Vasopressor and inotropic therapy: Inotropes and vasopressors may be required to provide additional hemodynamic support if optimal fluid resuscitation and heart rate control fail to correct the circulatory failure. The aim is to achieve adequate tissue perfusion, rather than a specific blood pressure (BP) that differs between subjects (e.g. a hypertensive patient may require a higher BP).
It is essential to recognize that vasoactive drugs are relatively ineffective in volume-depleted patients and that an adequate circulating volume has to be achieved before using these drugs. Likewise, acidosis (pH <7.1) and electrolyte derangements (e.g. hypokalaemia, hypomagnesemia) impair the actions of inotropic and vasopressor drugs and should be corrected to ensure effective therapy.
Monitoring of Vasopressor and Inotropic Therapy
Vasopressor and inotropic effects cannot be predicted in an individual, and the response must be monitored and titrated to specific and effective endpoints (e.g. MAP 65–70 mmHg, urine output >0.5 mL/kg/h). These agents are usually administered through central lines. This ensures rapid distribution, as they have a short half-life, enable delivery at high concentration, and within a narrow safety margin, and avoids tissue necrosis in the event of peripheral extravasation.
In general, hemodynamically unstable patients receiving vasoactive drugs require continuous intra-arterial BP monitoring, ideally using larger arteries (e.g. femoral), as smaller arteries (e.g. radial) tend to underestimate low systemic pressures. However, in practice, the radial artery, which is easily accessible, is preferred. Volume status is most conveniently assessed with a central venous catheter and ‘fluid challenges’, but, in complex cases, hemodynamic monitoring of cardiac output (CO), systemic vascular resistance (SVR), left-sided filling pressures, and lung water may be necessary to maintain tissue perfusion.
The selection of appropriate vasopressor therapy
Requires an understanding of the cardiovascular properties of each agent, a knowledge of the adrenergic receptor distribution (and the actions of these receptors), and an accurate assessment of the underlying hemodynamic disturbance. Activation of different receptors has specific effects. Thus:
• Alpha-receptors cause mainly peripheral vasoconstriction.
• Beta-1-receptors are chronotropic (i.e. increase heart rate) and inotropic (i.e. increase the force and velocity of myocardial contractility and consequently BP and CO).
• Beta-2-receptors cause vasodilation and bronchodilation.
A specific drug may activate several receptors, but the balance of receptor effects can vary between individual agents. For example, adrenaline has alpha, beta-1, and beta 2-receptor properties, with a significant contribution from the alpha-receptors. In comparison, dobutamine also has alpha, beta-1, and beta-2 properties, but the beta-1 and beta-2 effects are greater than alpha properties. Ideally, a single drug should be used, but, occasionally, the correct balance of receptor stimulation may require combinations of vasopressor and inotropic agents.
Both vasopressin and low-dose steroids (e.g. hydrocortisone 8 mg/h) have been shown to have a ‘catecholamine sparing’ effect, particularly in septic shock.
Opinion as to optimal therapy in specific situations differs considerably between institutions and countries, and the following treatment regimes are recommended in the absence of conclusive evidence:
• In septic shock, profound vasodilation causes hypotension despite a high CO. An increasing body of evidence supports the initial use of noradrenaline (norepinephrine) (± adrenaline (epinephrine)), which are primarily alpha-vasoconstrictors and act mainly to maintain BP and organ perfusion (without significantly reducing CO). However, prolonged sepsis may eventually impair cardiac contractility, requiring the addition of a beta-1 inotropic agent to maintain CO (e.g. dobutamine).
• In myocardial ischemia, the beta-1 properties of dobutamine increase cardiac contractility without increasing myocardial oxygen consumption, an important property in patients with myocardial ischemia. In addition, the beta-2 vasodilator properties reduce ‘afterload’ and increase CO, although, occasionally, this necessitates the use of small doses of noradrenaline (norepinephrine) to offset beta-2-mediated hypotensive effects.
• Cardiogenic shock. In systolic heart failure, most catecholamines (e.g. dopamine, noradrenaline (norepinephrine)) effectively support the circulation and allow the myocardium time to recover from post-ischemic stunning. Phosphodiesterase inhibitors (e.g. milrinone, enoximone) have a role for diastolic dysfunction and catecholamine resistance.
• Renal protection. Augmentation of MAP may prevent or ameliorate renal failure and this is an important use of inotropes. It can be achieved with several catecholamines (e.g. dopamine, noradrenaline). However, there is no evidence to support the use of low-concentration ‘renal dose’ dopamine to increase renal blood flow by stimulating dopaminergic receptors, and it is no longer recommended
| Vasoactive agent | Receptors (bold = main action) | Mid-range dose effects Inotrope contractility | Mid-range dose effects Chronotrope | Mid-range dose effects Vasoconstrictor |
| Inoconstrictors Adrenaline (epinephrine): Dopamine: | α, β1, β2 α, β1, β2 | ++++ +++ | +++ ++ | ++ − to ++ |
| Inodilators Dobutamine Milrinone Enoximone | (α), β1, β2 PDI/↑ cAMP PDI/↑ cAMP | +++ +++ +++ | + 0 0 | − to ± − − − |
| Vasoconstrictor noradrenaline (norepinephrine) Phenylephrine | α, β1 α, β1 | +/++ + | 0 0 | ++++ ++++ |
Other circulatory support techniques include cardiac pacemakers and ventilatory support to reduce cardiorespiratory work and pulmonary edema. Intra-aortic balloon pumps are valuable in the failing heart as a bridge to transplantation. They are sited in the descending aorta above the renal arteries. Diastolic balloon inflation enhances coronary and systemic perfusion pressures, whilst systolic deflation increases CO by reducing afterload. Complications include renal and mesenteric ischemia, infection, and aortic dissection. Other left ventricular assist devices are also being developed.