Comparison of dopamine and norepinephrine in the treatment of shock

Moderator – Dr V.Sachin kumar M.D Presenter - Dr CH.Santhosh P.G

BACKGROUND

Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about one agent is superior to the other.

Shock

Shock is the clinical syndrome that results from inadequate tissue perfusionTypes of shock Low stroke volume Vasodilation a) Hypovolemic a) Septic b) Cardiogenic b) Anaphylactic c) Obstructive c) Neurogenic

Cardiogenic Shock

Cardiogenic shock (CS) is characterized by systemic hypoperfusion due to severe depression of the cardiac index [<2.2 (L/min)/m2] and sustained systolic arterial hypotension (<90 mmHg) despite an elevated filling pressure [pulmonary capillary wedge pressure (PCWP) >18 mmHg].

Pathophysiology of cardiogenic shock

Dopamine

Dopamine has varying hemodynamic effects based on the dose. At low doses(<2mcg/kg/min) it dilates renovascular bed. At moderate doses(2-10mcg/kg/min) it has positive chronotropic and ionotropic effects as a consequence of beta -adrenergic receptor stimulation. At higher doses , vasoconstrictor effect resultsfrom alpha-receptor stimulation. It is started at an infusion rate of 2-5mcg/kg/min andthe dose is increased every 2-5 mins to maximum of 20-50mcg/kg/min

Adverse effects of dopamine

Norepinephrine

Norepinephrine is a potent vasoconstictor and ionotropic stimulant

It acts on alpha-1,alpha-2,beta-1 but not on beta-2 receptor.

Dosage -0.5 to 30mcg/min i.v

Adverse effects of norepinephrine

Study Method

Type of study - randomized trial

Duration - December 19 2003 to October 6th 2007.

Study place - Belgium, Austria , Spain.

Number of patients - 1679

Inclusion criteria

1. Age: 18 years or older2. Mean arterial pressure < 70mm Hg or Systolic blood pressure < 100mm Hg despite the fact that adequate amount of fluids(at least 1000ml of crystalloids or 500ml of colloids) had been administered.3. Signs of tissue hypo-perfusion like - altered mental state, mottled skin, urine output of < 0.5ml/kg/hr or serum lactate level > 2mmol/lt

Exclusion criteria

1. Age less than 18 years2. Who had already received vasopressor

agents(dopamine, noradrenaline,epinephrine or phenylephrine) for more than 4 hours during the current episode of shock

3. Had serious arrhythmias such as rapid atrial fibrillation(>160bpm) or ventricular tachycardia

4. Declared brain dead

Study design

A total of 1679 patients were enrolled- 858 in the dopamine group and 821 in norepinephrine group

The drug dose was determined according to the patients body weight

Dose of dopamine could be increased or decreased by 2mcg/kg/min upto maximum of 20mcg/kg/min

Dose of norepinephrine could be increased or decreased by 0.02mcg/kg/min upto maximum of 0.19mcg/kg/min

The patient was still hypotensive after the maximum dose of drug then open label norepinephrine or epinephrine or vasopressin was given

Open label dopamine was not allowed any timeIonotropic agents could be used if needed to increase

cardiac outputWhen the patients were weaned from vaso- pressor agents,

any open-label norepinephrine that was being administered was withdrawn first, af- ter which the trial-drug solution was withdrawn. If hypotension recurred, the trial-drug solution was resumed first (at the same maximal dose) and an open-label solution of norepinephrine was added if needed.

Measured variables

1.Vital signs2.Systolic and diastolic arterial pressures3.Heart rate4.Central venous pressure5.Vardiac output.6.Arterial and mixed venous blood gas levels7.Doses of vasoactive agents8.Respiratory conditions9.Biologic variables10.Data on daily fluid balance

The above data were recorded -every 6 hours for 48 hours -every 8 hours on days 3,4,5 -once a day on days 6,7,14,21 and 28

Statistical analysis Primary end point of the trail was rate of death at 28

days Secondary end point were rate of death in the icu,in the

hospital,at 6 months and at 12 months,the duration of stay in the icu and no.of days without need for organ support (i.e., vasopressors, ventilators, or renal-replacement therapy);

The time to attainment of hemodynamic stability (i.e., time to reach a mean arterial pressure of 65 mm Hg)16; the changes in hemodynamic variables

Results. The baseline characteristics of the groups were

similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P = 0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001)

A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P = 0.03 for cardiogenic shock, P = 0.19 for septic shock, and P = 0.84 for hypovolemic shock, in Kaplan–Meier analyses).

Conclusion Although there was no significant difference in the

rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events

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