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
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
Purpose
• Evaluate effects of low-dose dopamine c.f
placebo /no therapy in patients with or at risk
of ARF
Methods: Search strategy
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MEDLINE
– 1966 –January 2005
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EMBASE
– 1980- January 2005
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CINAHL
– 1982 – January 2005
•
CANCERLIT
– 1975 – Oct 2002
•
CENTRAL
– 4th quarter 2004
•
Renal Health library
Search: MEDLINE
1. Dopamine/low dose dopamine/renal dose
dopamine
– Limited to clinical trial and meta-analysis
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]
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
Selection
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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
Data Abstraction
• 2 independent reviewers
• Study authors contacted if any disagreement
– Consensus if persisted
• Agreement for inclusion studies statistically
tested [Cohen’s κ]
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
Exclusion Criteria – 70 studies
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•
•
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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
Hence
• 3359 patients identified in 61 trials
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
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]
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
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]
Patient profile
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Cardiac surgery
Vascular surgery
Other surgery
Iv Contrast dye
Nephrotoxics
Neonates
Miscellaneous
Data
• Average numbers per trial 40 [12 to 347]
• ANZICS trial included [328 patients; multicentre]
• Only 6 trials used dopamine therapeutically:
– Critical illness, contrast, malaria, CHF,
preeclampsia
Data
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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
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
Mortality
RRT
Adverse effects
• Arrhythmias & ischaemia [cutaneous,
myocardial, limb]
• 6 MI’s [4 on dopamine]
• Statistically not significant
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
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
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