Section 5: Hemodynamic Support – Vasopressors & Inotropes

In the simplest terms, shock is a state of circulatory failure resulting in inadequate oxygen delivery to the tissues. When cells are deprived of oxygen, they switch to inefficient anaerobic metabolism, producing lactic acid and leading to end-organ damage and, ultimately, death. While the end result is the same, the underlying causes of shock are vastly different. As a pharmacist, you must understand these differences because the choice of therapy—fluids, vasopressors, or inotropes—is entirely dependent on the type of shock. Treating cardiogenic shock with massive fluid boluses can be as dangerous as treating hypovolemic shock without them. Your ability to recognize the “flavor” of shock allows you to anticipate medication needs and identify potentially inappropriate orders.

The entire circulatory system can be distilled into three components: the “Pipes” (the blood vessels, which determine vascular resistance), the “Pump” (the heart, which provides forward flow), and the “Fluid” (the blood volume within the pipes). Every type of shock represents a failure of one or more of these components.

The Four Types of Shock: A Hemodynamic Fingerprint

In the ICU, shock is classified by its hemodynamic profile, which is a set of measurements that tells us what’s happening with the pipes, pump, and fluid. The key parameters are Central Venous Pressure (CVP) or other preload markers which reflect fluid volume, Cardiac Output (CO) which reflects pump function, and Systemic Vascular Resistance (SVR) which reflects the state of the pipes.

Shock Type	Primary Problem	CVP (Fluid)	CO (Pump)	SVR (Pipes)	Classic Example
Distributive	Pipes (Vasodilation)	Low	High (initially, “warm shock”)	Very Low	Sepsis, Anaphylaxis
Cardiogenic	Pump (Heart Failure)	High	Very Low	High (compensatory)	Post-Myocardial Infarction
Hypovolemic	Fluid (Volume Loss)	Very Low	Low	High (compensatory)	Hemorrhage, Dehydration
Obstructive	Obstruction to Flow	High (blood can’t get into the heart)	Very Low	High	Massive Pulmonary Embolism

To master vasopressors and inotropes, you must first master the language of the sympathetic nervous system: the adrenergic receptors. In retail pharmacy, you are intimately familiar with beta-blockers and alpha-agonists for chronic conditions. In the ICU, you will leverage this knowledge to understand how we manipulate the same receptors in acute, life-threatening situations. Every vasopressor and inotrope has a unique “receptor fingerprint”—its specific affinity for Alpha-1, Beta-1, and Beta-2 receptors—which determines its clinical effect. Your ability to recall these fingerprints is what allows you to predict a drug’s effects and select the right agent for the right type of shock.

The Receptor Master Table

Receptor	Primary Location	Physiologic Effect of Stimulation	The “Nickname”	Primary Drug Effect
Alpha-1 (α₁)	Vascular Smooth Muscle (Pipes)	Potent Vasoconstriction	“The Squeezer”	Increases SVR & MAP
Beta-1 (β₁)	Myocardium (Pump)	Inotropy (Contractility) Chronotropy (Heart Rate)	“The Kicker”	Increases Cardiac Output
Beta-2 (β₂)	Vascular & Bronchial Smooth Muscle	Vasodilation & Bronchodilation	“The Relaxer”	Can Decrease SVR & MAP
Vasopressin (V₁)	Vascular Smooth Muscle	Vasoconstriction (via non-adrenergic pathway)	“The Backup Squeezer”	Increases SVR & MAP
Angiotensin (AT₁)	Vascular Smooth Muscle	Potent Vasoconstriction (via RAAS pathway)	“The Master Squeezer”	Increases SVR & MAP

The Receptor Fingerprint of Common Agents

Drug	α₁ (Squeeze)	β₁ (Kick)	β₂ (Relax)	Other Receptors	Primary Use Case
Norepinephrine	+++	+	0		First-line for Septic Shock
Epinephrine	+++	+++	++		Anaphylaxis, 2nd-line in Sepsis, ACLS
Phenylephrine	+++	0	0		Pure Vasoconstriction (niche uses)
Dopamine	++ (Dose-dep)	++ (Dose-dep)	+ (Dose-dep)	D₁	Largely replaced; niche in bradycardia
Dobutamine	0/+	+++	+		First-line Inotrope for Cardiogenic Shock
Vasopressin	0	0	0	V₁ (+++)	Adjuvant in Septic Shock
Angiotensin II	0	0	0	AT₁ (+++)	Refractory Distributive Shock

In managing distributive shock (primarily sepsis), we use a stepwise approach to restore adequate blood pressure. The goal is to achieve a Mean Arterial Pressure (MAP) of ≥ 65 mmHg, the minimum pressure needed to ensure adequate perfusion to the vital organs. As the pharmacist, you are the steward of this ladder, ensuring the right drug is used first, the second is added appropriately, and the concentrations are standardized for safety.

First Line: Norepinephrine (Levophed®) – The Workhorse

Norepinephrine is the undisputed king of vasopressors and the first-line agent recommended by the Surviving Sepsis Campaign guidelines. Its receptor profile is nearly perfect for septic shock. The potent alpha-1 agonism directly counteracts the massive vasodilation (the “pipes” problem), while its modest beta-1 agonism provides a small amount of cardiac support without causing significant tachycardia. It reliably increases SVR and, therefore, MAP.

• Dosing: Initiated at 2-5 mcg/min (or ~0.02-0.05 mcg/kg/min) and titrated upwards, typically every 2-5 minutes, to achieve a MAP ≥ 65 mmHg. There is no true maximum dose.
• Pharmacist’s Role – Standard Concentration: Your most critical role is ensuring it is prepared in a standard concentration. A common standard is 16 mg in 250 mL of D5W (64 mcg/mL). This standardization is a cornerstone of medication safety.

Second Line: Vasopressin – The Adjuvant

Patients in septic shock have a relative deficiency of endogenous vasopressin. Adding exogenous vasopressin works via a completely different mechanism (V1 receptors) to cause vasoconstriction. It is not used as a primary agent but as an adjuvant to norepinephrine.

• When to Add: Vasopressin is typically added when the norepinephrine requirement is escalating (e.g., >15 mcg/min). The goal is a “catecholamine-sparing” effect, allowing you to decrease the norepinephrine dose and mitigate its side effects.
• Dosing: Vasopressin has a fixed, non-titratable dose for septic shock: 0.03 units/minute. It is an “on or off” drug.
• Pharmacist’s Role: Verifying the fixed dose and explaining the separate mechanism of action.

Third Line & Special Cases: Epinephrine & Angiotensin II

When a patient is in refractory shock (still hypotensive despite high doses of norepinephrine and vasopressin), additional agents are needed.

• Epinephrine: Its powerful alpha-1 and beta-1 effects provide a massive increase in both vasoconstriction and cardiac output. However, this comes at a cost: significant tachyarrhythmias and increased serum lactate. As the pharmacist, you must counsel the team that a rising lactate after starting epinephrine may be a drug effect, not a sign of worsening shock.
• Angiotensin II (Giapreza®): This is a synthetic human Angiotensin II that acts as a potent vasoconstrictor on AT₁ receptors. It is approved for adults with septic or other distributive shock. Your role is to be the expert on its place in therapy (refractory shock), its dosing (initiated at 20 ng/kg/min), and institutional guidelines for its use.

When the primary problem is pump failure (cardiogenic shock), vasopressors alone are not the answer. Squeezing the pipes (increasing SVR) against a failing heart only makes its job harder. In these situations, we need inotropes—medications that directly increase the force of cardiac contraction (inotropy) to improve cardiac output.

Dobutamine vs. Milrinone: The Great Debate

Feature	Dobutamine	Milrinone
Mechanism	Primarily a Beta-1 agonist. Increases cAMP -> increases intracellular calcium -> increases contractility.	Phosphodiesterase-3 (PDE3) inhibitor. Prevents breakdown of cAMP -> increases intracellular calcium -> increases contractility.
Primary Effect	Inotropy >> Vasodilation	Inotropy + significant Vasodilation (Inodilator)
Hemodynamics	CO, HR, SVR	CO, HR, SVR
Half-life	~2 minutes (rapid on, rapid off)	~2.5 hours (slower on, much slower off)
Elimination	Hepatic	Renal (requires dose adjustment in impairment)
Adverse Effects	Tachyarrhythmias	Hypotension, Arrhythmias
Pharmacist’s Role / Clinical Pearl	Easy to titrate due to short half-life. Effects may be blunted in patients on chronic beta-blocker therapy.	More effective in patients on beta-blockers as it bypasses the receptor. Long half-life makes it difficult to titrate in unstable patients. Must verify renal function.

Beyond selecting the right drug, the ICU pharmacist’s primary responsibility is to ensure these potent medications are used safely. Errors with vasopressors are common and can have devastating consequences.

Key Safety Verifications

• Line Access: All vasopressors are vesicants and can cause severe tissue necrosis if they leak out of the vein (extravasation). You must always confirm the patient has a central venous line for their administration. Peripheral administration is only acceptable in an extreme emergency for a very short duration until central access can be obtained.
• Standard Concentrations: Re-verify that all infusions are prepared according to your institution’s standard concentration policy. This prevents 10-fold or 100-fold errors during preparation or programming of the infusion pump.
• Drug & Diluent: Confirm the correct drug and diluent are used. For example, some drugs are incompatible with normal saline. Your double-check prevents inactivation or precipitation.

Essential Monitoring Parameters

When verifying pressor and inotrope orders, you should have a clear picture of the patient’s status. Key monitoring parameters include:

• Hemodynamics: Continuously monitor Mean Arterial Pressure (MAP), heart rate, and CVP.
• ECG: Watch for new or worsening tachyarrhythmias, which are a common side effect.
• Metabolic: Track serum lactate as a marker of tissue perfusion. Be aware of drug-specific effects (e.g., epinephrine can increase lactate). Monitor blood glucose (catecholamines can cause hyperglycemia).
• Electrolytes: Beta-agonists can drive potassium into cells, causing hypokalemia. Monitor potassium levels closely.
• End-Organ Perfusion: Assess urine output and mental status as key indicators of whether the medications are successfully restoring blood flow to the kidneys and brain.