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.
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.
- Are there any specific measures which can protect kidney function during the perioperative period?
- Does any one measure used to protect the kidneys during the perioperative period appear more effective than other methods?
- Does any one measure used to protect the kidneys during the perioperative period appear safer than other 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:
- dopamine and its analogues;
- calcium channel blockers;
- angiotensin-converting enzyme (ACE) inhibitors;
- hydration fluids;
- any other measures used to protect kidney function.
Types of outcome measures
Postoperative adverse outcomes. These included significant adverse outcomes such as acute renal failure, other serious morbidity, or death.
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
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):
- Anesthesia and Analgesia;
- Annals of Surgery;
- British Journal of Anaesthesia;
- Journal of Thoracic and Cardiovascular Surgery;
- 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).
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:
- presence or absence of any pre-existing renal dysfunction;
- nature of surgical procedures;
- Interventions used;
- 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.
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:
- methods used for renal protection;
- types of operation;
- studies on patients with pre-existing renal dysfunction.
We also undertook sensitivity analyses on randomized controlled trials with differing methodological quality.
Description of 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.
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 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 (I
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 (I
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.
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 (I
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 (I
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; I
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; I
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; I
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 (I
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 (I
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; I
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; I
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; I
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; I
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; I
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; I
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; I
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; I
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 (I
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 (I
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 (I
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).
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; I
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; I
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; I
Fractional excretion of sodium
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; I
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; I
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; I
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; I
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; I
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; I
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.
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.
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
- Top of page
- Authors' conclusions
- Data and analyses
- What's new
- Contributions of authors
- Declarations of interest
- Sources of support
- Index terms
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
#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
#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
#33 #31 or #32
#35 CONTROLLED-CLINICAL-TRIAL in PT(74668 records)
#34 RANDOMIZED-CONTROLLED-TRIAL in PT
#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)
#50 placebo* in TI
#51 placebo* in AB
#52 random* in TI
#53 random* in AB(373784 records)
#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
#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
#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
#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*
#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
#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?
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?
Acute renal failure
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
Mean and SD other measures: (Please specify clearly)
Pre-op Day1 Day 2 Day 3 Day ()
Free H2O Cl:
FE Na (%)
Drug company sponsorship?
Last assessed as up-to-date: 24 June 2007.
Protocol first published: Issue 2, 2002
Review first published: Issue 3, 2005
Contributions of authors
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
Sources of support
- Dunedin Hospital & Dunedin School of Medicine, Dunedin, New Zealand.
- None, New Zealand.
Medical Subject Headings (MeSH)
Creatinine [urine]; Postoperative Complications [*prevention & control]; Randomized Controlled Trials as Topic; Renal Insufficiency [*prevention & control]; Surgical Procedures, Operative [*adverse effects]; Urine
MeSH check words
* Indicates the major publication for the study