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Annals of Internal Medicine 2005; 142: 510-524 Issaam Oozeerally

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

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Annals of Internal Medicine 2005; 142: 510-524 Issaam Oozeerally

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  1. Meta-Analysis: Low-dose dopamine Increases urine output but does not prevent renal dysfunction or death Annals of Internal Medicine 2005; 142: 510-524 IssaamOozeerally

  2. 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

  3. Purpose • Evaluate effects of low-dose dopamine c.f placebo /no therapy in patients with or at risk of ARF

  4. 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

  5. Search: MEDLINE • Dopamine/low dose dopamine/renal dose dopamine • Limited to clinical trial and meta-analysis

  6. MEDLINE Search no. 2 Limited to RCTs [maximally sensitive strategy]

  7. 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

  8. 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

  9. Data Abstraction • 2 independent reviewers • Study authors contacted if any disagreement • Consensus if persisted • Agreement for inclusion studies statistically tested [Cohen’s κ]

  10. 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

  11. 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

  12. Hence • 3359 patients identified in 61 trials

  13. 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

  14. 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]

  15. 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

  16. 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]

  17. Patient profile • Cardiac surgery • Vascular surgery • Other surgery • Iv Contrast dye • Nephrotoxics • Neonates • Miscellaneous

  18. 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

  19. 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

  20. 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

  21. Mortality

  22. RRT

  23. Adverse effects • Arrhythmias & ischaemia [cutaneous, myocardial, limb] • 6 MI’s [4 on dopamine] • Statistically not significant

  24. 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

  25. 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

  26. 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

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