Selecting vasoactive therapy
It is critical to understand the physiology of the shock that you are treating, and the receptor targets for each vasoactive medication, so that you can tailor therapy to the particular clinical situation.
Low preload (LVEDP)
In distributive, obstructive, or hypovolemic shock, proper fluid resuscitation is critical to improving blood pressure, cardiac output, and end‐organ perfusion. Monitoring of hemodynamic parameters and filling pressures can be helpful in this setting.
In mixed shock states, invasive hemodynamic monitoring can be useful in determining the predominant mechanism of shock and to customize therapy to the physiology of the patient.
Receptors affected by vasoactive medications
Vasoactive medications often work as agonists or antagonists of adrenergic or parasympathetic receptors. These selected receptors represent the principal targets for vasoactive therapy in the intensive care setting (Table 12.2).
Key principles of vasoactive medication use
Diagnose and understand mechanism causing hypotension:
Physical examination, urine output, laboratory testing, imaging, and invasive hemodynamic monitoring can be important tools to differentiate the nature of the patient’s shock.
Dosage and selection of medication should be titrated to achieve a blood pressure sufficient to maintain end‐organ perfusion, as evidenced by metrics such as mentation, urine output, and blood lactate levels.
Critically ill patients also require frequent re‐evaluation for further hemodynamic insults, response to therapy, or side effects that may require changes in therapeutic strategy.Table 12.2 Action of vasoactive medications.ReceptorLocationActionα‐1 adrenergicVascular smooth muscle (peripheral, renal, coronary)Systemic vasoconstriction – increased SVRα‐2 adrenergicVascular smooth muscle and central nervous systemVasodilation – decreased SVR Sedationβ‐1 adrenergicCardiac muscleIncreased heart rate (chronotropy) and contractility (inotropy) Increased cardiac output Minimal vasoconstrictionβ‐2 adrenergicVascular smooth muscle (peripheral and renal)Vasodilation Reduced SVRDopamine (D1)Vascular smooth muscle (peripheral, renal, splanchnic, coronary, cerebral)Vasodilation in capillary bedsAcetylcholine (ACh)Parasympathetic nervous system (heart, sinoatrial and atrioventricular nodes, GI tract, eyes)Has chronotropic effects on heart Atropine is an antagonist of muscarinic ACh receptors Atropine can stimulate or accelerate AV node conductionPhosphodiesterase 3 (PDE‐3)Cardiac muscle and vascular smooth muscleIncreased contractility (inotropy) and improves diastolic relaxation (lusitropy) VasodilationVasopressin (V1, V2)Vascular smooth muscle and renal collecting ductV1 – stimulation causes vasoconstriction V2 – mediate water reabsorption in renal collecting system
Tailor vasoactive therapy to correct the specific hemodynamic derangements underlying the hypotension:This requires understanding adrenergic receptors and mechanisms of action.An example of this principle is the use of a pure alpha‐adrenergic agonist such as phenylephrine for hypotension resulting from cardiogenic shock. It might seem intuitive to use such a drug to improve hypotension from inadequately contracting the left ventricle. However, understanding the effect of such a drug on the hemodynamic equations noted above will allow you to conclude that phenylephrine use would be counterproductive. It would lead to decreased stroke volume from an increased afterload on the weakened left ventricle without the benefit of inotropic support.
Most vasoactive drugs act on multiple receptors, and many agents activate different receptors depending on the dose administered:The best example of this is dopamine, which preferentially stimulates β‐1 receptors at low doses and α receptors at higher doses.Similarly, dobutamine can increase myocardial contractility by stimulating β‐1 receptors. However, it can cause vasodilation by simultaneous activation of β‐2 receptors.The principle is to understand that vasoactive medications can have mixed hemodynamic effects, and often have different responses based on dose.
A given vasoactive agent can have both direct actions and reflex actions:The vascular system is closely regulated by multiple physiologic mechanisms including the autonomic nervous system that seeks to ensure cardiovascular stability.For example, phenylephrine‐induced vasoconstriction can lead to increased mean arterial pressure, which may lead to baroreceptor activation and a compensatory reflex bradycardia.
Responsiveness to the vasoactive medications can decrease over time due to a phenomenon known as tachyphylaxis:Up‐titration of doses or initiation of new agents with different receptor targets must be done regularly.
Central line access and arterial line monitoring are a must:Catecholamines and vasopressor agents are given as continuous infusions due to their short half‐lives. They carry significant risks of peripheral extremity ischemia due to potent vasoconstriction as well as skin necrosis if they extravasate. Central venous access is usually necessary.With all intravenous vasoactive infusions, invasive hemodynamic monitoring with an arterial line is needed because of rapid hemodynamic changes and side effects such as arrhythmias
Vasoactive medications in focus
| Epinephrine | |
| Receptor binding | α‐1, β‐1, β‐2 |
| Pharmacology | β receptor predominant at lower doses, α receptor predominant at higher doses |
| Dosing range |
0.01–0.10 μg/kg/min (for 70 kg adult, that is 0.7–7 μg/min)
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