Pharmacotherapy of Acute Cardiogenic Shock

1. Overview of Escalating Pharmacotherapy

Early, targeted vasoactive support restores perfusion, optimizes cardiac output and prevents end-organ injury in cardiogenic shock.

Goals of support:

Maintain Mean Arterial Pressure (MAP) ≥65 mmHg while preserving cardiac output
Augment contractility (Cardiac Index (CI) >2.2 L/min/m²) and optimize Systemic Vascular Resistance (SVR)
Minimize tachyarrhythmias, ischemia and excessive vasoconstriction

Guideline highlights:

Norepinephrine is first-line vasopressor
Dobutamine or milrinone for low-output states based on BP, arrhythmia risk and renal function
Vasopressin and epinephrine reserved for refractory hypotension

Triggers for escalation:

Persistent MAP <65 mmHg despite therapy
Markers of hypoperfusion: rising lactate, oliguria, altered mentation

2. First-Line Agents

Norepinephrine, dobutamine and milrinone form the backbone of vasoactive therapy.

Key Agents Comparison

Comparison of First-Line Vasoactive Agents in Cardiogenic Shock
Agent	Mechanism	Indication	Dose	Monitoring	Cautions
Norepinephrine	α₁ > β₁ agonist	MAP support	0.01–0.05 mcg/kg/min; titrate by 0.01–0.02 mcg/kg/min	MAP, HR, lactate, urine output	Ischemia risks; central line only
Dobutamine	β₁ > β₂ agonist	Low CI with adequate BP	2–10 mcg/kg/min; titrate by 2.5 mcg/kg/min every 15–30 min	Arrhythmias, BP drop, myocardial O₂ demand	Tachyarrhythmias; avoid in obstructive lesions
Milrinone	PDE-III inhibitor (inodilator)	Inotropy + afterload reduction	50 mcg/kg loading (omit if hypotensive), then 0.25–0.75 mcg/kg/min infusion	Hypotension, arrhythmias, thrombocytopenia	Prolonged half-life in renal dysfunction; avoid load in hepatic impairment

Clinical Pearls

Use a dedicated central venous catheter for all vasoactives; avoid peripheral infusions when possible.
Limit norepinephrine (NE) to <0.5 mcg/kg/min; consider adding vasopressin to reduce catecholamine dose if higher NE doses are required.
Milrinone may be preferred in beta-blocked patients or those with pulmonary hypertension; skip loading dose if blood pressure is low or borderline.

3. Second-Line and Adjunctive Therapies

When first-line therapy is insufficient, add non-adrenergic agents or potent catecholamines with caution.

Vasopressin (0.03 units/min fixed dose):
- V₁ receptor agonist; acts as a catecholamine-sparing agent.
- Fixed dose is often used to minimize ischemic complications.
- Monitor for splanchnic perfusion issues, digital ischemia, and serum sodium.
Epinephrine (0.01–0.1 mcg/kg/min):
- Potent α/β agonist; typically reserved for refractory shock.
- Increases lactate levels (can be non-hypoxic), myocardial oxygen demand.
- Monitor ECG for arrhythmias and lactate trends closely.

Combination strategies:

Aim to synergize vasoconstriction and inotropy, particularly in mixed shock phenotypes.
Carefully balance hemodynamic goals against the risks of arrhythmia and ischemia.

4. Pharmacokinetic and Pharmacodynamic Considerations

Increased Volume of Distribution (Vd): Capillary leak and aggressive fluid resuscitation can expand Vd.
Hypoalbuminemia: May lead to an increased free fraction of highly protein-bound drugs, potentially altering their effects.
Altered Clearance: Renal or hepatic dysfunction, as well as renal replacement therapy (RRT), can significantly impact drug clearance.
Implication: These factors necessitate careful consideration of loading versus maintenance doses and frequent reassessment of therapy.

5. Dose Adjustments in Organ Dysfunction

Renal replacement therapy:

Norepinephrine: Typically no significant dose adjustment is required.
Milrinone: Reduce infusion rate by approximately 50% during continuous renal replacement therapy (CRRT) due to clearance by the filter.

Hepatic impairment:

Milrinone: Consider avoiding the loading dose and using a lower maintenance infusion rate, as hepatic metabolism contributes to its clearance.

6. Administration and Infusion Devices

Central venous access is mandatory for the safe administration of most vasoactive infusions. Peripheral administration should be limited to emergent situations and for very short durations.
Utilize smart infusion pumps equipped with dose-error reduction software (DERS) and appropriate alarms.
Verify line patency, drug concentration, and pump settings meticulously at each titration and shift change.

7. Monitoring Plan for Efficacy and Toxicity

Hemodynamic goals:

MAP ≥65 mmHg
CI >2.2 L/min/m²
Central venous oxygen saturation (SvO₂) >65% (if monitored)
Lactate clearance (e.g., >10-20% reduction per 2-4 hours)

Perfusion markers:

Urine output >0.5 mL/kg/hr
Improving mentation
Normalizing capillary refill time

Toxicity surveillance:

Continuous ECG monitoring for arrhythmias.
Daily physical examination for signs of peripheral or visceral ischemia.

Titration frequency:

Adjust doses every 15–30 minutes based on response until hemodynamic stability is achieved, then monitor at least hourly or as clinically indicated.

8. Pharmacoeconomic Considerations

Drug cost ranking (approximate, may vary): Norepinephrine is generally less expensive than vasopressin, which is often less expensive than epinephrine. Milrinone costs can also be significant.
Resource needs: Management of cardiogenic shock with vasoactive agents requires intensive resources, including frequent hemodynamic monitoring, smart pump maintenance, and skilled nursing time.
Polypharmacy and the need for high-dose vasoactive therapy often correlate with longer ICU stays and increased overall healthcare costs.

9. Integration with Precipitant Management

Acute Myocardial Infarction (AMI):

Administer aspirin and a P2Y₁₂ inhibitor promptly.
Initiate unfractionated heparin infusion.
Coordinate urgent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) as indicated—early revascularization is critical for improving mortality.

Acute Decompensated Heart Failure (ADHF) Decongestion:

Initiate intravenous loop diuretics. Start with a dose at least equivalent to the patient’s chronic total daily oral dose, or double it if response is inadequate.
Consider a continuous infusion of loop diuretics if intermittent boluses yield inconsistent or suboptimal urine output.
Monitor serum potassium (K⁺), magnesium (Mg²⁺), and renal function closely during aggressive diuresis.

Diuretic resistance:

Consider adding a thiazide-like diuretic (e.g., oral metolazone or IV chlorothiazide) 30–60 minutes before the loop diuretic dose to promote sequential nephron blockade.
This strategy requires intensive electrolyte and renal function monitoring due to the risk of significant electrolyte disturbances and volume depletion.

10. Clinical Decision Algorithm

1. Initial Hypotension (MAP <65 mmHg)

Start Norepinephrine (NE)

Target MAP ≥65 mmHg

2. Assess Cardiac Index (CI) & Perfusion

CI Low (<2.2 L/min/m²) or ongoing hypoperfusion?

Yes

No (CI adequate OR MAP still low)

3. Add Inotrope

Dobutamine (if SBP adequate)

OR Milrinone (esp. if β-blocked/PHTN)

3. Refractory Hypotension

Add Vasopressin (0.03 U/min)

(Catecholamine-sparing)

4. Re-assess: Persistent Shock?

Yes

5a. Consider Epinephrine

(If ≥2 agents failing)

5b. Evaluate for MCS

(IABP, Impella, VA-ECMO)

Figure 1: Clinical Decision Algorithm for Escalating Pharmacotherapy in Cardiogenic Shock. This algorithm outlines a stepwise approach to vasoactive medication selection and escalation, emphasizing continuous reassessment and consideration for mechanical circulatory support (MCS) in refractory cases.

References

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Van Diepen S, Katz JN, Albert NM, et al. Contemporary management of cardiogenic shock: A scientific statement from the American Heart Association. Circulation. 2017;136(16):e232–e268.
Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17):e263–e421.
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Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(7):e21–e129.
Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock. N Engl J Med. 1999;341(9):625–634.

2025 PACUPrep BCCCP Preparatory Course

Pulmonary

Participants 432

Escalating Pharmacotherapy in Cardiogenic Shock

Lesson Objective