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Is There Still a Place for Dopamine in the Modern Intensive Care Unit?. R1 劉志中. Anesth Analg 2004;98:461-8. What we thought Dopamine Before…. Cardiovascular effect 2 to 5 µg · kg-1 · min-1: dopaminergic (80% to 100%), [beta]-adrenergic effects (5% to 20%).

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is there still a place for dopamine in the modern intensive care unit

Is There Still a Place for Dopamine in the Modern Intensive Care Unit?

R1 劉志中

Anesth Analg 2004;98:461-8

what we thought dopamine before
What we thought Dopamine Before…
  • Cardiovascular effect
    • 2 to 5 µg · kg-1 · min-1: dopaminergic (80% to 100%), [beta]-adrenergic effects (5% to 20%).
    • 5 to 10 µg · kg-1 · min-1: [beta]-adrenergic effects predominate, and [alpha]-adrenergic actions gradually become important.
    • 10 to 20 µg · kg-1 · min-1 : primarily [alpha]- and [beta]-adrenergic effects
what we thought low dose dopamine before
What we thought Low Dose Dopamine Before…
  • Prevention and treatment of acute renal failure
  • Protection of the gut
  • Relatively free of side effect
introduction
Introduction
  • Goldberg : a protective effect of low dose dopamine(<5µg · kg-1 · min-1) on renal function
  • The presumed protective effects on renal and splachnic perfusion have been repeatedly questioned.
renal effects
Renal effects
  • Augment renal blood flow
    • DA-1 recepter: renal vasodilation
    • DA-2 recepter on presynaptic nerve endings:

inhibition of NE release

    • Large doses: βeffect to increase C.O.
  • Trigger natriuresis and diuresis through a direct effect on the tubular cell function
renal effects1
Renal effects
  • Trigger natriuresis and diuresis through a direct effect on the tubular cell function
    • DA-1, DA-2 recepter on proximal tubule, thick ascending limb of the loop of Henle,cortical collecting tube : inhibit Na/K –ATPase  Natriuresis.
    • DA-2 recepters in the inner medullary collecting ducts  PGE2 production antagonizes ADH  increase free water clearance
renal effects2
Renal effects
  • Regional redistribution of blood flow within the kidney (potentially detrimental)
    • Preferentially increasing cortical blood flow
    • PGE2:enhance blood flow in inner medulla

shunting of blood away from the outer medulla which is very susceptible to ischemic injury in ARF.

Dopamine and the kidney: ten years on. Clin Sci (Lond) 1993; 84: 357–75.

renal effects3
Renal effects
  • Increasing urine output
    • renal hypoperfusion is a leading cause of ARF
    • The risk of inducing renal failure in normovolemic and hypovolemic patients
    • LDD increases urine output by enhancing cardiac output and thus not primarily by a direct renal effect
slide9
…During norepinephrine infusion, increasing doses of dopamine from 2 to 6 μg‧kg-1‧min-1,augments CO,diuresis,and sodium excretion in p’t treated for septic shock,without changes in creatinine clearance…

The renal and neurohumoral effects of the addition of low-dose dopamine in septic critically ill patients.

Intensive Care Med 2000; 26: 1685–9

controversy of ldd on renal function
Controversy of LDD on Renal function
  • Beneficial or detrimental ?
  • Increased urine output = improved renal function?
  • How strong is the clinical evidence on critically ill patient ?
slide11

Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial—Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group.Lancet 2000; 356: 2139–43

background
Background
  • Multicentre, rendomised , double-blind,placebo-controlled study in ICU patients at the risk of ARF to assess whether dopamine attenuated the rise in serum creatinine

Lancet 2000; 356: 2139–43

methods patients
Methods (patients)
  • Between March,1996 and April, 1999
  • Inclusion criteria:
  • presence of a central venous catheter
  • two or more of the pathophysiological changes of the SIRS over a 24 h period
  • At least one indicator of early renal dysfunction (urine output averaging <0·5 mL/kg hourly over 4 h or longer; serum creatinine concentration of >80 mol/L in less than 24 h in theabsence of creatine kinase >5000 IU/L or myoglobin in the urine)

Lancet 2000; 356: 2139–43

methods patients1
Methods (patients)
  • Exclusion criteria:
  • age under 18 years
  • an episode of acute renal failure within the previous 3 months
  • previous renal transplantation
  • use of dopamine at anydose during the current hospital stay
  • baseline serum creatinine concentration above 300 μmol/L
  • Enrolling physician’s belief that the drug could not be administered for 8 h or longer;
  • unsuitability for use of renal replacement therapy.

Lancet 2000; 356: 2139–43

methods
Methods

Lancet 2000; 356: 2139–43

methods1
Methods
  • Continuous infusion of dopamine at 2μg‧kg-1‧min-1 ( or equivalent volume for placebo) until ..
    • Renal replacement therapy
    • Patient died
    • a serious adverse event developed thatwas judged to be related to the trial infusion;
    • the patient’s SIRS and renal dysfunction had resolved for at least 24 h
    • the patient was discharged from ICU.

Lancet 2000; 356: 2139–43

results
Results

Lancet 2000; 356: 2139–43

results1
Results

Lancet 2000; 356: 2139–43

results2
Results
  • There was no difference in
  • Peak creatinine concentration
  • Increase from baseline to highest value during treatment
  • Who required renal replacement therapy
  • Duration of ICU stay
  • Hospital stay
  • Death

Lancet 2000; 356: 2139–43

interpretation
Interpretation
  • Administration of low-dose dopamine by continuous intravenous infusion to critically ill patients at risk of renal failure does not confer clinically significant protection from renal dysfunction.

Lancet 2000; 356: 2139–43

controversy of ldd on renal function1
Controversy of LDD on Renal function
  • Beneficial or detrimental ?
  • Increased urine output = improved renal function?
  • How strong is the clinical evidence on critically ill patient ?
ldd on renal effect
LDD on renal effect
  • LDD may increase urine output in critically ill patient,but it neither prevents nor improves ARF.
  • When dopamine does increase diuresis, it may actually increase the risk of ARF in normovolemic and hypovolemic patients.
effects on splachnic perfusion
Effects on Splachnic perfusion
  • The gut may be particularly susceptible to ischemia in shock
  • Disruption of the gut mucosal barrier is thought to play a key role in the development of multiple organ failure

~Am J Respir Crit Care Med 1998; 158: 444–51

effects on splachnic perfusion1
Effects on Splachnic perfusion
  • The gut may be particularly susceptible to ischemia in shock
  • Disruption of the gut mucosal barrier is thought to play a key role in the development of multiple organ failure

~Am J Respir Crit Care Med 1998; 158: 444–51

  • Theoratically,LDD may increase splanchnic blood flow by stimulation of the splachnic dopaminergic receptors
effects on splachnic perfusion2
Effects on Splachnic perfusion
  • Controversial for human data
  • Increasing splanchnic flow is not necessarily accompanied by an improvement of mucosal perfusion.
  • there is no evidence that LDD has beneficial effects on the splanchnic function or reduces the progression to multiple organ failure in sepsis.
  • Recent data even suggest a potentially detrimental effect of LDD on splanchnic oxygen uptake

~JAMA 1994; 272: 1354–7

effect on gastrointestinal motility
Effect on Gastrointestinal Motility
  • DA-2 :human enteric nervous system
  • In healthy volunteers: short-term DA could interrupt the fed gastrointestinal motility pattern
  • In critically ill pateints: DA (2.5 -5μg‧kg-1‧min-1)was found to be the most significant factor associated with poor gastric emptying
  • DA may aggravate digestive intolerance to enteral feeding.
respiratory effects
Respiratory Effects
  • Impaired the ventilatory drive in response to hypoxemia and probably hypercapnia by depressing the carotid body.
  • DA reduced arterial oxygen saturation by impairing V/Q matching in the lung.
  • Patients receiving LDD may be easier to wean, but with the potential danger of precipitating respiratory failure
endocrine and immunological effects
Endocrine and immunological effects
  • initial stress response: all anterior pituitary hormones is stimulated
  • more prolonged critical illness: a uniform suppression of the hypothalamic-pituitary axes ensues while cortisol secretion remains increased through a peripheral drive.
  • hypothalamic hypopituitarism : evoke inappropriate & harmful metabolic changes
slide30

DA infusion: 5μg‧kg-1‧min-1

NS :not significant

** : significant

as a vasopressor
As a vasopressor
  • DA: act largely by increasing cardiac output
  • NE: more specifically increases vascular resistance
  • Lethalphed :causing end-organ hypoperfusion and severe ischemia of vital organ.
as a vasopressor1
As a vasopressor
  • NE:
    • in effectively volume-resuscitated septic shock patients, the fear of end organ ischemia is unwarrant.
    • Faster restore MAP and lower serum lactate level than DA
    • No deleterios effects on splachnic perfusion ,even can increase PHi.
as a vasopressor2
As a vasopressor
  • Dopamine = Dobutamine+ NE ?
  • Don’t forget Its side effects !
  • Separate titration  more target intervention tailored by the patients conditions.
conclusion
Conclusion
  • There is indeed no evidence that low “renal” dose DA has any beneficial effect on renal function or on the outcome of patients with ARF.
  • There is no evidence that LDD has beneficial effects on hepatosplanchnic circulation
  • Recent data suggest that DA may even have detrimental effects on splanchnic oxygen uptake
conclusion1
Conclusion
  • DA suppresses the secretion and function of anterior pituitary hormones, aggravating the impairment of anabolism and cellular immune function.
  • DA aggravates the digestive tolerance of enteral feeding
  • suppresses the ventilatory drive.
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