Medications in Emergency Trauma Management

Selection of Vasopressors in Shock

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  Septic/vasodilatory shock

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    First choice

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      Norepinephrine

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    Additional choices

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      Epinephrine may be added to or replaced the Norepinephrine.

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      Vasopressin

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        Low-dose vasopressin may be added to decrease requirements for other adrenergic agents.

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        It is not recommended as a single agent.

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        Recommended in patients unresponsive to catecholamines or in the presence of acidosis/hypoxia

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      Dopamine

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        May be considered in patients with bradycardia or in patients without risk for or presence of tachyarrhythmias

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      Dobutamine

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        Norepinephrine with Dobutamine can be used in patients with myocardial dysfunction resulting in low cardiac output.

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      Phenylephrine

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        May be considered in patients with serious tachyarrhythmias due to norepinephrine

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        May be considered in patients with persistent hypotension with high cardiac output

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  Cardiogenic shock with myocardial infarction (MI)

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    First choice

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      Norepinephrine

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        Patients with severe hypotension (systolic blood pressure [SBP] <70 mm Hg)

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      Dopamine (Intropin)

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        Patients with SBP between 70–100 mm Hg

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        May increase the risk of arrhythmias

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    Additional choice

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      Dobutamine

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        May be given to improve cardiac output, but not recommended for patients with hypotension

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        Agent of choice in low output with increased afterload

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  Anaphylactic shock

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    First choice

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      Epinephrine

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  Cardiopulmonary resuscitation (CPR)

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    First choice

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      Epinephrine

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    Additional choice

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      Vasopressin for refractory pulseless cardiac arrest

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  Neurogenic shock

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    First choice

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      Phenylephrine

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        Commonly used

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        Causes peripheral vasoconstriction due to alpha-1 effect

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        May cause reflex bradycardia due to lack of beta activity and unopposed vagal tone

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    Additional choice

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      Norepinephrine

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        Preferred in patients with hypotension and bradycardia due to its alpha and beta activities

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      Epinephrine

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        May be considered in refractory hypotension

Receptors for Vasoactive Drugs

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  Alpha-1 adrenergic receptors

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    Peripheral arterial and venous vasoconstriction

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    Constriction of gastrointestinal and urinary sphincters

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  Alpha-2 adrenergic receptors

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    Reduce central and peripheral sympathetic outflow

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    Mainly found in the brain

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  Beta-1 adrenergic receptors

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    Increase the strength of cardiac contractions (inotropic effect)

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    Increase heart rate (chronotropic effect)

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  Beta-2 receptors

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    Mainly located in bronchioles and skeletal muscles

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    Causes vasodilation and bronchodilation

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  Dopamine receptors

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    Renal and splanchnic vasodilation

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  Vasopressin receptors

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    V-1

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      Causes vascular smooth muscle contraction leading to vasopressor effect

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    V-2

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      Located primarily in the kidney, causing water retention due to its antidiuretic effect

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    V-3:

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      Located in the central nervous system, modulates corticotrophin secretion

Cardiovascular Effects of Commonly used Vasopressors

Epinephrine

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  Alpha, beta-1, and beta -2 effects

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  Cardiovascular effects

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    Increase in heart rate (HR)

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    Increase in mean arterial pressure (MAP)

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    Increase in cardiac output (CO)

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    Increase in systemic vascular resistance (SVR)

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  Effects are dose dependent.

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  Increasing the dose is predominantly associated with the alpha effect.

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  Dose

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    Shock

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      Starting dose 0.1 μg/kg/min, titrated to achieve the target effect

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    Cardiopulmonary resuscitation (CPR):

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      Dose: 1 mg intravenous (IV) or intraosseous (IO), predominantly alpha effects

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      Shockable rhythm: ventricular fibrillation/primary ventricular fibrillation (VF/pVF)

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        First should be given after the second defibrillation

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      Nonshockable rhythm: pulseless electrical activity (PEA; asystole)

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        First dose should be given at the onset of cardiac resuscitation.

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      Continued 1 mg IV/IO every 3–5 min until return of the circulation

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  Side effects

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    Increase in myocardial oxygen demand

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    Mesenteric ischemia

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      More common than other vasopressors

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    Increase in lactate regardless of hypoxia/hypoperfusion

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      Increase in adenosine triphosphatase (ATPase)

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      Increase in adenosine triphosphate (ATP) production from glycolysis for the ATPase activity.

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      Glycolysis produces lactic acid.

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    Vasoconstriction of the uteroplacental vasculature leading to placental hypoperfusion and fetal hypoxia; should be avoided in pregnancy

Norepinephrine

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  Alpha and beta-1 effects

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  A low dose stimulates both alpha- and beta-adrenergic receptors, causing:

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    an increase in MAP.

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    an increase in HR.

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    an increase in SVR.

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  A high dose predominantly stimulates alpha receptors, causing:

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    minimal effect on the HR.

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    bradycardia.

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    an increase in SVR.

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    a reduction in cardiac output due to increase in afterload.

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  Dose

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    Starting dose

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      0.05 μg/kg/min, titrated to achieve the target effect

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    Low dose

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      2.5–5 mcg/min

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    High dose

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      >5 mcg/min

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  Side effects

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    Inadvertent boluses may precipitate profound hypertension that may cause myocardial infarction and cerebral ischemia.

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    Tachycardia is uncommon in adequately resuscitated patients.

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    Reflex bradycardia

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    Renal ischemia resulting in decreased urine output

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    Mesenteric ischemia

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    Increase in blood glucose

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    Extravasation of norepinephrine may cause tissue necrosis.

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      Treated with phentolamine 5–10 mg in 10 mL of normal saline injection into the area of extravasation within 12 hr

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    Vasoconstriction of the uteroplacental vasculature leading to placental hypoperfusion and fetal hypoxia. It should be avoided in pregnancy.

Dopamine

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  Dopaminergic, alpha-1, and beta-1 effects

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  Not the first-line agent for the alpha effect

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  Dose

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    Range

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      2–25 μg/kg/min

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    Beta dose

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      5–10 mcg/kg/min, titrated to target HR, BP, or cardiac output

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    Alpha dose

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      >10 mcg/kg/min, titrated to target BP

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    Low dose (dopaminergic)

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      Does have renal protection effect

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      Does not improve renal function

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      May have some diuretic effect

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  Side effects

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    Tachycardia

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    Arrhythmias

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    Wide QRS

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    Increase in myocardial oxygen consumption

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    Decrease in peripheral perfusion

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      Acute kidney injury (doses >20 hlsug/kg/min)

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      Mesenteric ischemia

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    Increase in blood glucose

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    Fixed, dilated pupils

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    Extravasation of dopamine (Intropin) can cause tissue necrosis.

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      Treated with injection of phentolamine 5–10 mg in 10 mL of normal saline injection into the area of extravasation within 12 hr

Dobutamine

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  Synthetic catecholamine, which is similar in structure to dopamine

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  Beta-1, beta-2, and ± alpha adrenergic effects

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  No dopaminergic effect

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  More prominent inotropic effects than chronotropic effects

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  Beta-2 vasodilator effect dominates over the alpha-1 constrictor effect in higher doses, causing reduction in SVR.

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  Increase CO due to:

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    positive inotropic effect.

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    decrease in peripheral resistance from vasodilatory effect.

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  Dose

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    Initial infusion: 1–2 mcg/kg/min, titrated to the response

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    Maximum does: 20 mcg/kg/min

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  Side effects

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    Significant tachycardia and hypertension

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    Hypotension in inadequately resuscitated patients

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    Ectopic heartbeats

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    Extravasation causes local blanching, tissue ischemia, or necrosis. It is treated with phentolamine.

Phenylephrine

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  Alpha-adrenergic effect

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  May be used in patients with hypotension due to vasodilation and adequate cardiac output

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  It causes the following:

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    Increase in MAP

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    Increase in SVR

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    Increase in central venous pressure (CVP)

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  Dose

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    Shock

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      0.1–0.5 mg as slow IV direct injection every 10–15 min (or 1–10 mg intramuscular/subcutaneous every 1–2 hr)

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    Paroxysmal supraventricular tachycardia (PSVT)

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      0.5–1 mg as rapid intravenous injection every 60–90 sec

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  Side effects

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    Bradycardia

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    Arrhythmias

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    Increase in myocardial oxygen consumption

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    Peripheral or mesenteric ischemia

Vasopressin

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  V-1 receptors effect

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    Vasoconstriction of the systemic, splanchnic, renal, and coronary vessels via noradrenergic pathway

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    Increase in MAP

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    Increase in SVR

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  V-2 receptors effect

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    Antidiuretic effect in the kidney causing water retention

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  V-3 receptors effect

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    Modulates corticotropin secretion in the central nervous system

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  Dose

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    Shock

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      0.03 U/min; titrate to response

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    Septic shock:

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      0.9–1.8 U/hr, run at a fixed rate

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    Refractory pulseless cardiac arrest

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      40 units IV X 1 dose

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  Side effects

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    GI ischemia

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    Cardiac effects

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      Coronary ischemia

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      Bradycardia

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      Arrhythmias

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      Decrease in cardiac output

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      Fluid retention

Milrinone

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  Phosphodiesterase inhibitor acts by causing an increase in intracellular cyclic adenosine monophosphate (cAMP) and calcium.

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  Effects

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    Improves cardiac output due to inotropic effect, and reduces afterload

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    Improves right heart function due to:

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      diastolic relaxation leading to right heart filling.

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      reduction in right atrial pressure and mean pulmonary artery pressure.

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      dilation of coronary arteries.

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    Pulmonary vasodilator

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  Uses

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    To improve cardiac output in patients with:

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      adrenergic receptors dysfunction due to downregulation or desensitization from chronic heart failure or use of beta blockers.

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      pulmonary hypertension.

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      severe congestive heart failure (CHF) refractory to other medical therapy.

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    Due to risk of worsening outflow obstruction, it is not recommended in patients with:

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      hypertrophic cardiomyopathy.

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      significant aortic valve disorder.

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      significant pulmonary valve disorder.

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  Dose

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    Hemodynamic effects are dose related.

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    50 mcg/Kg bolus over 10 min, followed by an infusion, or an infusion without a bolus

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    Infusion: 0.25–0.75 mcg/kg per min

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  Side effects

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    Ventricular arrhythmias

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    Supraventricular arrhythmias

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    Hypotension due to decreased peripheral vascular resistance

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    Hypokalemia

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    Thrombocytopenia

Midodrine

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  An alpha receptors agonist causing vasoconstriction

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  Given orally

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  Side effects

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    Bradycardia

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    Fainting

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    Dizziness

Cardiac Rhythm Disorders

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  Bradycardia

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    Sinus bradycardia

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    First-degree AV block

    

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    Second-degree AV block:

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      Mobitz type I (Wenckebach phenomenon)

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      Mobitz type II

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    Third-degree atrioventricular (AV) block

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  Tachycardia

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    Narrow QRS complex (<0.12 sec) supraventricular tachycardia

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      Regular rhythm

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        Sinus tachycardia

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        Atrial flutter

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        AV nodal reentry

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      Irregular rhythm

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        Atrial fibrillation (AF)

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        Atrial flutter with variable block

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        Atrial tachycardia with variable block

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        Multifocal atrial tachycardia

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    Wide QRS complex (≥0.12 sec) tachycardia

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      Regular rhythm

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        Monomorphic ventricular Tachycardia (VT)

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        Supraventricular tachycardia (SVT) with aberrancy

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      Irregular rhythm

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        AF with aberrancy

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        Preexcited AF (AF + Wolff-Parkinson-White syndrome [WPW])

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        Polymorphic VT

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        Torsades de pointes

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        Ventricular fibrillation (VF)

Manifestations of Cardiac Rhythm Disorders

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  Asymptomatic

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  Unstable patients with acute signs/symptoms

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    Ischemic chest discomfort

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    Hypotension

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    Cardiogenic shock

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    Acute heart failure

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  Acute cardiac arrest

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    VF

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    Pulseless ventricular tachycardia (pVT)

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    Asystole

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    Pulseless electrical activity (PEA)

Management of Bradycardia

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  Atropine

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    First choice

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    Dose: 1 mg IV bolus, repeated every 3–5 min until maximum dose of 3 mg

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    Mechanism of action

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      Anticholinergic (parasympatholytic) drug

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      Inhibits muscarinic acetylcholine receptors

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  Dopamine

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    May be used if atropine does not work

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    May be considered with or without transcutaneous pacemaker

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    Dose: 5–20 mcg/min infusion, titrated to patient response, tapered slowly

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    Mechanism of action

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      Chronotropic effect

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  Epinephrine

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    May be used if atropine does not work

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    May be considered with or without transcutaneous pacemaker (TCP)

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    Dose: 2–10 mcg/min infusion, titrated to patient response

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    Mechanism of action

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      Chronotropic effect