow and glomerular filtration rate are common. Postoperative renal dysfunction is mainly attributed to adverse events that occur during the perioperative period, including sepsis and hypotension, or contrast administration. Renal dysfunction following major surgery (for example, abdominal aortic aneurysm repair or coronary artery bypass surgery) is one of the recognized causes of significant postoperative morbidity and mortality. Acute renal failure in the postoperative period, when it occurs, is mostly due to renal parenchymal damage and requires aggressive supportive management, including renal dialysis, fluid and electrolyte management. The reported risk of perioperative renal failure varies because of variations in patient population and the definition of renal failure (Kellen 1994). The induction and maintenance of anaesthesia lowers systemic blood pressure, potentially predisposing the patient to renal ischaemia and eventual postoperative renal failure. However, in the vast majority of patients this alone rarely compromises postoperative renal function. Hence if postoperative renal dysfunction occurs, it is generally thought to be multi-factorial in nature.

Multiple tests for renal function are available. These tests can identify any changes in the renal status following operations. Creatinine clearance is one of the easiest, most common tests used in a clinical setting and identified as useful predictors of impending renal damage, particularly in cardiac surgery (Wang 2003; Wijeysundera 2006).

In the last few decades, attempts have been made to protect the kidneys both during surgery and in the immediate postoperative period. Various regimens, such as use of low-dose dopamine, dopexamine or diuretics, have been tried. It has been suggested that there is evidence for some success with such interventions (Welch 1995); no clear evidence of success (Renton 2005); or even a deterioration in renal function (Lassnigg 2000). Invasive haemodynamic monitoring and aggressive perioperative fluid management have been found to be useful (Wahbah 2000).

A number of publications are available on the subject of renal protection in the context of contrast media administration; a great deal of emphasis is currently placed on adequate hydration of patients (Gerlach 2000; Morcos 2004; Solomon 1994). Most anaesthetists believe that adequate hydration of the patient is one of the best methods of protecting the kidneys during the perioperative period.

The body retains water after surgery, particularly following major surgery. This is recognized to be a consequence of excess secretion of arginine vasopressin, resulting in fluid retention and dilutional hyponatraemia (Zacay 2002). A syndrome of inappropriate secretions of antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) can occur after surgery (Brazel 1996; Kovacs 1992; Lieh-Lai 1999). Hence changes in excretion of water and sodium are expected after normal surgical procedures.

There is no clear evidence in the literature to suggest that any of the measures are effective in protecting the kidneys during surgery. Hence we have embarked on this systematic review.

Objectives

This review is aimed at determining the effectiveness of various measures advocated to protect patients' kidneys during the perioperative period.

We considered the following questions.

  1. Are there any specific measures which can protect kidney function during the perioperative period?

  2. Does any one measure used to protect the kidneys during the perioperative period appear more effective than other methods?

  3. Does any one measure used to protect the kidneys during the perioperative period appear safer than other methods?

Methods

Criteria for considering studies for this review

Types of studies

We considered all randomized controlled trials of an intervention (as detailed below) versus control (placebo or no intervention), published in any language.

Types of participants

We included patients undergoing all types of major surgery where a specified intervention was used to protect the kidneys from possible damage during surgery. We did not include studies which specifically considered a paediatric population. We did not include studies on patients undergoing transplant surgery (heart, liver, or kidney) because of the complexity of the surgery and postoperative management of these patients.

Types of interventions

We included the following interventions used to maintain or protect kidney function during anaesthesia and surgery:

  1. dopamine and its analogues;

  2. diuretics;

  3. calcium channel blockers;

  4. angiotensin-converting enzyme (ACE) inhibitors;

  5. hydration fluids;

  6. any other measures used to protect kidney function.

Types of outcome measures

Primary outcomes

Postoperative adverse outcomes. These included significant adverse outcomes such as acute renal failure, other serious morbidity, or death.

Secondary outcomes

Any changes in perioperative renal function. These included the following measures:

- urine output;

- creatinine clearance (or glomerular filtration rate);

- renal plasma flow (or renal blood flow);

- free water clearance;

- fractional excretion of sodium.

Inclusion and exclusion criteria

For the purpose of the review, 'perioperative period' is taken as the period just before, during, and immediately after the surgery. The 'postoperative period' comprises a period of up to seven days after the conclusion of surgery. We have included only studies where the intervention was started just before or during the surgery, and which may have continued into the postoperative period. We did not include studies where the intervention was initiated after surgery or only in the postoperative period. We did not include surgery involving organ transplant such as heart, liver, or kidney transplants.

Search methods for identification of studies

Electronic searches

We searched the following electronic databases: Cochrane Central register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2); MEDLINE (1966 to June, 2007); and EMBASE (1988 to June, 2007). We used the search strategies given in Appendix 1.

We identified 136 studies from the MEDLINE search, 113 studies from the EMBASE search, and 177 from CENTRAL (426 studies in total).

Searching other resources

We originally handsearched six major journals in anaesthesia and vascular or thoracic surgery (1985 to 2004):

  1. Anesthesia and Analgesia;

  2. Anesthesiology;

  3. Annals of Surgery;

  4. British Journal of Anaesthesia;

  5. Journal of Thoracic and Cardiovascular Surgery;

  6. Journal of Vascular Surgery.

However, as these journals are properly indexed in MEDLINE, we decided for this update (given time and resource constraints) to rely on the electronic searches only and not handsearch these journals from 2004 onwards.

We also searched reference lists and bibliographical data from all retrieved articles and reviews for any additional, relevant material. We sought information from authors of published studies and contacted recognized experts on this topic about any unpublished data. We identified a further 25 studies by this method. Thus a total of 451 studies were considered potentially eligible for this review.

Data collection and analysis

Screening for eligibility

We evaluated all the studies obtained by the search methods for appropriateness of inclusion. We examined abstracts or summaries of publications. We obtained full publications for those studies which required further assessment. Two of the authors evaluated these studies without prior consideration of the results and consensus was reached on the final selection. Some of the selected studies were translated into English by colleagues in the local hospital or university.

Assessment of methodological quality

At least two authors independently assessed each included study for methodological quality on the basis of randomization, concealment of allocation, blinding, and acknowledgement of dropouts. An overall quality assessment was given as: good, moderately good, or poor (see Additional Table 1).

Table 1. . Methodological quality of included studies
Study IDRandomizationAllocation conceal:BlindingWithdrawals notedOverall quality
Amano 1994Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Amano 1995Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Ascione 1999Card allocation methodNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Berendes 1997Method not specifiedUnclearPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Bergman 2002Done by a list from pharmacypossiblePatients: likely; Researchers: likely; Care givers: likelyYesModerately good
Burns 2005Permuted block strategyYesPatients: yes; Researchers: yes; Care givers: yesYesGood
Carcoana 2003Computer-generated random number methodAdequatePatients: yes; Researchers: yes; Care givers: yesNot clearGood
Colson 1990Method unclearUnclearPatients: yes; Researchers: yes; Care givers: unknownNot indicatedModerately good
Colson 1992Method unclearUnclearPatients: yes; Researchers: yes; Care givers: unknownNot indicatedModerately good
Costa 1990Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Cregg 1999Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Dawidson 1991Random by card allocation methodNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
de Lasson 1995Method not specifiedUnclearPatients: yes; Researchers: yes; Care givers: unknownNot indicatedPoor
de Lasson 1997Method not specified, done by external bodyUnclearPatients: unknown; Researchers: unknown; Care givers: unknownYesModerately good
Dehne 2001Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Donmez 1998Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Dural 2000Sealed opaque envelope methodUnclearPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Durmaz 2003Last digit of recordsUnclearPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Fischer 2005Method not specifiedUnclearPatients: yes; Researchers: yes; Care givers: unknownNot indicatedPoor
Grubern 1988Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Halpenney 2002Random allocationUnclearPatients: yes; Researchers: yes; Care givers: unknownYesModerately good
Kleinschmidt 1997Method not specifiedUnclearPatients: yes; Researchers: yes; Care givers: unknownNot indicatedPoor
Kramer 2002Method not specifiedUnclearPatients: yes; Researchers: yes; Care givers: unknownYesModerately good
Kulka 1996Method not specifiedUnclearPatients: unknown; Researchers: yes; Care givers: unknownNot indicatedPoor
Lassnigg 2000Block randomization with sealed envelopesYesPatients: yes; Researchers: yes; Care givers: yesYesGood
Lau 2001Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Licker 1996Method not specifiedUnclearPatients: yes; Researchers: yes; Care givers: unknownYesModerately good
Loef 2004Method not specifiedUnclearPatients: yes; Researchers: yes; Care givers: unknownYesModerately good
Marathias 2006Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot clearPoor
Morariu 2005Method not specifiedUnclearPatients: yes; Researchers: yes; Care givers: unknownYesModerately good
Morgera 2002Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Myles 1993Table of random numbers by pharmacyAdequatePatients: yes; Researchers: yes; Care givers: yesYesGood
Nicholson 1996Envelopes with random numbersAdequatePatients: yes; Researchers: unknown; Care givers: unknownNot clearGood
O'Hara 2002Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Parks 1994Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Perez 2002Closed envelope methodUnclearPatients: yes; Researchers: yes; Care givers: unknownYesGood
Pull Ter Gunne 1990Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Ristikankane 2006Done by pharmacyBy pharmacyPatients: yes; Researchers: yes; Care giver: unknownYesGood
Ryckwaert 2001Method not specifiedUnclearPatients: yes; Researchers: yes; Care giver: unknownNot indicatedPoor
Sezai 2000Method not specifiedUnclearPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Shackford 1983Random number methodNot indicatedPatients: unknown; Researchers: unknown; Care givers: unknownYesPoor
Shim 2007Computer generated randomizationNot indicatedPatients: yes; Researchers: yes; Care giver: unknownNot indicatedModerately good
Tang 1999Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Tang 2002Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownYesPoor
Thompson 1986Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Urzua 1992Randomization by clinic numberNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Wahbah 2000Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Welch 1995Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Wijnen 2002Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Woo 2002Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownYesPoor
Yavuz 2002AMethod not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Yavuz 2002BMethod not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor
Zanardo 1993Method not specifiedNot usedPatients: unknown; Researchers: unknown; Care givers: unknownNot indicatedPoor

Data extraction

We used specifically designed data extractions forms to extract the relevant data (Appendix 2). Two authors (MZ, NC or PS) separately extracted and compared data. We resolved differences by discussion and reaching consensus. Wherever we considered it necessary, we attempted to contact the authors for further clarification, data, or both.

The data collected included:

  1. presence or absence of any pre-existing renal dysfunction;

  2. nature of surgical procedures;

  3. Interventions used;

  4. Mortality or morbidity data;

The results of the individual studies were reported in many different ways, including means, standard deviations (SD) , standard errors of the mean (SEM), median or interquartile ranges (IQR), or ranges. We converted standard errors of the means and interquartile ranges to standard deviations using appropriate formulae. We considered the interquartile range to be 1.35 times the standard deviation (for the purpose of this review we assumed that the data were normally distributed). We calculated the standard deviation as square root of sample size times the standard error of the mean.

We considered creatinine clearance as a surrogate measure of glomerular filtration rate (GFR). When data involved weights, we made an assumption of 70 kg to convert the data. When data were presented in graphical form, we extracted the numerical data from the graphs as accurately as possible. We converted all data to uniform measurements; thus urine output, creatinine clearance, renal plasma flow and free water clearance were expressed in ml/min and fractional excretion of sodium as a percentage.

We have chosen to look at data for the various renal function tests at 24 hours, two to four days and five to seven days in this review because these were the times the results were most frequently reported in the selected studies. We were reluctant to look at data earlier than 24 hours since this would have shown acute changes brought on by anaesthesia and surgery. Even though it is not specified in most of the publications, we have assumed that data on urine output at 24 hours is the average reading for urine output in the first 24 hours after surgery; the same applied for urine output results at two to four days and five to seven days postoperatively. For measurements such as creatinine clearance, renal plasma flow, free water clearance, and fractional excretion of sodium, we assumed that the data were obtained at the specified time.

Data analysis

We analysed data as per the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2008; Higgins 2008).

We pooled continuous outcomes with weighted mean differences. Initially we pooled the results using a fixed-effect model but substantial heterogeneity existed in many analyses and we explored the reasons for this. Because of the considerable heterogeneity seen in the results, we opted to present the data using a random-effects model.

Dichotomous outcomes (acute renal failure and mortality) were very rare events and hence we have presented these as odds ratio, using the Peto method.

We undertook subgroup analyses for the following situations:

  1. methods used for renal protection;

  2. types of operation;

  3. studies on patients with pre-existing renal dysfunction.

We also undertook sensitivity analyses on randomized controlled trials with differing methodological quality.

Results

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

Of the 451 studies obtained from the search strategy, we examined 127 studies further after obtaining copies of the publications. Of these, we included 53 studies in the review and excluded 74. We did not include three studies in the analysis since we could not confirm that these were not duplicate publications (see below). We have provided the reasons for excluding studies in the table 'Characteristics of excluded studies'. Studies in languages other than English (German, Turkish, Serbian, Russian, and Japanese) were translated with the help of volunteers. All of these studies were available as full publications. We have had only limited success in receiving adequate information and feedback from the authors that we have attempted to contact, in spite of repeated attempts. All of the included and excluded studies were published between 1976 and 2007.

The 53 included studies comprised a total of 2327 patients; 1293 of these received some form of intervention to protect the kidneys and 1034 acted as controls. Twelve studies had multiple arms (Berendes 1997; Carcoana 2003; Colson 1992; Costa 1990; Dehne 2001; Donmez 1998; Dural 2000; Kleinschmidt 1997; Lassnigg 2000; Wahbah 2000; Yavuz 2002B; Zanardo 1993). We have used the data from each arm separately for analysis of the interventions; whenever we did this, we adjusted (reduced) the number in the control groups in the appropriate sections. Berendes 1997 had three treatment arms, increasing strengths of dopexamine, in cardiac surgery; another arm acted as control. We have combined the three treatment groups for the purpose of analysis. Carcoana 2003 had three treatment arms and a control arm; one treatment group received dopamine infusion during the surgery, one group received a bolus of mannitol in the pump prime, and the third group received both treatments. We have excluded the third arm of the study. Colson 1992 had two treatment arms and one control arm for the study; one treatment group received a calcium channel blocker and the second group received an angiotensin-converting enzyme (ACE) inhibitor. Costa 1990 also had three arms, two treatment arms and one control arm; we have excluded the arm which used multiple interventions (dopamine and SNP). Dehne 2001 had two control groups, one in patients with normal renal function and one for the patients with pre-existing renal dysfunction. Their intervention groups (two) used dopexamine and matched the control for the presence or absence of pre-existing renal failure. Donmez 1998 used two interventions, one receiving verapamil and the other receiving nimodipine. Dural 2000 had three arms; one arm received dopamine, another arm received mannitol, and the third arm was the control group. Kleinschmidt 1997 had two intervention groups, pentoxyfilline and gamma hydroxybutyrate, and one control group. Lassnigg 2000 had three arms, two active (dopamine or frusemide) and one control. In the case of Wahbah 2000, we used only one of three treatment arms because two arms combined multiple interventions (dopamine and mannitol, or dopamine and frusemide). This study contained a fourth control arm. Yavuz 2002B had three treatment arms and one control arm; one treatment arm used two interventions simultaneously and we excluded this arm in the appropriate sections. Zanardo 1993 used two doses of dopamine by infusion and we have combined the two groups in the analysis. Because of the exclusions, due to the reasons given above, a total of 72 patients were excluded from this review. We were then left with a total of 2255 patients: 1221 of whom received various treatments and 1074 who acted as controls.

We identified three studies which were published both in abstract form and as full papers. We were unable to confirm whether they were duplicate papers and hence considered only the full papers for inclusion in the analysis (Kulka 1996; O'Hara 2002; Ryckwaert 2001) for this review. We have referred to the abstract publications (Kulka 1993; O'Hara 2002A; Ryckwaert 1995) in the table '''Characteristics of excluded studies".

The details of participants' sex were not available in all studies so we did not make an attempt to separately document this information. All included studies except one (Cregg 1999) involved adult populations; the Cregg study involved correction of scoliosis surgery and included a younger age group.

Thirty-four studies involved patients undergoing cardiac surgery (Amano 1994; Amano 1995; Ascione 1999; Berendes 1997; Bergman 2002; Burns 2005; Carcoana 2003; Colson 1990; Costa 1990; Dehne 2001; Donmez 1998; Dural 2000; Durmaz 2003; Fischer 2005; Kleinschmidt 1997; Kramer 2002; Kulka 1996; Lassnigg 2000; Loef 2004; Marathias 2006; Morariu 2005; Morgera 2002; Myles 1993; Ristikankare 2006; Ryckwaert 2001; Sezai 2000; Shim 2007; Tang 1999; Tang 2002; Urzua 1992; Woo 2002; Yavuz 2002A; Yavuz 2002B; Zanardo 1993); 11 trials (Colson 1992; Dawidson 1991; de Lasson 1995; de Lasson 1997; Halpenny 2002; Licker 1996; Nicholson 1996; Pull Ter Gunne 1990; Shackford 1983; Welch 1995; Wijnen 2002) were on patients undergoing abdominal aortic surgery (for aortic aneurysm and occlusive arterial diseases); four trials were on patients undergoing biliary surgery (Gubern 1988; Parks 1994; Thompson 1986; Wahbah 2000); one was for laparoscopic colorectal surgery (Perez 2002); one for partial nephrectomy (O'Hara 2002); and one for correction of scoliosis (Cregg 1999). Four studies involved patients with pre-existing renal dysfunction (Bergman 2002; Costa 1990; Durmaz 2003; Marathias 2006).

Various treatment measures were used in the different trials to protect the kidneys during the perioperative period. The interventions included dopamine and its analogue or agonist (dopexamine or fenoldopam) in 20 studies (Berendes 1997; Carcoana 2003; Costa 1990; Cregg 1999; de Lasson 1995; Dehne 2001; Dural 2000; Halpenny 2002; Lassnigg 2000; Myles 1993; O'Hara 2002; Parks 1994; Perez 2002; Tang 1999; Wahbah 2000; Welch 1995; Woo 2002; Yavuz 2002A; Yavuz 2002B; Zanardo 1993); diuretics (mannitol, frusemide) in six trials (Carcoana 2003; Dural 2000; Gubern 1988; Lassnigg 2000; Nicholson 1996; Shim 2007); calcium channel blockers (diltiazem, nicardipine, felodipine, verapamil, nimodipine) in seven trials (Amano 1995; Bergman 2002; Colson 1992; de Lasson 1997; Donmez 1998; Gubern 1988; Yavuz 2002B); ACE inhibitors (captopril, enalapril) in four trials (Colson 1990; Colson 1992; Licker 1996; Ryckwaert 2001); N-acetylcysteine in three trials (Burns 2005; Fischer 2005; Ristikankare 2006); and, in one trial each, glutathione (Amano 1994), prostaglandin (Morgera 2002), theophylline (Kramer 2002), clonidine (Kulka 1996), human natriuretic peptide (Sezai 2000), dexamethasone (Loef 2004; Morariu 2005), pentoxifylline (Kleinschmidt 1997), gamma hydroxybutyrate (Kleinschmidt 1997), anti-oxidant therapy (Wijnen 2002), phenylephrine (Urzua 1992), ursodeoxycholic acid (Thompson 1986), preoperative haemodialysis (Durmaz 2003); and surgical measures such as off-pump cardiac surgery (Ascione 1999; Tang 2002) and an extraperitoneal approach to aortic surgery (Lau 2001). Four studies looked at the effect of hydration fluids (Dawidson 1991; Marathias 2006; Pull Ter Gunne 1990; Shackford 1983).

We have done subgroup analysis of trials to observe the effects of different interventions on renal protection in the perioperative period. These subgroups included dopamine and its analogue or agonist; diuretics; calcium channel blockers; ACE inhibitors; and hydration fluids. We also undertook subgroup analysis to observe the effect of the type of surgery; this included: cardiac surgery, abdominal aortic surgery, and other surgeries. We did limited subgroup analysis of studies with pre-existing renal impairment.

We also did a limited sensitivity analysis on methodological quality.

Risk of bias in included studies

Even though we included 53 studies in the review, the overall methodological quality of the studies was poor. We have used a quality assessment system (see 'Methodological quality of studies' additional Table 1) using method of randomization, allocation concealment, and blinding as the criteria. We have scored the methodological quality of the selected studies as good, moderately good, or poor. When the randomization, allocation concealment and blinding (patients, researchers, care givers and nurses) were adequately described we classified the study as a good quality study. When randomization, allocation concealment and blinding (patients, researchers, and care givers and nurses) were stated to have been done but no details were given in the publication we classified the study as moderately good. When we found no evidence of allocation concealment and blinding we classified the study as poor quality.

The methodological quality assessment identified seven studies of good quality (Burns 2005; Carcoana 2003; Lassnigg 2000; Myles 1993; Nicholson 1996; Perez 2002; Ristikankare 2006) and another nine studies where the methodological quality was considered moderately good (Bergman 2002; Colson 1990; Colson 1992; de Lasson 1997; Halpenny 2002; Kramer 2002; Licker 1996; Morariu 2005; Shim 2007). The majority of studies that we assessed (37 studies) were classified as being of poor methodological quality (see 'Methodological quality of studies' additional Table 1). We had no success in obtaining data on concealment of allocation, blinding and method of randomization from the authors of most of the trials. Some of the trials were old, with very little chance of contacting the authors. We received replies from only three authors.

None of the publications mentioned any conflict of interest with respect to the drugs used and hence we assumed that none existed. The following studies acknowledged pharmaceutical company sponsorships: de Lasson 1995; de Lasson 1997; Halpenny 2002; Kramer 2002; Lassnigg 2000; Thompson 1986.

Effects of interventions

We collected and analysed data from 53 studies. The dichotomous data (mortality and acute renal failure) were rare events, so we used the Peto method of analysis and reported the results as Peto odds ratios (OR) with 95% confidence intervals (CI). We presented all continuous data results as weighted mean difference (WMD) with 95% CI. Results were plagued by heterogeneity throughout the analysis, so we used a random-effects model instead of a fixed-effect model. We undertook subgroup analysis for treatment measures and type of surgery. We were able to do only limited subgroup analysis for studies with pre-existing renal impairment due to the lack of an adequate number of trials. A limited sensitivity analysis was done for studies with high methodological quality. In order to make the review less cumbersome for the reader, study results are listed in the text only where they were considered essential; references to the appropriate 'Comparisons and data' tables are given.

Mortality

Data on perioperative mortality was reported in 27 studies. Many of the cases of mortality were due to a combination of factors, including surgical causes and pathology. The risk of mortality was very low and no statistically significant difference existed between the treatment and control groups (OR 1.19, 95% CI 0.66 to 2.12) (see Analysis 1.1; Figure 1).

Figure 1.

Forest plot of comparison: 1 All renal protective interventions versus no intervention: Adverse outcomes, outcome: 1.1 Mortality (reported).

Acute renal failure

Acute renal failure in the postoperative period was reported in 30 studies (see 'Analysis 1.2'). Other studies reported no cases of acute renal failure in the study population in the postoperative period. The studies did not specify criteria for diagnosing acute renal failure (ARF). In Lassnigg 2000 the quoted figures were for acute renal injury (ARI), suggested by an increase in creatinine of more than 0.5 mg/dl; only two out of seven patients with ARI required renal replacement therapy, both cases belonging to the treatment group. The odds for developing acute renal failure showed no statistically significant difference between the treatment and control groups (OR 0.66, 95% CI 0.33 to 1.31) (see Analysis 1.2; Figure 2).

Figure 2.

Forest plot of comparison: 1 All renal protective interventions versus no intervention: Adverse outcomes, outcome: 1.2 Acute renal failure (reported).

Effectiveness of measures used for renal protection

In this section we combined the data from the 53 identified studies to observe the ability of treatments to protect the kidneys in the perioperative period compared to control.

Urine output

Urine output was estimated in 21 studies (see 'Data and analyses' Analysis 2.1). Eighteen studies (see Analysis 2.1.1) estimated urine output at 24 hours after surgery. These involved 383 patients in the treatment group and 298 patients in the control group. There was no significant difference in favour of one group, the WMD in urine output being only 0.12 ml/min at 24 hours (95% CI -0.08 to 0.32). There was significant heterogeneity (I2 = 82%) and we looked closely at the reasons for this. The type of surgery (cardiac, aortic, other types) was a possible cause. Age of the participants was unlikely to have been a cause since most of the patients in the included trials were between 55 and 65 years of age (see 'Characteristics of included studies'). The methodological quality of the studies was variable, the majority being of poor quality (see 'Methodological quality of included studies' Table 1). The duration and extent of the treatment varied markedly amongst the various studies. The funnel plot for this comparison suggested no evidence of reporting bias. Other causes of heterogeneity might have included gender differences, smoking status, state of nutrition, alcohol intake, and co-morbidities such as hypertension and diabetes; however, there were not enough data to prove or disprove the influence of these factors.

Nine studies (see ' Analysis 2.1.2) examined urine output at two to four days after surgery. The result favoured the treatment group (WMD 0.19 ml/min, 95% CI 0.02 to 0.36). There was significant heterogeneity (I2 = 79%).

Only five studies (see Analysis 2.1.3) measured urine output for the fifth to seventh postoperative days. There was no significant difference between those participants who received treatment and those who did not (WMD 0.40 ml/min, 95% CI -0.10 to 0.90). Ryckwaert 2001 showed very large urine outputs compared to the other studies but had small weighting and thus was unlikely to have affected the results.

Creatinine clearance

Thirty-three trials estimated creatinine clearance in the postoperative period (see 'Data and analyses' Analysis 2.2). Thirty trials estimated creatinine clearance at 24 hours after surgery (see Analysis 2.2.1); this included 632 people in the treatment group and 524 in the control group. Treatment groups had an improved creatinine clearance (WMD 6.95 ml/min, 95% CI 0.16 to 13.74). However, significant heterogeneity was present (I2 = 86%). We examined the reasons for this. One study (Berendes 1997) with 30 people in the treatment group (out of 535) was weighted heavily in the study, favouring treatment. Two Japaneses studies (Amano 1994; Sezai 2000) showed similar results, the latter with 20 people in the treatment group had a considerable effect on the result. These three studies were considered to be methodologically poor quality studies. The wide variability in the degree and duration of treatment in the different studies could be a cause for the heterogeneity. Few of the included studies showed very large standard deviations. The funnel plot for this comparison suggested no evidence of reporting bias. As we pointed out in the previous section on urine output, causes of heterogeneity might have also included gender differences, smoking status, state of nutrition, alcohol intake, and co-morbidities such as hypertension and diabetes; we have no access to such data to establish these as the causes for heterogeneity.

We examined creatinine clearance at two to four days after operation in 18 studies (387 participants receiving treatment, 324 controls) (see Analysis 2.2.2). The results showed a significant benefit with treatment (WMD 9.93 ml/min, 95% CI 1.09 to 18.77), but there was considerable heterogeneity (I2 = 79%). It is of interest to note that both Amano 1994 and Sezai 2000 heavily favoured the treatment group.

Ten studies (see Analysis 2.2.3) measured creatinine clearance on the fifth to seventh days postoperatively. Individual study results were mixed and analysis showed no overall advantage with treatment (WMD 4.07 ml/min, 95% CI -9.00 to 17.15; I2 = 75%).

Free water clearance

Free water clearance was measured in 11 studies at 24 hours after an operation (see 'Data and analyses' Analysis 2.3.1). Data analysis did not favour either treatment or control (WMD -0.06 ml/min, 95% CI -0.23 to 0.12; I2 = 26%). Free water clearance on the third day showed no difference in five studies (WMD -0.10 ml/min, 95% CI -0.37 to 0.17; I2 = 46%) or on the seventh day in four studies (WMD 0.02 ml/min, 95% CI -0.24 to 0.28; I2 = 44%).

Fractional excretion of sodium

Fractional excretion of sodium was measured as a percentage at 24 hours after operation in 12 studies (see 'Data and analysis' Analysis 2.4.1) and on the second to fourth days after operation in four trials (Amano 1994; Halpenny 2002; Loef 2004; Shackford 1983). We did not analyse these data due to the reasons given in the Discussion section.

Renal plasma flow

Three studies (see 'Data and analyses' Analysis 2.5.1) measured renal plasma flow at the end of the operation and three studies measured it at 24 hours after operation (see Analysis 2.5.2). Analysis showed no difference at the end of the operation (WMD 46.37 ml/min, 95% CI -68.61 to 161.34; I2 = 0%) or at 24 hours after operation (WMD 59.15 ml/min, 95% CI -1.80 to 120.10; I2 = 0%).

Effect of various interventions on renal protection

The majority of studies looked at dopamine and its analogues, though there were some trials using other measures to protect the kidneys in the perioperative period.

Dopamine or its analogues

Infusions of dopamine, its analogue (dopexamine), or agonist (fenoldopam) were used as the treatment in 20 studies (Berendes 1997; Carcoana 2003; Costa 1990; Cregg 1999; de Lasson 1995; Dehne 2001; Dural 2000; Halpenny 2002; Lassnigg 2000; Myles 1993; O'Hara 2002; Parks 1994; Perez 2002; Tang 1999; Wahbah 2000; Welch 1995; Woo 2002; Yavuz 2002A; Yavuz 2002B; Zanardo 1993).

Urine output at 24 hours after operation was studied in 11 trials (see 'Data and analyses' Analysis 3.1.1). There was considerable heterogeneity (I2 = 92%) and no difference between the intervention and control groups (WMD 0.12 ml/min, 95% CI -0.29 to 0.53). Urine flow at two to four days also showed no significant increase with the intervention, in seven studies (see Analysis 3.1.2); the urine flow difference was 0.41 ml/min (95% CI 0.00 to 0.82) and there was high heterogeneity (I2 = 92%). On the fifth to seventh day the treatment did not offer any advantages (see Analysis 3.1.3) (WMD 0.18 ml/min, 95% CI -0.06 to 0.42; I2 = 71%).

Creatinine clearance was studied in 14 trials following the administration of dopamine or its analogues (see 'Data and analyses' Analysis 3.2). All 14 trials reported creatinine clearance at 24 hours; eight studies at two to four days; and six studies at five to seven days after an operation. Analysis did not show any significant difference between the interventions and control groups at 24 hours (WMD 4.55 ml/min, 95% CI -10.58 to 19.68) and showed considerable heterogeneity (I2 = 88%); one study, in particular, favoured the treatment group (Berendes 1997). There were no differences at two to four days (WMD -3.17 ml/min, 95% CI -14.00 to 7.66; I2 = 0%); or at five to seven days after the operation (WMD -3.91 ml/min, 95% CI -12.24 to 4.43; I2 = 7%).

Free water clearance in ml/min was looked at 24 hours following surgery in six trials (see 'Data and analyses' Analysis 3.3.1). The results showed no difference between treatment and control groups (WMD 0.03 ml/min, 95% CI -0.17 to 0.22; I2 = 0%). Fractional excretion of sodium at 24 hours was reported in five trials (see 'Data and analyses' Analysis 3.4). As in the previous section, we did not analyse this data.

Renal blood flow in ml/min was studied at 24 hours after surgery in only in two trials (see 'Data and analyses' Analysis 3.5) (de Lasson 1995; O'Hara 2002). There was no difference (WMD 75.36 ml/min, 95% CI -63.27 to 213.98; I2 = 45%).

Diuretics

Mannitol or frusemide (furosemide) were used as treatment in six studies (Carcoana 2003; Dural 2000; Gubern 1988; Lassnigg 2000; Nicholson 1996; Shim 2007). Data were available for only five studies (see 'Data and analyses' Analysis 4.1). The urine output did not show a significant difference between groups at 24 hours in four studies (WMD 0.10 ml/min, 95% CI -0.12 to 0.33; I2 = 0%) (see 'Data and analyses' Analysis 4.1.1); at two to four days in three studies (WMD 0.17 ml/min, 95% CI -0.06 to 0.40; I2 = 0%); and on the seventh day in one study. No significant differences existed on any occasion.

Creatinine clearance was measured at 24 hours in three studies (Carcoana 2003; Lassnigg 2000; Nicholson 1996). This measure showed no statistically significant differences (see Analysis 4.2.1) (WMD -18.02 ml/min, 95% CI -41.78 to 5.75; I2 = 55%). The same was true on the second to fourth day (see Analysis 4.2.2) (WMD 2.33 ml/min, 95% CI -14.76 to 19.42; I2 = 0%).

Only one study looked at fractional excretion of sodium (Lassnigg 2000).

Calcium channel blockers

Calcium channel blockers such as diltiazem, nicardipine and felodipine were used in seven studies (Amano 1995; Bergman 2002; Colson 1992; de Lasson 1997; Donmez 1998; Gubern 1988; Yavuz 2002B). Three studies looked at urine output at 24 hours after treatment; there was no difference between treatment and control groups (WMD 0.28 ml/min, 95% CI -0.10 to 0.66; I2 = 0%) (see 'Data and analyses' Analysis 5.1.1). Four studies looked at the creatinine clearance at 24 hours postoperatively (see Analysis 5.2.1). There was no advantage for treatment (WMD 0.11 ml/min, 95% CI -16.03 to 16.26; I2 = 66%). There were 151 patients in the four studies. Only Yavuz 2002B looked at creatinine clearance on the third and seventh postoperative days, and showed no differences.

Three studies measured free water clearance at 24 hours (see Analysis 5.3.1) and showed no difference (WMD -0.09 ml/min, 95% CI -0.47 to 0.29; I2 = 43%).

ACE inhibitors

Four trials (Colson 1990; Colson 1992; Licker 1996; Ryckwaert 2001) looked at the usefulness of ACE inhibitors (enalapril or captopril) as renal protective agents. Data from three studies show that the renal plasma flow in ml/min at the end of the operation (see 'Data and analyses' Analysis 6.1.1) was not significantly different (WMD 46.37 ml/min, 95% CI -68.61 to 161.34; I2 = 0%). Ryckwaert 2001 did not give the renal plasma flow at the end of operation, only on the seventh day.

Hydration fluid

Four trials studied the role of intravenous fluids such as colloids and hypertonic saline (Dawidson 1991; Marathias 2006; Pull Ter Gunne 1990; Shackford 1983). Two studies (Pull Ter Gunne 1990; Shackford 1983) looked at creatinine clearance at 24 hours (see 'Data and analyses' Analysis 7.1.1) and there was no difference (WMD -10.34ml/min, 95% CI -29.57 to 8.88; I2 = 0%).

Cardiac surgery

Urine output

Thirteen studies looked at the influence of different interventions on urine output following cardiac surgery (see 'Data and analysis' Analysis 8.1). Eleven studies (see Analysis 8.1.1) looked at 24-hour urine output and the results suggested some benefit for intervention compared to no intervention. Urine output increased by 0.25 ml/min in the treatment group (95% CI 0.08 to 0.41) but with moderate heterogeneity in results (I2 = 61%). Five studies (see Analysis 8.1.2) looked at urine output two to four days after surgery. This measurement showed no difference between the intervention and control groups (WMD 0.17 ml/min, 95% CI -0.06 to 0.40; I2 = 88%).

Creatinine clearance

Twenty studies (see 'Data and analyses' Analysis 8.2) looked at creatinine clearance following cardiac surgery. Eighteen studies looked at creatinine clearance at 24 hours (see Analysis 8.2.1) and the results suggested no significant improvement in creatinine clearance with treatment compared to control (WMD 9.0 ml/min, 95% CI -0.11 to 18.11). Heterogeneity was high (I2 = 89%). Creatinine clearance at two to four days following cardiac surgery was reported in 10 studies (see Analysis 8.2.2) and on the fifth to seventh day in four studies (see Analysis 8.2.3). There was evidence of beneficial effects of treatment in the later postoperative days. Creatinine clearance improved on the second to fourth postoperative days (WMD 12.98 ml/min, 95% CI 1.03 to 24.92; I2 = 87%) and on the fifth to seventh postoperative days (WMD 23.21 ml/min, 95% CI 14.63 to 31.80; I2 = 0%). However, it is worthwhile noting that Sezai 2000 (using atrial natriuretic peptide infusion as the treatment) estimated the glomerular filtration rate (GFR), which considerably favoured the treatment group at 24 hours and on the second postoperative day. Ryckwaert 2001 reported results that favoured the treatment group on the seventh postoperative day (this study used preoperative enalapril infusion, for two days).

Free water clearance

Free water clearance in ml/min was measured at 24 hours in six studies (see 'Data and analyses' Analysis 8.3.1). The results suggested no significant benefit with treatment at 24 hours (WMD 0.09 ml/min, 95% CI -0.17 to 0.35), with moderate heterogeneity (I2 = 51%). A significant difference was reported from the second to the fourth day (WMD -0.23 ml/min, 95% CI -0.44 to -0.03; I2 = 8%).

Fractional excretion of sodium

Six studies documented fractional excretion of sodium at 24 hours and two studies at two to four days postoperatively (see Data and analyses' Analysis 8.4).

Aortic surgery

Urine output

Five studies measured urine output at 24 hours following elective aortic surgery. There was no demonstrable benefit from treatment (see 'Data and analyses' Analysis 9.1.1) (WMD -0.09 ml/min, 95% CI -0.12 to 0.31; I2 = 0%). Two trials measured urine output between the second and fourth days and between the fifth and seventh postoperative days (see Analysis 9.1.2 and Analysis 9.1.3) and showed no difference with treatment (WMD 0.26 ml/min, 95% CI -0.20 to 0.72; I2 = 54% and WMD -0.09 ml/min, 95% CI -0.39 to 0.21; I2 = 23%, respectively).

Creatinine clearance

Eight studies (see 'Data and analyses' Analysis 9.2) looked at creatinine clearance following elective aortic surgery. All eight studies estimated creatinine clearance at 24 hours after surgery (see Analysis 9.2.1) and the results suggested no benefit resulting from treatment (WMD 7.10 ml/min, 95% CI -2.11 to 16.31; I2 = 27%). The same conclusions were drawn from four trials which measured creatinine clearance on the second to fourth days and on the fifth to seventh postoperative days (see Analysis 9.2.2, Analysis 9.2.3). The WMD results were 3.59 ml/min (95% CI -10.35 to 17.54; I2 = 0%) and -12.85 ml/min (95% CI -26.41 to 0.72; I2 = 5%), respectively. It is interesting to note that heterogeneity was low in these results.

Free water clearance

Five trials studied this outcome at 24 hours after aortic surgery (see 'Data and analyses' Analysis 9.3.1). The results showed no significant benefit from treatment (WMD -0.25 ml/min, 95% CI -0.51 to 0.01; I2 = 0%). Two studies looked at free water clearance on the second to fourth days and on the fifth to seventh postoperative days (see Analysis 9.3.2 and Analysis 9.3.3). There were no differences (WMD 0.37 ml/min, 95% CI -0.12 to 0.85; I2 = 0% and WMD 0.24 ml/min, 95% CI -0.13 to 0.61; I2 = 0%), respectively.

Fractional excretion of sodium

Five studies reported this outcome (see 'data and analyses' Analysis 9.4.1) at 24 hours and two studies (see Analysis 9.4.2) reported the results on the second to fourth days postoperatively.

Renal plasma flow

Four trials estimated renal plasma flow following aortic surgery (see 'Data and analyses' Analysis 9.5). Analysis of results at the end of the operation in two studies (see Analysis 9.5.1) showed no statistically significant difference between treatment and control groups (WMD 50.29 ml/min, 95% CI -92.83 to 193.40; I2 = 28%). The same held true for renal plasma flow at 24 hours after operation in two studies (see Analysis 9.5) (WMD 45.86 ml/min, 95% CI -18.64 to 110.36; I2 = 0%).

Biliary surgery

Urine output

Only two trials looked at urine output at 24 hours, two to four days, and five to seven days after biliary surgery (see 'Data and analyses' Analysis 10.1). There was some evidence from these two studies that the urine output was less following the use of an intervention (WMD -0.59 ml/min, 95% CI -0.99 to -0.19; I2 = 18%) at 24 hours but it was not different at two to four days (WMD 0.24 ml/min, 95% CI -0.22 to 0.69; I2 = 26%) and favoured control at five to seven days (WMD 0.23 ml/min, 95% CI 0.09 to 0.37; I2 = 0%).

Creatinine clearance

Three trials measured creatinine clearance in ml/min at 24 hours (see 'Data and analyses' Analysis 10.2.1). There was no benefit from the use of an intervention (WMD -2.84 ml/min, 95% CI -14.07 to 8.39; I2 = 46%). The same was true for creatinine clearance values from three trials measuring creatinine clearance on the second to fourth postoperative days (see Analysis 11.2.2) (WMD 0.42 ml/min, 95% CI -16.68 to 17.52; I2 = 8%) and from two trials at five to seven days postoperatively (WMD 0.58 ml/min, 95% CI -16.43 to 17.60; I2 = 28%).

Pre-existing renal impairment

Four studies (Bergman 2002; Costa 1990; Durmaz 2003; Marathias 2006) included patients with pre-existing renal impairment. All these trials involved patients undergoing cardiac surgery. Bergman 2002 used diltiazem infusions; Costa 1990 used dopamine or dopexamine infusions; Durmaz 2003 used preoperative haemodialysis; and Marathias 2006 used preoperative hydration. The data were insufficient for any meaningful subgroup analysis.

High methodological quality studies

We identified only seven studies (Burns 2005; Carcoana 2003; Lassnigg 2000; Myles 1993; Nicholson 1996; Perez 2002; Ristikankare 2006) with high methodological quality and nine studies with moderately good methodological quality (Bergman 2002; Colson 1990; Colson 1992; de Lasson 1997; Halpenny 2002; Kramer 2002; Licker 1996; Morariu 2005; Shim 2007) (see 'Methodological quality of studies' additional Table 1 ). The data from these studies were subjected to sensitivity analysis. Unfortunately reports on Perez 2002 contained data that were unsuitable for analysis, which was confirmed by contacting the authors.

The available data enabled us to study 24-hour urine output in four studies of high methodological quality (see 'Data and analyses' Analysis 11.1.1). There was no significant difference between treatment and control groups (WMD 0.22 ml/min, 95% CI -0.02 to 0.47; I2 = 16%) in any of these studies. Analysis of four studies of moderate methodological quality also showed that there was no advantage of treatment (WMD 0.07 ml/min, 95% CI -0.20 to 0.35; I2 = 0%).

We were also able to compare creatinine clearance at 24 hours in four studies with high methodological quality (see 'Data and analyses' Analysis 11.2.1). This showed no statistically significant difference between treatment and control groups (WMD -9.12 ml/min, 95% CI -20.59 to 2.35; I2 = 0%). Four studies with moderate methodological quality (see Analysis 11.2.2) showed some advantage for treatment (WMD 14.67 ml/min, 95% CI 7.88 to 21.47; I2 = 0%).

These results suggested that high quality studies, though small in number, showed no overall advantage for treatment over control.

We compared the reports of mortality and acute renal failure in the high and moderately good methodological quality studies (see 'Data and analyses' Analysis 11.3 , Analysis 11.4). In the high methodological quality trials (six trials) the mortality figures gave an OR of 1.26 (95% CI 0.49 to 3.19; I2 = 0%) and the acute renal failure (as judged by the trialists) OR was 1.38 (95% CI 0.46 to 4.12; I2 = 28). These values suggest no difference between controls and treatment groups. We were unable to obtain results from the moderately good methodological studies.

Discussion

Renal dysfunction following major surgery is one of the causes of postoperative morbidity and mortality. The cause of renal failure in the postoperative period is thought to be multi-factorial. Over the last three or four decades many studies have tried to identify interventions that could provide renal protection in the perioperative period. Many different interventions have been tried, such as continuous infusions of dopamine or its analogues, use of diuretics such as mannitol, and diligent use of ACE inhibitors and calcium channel blockers, to name a few. None of these interventions have a good evidence base.

A major outcome of interest, mortality, was reported in a number of studies. Only a small number of deaths were reported in the trials and the review showed that there was no advantage for treatment groups over control groups. Similarly, another outcome of major importance, acute renal failure following operation, was reported in only a few of the included studies. There was no evidence that interventions offered any advantage to the patients. However, it is important to recognize that the methodological quality of many of the included studies was poor and that the number of reported cases was small. As a result, the statistical tests may not have detected a true difference between treatment and control groups.

Many physiological and biochemical variables can be used as markers of change in renal function. The various trials included in this review used a number of different markers as indicators of altered renal function. Each test has significant limitations and the results of the analysis must be interpreted in the context of these limitations.

  • Plasma creatinine is the most frequently measured marker of renal function. It makes the assumption that plasma creatinine remains constant and the clearance of creatinine is solely by glomerular filtration. Thus plasma creatinine is an indirect determinant of glomerular filtration rate (GFR). However, there has to be a greater than 50% reduction in GFR before there is a change in plasma creatinine. Plasma creatinine also reflects an individual's muscle mass and alterations in muscle mass will influence the plasma creatinine concentration, which does not reflect changes in GFR. There is a small amount of tubular excretion of creatinine which, in terms of normal GFR, is insignificant. However, with severe renal impairment tubular secretion of creatinine has a greater role and, therefore, plasma creatinine does not accurately reflect GFR. GFR is usually determined by the clearance of an inert substance which is freely filtered at the glomerulus and has no tubular secretion or reabsorption. The gold standard has been estimation of inulin clearance. Creatinine clearance correlates well with GFR. For accuracy, it is essential that creatinine clearance is determined correctly. This requires a timed and complete collection of urine along with a plasma creatinine determination. A variety of formulae have been derived using plasma creatinine, body weight, and age to estimate creatinine clearance and hence GFR. When renal function is stable these estimates correlate well with measured GFR (r = 0.9).

  • Urine output is a non-specific measure of renal function. Clearly if there is no urine production then there is no glomerular filtration. However, urine output can be influenced by a number of factors that regulate renal tubular handling of water. Oliguria (less than 400 ml urine/24 hr) may just reflect excess salt and water retention by the kidney due to a low fluid intake and not necessarily impaired renal function or the effects of increased anti-diuretic hormone (ADH) release, a normal response to surgery or stress.

  • In clinical practice, renal blood flow is rarely determined. Renal blood flow can be determined by clearance techniques using the Fick principle.

  • Free water clearance measures urinary concentrating ability. Any form of damage to the kidney impairs urinary concentrating ability. With renal tubular injury, free water clearance is impaired. Likewise, free water clearance is modified by diuretic therapy.

  • The fractional excretion of sodium has been used as a marker of renal function. More correctly, it reflects renal tubular reabsorption of sodium. The normal physiological response to a reduction in renal perfusion and glomerular filtration is to activate the tubular glomerular feedback mechanism leading to increased sodium reabsorption, along with water. The net effect is to increase blood pressure and hence renal perfusion. In the acute situation (the first 24 hours after an event affecting renal function), a low fractional sodium excretion (FeNa < 1%) indicates impaired renal perfusion. With any form of established renal damage, or the use of diuretics, the fractional excretion of sodium is increased and becomes impossible to interpret. It is, therefore, essential that the changes in markers of renal function that were recorded in the analysed papers are examined critically for the variables which influence the measurements reported. Conclusions drawn from the results should also be closely examined for the validity of the renal function measures that were used. The inability to correctly interpret the results prompted us not to analyse the data on FeNa but instead to provide the raw data.

When all treatments are combined and compared to the controls there were only minimal benefits for treatment. The urine output at 24 hours and urine output and creatinine clearance at two to four days after operation slightly improved with treatment; all other tests showed no significant differences. Even these results had significant heterogeneity and thus must be interpreted with great caution. Given the large range of treatments, operations types, and methods used to protect the kidneys, it is not surprising that large amounts of heterogeneity exist. Even when there were small statistically significant results identified, the clinical significance of these changes was not great since most of the changes returned to normal on the second to third or fifth to seventh days. The heterogeneity could have been due to multiple causes, including differences in the nature of treatment, duration of treatment, patients' conditions, and of course the methodological quality of the studies. We have used subgroup analysis to explore this further.

We performed subgroup analyses for the different interventions that were studied. Dopamine and its analogues showed no improvement in urine output or other tests such as creatinine clearance, free water clearance, or fractional excretion of sodium. Overall, from the studies available, it appears that dopamine and its analogues do not offer much protection to the kidneys. It is worth noting that in a multi-centre study of patients in intensive care units (ANZICS CTG 2000), no significant benefit of dopamine was demonstrated for these seriously ill patients.

It is important that we emphasize that the lack of statistical significance indicated in this review could be due to many factors. We have already discussed heterogeneity as a significant factor; causes of heterogeneity being different types and durations of operations, gender differences, smoking status, state of nutrition, age, alcohol intake, and co-morbidities such as hypertension, diabetes, or other unknown causes. The potential role of publication (or small sample) bias is also important. One of the common methods employed to recognize publication bias is the funnel plot. The most common reasons for small sample bias are lack of statistical significance in the outcomes; small numbers of cases investigated in trials; lack of allocation concealment; and inadequate blinding. All of these may result in misleading positive outcomes, leading to publication bias. Apart from visual examination of funnel plots there are various complicated statistical methods available, but none are wholly satisfactory in recognizing and avoiding small sample bias. A high level of suspicion is always required when interpreting reviews consisting of poor quality studies and studies with small sample sizes, as in this review.

The results from the use of diuretics were disappointing and offered no real advantage for the patients who received the treatment. The same is true for use of calcium channel blockers and ACE inhibitors, both apparently offered no advantages. The use of hydration fluids also showed that there is no obvious advantage for clear fluids over specialised colloid solutions, though the quality of the studies and the information available were poor. It is interesting to note that only four studies investigated the role of different types of intravenous fluids in the perioperative setting, although in most studies patients were well hydrated. Wahbah 2000 makes special mention of the fluid status of patients. Is it simply that kidneys are their happiest when they have a good pre-load to wash out toxic substances?

In the subgroup of surgical procedures cardiac surgery, aortic surgery and biliary surgery were considered for analysis. In cardiac surgery, interventions helped to increase urine output at 24 hours after surgery but a high level of heterogeneity made the results unconvincing. Creatinine clearance also improved slightly with treatment in cardiac surgery patients at two to four days and five to seven days after surgery. None of the other tests showed any significant changes. From this evidence it appears that any advantage for treatment is only minimal and does not consistently extend throughtout the postoperative period.

No benefit was noted in other forms of surgery. However, the number and quality of studies in these areas are limited.

One area of interest for this review was to look at the beneficial effects of treatment in patients with pre-existing renal impairment. Unfortunately only four studies (Bergman 2002; Costa 1990; Durmaz 2003; Marathias 2006) looked at this issue; none were of particularly good methodological quality and the results were uncertain.

We did a sensitivity analysis of studies with high and moderately high methodological quality. The results substantiated the overall findings on identifiable renal protection effects for various interventions in the perioperative period.

It is important to remember that the effect of ADH is part of the usual stress response of surgery. Both urine output and free water clearance in the first 12 to 24 hours after surgery are reduced because of the influence of ADH. Fractional excretion of sodium is increased with the use of diuretics. Hence we would question the worth of measurements of urine output, free water clearance, and fractional excretion of sodium as measures of renal function in the perioperative period. Glomerular filtration rate (and creatinine clearance) is a good measure of renal function and so is renal plasma flow measurement; but these need to be measured accurately in order to draw any meaningful conclusions.

Authors' conclusions

Implications for practice

There is no convincing evidence to suggest that pharmacological or other interventions used to protect the kidneys during surgery are of benefit to patients. However, there is a lack of studies of high quality on this topic.

Implications for research

A number of studies are available on the use of various pharmaceutical agents to protect renal function during surgery. However many of the studies do not demonstrate high quality methodology. Further high quality research is needed to establish the usefulness of interventions during surgery to protect the kidneys from adverse effects. One particular area for further research could be the role of interventions in patients with pre-existing renal dysfunction and undergoing major operations.

Acknowledgements

June 2008: as part of the pre-publication editorial process, this updated (conclusions not changed) review has been commented on by two editors (statistical and content).

We would like to thank Anna Lee, Nathan Pace, Mike Bennett, Giovanni Strippoli, Giuseppe Remuzzi, Amy Arkel, Janet Wale and Nete Villebro for their valuable suggestions during the editorial process of the previous review. We are very grateful to Dr Ian Gilmore for his contribution as an author to that previous version of this review. Our special thanks to Jane Cracknell, the Co-ordinator for the Cochrane Anaesthesia Review Group, for her encouragement, support, help and great patience.

We are also grateful to Toni Yalovitch, Mina Nishimori and Murat Genc for their assistance with manuscript translation, from Slovakian, Japanese and Turkish respectively.

Data and analyses

Download statistical data

Comparison 1. All renal protective interventions versus no intervention: Adverse outcomes (mortality, acute renal failure)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Mortality (reported)271342Peto Odds Ratio (Peto, Fixed, 95% CI)1.19 [0.66, 2.12]
2 Acute renal failure (reported)301385Peto Odds Ratio (Peto, Fixed, 95% CI)0.66 [0.33, 1.31]
Analysis 1.1.

Comparison 1 All renal protective interventions versus no intervention: Adverse outcomes (mortality, acute renal failure), Outcome 1 Mortality (reported).

Analysis 1.2.

Comparison 1 All renal protective interventions versus no intervention: Adverse outcomes (mortality, acute renal failure), Outcome 2 Acute renal failure (reported).

Comparison 2. All renal protective interventions versus no intervention
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Urine output21 Mean Difference (IV, Random, 95% CI)Subtotals only
1.1 Urine output: 24 hours (ml/min)18681Mean Difference (IV, Random, 95% CI)0.12 [-0.08, 0.32]
1.2 Urine output: 2-4 days (ml/min)9350Mean Difference (IV, Random, 95% CI)0.19 [0.02, 0.36]
1.3 Urine output: 5-7 days (ml/min)5112Mean Difference (IV, Random, 95% CI)0.40 [-0.10, 0.90]
2 Creatinine clearance33 Mean Difference (IV, Random, 95% CI)Subtotals only
2.1 Creatinine clearance: 24 hours (ml/min)301156Mean Difference (IV, Random, 95% CI)6.95 [0.16, 13.74]
2.2 Creatinine clearance: 2-4 days (ml/min)18711Mean Difference (IV, Random, 95% CI)9.93 [1.09, 18.77]
2.3 Creatinine clearance: 5-7 days (ml/min)10296Mean Difference (IV, Random, 95% CI)4.07 [-7.00, 17.15]
3 Free water clearance12 Mean Difference (IV, Random, 95% CI)Subtotals only
3.1 FWC: 24 hrs (ml/min)11350Mean Difference (IV, Random, 95% CI)-0.06 [-0.23, 0.12]
3.2 FWC: 2-4 days (ml/min)5172Mean Difference (IV, Random, 95% CI)-0.10 [-0.37, 0.17]
3.3 FWC: 5-7 days (ml/min)4152Mean Difference (IV, Random, 95% CI)0.02 [-0.24, 0.28]
4 Fractional excretion of sodium13 Mean Difference (IV, Random, 95% CI)Totals not selected
4.1 Fe Na: 24 hrs (%)12 Mean Difference (IV, Random, 95% CI)Not estimable
4.2 2-4 days (%)4 Mean Difference (IV, Random, 95% CI)Not estimable
5 Renal plasma flow6 Mean Difference (IV, Random, 95% CI)Subtotals only
5.1 RPF: end of operation (ml/min)362Mean Difference (IV, Random, 95% CI)46.37 [-68.61, 161.34]
5.2 RPF: 24 hrs (ml/min)371Mean Difference (IV, Random, 95% CI)59.15 [-1.80, 120.10]
Analysis 2.1.

Comparison 2 All renal protective interventions versus no intervention, Outcome 1 Urine output.

Analysis 2.2.

Comparison 2 All renal protective interventions versus no intervention, Outcome 2 Creatinine clearance.

Analysis 2.3.

Comparison 2 All renal protective interventions versus no intervention, Outcome 3 Free water clearance.

Analysis 2.4.

Comparison 2 All renal protective interventions versus no intervention, Outcome 4 Fractional excretion of sodium.

Analysis 2.5.

Comparison 2 All renal protective interventions versus no intervention, Outcome 5 Renal plasma flow.

Comparison 3. Dopamine and analogues versus no intervention
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Urine output11 Mean Difference (IV, Random, 95% CI)Subtotals only
1.1 24 hours (ml/min)11379Mean Difference (IV, Random, 95% CI)0.12 [-0.29, 0.53]
1.2 2-4 days (ml/min)7231Mean Difference (IV, Random, 95% CI)0.41 [0.00, 0.82]
1.3 5-7 days (ml/min)5145Mean Difference (IV, Random, 95% CI)0.18 [-0.06, 0.42]
2 Creatinine clearance14 Mean Difference (IV, Random, 95% CI)Subtotals only
2.1 24 hours (ml/min)14455Mean Difference (IV, Random, 95% CI)4.55 [-10.58, 19.68]
2.2 2-4 days (ml/min)8233Mean Difference (IV, Random, 95% CI)-3.17 [-14.00, 7.66]
2.3 5-7 days (ml/min)6147Mean Difference (IV, Random, 95% CI)-3.91 [-12.24, 4.43]
3 Free water clearance6 Mean Difference (IV, Random, 95% CI)Subtotals only
3.1 24 hours (ml/min)6166Mean Difference (IV, Random, 95% CI)0.03 [-0.17, 0.22]
4 Fractional excretion of sodium5 Mean Difference (IV, Random, 95% CI)Totals not selected
4.1 24 hours (%)5 Mean Difference (IV, Random, 95% CI)Not estimable
5 Renal plasma flow (24 hrs)248Mean Difference (IV, Random, 95% CI)75.36 [-63.27, 213.98]
Analysis 3.1.

Comparison 3 Dopamine and analogues versus no intervention, Outcome 1 Urine output.

Analysis 3.2.

Comparison 3 Dopamine and analogues versus no intervention, Outcome 2 Creatinine clearance.

Analysis 3.3.

Comparison 3 Dopamine and analogues versus no intervention, Outcome 3 Free water clearance.

Analysis 3.4.

Comparison 3 Dopamine and analogues versus no intervention, Outcome 4 Fractional excretion of sodium.

Analysis 3.5.

Comparison 3 Dopamine and analogues versus no intervention, Outcome 5 Renal plasma flow (24 hrs).

Comparison 4. Diuretics versus no intervention
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Urine output5 Mean Difference (IV, Random, 95% CI)Subtotals only
1.1 24 hours (ml/min)4141Mean Difference (IV, Random, 95% CI)0.10 [-0.12, 0.33]
1.2 2-4 days (ml/min)3120Mean Difference (IV, Random, 95% CI)0.17 [-0.06, 0.40]
1.3 5-7 days (ml/min)128Mean Difference (IV, Random, 95% CI)0.02 [-0.28, 0.32]
2 Creatinine clearance4 Mean Difference (IV, Random, 95% CI)Subtotals only
2.1 24 hours (ml/min)3123Mean Difference (IV, Random, 95% CI)-18.02 [-41.78, 5.75]
2.2 2-4 days (ml/min)3120Mean Difference (IV, Random, 95% CI)2.33 [-14.76, 19.42]
2.3 5-7 days (ml/min)128Mean Difference (IV, Random, 95% CI)6.30 [-17.46, 30.06]
Analysis 4.1.

Comparison 4 Diuretics versus no intervention, Outcome 1 Urine output.

Analysis 4.2.

Comparison 4 Diuretics versus no intervention, Outcome 2 Creatinine clearance.

Comparison 5. Calcium channel blockers versus no intervention
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Urine output3 Mean Difference (IV, Fixed, 95% CI)Subtotals only
1.1 Urine output: 24 hours (ml/min)370Mean Difference (IV, Fixed, 95% CI)0.28 [-0.10, 0.66]
2 Creatinine clearance4 Mean Difference (IV, Random, 95% CI)Subtotals only
2.1 24 hours (ml/min)4151Mean Difference (IV, Random, 95% CI)0.11 [-16.03, 16.26]
2.2 2-4 days (ml/min)130Mean Difference (IV, Random, 95% CI)41.7 [-5.66, 89.06]
2.3 5-7 days (ml/min)130Mean Difference (IV, Random, 95% CI)22.30 [-10.58, 55.18]
3 Free water clearance3 Mean Difference (IV, Random, 95% CI)Subtotals only
3.1 24 hours (ml/min)391Mean Difference (IV, Random, 95% CI)-0.09 [-0.47, 0.29]
Analysis 5.1.

Comparison 5 Calcium channel blockers versus no intervention, Outcome 1 Urine output.

Analysis 5.2.

Comparison 5 Calcium channel blockers versus no intervention, Outcome 2 Creatinine clearance.

Analysis 5.3.

Comparison 5 Calcium channel blockers versus no intervention, Outcome 3 Free water clearance.

Comparison 6. ACE inhibitors versus no intervention
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Renal plasma flow3 Mean Difference (IV, Random, 95% CI)Subtotals only
1.1 RPF: end of operation (ml/min)362Mean Difference (IV, Random, 95% CI)46.37 [-68.61, 161.34]
Analysis 6.1.

Comparison 6 ACE inhibitors versus no intervention, Outcome 1 Renal plasma flow.

Comparison 7. Hydration fluid versus control
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Creatinine clearance2 Mean Difference (IV, Random, 95% CI)Subtotals only
1.1 24 hours (ml/min)277Mean Difference (IV, Random, 95% CI)-10.34 [-29.57, 8.88]
1.2 2-4 days (ml/min)158Mean Difference (IV, Random, 95% CI)-6.00 [-32.65, 20.65]
1.3 5-7 days (ml/min)119Mean Difference (IV, Random, 95% CI)-25.0 [-52.14, 2.14]
Analysis 7.1.

Comparison 7 Hydration fluid versus control, Outcome 1 Creatinine clearance.

Comparison 8. Cardiac surgery: subgroup analysis
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Urine output13 Mean Difference (IV, Random, 95% CI)Subtotals only
1.1 24 hours (ml/min)11520Mean Difference (IV, Random, 95% CI)0.25 [0.08, 0.41]
1.2 2-4 days (ml/min)5252Mean Difference (IV, Random, 95% CI)0.17 [-0.06, 0.40]
2 Creatinine clearance20 Mean Difference (IV, Random, 95% CI)Subtotals only
2.1 24 hours (ml/min)18808Mean Difference (IV, Random, 95% CI)9.00 [-0.11, 18.11]
2.2 2-4 days (ml/min)10458Mean Difference (IV, Random, 95% CI)12.98 [1.03, 24.92]
2.3 5-7 days (ml/min)4137Mean Difference (IV, Random, 95% CI)23.21 [14.63, 31.80]
3 Free water clearance7 Mean Difference (IV, Random, 95% CI)Subtotals only
3.1 24 hours (ml/min)6196Mean Difference (IV, Random, 95% CI)0.09 [-0.17, 0.35]
3.2 2-4 days (ml/min)387Mean Difference (IV, Random, 95% CI)-0.23 [-0.44, -0.03]
4 Fractional excretion of sodium7 Mean Difference (IV, Random, 95% CI)Totals not selected
4.1 24 hours (%)6 Mean Difference (IV, Random, 95% CI)Not estimable
4.2 2-4 days (%)2 Mean Difference (IV, Random, 95% CI)Not estimable
Analysis 8.1.

Comparison 8 Cardiac surgery: subgroup analysis, Outcome 1 Urine output.

Analysis 8.2.

Comparison 8 Cardiac surgery: subgroup analysis, Outcome 2 Creatinine clearance.

Analysis 8.3.

Comparison 8 Cardiac surgery: subgroup analysis, Outcome 3 Free water clearance.

Analysis 8.4.

Comparison 8 Cardiac surgery: subgroup analysis, Outcome 4 Fractional excretion of sodium.

Comparison 9. Aortic surgery: subgroup analysis
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Urine output5 Mean Difference (IV, Random, 95% CI)Subtotals only
1.1 24 hours (ml/min)5118Mean Difference (IV, Random, 95% CI)0.09 [-0.12, 0.31]
1.2 2-4 days (ml/min)255Mean Difference (IV, Random, 95% CI)0.26 [-0.20, 0.72]
1.3 5-7 days (ml/min)255Mean Difference (IV, Random, 95% CI)-0.09 [-0.39, 0.21]
2 Creatinine clearance8 Mean Difference (IV, Random, 95% CI)Subtotals only
2.1 24 hours (ml/min)8241Mean Difference (IV, Random, 95% CI)7.10 [-2.11, 16.31]
2.2 2-4 days (ml/min)4155Mean Difference (IV, Random, 95% CI)3.59 [-10.35, 17.54]
2.3 5-7 days (ml/min)4116Mean Difference (IV, Random, 95% CI)-12.85 [-26.41, 0.72]
3 Free water clearance5 Mean Difference (IV, Random, 95% CI)Subtotals only
3.1 24 hours (ml/min)5154Mean Difference (IV, Random, 95% CI)-0.25 [-0.51, 0.01]
3.2 2-4 days (ml/min)285Mean Difference (IV, Random, 95% CI)0.37 [-0.12, 0.85]
3.3 5-7 days (ml/min)285Mean Difference (IV, Random, 95% CI)0.24 [-0.13, 0.61]
4 Fractional excretion of sodium5 Mean Difference (IV, Random, 95% CI)Totals not selected
4.1 24 hours (%)5 Mean Difference (IV, Random, 95% CI)Not estimable
4.2 2-4 days (%)2 Mean Difference (IV, Random, 95% CI)Not estimable
5 Renal plasma flow4 Mean Difference (IV, Random, 95% CI)Subtotals only
5.1 End of operation (ml/min)244Mean Difference (IV, Random, 95% CI)50.29 [-92.83, 193.40]
5.2 24 hours (ml/min)247Mean Difference (IV, Random, 95% CI)45.86 [-18.64, 110.36]
Analysis 9.1.

Comparison 9 Aortic surgery: subgroup analysis, Outcome 1 Urine output.

Analysis 9.2.

Comparison 9 Aortic surgery: subgroup analysis, Outcome 2 Creatinine clearance.

Analysis 9.3.

Comparison 9 Aortic surgery: subgroup analysis, Outcome 3 Free water clearance.

Analysis 9.4.

Comparison 9 Aortic surgery: subgroup analysis, Outcome 4 Fractional excretion of sodium.

Analysis 9.5.

Comparison 9 Aortic surgery: subgroup analysis, Outcome 5 Renal plasma flow.

Comparison 10. Biliary surgery: subgroup analysis
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Urine output2 Mean Difference (IV, Random, 95% CI)Subtotals only
1.1 Urine output: 24 hrs (ml/min)243Mean Difference (IV, Random, 95% CI)-0.59 [-0.99, -0.19]
1.2 Urine output: 2-4 days (ml/min)243Mean Difference (IV, Random, 95% CI)0.24 [-0.22, 0.69]
1.3 Urine output: 5-7 days (ml/min)243Mean Difference (IV, Random, 95% CI)0.23 [0.09, 0.37]
2 Creatinine clearance4 Mean Difference (IV, Random, 95% CI)Subtotals only
2.1 24 hours (ml/min)383Mean Difference (IV, Random, 95% CI)-2.84 [-14.07, 8.39]
2.2 2-4 days (ml/min)374Mean Difference (IV, Random, 95% CI)0.42 [-16.68, 17.52]
2.3 5-7 days (ml/min)243Mean Difference (IV, Random, 95% CI)0.58 [-16.43, 17.60]
Analysis 10.1.

Comparison 10 Biliary surgery: subgroup analysis, Outcome 1 Urine output.

Analysis 10.2.

Comparison 10 Biliary surgery: subgroup analysis, Outcome 2 Creatinine clearance.

Comparison 11. High and moderate methodological quality studies: sensitivity analysis
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Urine output at 24 hrs8 Mean Difference (IV, Random, 95% CI)Subtotals only
1.1 High methodological quality4303Mean Difference (IV, Random, 95% CI)0.22 [-0.02, 0.47]
1.2 Moderate methodological quality494Mean Difference (IV, Random, 95% CI)0.07 [-0.20, 0.35]
2 Creatinine clearance at 24 hrs8 Mean Difference (IV, Random, 95% CI)Subtotals only
2.1 High methodological quality4234Mean Difference (IV, Random, 95% CI)-9.12 [-20.59, 2.35]
2.2 Moderate methodological quality4126Mean Difference (IV, Random, 95% CI)14.67 [7.88, 21.47]
3 Mortality9744Odds Ratio (M-H, Fixed, 95% CI)1.26 [0.49, 3.19]
3.1 High methodological quality6645Odds Ratio (M-H, Fixed, 95% CI)1.26 [0.49, 3.19]
3.2 Moderate methodological quality399Odds Ratio (M-H, Fixed, 95% CI)Not estimable
4 Acute renal failure12838Odds Ratio (M-H, Fixed, 95% CI)1.38 [0.46, 4.12]
4.1 High methodological quality6645Odds Ratio (M-H, Fixed, 95% CI)1.38 [0.46, 4.12]
4.2 Moderate methodological quality6193Odds Ratio (M-H, Fixed, 95% CI)Not estimable
Analysis 11.1.

Comparison 11 High and moderate methodological quality studies: sensitivity analysis, Outcome 1 Urine output at 24 hrs.

Analysis 11.2.

Comparison 11 High and moderate methodological quality studies: sensitivity analysis, Outcome 2 Creatinine clearance at 24 hrs.

Analysis 11.3.

Comparison 11 High and moderate methodological quality studies: sensitivity analysis, Outcome 3 Mortality.

Analysis 11.4.

Comparison 11 High and moderate methodological quality studies: sensitivity analysis, Outcome 4 Acute renal failure.

Appendices

Appendix 1. Search strategies employed

Search strategy for MEDLINE (1966 to June, 2007)

#1 explode "Kidney-Failure" / all SUBHEADINGS in MIME,MJME,PT
#2 explode "Kidney-Failure-Acute" / all SUBHEADINGS in MIME,MJME,PT
#3 explode "Kidney-Failure-Chronic" / all SUBHEADINGS in MIME,MJME,PT
#4 explode "Kidney-Function-Tests" / all SUBHEADINGS in MIME,MJME,PT
#5 explode "Glomerular-Filtration-Rate" / all SUBHEADINGS in MIME,MJME,PT
#6 explode "Renal-Circulation" / all SUBHEADINGS in MIME,MJME,PT
#7 explode "Renal-Plasma-Flow" / all SUBHEADINGS in MIME,MJME,PT
#8 explode "Renal-Insufficiency" / all SUBHEADINGS in MIME,MJME,PT
#9 kidney
#10 glomerul* near filtration
#11 renal near (failure or protect* or function*)
#12 (kidney function test*) or (renal function test*)
#13 (free water clearance) or (fractional excretion of sodium)
#14 urine near (output or flow)
#15 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14
#16 explode "Angiotensin-Converting-Enzyme-Inhibitors" / all SUBHEADINGS in MIME,MJME,PT
#17 diuretic* or mannitol or frusemide or furosemide
#18 (explode "Fluid-Therapy" / all SUBHEADINGS in MIME,MJME,PT) or (fluid* near therap*)
#19 (explode "Infusions-Intravenous" / all SUBHEADINGS in MIME,MJME,PT) or (intravenous near fluid*) or hydration
#20 explode "Angiotensin-Converting-Enzyme-Inhibitors" / all SUBHEADINGS in MIME,MJME,PT
#21 (angiotensin converting enzyme inhibitor*) or (ACE inhibitor*)
#22 explode diuretics / all subheadings or explode mannitol / all subheadings or explode Furosemide / all subheadings
#23 explode "Dopamine-" / all SUBHEADINGS in MIME,MJME,PT
#24 explode "Dopamine-Agonists" / all SUBHEADINGS in MIME,MJME,PT
#25 dopamin*
#26 #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25
#27 explode "Perioperative-Care" / all SUBHEADINGS
#28 (explode "Intraoperative-Period" / all SUBHEADINGS in MIME,MJME,PT) or (explode "Intraoperative-Care" / all SUBHEADINGS in MIME,MJME,PT) or (explode "Intraoperative-Complications" / all SUBHEADINGS in MIME,MJME,PT)
#29 peri?operativ* or intra?operativ*
#30 #27 or #28 or #29
#31 #15 and #26 and #30
#32 reno?protect*
#33 #31 or #32
#35 CONTROLLED-CLINICAL-TRIAL in PT(74668 records)
#34 RANDOMIZED-CONTROLLED-TRIAL in PT
#36 RANDOMIZED-CONTROLLED-TRIALS
#37 RANDOM-ALLOCATION
#38 DOUBLE-BLIND-METHOD
#39 SINGLE-BLIND-METHOD
#40 #34 or #35 or #36 or #37 or #38 or #39
#41 (TG=ANIMALS) not ((TG=HUMAN) and (TG=ANIMALS))
#42 #40 not #41
#43 CLINICAL-TRIAL in PT
#44 explode CLINICAL-TRIALS / all subheadings
#46 (clin* near trial*) in AB(107975 records)
#45 (clin* near trial*) in TI
#47 (singl* or doubl* or trebl* or tripl*) near (blind* or mask*)
#48 (#47 in TI) or (#47 in AB)
#49 PLACEBOS
#50 placebo* in TI
#51 placebo* in AB
#52 random* in TI
#53 random* in AB(373784 records)
#54 RESEARCH-DESIGN
#55 #43 or #44 or #45 or #46 or #48 or #49 or #50 or #51 or #52 or #53 or #54
#56 (TG=ANIMALS) not ((TG=HUMAN) and (TG=ANIMALS))
#57 #55 not #56
#58 #57 not #42
#59 #42 or #58
#60 #33 and #59

Search strategy for EMBASE (1988 to June, 2007)

#1 explode "kidney-failure" / all SUBHEADINGS in DEM,DER,DRM,DRR
#2 (explode "kidney-failure" / all SUBHEADINGS in DEM,DER,DRM,DRR) or (explode "kidney-function-test" / all SUBHEADINGS in DEM,DER,DRM,DRR)
#3 explode "glomerulus-filtration-rate" / all SUBHEADINGS in DEM,DER,DRM,DRR
#4 (explode "kidney-circulation" / all SUBHEADINGS in DEM,DER,DRM,DRR) or (explode "kidney-clearance" / all SUBHEADINGS in DEM,DER,DRM,DRR)
#5 explode "kidney-plasma-flow" / all SUBHEADINGS in DEM,DER,DRM,DRR
#6 explode "urine-flow-rate" / all SUBHEADINGS in DEM,DER,DRM,DRR
#7 explode "urine-volume" / all SUBHEADINGS in DEM,DER,DRM,DRR
#8 kidney
#9 glomerul* near filtration
#10 renal near (failure or protect* or function*)
#11 kidney function test* or renal function test*
#12 free water clearance or fractional excretion of sodium
#13 urine near (output or flow)
#14 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13
#15 explode "dipeptidyl-carboxypeptidase-inhibitor" / all SUBHEADINGS in DEM,DER,DRM,DRR
#16 diuretic* or mannitol or frusemide or furosemide
#17 fluid* near therap*
#18 explode "fluid-therapy" / all SUBHEADINGS in DEM,DER,DRM,DRR
#19 "intravenous-drug-administration" / all SUBHEADINGS in DEM,DER,DRM,DRR
#20 (intravenous near fluid*) or hydration
#21 explode "diuretic-agent" / all SUBHEADINGS in DEM,DER,DRM,DRR
#22 explode "diuretic-agent" / all SUBHEADINGS in DEM,DER,DRM,DRR
#23 explode "mannitol-" / all SUBHEADINGS in DEM,DER,DRM,DRR
#24 explode "furosemide-" / all SUBHEADINGS in DEM,DER,DRM,DRR
#25 angiotensin converting enzyme inhibitor* or ACE inhibitor*
#26 explode "dopamine-" / all SUBHEADINGS in DEM,DER,DRM,DRR
#27 explode "dopamine-receptor-stimulating-agent" / all SUBHEADINGS in DEM,DER,DRM,DRR
#28 dopamin*
#29 #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28
#30 explode "perioperative-period" / all SUBHEADINGS in DEM,DER,DRM,DRR
#31 (explode "intraoperative-period" / all SUBHEADINGS in DEM,DER,DRM,DRR) or (explode "peroperative-care" / all SUBHEADINGS in DEM,DER,DRM,DRR)
#32 peri?operativ* or intra?operativ*
#33 #30 or #31 or #32
#34 #14 and #29 and #33
#35 "RANDOMIZED-CONTROLLED-TRIAL"/ all subheadings
#36 "RANDOMIZATION"/ all subheadings
#37 "CONTROLLED-STUDY"/ all subheadings
#38 "MULTICENTER-STUDY"/ all subheadings
#39 "PHASE-3-CLINICAL-TRIAL"/ all subheadings
#40 "PHASE-4-CLINICAL-TRIAL"/ all subheadings
#41 "DOUBLE-BLIND-PROCEDURE"/ all subheadings
#42 "SINGLE-BLIND-PROCEDURE"/ all subheadings
#43 #35 or #36 or #37 or #38 or #39 or #40 or #41 or #42
#44 (RANDOM* or CROSS?OVER* or FACTORIAL* or PLACEBO* or VOLUNTEER*) in TI,AB
#45 (SINGL* or DOUBL* or TREBL* or TRIPL*) near ((BLIND* or MASK*) in TI,AB)
#46 #43 or #44 or #45
#47 HUMAN in DER
#48 (ANIMAL or NONHUMAN) in DER
#49 #47 and #48
#50 #48 not #49(2675100 records)
#51 #46 not #50
#52 #34 and #51

Search strategy for CENTRAL (The Cochrane Library, Issue 2, 2007)

#1MeSH descriptor Kidney Failure explode all trees
#2MeSH descriptor Kidney Failure, Acute explode all trees
#3MeSH descriptor Kidney Failure, Chronic explode all trees
#4MeSH descriptor Kidney Function Tests explode all trees
#5MeSH descriptor Glomerular Filtration Rate explode all trees
#6MeSH descriptor Renal Circulation explode all trees
#7MeSH descriptor Renal Plasma Flow, Effective explode all trees
#8MeSH descriptor Renal Insufficiency explode all trees
#9kidney
#10glomerul* near filtration
#11renal near (failure or protect* or function*)
#12kidney function test*
#13renal function test*
#14free water clearance
#15(fractional excretion) of sodium
#16urine near (output or flow)
#17(#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16)
#18MeSH descriptor Angiotensin-Converting Enzyme Inhibitors explode all trees
#19diuretic* or mannitol or frusemide or furosemide
#20MeSH descriptor Fluid Therapy explode all trees
#21fluid* near therap*
#22MeSH descriptor Infusions, Intravenous explode all trees
#23(intravenous near fluid*) or hydration
#24angiotensin converting enzyme inhibitor*
#25ACE inhibitor*
#26MeSH descriptor Diuretics explode all trees
#27MeSH descriptor Mannitol explode all trees
#28MeSH descriptor Furosemide explode all trees
#29MeSH descriptor Dopamine explode all trees
#30MeSH descriptor Dopamine Agonists explode all trees
#31dopamin*
#32(#17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31)
#33MeSH descriptor Perioperative Care explode all trees
#34MeSH descriptor Intraoperative Care explode all trees
#35MeSH descriptor Intraoperative Complications explode all trees
#36MeSH descriptor Intraoperative Period explode all trees
#37perioperativ* or intraoperativ*
#38(#33 OR #34 OR #35 OR #36 OR #37)
#39(#17 AND #32 AND #38)

Appendix 2. data extraction form

Data extraction form

Study ID:                                  Language: English/

What was the surgical procedure? 

What was the study intervention?

How many patients were studied?

How many in the intervention group?

How many in the control group?

Were the inclusion criteria clearly defined?

Were the exclusion criteria clearly defined?

Age group         Intervention                   Control

Male: Female numbers:

Was there randomization of allocation in the groups?

Was there adequate information about randomization?

Was there allocation concealment?

Was the allocation concealment adequate?

Were there any withdrawals from the study?

How many people withdrew from each group?

Was there blinding in the study?

Study details:

What was the actual nature of the intervention?

When did the intervention start and finish?

What was the actual nature of the control group?

When did the control group start and finish?

Were the two groups treated equally?

What were the outcomes studied?

Mortality

Acute renal failure

Urine output

Creatinine clearance

Free water clearance

Fractional excretion of sodium

Renal blood flow

When were the outcomes measured?

Pre-operative    Postop: 24h       Postop: 48h       Postop: 72h       Postop: day (note)

Was the outcome assessment blinded?

Was there intention to treat analysis?

Is mean and standard deviation given?

Other measures of presentation of data

Graphic data?

Results:

Mean and SD    other measures: (Please specify clearly)

Outcomes: (Times)

Pre-op Day1    Day 2   Day 3   Day ()

Mortality:                   
Intervention     
Control

ARF:                           
Intervention                  
Control

Urine output:                
Intervention                  
Control
 
Creatinine clearance:    
Intervention                  
Control
 
Free H2O Cl:               
Intervention                  
Control
 
GFR:                           
Intervention                  
Control
 
FE Na (%)                   
Intervention                  
Control

Remarks:

Drug company sponsorship?

Other comments:

What's new

DateEventDescription
7 August 2008New citation required but conclusions have not changedNew review team; review has undergone substantial work
7 August 2008New search has been performedThe following changes from the previous published review are made in this updated review.

1.We have modified the search strategy and updated it until June 2007.
2. A change in members of the review team from the first published review to the present update. Some of the original review authors were no longer available, and other authors have joined the review team.
3. Modifed search strategy in June 2007 identified further studies, which are incorporated in the updated review.
4. Some of the previous studies included in the review have been dropped following further detailed evaluation of the studies and new ones were added.
5. There are minor changes in the results following the above modifications, but the conclusions remain the same.

History

Protocol first published: Issue 2, 2002
Review first published: Issue 3, 2005

Contributions of authors

Mathew Zacharias
Contact reviewer. Involved with development of the protocol, search strategy, retrieval of the papers, screening of papers, data extraction and data input, writing the protocol and review including updated review

Dr Niam Conlon
Screening of papers, extraction of data, checking data input and writing the updated review

Associate Prof Peter Herbison
Statistical and general advice, checking the review

Dr Palvannan Sivalingam
Co-reviewer. Involved with development of the protocol and screening of the papers, data extraction and checking of data input, checking the review including the update

Prof Robert Walker
Specialist advice on kidney and renal function tests

Dr Karen Hovhannisyan
Development of new search strategy and search

Declarations of interest

None known

Sources of support

Internal sources

  • Dunedin Hospital & Dunedin School of Medicine, Dunedin, New Zealand.

External sources

  • None, New Zealand.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Amano 1994

MethodsConsecutive patients for coronary artery bypass graft (CABG); randomization done, but method not clear; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsCoronary artery bypass surgery.
Glutathione group n = 10, age, mean = 58.2, SD = 2.5; control group n = 9, age, mean 56.8, SD 2.5
InterventionsGlutathione 200 mg/kg IV before bypass and same dose repeated during 1st and 2nd postoperative days.
Control group had saline in the same manner
OutcomesUrine output, creatinine clearance, fractional excretion of sodium
NotesNo response to letter for details
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Amano 1995

MethodsConsecutive patients for CABG; randomization method not clear; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsCoronary artery bypass surgery. Diltiazem group n = 13, age, mean = 54.5, SD = 1.8; control group n = 10, age, mean = 54.2, SD = 1.6
InterventionsDiltiazem 0.1 mg/kg bolus, followed by infusion of 2 mcg/kg/min until end of aortic cross clamping, followed by nasogastric administration every 8 hours for 24 hrs; control group received 5% dextrose in the same manner
OutcomesUrine output, creatinine clearance, free water clearance, fractional excretion of sodium
NotesNo response to letter for details
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Ascione 1999

MethodsPatients having CABG; randomization by card allocation; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsCoronary artery bypass surgery. Off pump n = 25, age, mean = 59.4, SD = 10.5; control (on pump), n = 26, age, mean = 63.8, SD = 6.7
InterventionsOn pump and off pump used for revascularization of coronary arteries
OutcomesCreatinine clearance
NotesInadequate response to letter from the contact author
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Berendes 1997

MethodsPatients having CABG; randomization done, method unclear; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsCoronary artery bypass surgery. Dopamine 0.5 mcg/kg/min, n = 10, age, mean = 60, SD = 7.1; dopamine 1 mcg/kg/min, n = 10, age, mean = 62, SD = 8.2; dopamine 2 mcg/kg/min, n = 10, age, mean = 62, SD = 10.2; placebo, n = 14, age, mean = 62, SD = 6.3
InterventionsDifferent doses of diltiazem, after induction of anaesthesia and for 24 hours postoperation
OutcomesCreatinine clearance
NotesDid not contact authors; old study and no additional information required
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Bergman 2002

MethodsPatients undergoing cardiac surgery with cardiopulmonary bypass; randomization done using list from hospital pharmacy; allocation concealment method unclear; blinding of patients, researchers and care givers is unknown, but strong possibility; study of moderate methodological quality
ParticipantsCardiac surgery. diltiazem group, n = 12, age, mean = 72, range, 69-76; placebo group, n = 12; age, mean = 73, range, 69-74. All participants had high serum creatinine
InterventionsDiltiazem 0. 25 mg/kg infusion for 15 min, followed by infusion of 1.7 mcg/kg/min for 24 hours
OutcomesGlomerular filtration rate (GFR)
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Burns 2005

MethodsHigh risk patients undergoing cardiac surgery; randomization by pharmacy by permuted block strategy (alternate blocks of 4 or 6); Allocation concealed by central randomization and drug (or placebo) dispensed by pharmacy by colour and consistency matching; everyone blinded to the nature of drugs
ParticipantsCardiac surgery. N-acetyl cysteine, 4 doses or 600mg or placebo 4 doses of 5% dextrose. Intervention group, n = 148, age, mean = 68.9, SD = 8.9; placebo group, n = 147; age = 69.2, SD = 9.7. Three patients from NAC group and 4 patients from placebo group withdrawn
InterventionsN-acetyl cysteine or placebo given. 1st dose after induction of anaesthesia, 2nd dose at end of bypass, 3rd dose at 12 hrs in ICU and 4th dose at 24hrs
OutcomesData available only on mortality and acute renal failure
NotesContacted the authors successfully for data
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Carcoana 2003

MethodsPatients for cardiac surgery; randomization by computer generated random number tables by Pharmacy; allocation concealment clearly stated. Patients, researchers and care givers were blinded; study with good methodological quality
ParticipantsCardiac surgery. Placebo group, n = 24, age, mean = 63.3, SD = 8.8; mannitol group, n = 26, age, mean = 64.3, SD = 8.9; Dopamine group, n = 25, age, mean = 63.8, SD = 9.8; mannitol + dopamine group, n = 25, age, mean = 63.4, SD = 7.8 (this group excluded in review)
InterventionsMannitol 1 g/kg into pump, dopamine 2 mcg/kg/min during surgery or both together as treatment; saline as placebo
OutcomesUrine output, creatinine clearance
NotesNo further information sought from authors
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Colson 1990

MethodsPatients having CABG; randomization & double blinding done, but method not specified; method of allocation concealment is unclear; blinding of patients, researchers and care givers is unknown, but possible it was adequate; poor methodological study
ParticipantsCoronary artery bypass surgery. Captopril group n = 8, age, mean = 56, SD = 3; control group n = 8, age, mean = 60, SD =2
InterventionsCaptopril 100 mg orally tid for 2 days preoperatively, last dose being 2 hrs before surgery; placebo tablets for control group
OutcomesRenal plasma flow
NotesOld study; no attempt made to contact authors
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Colson 1992

MethodsPatients having abdominal aortic aneurysm (AAA) surgery; randomization and double blinding of treatments done, but method not specified; method of allocation concealment is unclear; blinding of patients, researchers and care givers is unknown, but possible it was adequate; poor methodological quality study
ParticipantsAbdominal aortic surgery. Enalapril group n = 8, age, mean = 58, SD = 4; control group n = 8, age, mean = 63, SD = 1; nicardipine group n = 8; age, mean = 63, SD = 3
InterventionsEnalapril 10 mg orally BD for 2 days preoperation; placebo capsules for control group
OutcomesGFR, renal plasma flow; fractional excretion of sodium
NotesOld study; no attempt made to contact authors.
The same study (with alternative treatment is quoted "Colson 1992A")
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Costa 1990

MethodsPatients with pre-operative renal dysfunction having CABG; randomization method not specified; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsCoronary artery bypass surgery. Dopamine group n = 12, age, mean = 60.3, SD = 12.3; control group n = 12, age, mean = 61.3, SD = 8.9; dopamine and SNP group, n = 12, age, mean = 54.2, SD = 8.7 (this group excluded from review)
InterventionsDopamine infusion 2.5 mcg/kg/min during the operation (unsure for how long); control group had no treatment
OutcomesCreatinine clearance, free water clearance, fractional excretion of sodium
NotesOld study; no attempt made to contact authors. Excluded parallel treatment group
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Cregg 1999

MethodsIdiopathic scoliosis surgery patients; randomization method not specified; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsCorrective spinal surgery for scoliosis. Dopamine group, n = 15, age, mean = 14.6, SD = 3.6; control group, n = 15, age, mean = 12.1, SD = 2.8
InterventionsDopamine infusion 3 mcg/kg/min after induction for 24 hrs; control group received 5% dextrose for 24 hrs
OutcomesUrine output, fractional excretion of sodium
NotesUnable to contact the author;
the only study selected which is on a paediatric population
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Dawidson 1991

MethodsConsecutive patients for abdominal aortic surgery; randomization by random card method; allocation concealment not used; blinding of patients, researchers and care givers is unknown, but possible; poor methodological quality study
ParticipantsCorrective abdominal aortic surgery. Dextran 60 group, n = 10, age, mean = 62, SD = 10.4; Ringer's lactate group, n = 10, age, mean = 66.1, SD = 13.7
InterventionsDextran 60 infusion during operation and Ringer's lactate solution during surgery, ratio being 1:3 for the solutions
OutcomesUrine output; mortality data
NotesToo old study to get any more information
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

de Lasson 1995

MethodsConsecutive patients for abdominal aortic surgery; randomization method unclear; allocation concealment not used; blinding of patients and care givers is unknown, researcher blinded; poor methodological quality study
ParticipantsAbdominal aortic surgery. Dopamine group n = 12, age, mean = 63; placebo n = 12, age, mean = 60
InterventionsDopamine infusion 3 mcg/kg/min during operation and for 24 hrs
OutcomesUrine output, GFR, renal plasma flow, free water clearance
NotesNo reply from authors
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

de Lasson 1997

MethodsPatients for abdominal aortic surgery; randomization method not stated; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsAbdominal aortic surgery. Felodipine group n = 11, age, mean = 65; control group n = 12, age, mean = 60
InterventionsFelodipine 5 mg slow release tab for 5 days preoperatively, last dose 1-2 hrs before surgery; placebo tablets as control
OutcomesUrine output, GFR, renal plasma flow, free water clearance, fractional excretion of sodium
NotesNo reply from authors
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Dehne 2001

MethodsCABG patients, randomized into 4 groups. Method of randomization unclear; allocation concealment or blinding not mentioned. Methodological quality poor
ParticipantsAortocoronary bypass surgery. Patients into 4 groups; Group (1), controls with normal renal function: n = 12; age: mean = 62.6, SD = 8.0; group (2), dopexamine infusion in patients with normal renal function: n = 12; age: mean = 64.0, SD = 7.5; group (3), controls with abnormal renal function; n = 12; age, mean = 62.4, SD = 7.5; group (4), dopexamine infusion in patients with abnormal renal function: n = 12; age, mean = 65.4, SD = 8.1
InterventionsDopexamine 1 mcg/kg/min after induction of anaesthesia, until the end of surgery in groups 2 and 4; not sure how the controls were treated
OutcomesUrine output, creatinine clearance
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Donmez 1998

MethodsCABG patients. Patients were randomized, but method of randomization and allocation concealment not described
ParticipantsCABG patients. All patients received dopamine 2mg/kg/min infusion. Group (1) verapamil 5mg added to prime solution: n = 25; age, mean = 58.3, SE = 1.9; group (2), nimodipine 1-15mcg/kg/min during bypass; n = 25; age, mean = 56.1, SE = 2.6; group (3), control group; normal saline infusion only; n = 25; age, mean = 56.5, SE = 2.0
InterventionsVerapamil 5 mg in prime in group (1); group (2) received infusion of nimodipine 1-15 mcg/kg/min during bypass; group (3), control group received normal saline only
OutcomesCreatinine clearance
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Dural 2000

MethodsCABG patients; randomized by opaque sealed envelopes; allocation concealment unclear; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsCoronary artery surgery. Dopamine group n = 12, age, mean = 53.2, SD = 10.9; mannitol group, n = 12, age, mean = 55.4, SD = 8.4; control group, n = 12, age, mean = 53.7, SD = 8.3
InterventionsDopamine 3 mcg/kg/min started after induction, until end of operation; mannitol 1 mg/kg/hr from induction unto end of operation; no treatment for control group
OutcomesUrine output
NotesNo reply so far from authors
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Durmaz 2003

MethodsCABG. Randomization by last digits of medical records number. Patients were prospectively allocated preoperatively by way of randomization sequence. No mention of allocation concealment
ParticipantsCABG in patients with renal dysfunction. Preoperative dialysis group, n = 21; age, mean = 58.1, SD = 11.8; control group (no preoperative dialysis), n = 23; age, mean = 54.3, SD = 11.1
InterventionsPreoperative haemodialysis in the intervention group; control group had no preoperative haemodialysis.
OutcomesMortality, acute renal failure
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Fischer 2005

MethodsCABG. Used retrospective review of data from a randomized, double blinded, trial. No details are given about the method of randomization or allocation concealment, but confirms double-blind status. Methodology poor
ParticipantsCABG patients, age: mean = 66, SD = 9. Intervention group received N-acetyl cysteine during bypass, n = 20; placebo group, n = 20, not sure what they received
InterventionsN-acetyl cysteine, 100 mg/kg in prime, followed by 20 mg/kg per hour until end of bypass. Unsure what placebo group received
OutcomesMortality
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Gubern 1988

MethodsPatients for biliary surgery (on patients with some renal impairment); randomization method not detailed; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsBiliary tract surgery. Mannitol group n = 17, age, mean = 65.9, SD = 12; control group n = 14, age, mean = 68.5, SD = 9.9
InterventionsMannitol 50 g intravenously 1 hour preoperation and for 2 days; Control treatment had no treatment
OutcomesUrine output, GFR
NotesStudy too old to try to obtain details
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Halpenny 2002

MethodsPatients for AAA; randomization and blinding mentioned in text, but not detailed; allocation concealment not used; blinding of patients, researchers and care givers is unknown, but possible; overall poor methodological quality study
ParticipantsAbdominal aortic surgery. Fenoldopam group n = 14, age, mean = 70, SD = 5; control group n = 13, age, mean = 69, SD = 6
InterventionsFenoldopam infusion 0.1 mcg/kg/min (only during aortic cross clamping); placebo for control group
OutcomesUrine output, creatinine clearance, free water clearance, fractional excretion of sodium
NotesNo response from authors
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Kleinschmidt 1997

MethodsCABG patients. Three groups, randomization not described, no indication of concealment allocation, but indicated double-blind status. Methodological quality poor
ParticipantsCABG. Pentoxyfylline group, n = 14, age, mean = 61.7, SD = 8.0; gamma-hydroxybutyrate group, n = 13, age, mean = 62.3, SD = 3.9; control group, n = 13, age, mean = 62.9, SD = 6.2
InterventionsPentoxyphylline 1 mg/kg bolus, followed by 1 mg/kg/hour during operation. Gamma hydroxybutyrate bolus of 25 mg/kg, followed by 25 mg/kg/hour during operation. Control group received normal saline infusion
OutcomesCreatinine clearance, fractional excretion of sodium
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Kramer 2002

MethodsPatients for CABG; randomized and double-blinded study; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsCoronary artery bypass surgery. Theophylline group n = 28, age, mean = 60.4, SD = 10.1; control group n = 28, age, mean = 60.3, SD = 8.1
InterventionsTheophylline bolus of 4 mg/kg over 30 min, followed by infusion of 0.25 mg/kg/hr for 96 hrs; control group received saline
OutcomesGFR
NotesNo response from author
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Kulka 1996

MethodsPatients for CABG; randomization method not described; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsCoronary artery bypass surgery. Clonidine group n = 23, age, mean = 58, SD = 7; control n = 25, age, mean = 57, SD = 2
InterventionsPreoperative infusion of clonidine 4 mcg/kg over 15 min, 1 hr before surgery; placebo in control group
OutcomesUrine volume, creatinine clearance
NotesNo response from author
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Lassnigg 2000

MethodsPatients undergoing cardiac surgery; randomization by sealed envelopes; allocation concealment unclear, but strong possibility; blinding of patients, researchers and care givers done; good methodological quality study
ParticipantsCardiac surgery. Dopamine group n = 42, age, mean = 63, SD = 10; control group n = 40, age, mean = 65, SD = 10; frusemide (furosemide) group n = 41, age, mean = 63, SD = 10
InterventionsDopamine infusion 2 mcg/kg/min for 48 hrs; saline in control group; 05 mcg/kg/min frusemide infusion for 48 hrs
OutcomesUrine volume, creatinine clearance, fractional excretion of sodium
NotesNeed to contact authors uncertain. Same study (with alternative treatment) is quoted in "Lassnigg 2000A"
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Lau 2001

MethodsAbdominal aortic repair patients. Randomization done, but method not specified. Allocation concealment unclear or not done. Poor methodological quality
ParticipantsAAA repair. Intervention is extraperitoneal approach; n = 10; age, mean = 69.8, SEM=3.1. Control group is intraperitoneal approach; n=10; age, mean=74.3, SEM=2.5
InterventionsExtraperitoneal approach for AAA repair compared with transperitoneal approach
OutcomesMortality
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Licker 1996

MethodsInfrarenal aortic surgery; randomization method not clear; allocation concealment not used; blinding of patients, researchers and care givers is unknown, but likely; overall poor methodological quality study
ParticipantsAbdominal aortic surgery. Enalapril group n = 11, age, mean = 69; control group n = 9, age, mean = 68
InterventionsEnalapril bolus 50 mcg/kg injection 25 min before anaesthesia; saline inj in control group
OutcomesUrine output, creatinine clearance, renal plasma flow, free water clearance, fractional excretion of sodium
NotesContacted authors to confirm or exclude duplicate reporting; no response; used only full publication in review
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Loef 2004

MethodsCABG surgery. Method of randomization unclear, allocation concealment not stated, double-blind status stated. Methodological quality moderately poor
ParticipantsCABG surgery. Dexamethasone group, n = 10, age, mean = 67.7, range = 58-76; control group, n = 10, age, mean = 59.6, range = 47-76
InterventionsDexamethasone 1 mg/kg before induction of anaesthesia, followed by 0.5 mg/kg 8 hours later. Control group received a placebo, nature of which is unsure
OutcomesUrine output, creatinine clearance, free water clearance, fractional excretion of sodium
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Marathias 2006

MethodsCardiac surgery (open heart) in patients with high creatinine. Randomization done, but method unclear. Allocation concealment not stated. Poor methodological quality
ParticipantsOpen heart surgery in patients with renal impairment (high creatinine). Intervention was fluid hydration preoperatively for 12 hours using half normal saline; n = 30; age, mean = 64, SEM = 1.7. Control group had fluid restriction for 12 hours preoperatively; n = 15; age, mean = 64.2, SEM = 2.8
InterventionsPreoperative fluid hydration using half isotonic saline, 1 ml/kg/hour for 12 hours; control group had no fluid hydration
OutcomesMortality, acute renal failure
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Morariu 2005

MethodsCABG patients. Intervention dexamethasone IV; randomized, but method of randomization unclear. Allocation concealment not stated, but patients were double-blinded. Methodological quality poor
ParticipantsCABG patients. Intervention was dexamethasone and control group received a placebo, the nature of which is unclear. Dexamethasone group; n = 10; age, mean = 67.8, 95% CI = 63.4-72.1. Control group, n = 10; age, mean = 59.5; 95% CI = 53.4-65.5
InterventionsDexamethasone 1 mg/kg at induction, followed by 0.5 mg/kg 8 hours later; placebo in the control group at the same time
OutcomesMortality
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Morgera 2002

MethodsHigh risk patients for CABG; randomization not described; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsCoronary artery bypass surgery. Prostaglandin group n = 17, age, mean = 62, SD = 5.5; control group n = 17, age, mean = 61, SD = 7
InterventionsProstaglandin infusion 2 ng/kg/min at start of anaesthesia and for 48 hrs; control group treatment not described
OutcomesUrine volume, creatinine clearance
NotesNo response to letter
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Myles 1993

MethodsPatients for CABG; randomization by random number generated by pharmacy; allocation concealment adequate; blinding of patients, researchers and care givers are adequate; good methodological quality study
ParticipantsCoronary artery bypass surgery. dopamine group n = 25, age, mean = 62.2, SD = 8; control group n = 24, age, mean = 61, SD = 10
InterventionsDopamine infusion 3 mcg/kg/min for 24 hrs; 5% dextrose infusion for control group
OutcomesUrine output, creatinine clearance
NotesNo need for further information
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Nicholson 1996

MethodsConsecutive patients for AAA surgery; randomization by sealed envelope (random number); allocation concealment adequate; blinding of patients done, but that of researchers and care givers unknown, but is possible; moderate methodological quality study
ParticipantsAbdominal aortic surgery. Mannitol group n = 15, age, mean = 68; control group n = 13, age, mean = 71
InterventionsMannitol 0.3 g/kg before cross-clamp; normal saline for control group
OutcomesUrine output, creatinine clearance
NotesNeed for further information uncertain
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

O'Hara 2002

MethodsPartial nephrectomy in patients with single kidney; Randomization mentioned in text, no details given; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsPartial nephrectomy. Dopamine group n = 13, age, mean = 64.6, SD = 8; Control group n = 11, age, mean = 62.4, SD = 8.8
InterventionsDopamine infusion 3 mcg/kg/min during surgery and for 1 hr afterwards; no intervention in control group
OutcomesUrine output, GFR, renal blood flow
NotesNo response to letter
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Parks 1994

MethodsSurgery for obstructive jaundice; randomized, but no details given. allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsElective surgery for obstructive jaundice. Control group, n = 10, age not given; dopamine group, n = 13, age not given
InterventionsControl group had pre-op IV fluids and frusemide on induction; dopamine group had the above + infusion of dopamine 3 mcg/kg/min for 48 hours
OutcomesUrine output, creatinine clearance
NotesOld study, no real need for further information
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Perez 2002

MethodsLaparoscopic colorectal surgery; randomization done by use of sealed envelopes; allocation concealment not used; blinding of patients, researchers done, but that of care givers is unknown; overall good methodological quality study (unfortunately no relevant observations useful for this review)
ParticipantsElective laparoscopic colorectal surgery patients. Dopamine group, n = 19, age, mean = 64.3, SD = 9.4; control group, n = 18, age, mean = 61.3, SD = 16.7
InterventionsDopamine infusion, 2 mcg/kg/min during the operation; control group received saline in the same manner
OutcomesUrine output, creatinine clearance
NotesMailed authors for data because only the difference is given in the text. the data from authors contains details only during and for 2 hours after the operations. Continuous data not suitable for analysis
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Pull Ter Gunne 1990

MethodsPatients undergoing AAA surgery; randomized, method not described; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsAortic surgery for aneurysm. Preoperative hydration group, n = 11, age, mean = 65, SD, 9. Control group, n = 8, mean = 71, SD = 10
InterventionsTreatment group optimally hydrated preoperatively (guided by PCWP); control treatment no special treatment
OutcomesCreatinine clearance
NotesUnlikely to get authors to respond after this long after the study
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Ristikankare 2006

MethodsCardiac surgery patients with high creatinine levels (abnormal renal function). Randomization and allocation concealment methods not stated, but done by hospital pharmacy. Double-blind status stated. Methodological quality moderately good
ParticipantsCardiac surgery (bypass) patients. N-acetyl cysteine group, n = 38, age, mean = 72, range = 44-87; control group, n = 42, age, mean = 69, range = 51-81
InterventionsN-acetyl cysteine group received loading dose of the drug 150 mg/kg in 15 min, followed by 50 mg/kg for next 4 hours, thereafter 100 mg/kg for next 16 hours. Placebo group received similar amount of saline (0.9%) over the same time
OutcomesMortality, acute renal failure
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Ryckwaert 2001

MethodsCardiac surgery patients; randomized, but method not specified; allocation concealment unclear; blinding of patients, researchers and care givers is unknown, but is likely; overall poor methodological quality study
ParticipantsCardiac surgery (CABG). Enalapril group n = 7, mean = 60.1, SD = 3.6; control group n = 7, age, mean = 66.3, SD = 4.2
InterventionsEnalapril, 1 mg, 6 hourly for 2 days
OutcomesUrine output, GFR, renal plasma flow
NotesUnable to contact authors
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Sezai 2000

MethodsCABG patients. Randomization done, but details unclear. Allocation concealment not detailed. Blinding is done. Methodological quality moderately good
ParticipantsCABG patients. Atrial natriuretic peptide group, n=20, age, mean = 62.1, SD = 7.9; control group, n = 20, age, mean = 64.8, SD = 5.2
InterventionsIntervention group received atrial natriuretic peptide infusion, 0.03-0.05 mcg/kg/min for 20 hours, starting during operation, then reduced to 0.02 mcg/kg/min for another 4 hours. Control group received placebo (nature not described). All patients received dopamine and dobutamine at the end of bypass
OutcomesUrine output, GFR
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Shackford 1983

MethodsPatients for aortic reconstruction; randomized by random number method; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsElective aortic reconstruction surgery. Hypertonic saline group, n = 30, age, mean = 60.5, SD = 8.2; Ringer's lactate group, n = 28, age, mean= 61.7, SD = 8.5
InterventionsHypertonic saline intraoperatively and Ringer's lactate solution intraoperatively
OutcomesUrine output, creatinine clearance, fractional excretion of sodium
NotesVery old study
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Shim 2007

MethodsCardiac surgery (off-pump coronary artery surgery). Randomization using computer generated randomization table. Allocation concealment not stated, but blinding seems adequate. Methodological quality moderately good
ParticipantsOff-pump coronary artery surgery. Mannitol group, n = 25, age, mean = 63, SD = 8; control group, n = 25, age, mean = 63, SD = 8
InterventionsMannitol 0.5 g/kg in 10 min during grafting; control group 2.5 ml/kg normal saline during the same time period
OutcomesAcute renal failure
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Tang 1999

MethodsConsecutive patients for CABG; randomization method unclear; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsCoronary artery bypass surgery. Dopamine group n = 20, age, mean = 61, SD = 10.3; control group n = 20, age, mean = 56.3, SD = 8.7
InterventionsDopamine infusion, 2.5-4 mcg/kg/min for 48 hrs; control group without any intervention
OutcomesUrine output
NotesNo need to contact authors
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Tang 2002

MethodsCoronary artery surgery. Randomization done, but method not clear. No evidence of allocation concealment or blinding. Methodological quality poor
ParticipantsCoronary artery surgery. Beating heart surgery group, n = 20, age, mean = 64.8, SD = 6.9; conventional bypass group (control), n = 20, age, mean = 62.1, SD = 9.3
InterventionsIntervention is off-pump coronary artery surgery and control group is on pump coronary artery surgery
OutcomesMortality, acute renal failure
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Thompson 1986

MethodsSurgery for obstructive jaundice. Randomized, but method of randomization, allocation concealment and blinding not stated. Methodological quality poor
ParticipantsSurgery for obstructive jaundice. Oral ursodeoxycholic acid group, n = 20, age, mean = 57.0, range = 18-72. Control group, n = 20, age, mean = 56.5, range = 45-78
InterventionsIntervention oral ursodeoxycholic acid 900 mg, 8 hourly for 48 hours in the immediate preoperative period. Control group had no additional treatment
OutcomesMortality, acute renal failure, creatinine clearance
NotesToo old study to contact authors
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Urzua 1992

MethodsCABG surgery. Quasi randomization by using last digits of their notes, no allocation concealment or blinding
ParticipantsCABG. Phenylephrine group, n = 7, age, mean = 55, SD = 7. Control group, n = 14, age, mean = 54, SD = 7
InterventionsIntervention is to maintain mean perfusion pressure above 70 mmHg during surgery. Control group had no intervention
OutcomesAcute renal failure, urine output, creatinine clearance, free water clearance, fractional excretion of sodium
NotesTo old study to contact authors
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Wahbah 2000

MethodsPatients for biliary surgery; randomization method unclear; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsBiliary tract surgery. Dopamine group n = 10, age, median = 50, range = 37-60; control group n = 10, age, median = 44.5, range = 36-60; dopamine + mannitol group n = 10, age, median = 51, range = 44-58; dopamine + frusemide (furosemide) group n = 10, age, median = 61, range = 55-71 (excluded the last 2 groups from review)
InterventionsDopamine infusion 2.5 mcg/kg/min during surgery and for 2 days; control group had no treatment
OutcomesUrine output, creatinine clearance
NotesNo need to contact authors. Excluded 2 parallel treatment groups in the study
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Welch 1995

MethodsInfrarenal aortic surgery; Randomization method not described; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsAbdominal aortic surgery. Dopexamine group n = 15, age, mean = 63.5; control group n = 17, age, mean = 62.1
InterventionsDopexamine 2 mcg/kg/min infusion during surgery; saline in control group
OutcomesCreatinine clearance
NotesNeed to contact authors uncertain
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Wijnen 2002

MethodsAAA surgery (infrarenal). Randomized, but method of randomization, allocation concealment and blinding not stated in the text. Methodological quality poor
ParticipantsElective AAA repair. Antioxidant group, n = 20, age, mean = 67, range = 51-75; control group, n = 22, age, mean = 70, range = 59-82
InterventionsIntervention was multiple antioxidant therapy as follows: vitamin E 200 mg orally for 5 days before surgery + vitamin C 200 mg orally on morning of surgery + allopurinol 300 mg orally 1 day before surgery and 300 mg at induction + N-acetyl cysteine 150 mg/kg bolus, followed by infusion of 200 mg/kg over 12 hours preoperatively + mannitol 10%, 500 ml over 12 hours from the time of surgery. Control group had no intervention
OutcomesCreatinine clearance
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Woo 2002

MethodsConsecutive patients undergoing cardiac surgery; block randomized with sealed envelopes; allocation concealment described in follow-up correspondence; blinding of patients done, but researchers and care givers not blinded; moderate methodological quality of study
ParticipantsElective cardiac surgery patients (with high risk of postoperative renal dysfunction). Dopamine group, n = 20, age, mean = 64.5, range 58-82; control group, n = 22, age, mean = 66.5, range 48-84)
InterventionsDopamine infusion 3 mcg/kg/min during operation and for 48 hrs postoperation; saline infusion for the control group
OutcomesData on urine output obtained following correspondence
NotesContacted the author and obtained excellent response
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Yavuz 2002A

MethodsElective CABG patients; randomized, but method not described; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsElective CABG patients. Dopamine group, n = 11, age, mean = 55.7, SD = 5.2; control group, n = 11, age, mean = 56.4, SD = 9.5
InterventionsDopamine 2 mcg/kg/min infusion, started 24 hrs before surgery and continued for 48 hrs after surgery; control group had no treatment
OutcomesCreatinine clearance, free water clearance
NotesContacted the author (e-mail), but no response yet
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Yavuz 2002B

MethodsCABG patients; randomized, but method of randomization unclear; allocation concealment not used; blinding of patients, researchers and care givers is unknown; poor methodological quality study
ParticipantsElective CABG patients. Control group, n = 15, age, mean = 61.3, SD = 8.3; dopamine group, n = 15, age, mean = 58.3, SD = 5.3; diltiazem group, n = 15, age, mean = 60.3, SD = 7.1; dopamine + diltiazem group, n = 15, age, mean = 58.7, SD = 7.1 (excluded this group from review)
InterventionsDopamine and diltiazem 2 mcg/kg/min, started 24 hrs preoperation and continued for 48 hrs postoperation; no mention of how control group was treated
OutcomesCreatinine clearance, free water clearance
NotesContacted (e-mail) to author, no response yet
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoD - Not used

Zanardo 1993

  1. a

    CABG = coronary artery bypass graft; AAA = abdominal aortic aneurysm; GFR = glomerular filtration rate

MethodsCABG surgery. Randomization done, but method of randomization, allocation concealment and blinding not described. Methodological quality poor
ParticipantsDiltiazem infusion (2 doses): Group 1, diltiazem 1 mcg/kg/min, n = 11, age, mean = 58.1, SD = 10.7; Group 2, diltiazem 2 mcg/kg/min, n = 12, age, mean = 58.3, SD = 5.8; control group, n = 12, age, mean = 57.8, SD = 10.1
InterventionsIntervention, group 1, diltiazem 1 mcg/kg/min and group 2, diltiazem 2 mcg/kg/min, both started after chest opening, until 24 hours in ICU. Control group had no additional treatment
OutcomesAcute renal failure
NotesOld study, unlikely to get more data
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Abe 1993Treatment only for very short duration during surgery
Aho 2004Not a randomized controlled trial
Amar 2001Treatment started only after operation
Antonucci 1996There is no control group
Baldwin 1994Treatment started only in the postoperative period
Boldt 2000A phase 2 trial, looking for side effects; no controls
Boldt 2006No control group without treatment in the trial
Boutros 1979This is not a randomized controlled trial
Bove 2005No control group without treatment in the trial
Caglikulekci 1998Not a randomized controlled trial
Cahill 1987Not very relevant to the review; no randomization
Caimmi 2003The control group received active treatment with dopamine, dobutamine or frusemide; some controls started in postoperative period only
Christakis 1992No data relevant to the review
Christenson 1995Not a randomized controlled trial
Dementi'eva 1996Data not relevant to the review
Feindt 1995Data not relevant to the review
Fischer 2002A retrospective study only
Fisher 1998Follow up only for 12 hours
Franklin 1997The intervention started in the postoperative period only
Frumento 2006Postoperative study in the intensive care unit
Garwood 2003This is an observational study, not a randomized controlled trial or controlled trial
Gatot 2004Started in the postoperative period in the intensive care unit
Gerola 2004Data not relevant to the review
Gilbert 2001Not a randomized controlled study; there is only treatment and no controls
Goto 1992No control group
Grundmann 1985This is a postoperative study
Halpenny 2001Started the intervention only towards the end of operation and continued only for 16 hours
Hayashida 1997Not a randomized controlled trial
Hayashida 2000Study lasted only 6-14 hours
Izumi 2006Retrospective study
Junnarkar 2003Not a randomized controlled trial
Kulka 1993This is a conference abstract; data published as Kulka 1996 (included)
Kumle 1999No control groups
Kuraoka 1995Not a randomized controlled trial
Lema 1995This is not a randomized controlled trial or controlled trial
Lema 1998Control group had received active treatment
Lemmer 1996No relevant data for the review
Levy 1995The intervention is not relevant for the review
Licker 1999We could not exclude if this study contained the same data as in Licker 1996; hence excluded this publication from analysis
Lim 2002Postoperative study
Loef 2002Not a randomized controlled trial
MacGregor 1994No control group; intervention mostly in the intensive care unit
Neimark 2005The data not relevant to the review
Nguyen 2001Not a randomized controlled trial
Nguyen 2002Not a randomized controlled trial
Niiya 2001Study started in the postoperative period only
Nuutinen 1976No randomization or controls
O'Hara 2002AConference abstract only; data published as O'Hara 2002 (included)
Oliver 2006No control group
Ovrum 2004Not a randomized controlled trial
Pain 1991The treatment using intravenous hydration is only during the preoperative period; no randomization
Paul 1986Randomization method inadequate; 2 treatments were given to the treatment groups (both dopamine and mannitol)
Pavoni 1998Postoperative study
Petry 1992No control group
Piper 2003Intervention started only in intensive care unit
Plusa 1991No control group; only 2 treatments
Priano 1993No relevant data for the review
Prifti 2001Study did not look at renal function
Regragui 1995No clear intervention in the study
Riess 2000Not a randomized controlled trial
Ryckwaert 1995Abstract publication only; data published as Ryckwaert 2001 (included)
Sanders 2001Study of intravenous fluid administration in the preoperative period only; no relevant data reported
Sezai 2006Not a randomized controlled trial
Sherry 1997Study started in intensive care unit
Skillman 1975There is no relevant data for the review
Stanitsh 2002Multiple measures used for the purpose of renal protection in the intervention group (mannitol + dopamine or frusemide)
Straka 2004There is no renal data in the study
Tataranni 1994Not a randomized controlled trial
Torsello 1993Used only retrospective controls
Tripathy 1996No control group
Ueki 1995Not a randomized controlled trial
Vogt 1996No control group
Vogt 1999No control group
Welch 1993The renal function tests were done only for very short periods of time

Ancillary