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

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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


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

…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 ?


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

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


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

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.


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

Time to Wake Up !!


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