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Meta-Analysis: Low-dose dopamine Increases urine output but does not prevent renal dysfunction or death
Annals of Internal Medicine 2005; 142: 510-524
Issaam Oozeerally
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Dopamine
• Catecholamine• Dose dependent effects on systemic and renal
vasculature• At low doses increases renal blood flow and
promotes natriuresis [D1, D2, D4 receptors]• 1st clinical use in heart failure
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Purpose
• Evaluate effects of low-dose dopamine c.f placebo /no therapy in patients with or at risk of ARF
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Methods: Search strategy
• MEDLINE– 1966 –January 2005
• EMBASE– 1980- January 2005
• CINAHL– 1982 – January 2005
• CANCERLIT– 1975 – Oct 2002
• CENTRAL– 4th quarter 2004
• Renal Health library
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Search: MEDLINE
1. Dopamine/low dose dopamine/renal dose dopamine
– Limited to clinical trial and meta-analysis
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MEDLINE Search no. 2
1 [Dopamine] 2 [Renal disease] 3 [physiology]
Low Kidney Diseases Kidney Function Tests
Renal Kidney Urine
Kidney Renal circulation
Dose
Limited to RCTs [maximally sensitive strategy]
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Rest of the search
• Modification of search from other databases– Strategy not specified – Authors happy to be contacted
• Screened reference lists from articles against recent review articles to identify additional studies
• No language restrictions
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Selection
• RCTs/quasi-randomization trials• Any sample size• Low dose dopamine vs. placebo/nil• Outcomes:
– All cause mortality– Requirement for RRT– Renal physiological variables [UO, Creat, CrCl day 1, 2, 3]– Adverse effects
• Studies with pharmacologic co-interventions [e.g. mannitol, diuretics]
• A priori adverse effects:– Ischaemia [myocardial, limb, cutaneous] or arrhythmias
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Data Abstraction
• 2 independent reviewers• Study authors contacted if any disagreement– Consensus if persisted
• Agreement for inclusion studies statistically tested [Cohen’s κ]
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Validity assessment
• Individual studies methodology looked into– Randomization– Blinding– Outcome assessors– Reasons for withdrawals
• Fluids and diuretic therapies– Standard or equally applied in both arms
• Attempted to contact all authors of selected trials
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Exclusion Criteria – 70 studies
• Small sample [3 patients]• Dopamine dose >5mcg• Not randomized cross-over study• Combined intervention c.f control• Duplicate • Wrong topic• Editorial• 4 RCTs without group data available from authors• No additional data provided
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Hence
• 3359 patients identified in 61 trials
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Data Analysis
• Pooled by outcome– E.g. mortality, RRT
• If different doses of dopamine used data was combined
• Random effects model used• Binary outcomes [RRT, mortality, adverse
effects] reported as relative risk• Summary of relative risk : log scale – Used to calculate weight of study
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Data Analysis [cont]
• If heterogeneity between studies; weight was adjusted
• Clinical outcomes occurred infrequently and different statistical tests i.e. effect measures were undertaken– Similar results [not presented]
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Data Analysis [cont.]
• Renal physiologic outcomes:– Relative change in dopamine gp c.f. control• Mean values were taken• Lack of standardized data e.g. weight
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Data Analysis [cont]
• Between study homogeneity for each pool– [concept when there is more variation than
chance alone]– Calculated statistically [I2 and Cochran Q-test]
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Patient profile
• Cardiac surgery• Vascular surgery• Other surgery• Iv Contrast dye• Nephrotoxics• Neonates• Miscellaneous
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Data
• Average numbers per trial 40 [12 to 347]• ANZICS trial included [328 patients; multi-
centre]• Only 6 trials used dopamine therapeutically:– Critical illness, contrast, malaria, CHF,
preeclampsia
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Data
• Median dopamine dose 2.5 mcg• 31 hours median [0.4 to 192 hours]• 12 trials randomization not reported• 11 trials fluids up to the clinician
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Clinical outcomes
• No effect on mortality [0.96] or need for RRT [0.93]– No statistical evidence of heterogeneity
• ANZICS trial and most heavily weighted trial removed and data analysed again– No change
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Mortality
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RRT
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Adverse effects
• Arrhythmias & ischaemia [cutaneous, myocardial, limb]
• 6 MI’s [4 on dopamine]• Statistically not significant
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Renal Physiologic Outcomes
• Statistically significant increase in urine output on day 1
• Decrease in creat and increase in creat clearance on day 1
• Substantial heterogeneity
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Conclusion
• 24% increase in urine output on day 1– Probably explains continued popularity
• ANZICS trial – same results• ANZICS trial – removal of data• Adverse effects – under reported
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Discussion
• Methodology– Search strategies not specified– Age and sample size– Combining dopamine doses
• Stats– If no events arbitrary figure of 0.5 given– Study weight adjusted in presence of
heterogeneity– Use of relative risk