of Acute Renal Failure Role of vasoactive drugs and diuretic agents Armand R.J. Girbes Prof.dr. A.R.J. Girbes Chairman department of Intensive Care VU University Medical Center Netherlands
(Failure of) Renal function Acid-base control Renin production Erythropoietin production Control of electrolyte balance Excretion of (metabolized) drugs Measurable Urine production Excretion Nitrogen waste products Definition ARF No consensus
Definition Acute & sustained increase in screat > 44 microm/l (baseline Creat < 221microM/l) > 20% rise (baseline Creat > 221 microm/l) Oliguria < 0.5 ml/kg/min (sustained)
Definition RIFLE classification Three severity categories
Incidence (depends on definition & case mix) 1 25% in ICU patients Mostly part of MODS Always bad news for the ICU patient Mortality increases ± twofold Metnitz, CCM 2002
Based on Knowledge of pathophysiology Rational thinking Animal experiments Evidence Based Medicine RCT Major causes Pre-Renal Renal Post-Renal
Acute tubular necrosis {=AKI Acute Kidney Injury} Ischemia ~ systemic hypotension ~ intrarenal vasoconstriction ~ fall in RBF Local (tubular) damage ~ inflammatory cells & cytokines Oxygen radicals ~ intraglomerular thrombosis ~ tubular obstruction ~ tubular back leak
Predisposition risk factors Diabetic nephropathy Preexisting renal function loss High age CHF ARF in previous history Low effective circulating volume
Recognize risks surveillance armée Avoid harm Treat
Just too late Acute Renal Failure
Too late
Real prevention - avoid
Acknowledge physiology Kidney needs blood flow Kidney needs perfusion pressure
Vasoactive drugs and fluids Maintenance of RBF and perfusion pressure Maintain optimal haemodynamics Optimal??
Optimal systemic haemodynamics? Optimal filling Further filling no further increase CO Start early In sepsis: SvO2 > 70% lower mortality/organ dysfunction Sufficient perfusion pressure Failure dopamine start NE diuresis Rivers et al. 2001 Martin et al. 1993 Girbes & Groeneveld 2000
Norepinephrine (after optimal fluid resuscitation) Does not deteriorate renal function Can improve renal function GFR Diuresis No RCT available ml/min/1.73 m 2 GFR 160 * + 140 + + + 120 100 0 40 80 150 0 noradrenaline in ng/kg/min
Regional haemodynamics Dopamine Pre- and preferential postglomerular vasodilatation RBF GFR Girbes et al. 1991, 1992, 1996, 2004
Dopamine renal haemodynamics Simplification Dopamine does not increase medullary oxygenation Dopamine does not increase RBF in all patients Low GFR Post surgery Tachyfylaxia receptor down regulation Danger!!! Dopamine is a diuretic Other side effects
First author Patient Group DOPAMINE routine administration Endpoint Conclusion Costa, 1990 CABG CreatCx No difference Swygert, 199l LiverTx GFR, dialysis No difference Myles, 1991 Post cardiac surgery screat, CreatCx No difference Baldwin, 1994 Major vascular surgery screat, CreatCx No difference Parks, 1994 Obstructive Jaundice screat, CreatCx No difference Kadieva,1993 RenalTx screat, Biopsy (tub.necr.) No difference Chertow, 1996 Acute renal failure mortality, dialysis No difference ANZIS, 2000 Early renal dysfunction GFR/sCreat No difference Lassnigg, 2000 Cardiac surgery patients screat No difference Carcoana, 2003 Cardiac surgery patients Beta-2 microglobulin excr Dopamine increases B2M Gatot, 2004 Cardiac surgery patients Creat and stability Dopamine better
Dopamine
Dopamine Effect on mortality
Dopamine Effect on need for CRRT
Dopamine Effect on diuresis day 1
Clinical trials low-dose dopamine No benefit of - preventive - dopamine
Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomized trial ANZICS clinical trials group Lancet 2000; 356:2139-43
n = 328 2 µg/kg/min dopamine vs placebo Inclusion criteria age > 18 years 2 signs of SIRS early renal dysfunction < 0.5 ml/kg/hr in 4 hours OR rise screat > 80 µm/l Lancet, 2000
dopamine (n=161) placebo (n=163) Age 63 ± 15 61 ± 17 M/F 94/67 102/61 APACHE II 21 ± 6 21 ± 8 Shock at start infusion 93 102 On ventilator at start 138 141 Prerenal dysfunction 152 154 Baseline creatinine 183 ± 85 182 ± 81 Oliguria 109 113 MAP 80 ± 15 80 ± 16 CVP 14 ± 8 13 ± 7 Lancet, 2000
Primary endpoint peak serum creatinine concentration Secondary endpoints duration mechanical ventilation ICU stay / hospital stay survival Lancet, 2000
dopamine placebo Peak creatinine 245 ± 144 249 ± 147 Increase in creatinine 62 ± 107 66 ± 108 Creatinine > 300 µm/l n=56 n=56 CRRT n=35 n=40 Urine output (ml/hr) baseline 37 ± 40 50 ± 59 after 1 h 71 ± 81 72 ± 77 after 24 h 96 ± 101 92 ± 72 after 48 h 99 ± 83 109 ± 95 Lancet, 2000
Subgroup analysis time to recovery of normal renal function Lancet, 2000
ANZICS Not purely on prevention Renal function loss already started
Diuretic agents Rationale Inhibit oxygen consuming processes TranscellularNa + transport Cortical vasodilatation (loop diuretics) Reduce intratubular obstruction & back leak of filtrate
Diuretics possible drawbacks & pitfalls Masks hypovolemia Neurohumoral activation increase of SVR Maldistribution of RBF diversion of medullary perfusion tubular dysfunction
Lassnigg et al. RCT Acute Renal Failure Elective cardiac surgery n=123 Serum creatinine < 2.0 mg/dl dopamine n=42 frusemide n=41 placebo n=40 200 mg/50 50 mg/50 NaCl 0.9% 2 mcg/kg/min 0.5 mcg/kg/min
Demographic Acute Renal Failure Lassnigg et al. 2000
Lassnigg et al. Acute Renal Failure Dopa n=42 Placebo n=40 Frusemide n=41
Conclusion Dopamine: no benefit Acute Renal Failure Frusemide: increases risk for renal impairment
Mannitol Acute Renal Failure Osmotic diuretic Free radical scavenger Transient increase of circulating volume Augmenting RBF flushes the tubules No clinical studies proof Rhabdomyolysis
Acetylcysteïne Acute Renal Failure Conflicting results Recent favorable results in large study primary angioplasty (Marenzi et al. NEJM, 2006) Meta-analyses suggest benefit for contrast nephropathy (Birck et al. Lancet, 2003) Favorable efficacy versus side effects profile Off-pump cardiac surgery Sajja et al. J Thorac & Cardiovasc Surg Feb 2007 N=116 Suggests favorable (short-term) effect
Fenoldopam Acute Renal Failure Selective DA1 agonist Induces renal vasodilation Indication: severe hypertension Girbes et al. 1991, Murphy et al. 2001
ARF prevention Fenoldopam
Final conclusions Acute Renal Failure Good intensive care medicine Fluid resuscitation Flow & pressure Diuretics Do not exclude NE May be harmful Dopamine Do not use as prophylactic Anticipate!! E.g. rhabdomyolysis, acute interstitial nephritis Use acetylcystein for prevention of contrast nephropathy
of Acute Renal Failure There are no magic bullets Just high quality anesthesia & intensive care Do basic things well
Thank you! Presentation available at: www.armandgirbes.com (after the congress)