Milrinone

Milrinone, one of the most important inodilators for cardiac anaesthesia and ICU. 

Milrinone is a phosphodiesterase-III inhibitor that increases cAMP → inotropy + lusitropy + vasodilation (“inodilator”). 

It’s β-independent, useful post-CPB or in β-blocked hearts, but causes hypotension and arrhythmia, prolonged in renal failure.

Load **50 mcg/kg over 10 min**, infuse **0.25–0.75 mcg/kg/min** (reduce if renal impairment). Combine with **norepinephrine** when needed to maintain MAP.

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# 1) Receptor-level action → clinical effects

**Primary mechanism:**

* **Selective phosphodiesterase-III (PDE-3) inhibitor** → prevents breakdown of cyclic AMP (cAMP) in **cardiac myocytes** and **vascular smooth muscle**.

**Resulting downstream effects:**

* ↑ **cAMP** → ↑ intracellular **Ca²⁺** availability in myocardium → **positive inotropy**.

* ↑ cAMP in vascular smooth muscle → ↓ intracellular Ca²⁺ → **vasodilation** (both systemic & pulmonary).

* Also enhances **lusitropy** (myocardial relaxation) → improves diastolic filling.

**Net clinical effects:**

* ↑ cardiac contractility and stroke volume (inotropy).

* ↓ preload and afterload (inodilator).

* ↓ pulmonary artery pressure & PVR (helpful in RV failure, post-CPB, pulmonary hypertension).

* **No direct chronotropic or β-receptor stimulation** → safe in β-blocked patients.

* Can cause **hypotension** if preload low.

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# 2) Vial strength, preparation & basic pharmacokinetics (+ disadvantages)

**Vials:** 10 mg/10 mL (1 mg/mL).

**Typical infusion preparation:**

* Dilute **10 mg in 100 mL** (0.1 mg/mL).

**Pharmacokinetics:**

* **Onset:** 5–15 min (after bolus).

* **Peak:** ~10 min.

* **Duration:** 2–4 h after stopping (depends on renal function).

* **Elimination:** **renal (unchanged drug)**.

* **Half-life:** 2.3 h (normal renal function), **up to 10 h** if renal failure.

**Disadvantages:**

* **Hypotension** from vasodilation (especially if preload inadequate).

* **Arrhythmia risk** (ventricular > atrial, though less than adrenaline/dobutamine).

* **Prolonged action in renal impairment.**

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# 3) Practical dosing

## A. Anaesthesia / Cardiac theatre

**Indications:** post-CPB low cardiac output, RV dysfunction, pulmonary hypertension, weaning from bypass, β-blockade blunting.

* **Loading dose:** 50 mcg/kg IV over 10 min (may omit if hypotensive).

* **Maintenance infusion:** **0.25–0.75 mcg/kg/min**, titrate by 0.1–0.2 increments.

* Start low if systemic BP borderline or patient hypovolaemic.

* If significant hypotension, combine with **norepinephrine** or **vasopressin**.

**Typical 70-kg patient:**

* Load 3.5 mg over 10 min, then start 0.3 mcg/kg/min → 1.26 mg/h → **12.6 mL/h** (if 0.1 mg/mL solution).

## B. ICU

**Indications:**

* Post-cardiac surgery LCOS, RV failure, pulmonary hypertension crisis, or severe systolic heart failure refractory to catecholamines.

**Dosing:**

* **0.25–0.75 mcg/kg/min**, titrate to cardiac index, ScvO₂, lactate, and filling pressures.

* Avoid bolus in unstable hypotensive patients.

* Combine with **vasopressor** if MAP <65 mmHg.

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# 4) Special populations — dosing cautions

### Pregnancy

* Limited data; use only if benefit outweighs risk (e.g., severe heart failure or pulmonary hypertension in obstetric anaesthesia).

### Lactation

* Unknown excretion; avoid breastfeeding during continuous infusion; safe after discontinuation due to short exposure.

### Hepatic impairment

* Metabolism minimal → no major adjustment.

### Renal impairment

* **Reduce dose:**

  * CrCl 30–50 mL/min → 0.23 mcg/kg/min

  * CrCl 10–30 → 0.2 mcg/kg/min

  * CrCl <10 → 0.13 mcg/kg/min

* Avoid loading dose. Monitor for prolonged hypotension and arrhythmia.

### Obesity

* Dose on **Ideal/Adjusted Body Weight**; avoid overshoot due to hypotension risk.

### Paediatrics

* **Bolus:** 50 mcg/kg over 10 min.

* **Infusion:** 0.25–0.75 mcg/kg/min (same range).

* Neonates: prolonged half-life; start lower (0.25 mcg/kg/min).

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# 5) Drug interactions (clinically key)

* **Loop diuretics (furosemide):** precipitate in same line — use separate lumen.

* **Other vasodilators (nitroglycerin, nitroprusside):** additive hypotension.

* **Catecholamines (dobutamine, adrenaline):** synergistic for inotropy—common combination in LCOS.

* **Beta-blockers:** effects preserved (not receptor-mediated).

* **Norepinephrine:** balances systemic BP; often co-infused.

* **Dopamine/dobutamine:** may further increase arrhythmia risk if used together long-term.

* **Digoxin:** additive arrhythmogenicity possible.

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# 6) Significant complications & management

| Complication                          | Mechanism / Features                       | Management                                                                       |

| ------------------------------------- | ------------------------------------------ | -------------------------------------------------------------------------------- |

| **Hypotension**                       | Peripheral vasodilation from ↑ cAMP in VSM | Volume resuscitate; reduce rate; start vasopressor (norepi/vasopressin).         |

| **Ventricular arrhythmias**           | Excess cAMP, Ca²⁺ overload                 | Reduce/stop infusion; correct K⁺, Mg²⁺, acid-base; antiarrhythmics if sustained. |

| **Tachycardia / palpitations**        | Mild β₁ stimulation                        | Usually self-limiting; adjust dose.                                              |

| **Thrombocytopenia (rare)**           | Idiosyncratic                              | Stop drug; monitor platelets.                                                    |

| **Prolonged effect in renal failure** | Accumulation                               | Adjust dose; extend interval; consider CRRT clearance if severe.                 |

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