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Dr. Suman ChowdhuryHMO, MU-IIICMCH
Potential Therapies :
PressorsIntra-aortic Balloon Pump (IABP)FibrinolyticsRevascularization: CABG/PCIRefractory shock: ventricular assist device, cardiac transplantation
Pressors:
DopamineDobutamineNorepinephrineVasopression
Dopamine
Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome Laboratories in London, England.Dopamine has the chemical formula: C6H3(OH)2-CH2-CH2-NH2
Its chemical name is "4-(2aminoethyl)benzene-1, 2-diol" and its abbreviation is "DA."As a member of the catecholamine family, dopamine is a precursor to norepinephrine (noradrenaline) and then epinephrine (adrenaline) in the biosynthetic pathways for these neurotransmitters.
The market preparation of Inj. Dopamine is:
Inj. Dopamine: Each ampule contains 200 mg in 5ml
The effects of dopamine depend on the dose administered. In lower doses (<4 μg/kg per minute), dopamine increases renal blood flow by stimulating dopaminergic (DA1) receptors in the kidney and causes peripheral vasodilation through DA2 receptors that inhibit the release of norepinephrine.
At intermediate dosages (At intermediate dosages (5–10 5–10 μμg/kg/minuteg/kg/minute), dopamine improves ), dopamine improves cardiac function and increases blood cardiac function and increases blood pressure through increased βpressure through increased β11 receptor receptor activation without elevating myocardial activation without elevating myocardial oxygen consumption.oxygen consumption.
Recent study found that an average dose of 17 μg/kg per minute was needed to optimize coronary perfusion pressure in a group of patients that developed cardiogenic shock after myocardial infarction. Dopamine at such high levels increases myocardial oxygen demand, produces tachycardia, and may limit renal perfusion. It should be used with caution in patients with cardiogenic shock because it may adversely influence the balance of myocardial oxygen delivery and consumption.
The market preperation of Inj. Dobutamine is:
Inj. Dobutamine: Each ampule contains 250 mg in 5 ml
Dobutamine is the inotropic drug of choice for the management of congestive heart failure and cardiogenic shock. It is a β1-adrenergic agonist that has minimum chronotropic and peripheral vasoconstrictive effects. It has a significant advantage over dopamine in that it does not cause the release of nor epinephrine.
Furthermore, it does not require the presence of nor epinephrine at the nerve terminals for effect. Because of its minimum chronotropic effect, dobutamine can improve ventricular performance without significantly increasing myocardial oxygen demand. Dobutamine’s greatest potential is realized in patients with reduced cardiac indices and increased filling pressures.
Because it is a vasodilator, dobutamine reduces filling pressures and wall tensions in patients with dilated ventricles. This permits better myocardial nutrient flow during diastole. A recent study found a 33% improvement in cardiac index, a decrease in systemic vascular resistance, and no change in heart rate or systemic blood pressure when dobutamine was given in doses that averaged 8.5 μg/kg per minute.
The drug may be given in doses up to 40 μg/kg per minute without significantly increasing heart rate. When three-vessel coronary artery disease is present, dobutamine may create a steal and direct blood away from ischemic areas.
Traits Dopamine Dobutamine1. Chemical nature Dopamine is a
neurotransmitter and a neurohormone
Dobutamine is a sympathomimetic drug
2. Receptors Action depends on D1, β1, α (at low dose) and β1, α, D1, β2 (at high dose) receptors
Action depends on the activity on β1, β2 and α1 receptors
3.Haemodynamic Effect*
BP HR CO SVR PVR SBF BP HR CO SVR PVR SBF
↑/↑↑ ↔/↑ ↑/↑↑ ↑/↑↑ ↔/↑ ↔/↑ ↔/↓ ↑ ↑↑ ↓ ↓ ↔
4. In cardiogenic shock
When SBP is 70-100 mmHg with signs and symptoms of shock
When SBP is > 100 mmHg with no signs and symptoms of shock
5. Septic shock As pressor agent alternative to Nor adrenaline after initial resuscitaion when MBP is Still < 65mmHg
As ionotropes during initial 6 hours of resuscitation after fluid management, Specially in low cardiac output
* SVR=Systemic vascular resistance; PVR= Pulmonary vascular resistance; SBF= Splanchnic blood flow; MBP= Mean blood pressure; SBF= Systemic blood flow.
In case of cardiogenic shock, we are frequently practising Inotropes in wards, preferably Inj. Dopamine and Inj. Dobutamine. However, we are not using the actual dose required to act as inotropes in case of cardiogenic shock. The traditional dose is much less than the actual dose, in fact! But, we don’t even bother to think to change it, rather practicing only as because our ancestors used to practise it!!!
2 ampules Inj. Dopamine are mixed with 500 cc of Inj. N/S or Inj. 5% DA.So, 510 cc(500+2×5) fluid contains 400mg Dopamine, i.e.
(510cc ×15 ×4)μd fluid contains (400 × 1000) μg of Dopamine
Or,30600 μd of fluid contains 400000 μg of
Dopamine or1 μd of fluid contains (400000 ÷ 30600) ≈13 μg of
Dopamine
So, when we use 32-40 μd/min of fluid (Containing Inj. Dopamine) in average weighted person, we actually give (13 × 32) μg/min or, 416 μg/min, which is too less to produce inotropic effect in cardiogenic shock. Sometimes, the dose is increased maximally up to 40 μg/min, i.e. 520 μg/min( In a 6okg weighted patient).
Epinephrine Epinephrine Infusion starting from 0.05Infusion starting from 0.05μμg/kg/min g/kg/min
Norepinephrine Norepinephrine Infusion starting from 0.05Infusion starting from 0.05μμg/kg/min g/kg/min
Dobutamine Dobutamine Infusion starting from 2.5–25Infusion starting from 2.5–25μμg/kg/min g/kg/min
Dopamine Dopamine Infusion starting from 2.5–30Infusion starting from 2.5–30μμg/kg/min g/kg/min
Courtesy: Oxford HandbookOf Critical Care Medicine
So, the heighest inotropic dose in cardiogenic shock is 25-30 μg/min/kg. In a average weighted (60kg) person we can give (20 × 60) μg/min or, 1200 μg/min !!! But we are only giving 520 μg/min! The same is also true for Dobutamine.
As we try to avoid extra fluid (In cardiogenic shock)through infusion, we can concentrate the drug, so that less amount of fluid is required. For that reason, we can give the inotropes in the following way:
Inj. N/S 90 CC + Inj. Dopamine 2 amp(400mg) I.V @ 2.5-30 μd/min
Maximum dose will be I.V. @ 30 μd/min
If we add 2 ampules of Inj. Dopamine in 90 cc of Inj. Normal saline, we can easily calculate the dose as follows:(90+10) or, 100 cc fluid contains 400 mg of DopamineSo, (400×1000) μg Dopamine is in = 100×4×15μd fluid400000 μg Dopamine = 6000 μd fluidSo, If we want to give Dopamine @2.5 μg/kg/min in a patient of 60 kg, we should give 150 μg/min.
Now, 400000μg/min Dopamine = 6000μd/min of fluidSo, 150 μg/min Dopamine = (6000÷400000)×150
= 2.25 μd/min
Therefore, the lowest dose of Inj. Dopamine, in a patient of 60 kg with cardiogenic shock, will be 2.25 μd/min. The dose can be as high as ≈30 μd/min.
The same calculation can also be applicable for Inj. Dobutamine!
S0, the regime should be Inj. Normal saline 90 cc + Inj. Dopamine (200mg) 2 ampules I.V. @ 3-30μd/min.
And not the Traditional one, i.e. Inj. Normal saline(or, Inj. 5% DNS) 500 cc + Inj. Dopamine (200mg) 2 ampules I.V. @ 32 (as if, its an universal constant!!!) μd/min.
