“Pressors” in Distributive Shock in Adults

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“Pressors” in Distributive Shock in Adults

Thank you, Dr Dastmalchi, for requesting this POTD. I will review “pressors” for cardiogenic shock separately

  • Vasopressors- Pure vasoconstriction without any inotropy eg Phenylephrine and Vasopressin

  • Inotrope- Increase cardiac contractility à improving SV and cardiac output without any vasoconstriction eg Milrinone

  • Inopressors - a combination of vasopressors and inotropes, because they lead to both increased cardiac contractility and increased peripheral vasoconstriction eg Norepinephrine, Epinephrine and Dopamine

Norepinephrine- Inopressor

  • First line vasopressor in septic shock per Surviving Sepsis Guidelines

  • Less arrhythmogenic than Epinephrine and Dopamine


Mechanism of action

  • Stimulates alpha-1 and alpha-2 receptors

  • Small amount of beta-1 agonist- modest inotropic effect

  • Increased coronary blood flow and afterload

  • Increases venous tone and return with resultant increased preload

Adverse effects

  • Norepinephrine is considered safer than both Epinephrine and Dopamine.

  • ARR of 11% compared to dopamine with NNT 9

  • NE superior in improving CVP, urinary output, and arterial lactate levels compared to Epinephrine, Phenylephrine, and Vasopressin.

Indications

  • First-line pressor choice in distributive shock, including both neurogenic and septic shock

  • Norepinephrine as the only first-line pressor per SSC guidelines

Dosing

  • Use weight-based dosing to avoid the adverse effects associated with norepinephrine use

  • Weight-based dosing is based on GFR

  • Norepinephrine has a rapid onset of action (minutes) and can be titrated every 2-5 minutes

Epinephrine- Inopressor

Mechanism of action

  • Beta-1 and beta-2 receptors agonism à more inotropic effects than norepinephrine

  • Epinephrine greatly increases chronotropy (heart rate) and thus stroke volume

  • Some stimulatory effect on alpha-1 receptors

  • Lower doses (1-10 mcg/min) à a beta-1 agonist

  • Higher doses (greater than 10 mcg/min) à an alpha-1 agonist

Adverse effects

  • Associated with an increased risk of tachycardia and lactic acidosis

  • Hyperglycemia

  • Increased incidence of arrhythmogenic events associated with epinephrine

  • More difficult use lactate as a marker of the patient’s response to treatment

Indications

  • SSC guidelines recommend epinephrine as a second-line agent, after norepinephrine

  • “push-dose pressor”

  • Due to beta-2 receptors agonism causing bronchodilation, epinephrine is first-line agent for anaphylactic shock

Dosing

  • Guidelines for anaphylactic shock recommend an initial bolus of 0.1 mg (1:10,000) over 5 minutes, followed by an infusion of 2-15 mcg/min however associated with adverse cardiovascular events

  • For septic shock start epinephrine at 0.05 mcg/kg/min (generally 3-5 mcg/min) and titrate by 0.05 to 0.2 mcg/kg/min every 10 minutes. maximum drip rate is 2 mcg/kg/min

Dopamine- Inopressor

  • Fallen out of favor

  • Associated with higher arrhythmogenic events

Mechanism of action

  • Effects are dose-dependent

  • Low doses à dopaminergic receptors à leads to renal vasodilation à increased renal blood flow and GFR although studies failed to demonstrate improved renal function with dopamine use clinically

  • Moderate doses à beta-1 agonism à increased cardiac contractility and heart rate

  • High doses à alpha-1 adrenergic effects à arterial vasoconstriction and increased blood pressure

Adverse Effects

  • Several large, multi-center studies that demonstrate increased morbidity associated with its use

  • Significantly higher rates of dysrhythmias à NNH 9

Indications

  • Rescue medication when shock is refractory to other medications

Dosing

  • Start at 2 mcg/kg/min and titrate to a maximum dose of 20 mcg/kg/min.

  • Less than < 5 mcg/kg/min à vasodilation in the renal vasculature

  • 5-10mcg/kg/min à beta-1 agonism

  • 10 mcg/kg/min à alpha-1 adrenergic

Vasopressin- Vasopressor

  • Add vasopressin (doses up to 0.04 units/min) to norepinephrine to help achieve MAP target or decrease norepinephrine dosage

  • Restore catecholamine receptor responsiveness, particularly in cases of severe metabolic acidosis.

  • pH independent

  • Pure pressor à increase vasoconstriction with minimal effects on chronotropy or ionotropy

Mechanism of action

  • At low doses (< 0.04 units/min) à increases vascular resistance (V1)

  • No effect on heart rate and cardiac contractility

Adverse Effects

  • Vasopressin has been shown to be as safe as norepinephrine at lower doses

  • Increases SVR and afterload and decreases cardiac output although unclear if effect significant at lower doses

Indications

  • Second line vasopressors per SSC guidelines for septic shock

  • pH independent- Vasopressin in combination with epinephrine demonstrated improved ROSC in cardiac arrest patients with initial arterial pH <7.2 compared with epinephrine alone

Dosing

  • Steady dose at 0.03-0.04 units/min

  • Vasopressin is not titrated to clinical effect as are other vasopressors

  • Think about it more as a replacement therapy and treatment of relative vasopressin deficiency

Phenylephrine- Vasopressor

  • Pure pressor à increase vasoconstriction with minimal effects on chronotropy or ionotropy

  • SSC guidelines does not make rated recommendations on Phenylephrine

  • Limited clinical trial data

Mechanism of action

α1 agonism with peripheral vasoconstriction

Adverse Effects

  • Bradycardia - decrease in heart rate mediated by the carotid baroreceptor reflex 2/2 increase in SVR

  • Increases SVR and afterload and decreases cardiac output

Indications

  • Patients that are susceptible to beta-adrenergic generated arrhythmia

  • Push dose formulation

  • Refractory shock

Dosing

0.1-2mcg/kg/min (onset: minutes, duration: up to ~20 minutes)

References:

Emdocs

LITFL

Pollard, Sacha, Stephanie B. Edwin, and Cesar Alaniz. "Vasopressor and inotropic management of patients with septic shock." Pharmacy and Therapeutics 40.7 (2015): 438.

Amlal, Hassane, Sulaiman Sheriff, and Manoocher Soleimani. "Upregulation of collecting duct aquaporin-2 by metabolic acidosis: role of vasopressin." American Journal of Physiology-Cell Physiology 286.5 (2004): C1019-C1030.

Khanna, Ashish, and Nicholas A. Peters. "The Vasopressor Toolbox for Defending Blood Pressure."

Turner, DeAnna W., Rebecca L. Attridge, and Darrel W. Hughes. "Vasopressin associated with an increase in return of spontaneous circulation in acidotic cardiopulmonary arrest patients." Annals of Pharmacotherapy 48.8 (2014): 986-991.

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Targeted Temperature Management

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Great job on resuscitating that V fib cardiac arrest and achieving sustained ROSC. 

Now what? Cool them!

Whether you cool them or not could determine whether your patient goes into multisystem organ failure in the ICU or walks out of the hospital few weeks later.

 

What:

Targeted temperature management (TTM) to improve survival and neurological outcomes among comatose survivors of patients with cardiac arrest

 

Who:

Adults with out-of-hospital cardiac arrest with an initial shockable rhythm and nonshockable rhythm

 

Inclusion criteria (must meet all criteria)

  • Postcardiac arrest status (any rhythm as a cause of arrest is eligible)

  • ROSC < 30 minutes from EMS/code team arrival

  • Time at induction < 6 hours from ROSC

  • Comatose status (patient does not follow commands)

  • MAP ≥ 65 mm Hg (may include use of vasopressor drugs)

Exclusions may include

  • DNR advanced directive, MOLST, poor baseline status, or terminal disease

  • Traumatic etiology for the arrest

  • Active bleeding or known intracranial bleeding (relative)

  • Cryoglobulinemia (relative)

  • Pregnancy (relative; consider obstetrician/gynecologist consultation)

  • Recent major surgical procedure (relative)

  • Severe sepsis/septic shock as cause of arrest (relative)

Why:

  • Decreased fever-related tissue injury

  • Reduction in ischemic-reperfusion injury

  • Cerebral metabolic rate decreases by a 6-7% for every 1ºC drop in body temperature which reducing oxygen demand, preserving phosphate compounds and preventing lactate production and acidosis

  • Bernard, et al (2002) found an Absolute Risk Reduction (ARR) for death or severe disability of 23%, NNT was 4.5

  • The Hypothermia After Cardiac Arrest (HACA) Group (2002) found an ARR for unfavourable neurological outcome of 24%, and NNT of 4


How:

  • IV cold saline 2-3 mL/kg

  • Cooling vest and cooling machine- Arctic Sun

  • If shivering does not occur, do not use neuromuscular blockade

  • If paralysis employed, titrate to degree of shivering- do not need train-of-four monitoring

  • Sedation of choice is institution dependent (MMC CICU uses Fentanyl and Midazolam)

When:

Initiation of TTM within122 minutesof hospital admission was associated with improved survival.
Most guidelines recommend initiation within6 hours

What temperature should be targeted:

This remains controversial, with guidelines accepting a range of temperature targets from 33-36C. Available evidence shows no benefit to hypothermia (33C) compared to normothermia (36C). In the absence of evidence, targeting 36C is prudent

  • TTM36 is more hemodynamically stable than TTM33, which is relevant because these are often very unstable patients.

  • TTM36 avoids electrolytic shifts associated with raising and lowering the temperature.

  • Hypothermia at 33C suppresses immune function and associates with increased rates of pneumonia.

  • TM33 will induce bradycardia, which is dangerous in patients with underlying torsades de pointes.

References

Bernard SA et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557-63. PMID 11856794

Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549-56. PMID 11856793

Nielsen N et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med 2013; 369: 2197-206. PMID 24237006

Stanger, Dylan, et al. "Door‐to‐targeted temperature management initiation time and outcomes in out‐of‐hospital cardiac arrest: insights from the Continuous Chest Compressions Trial." Journal of the American Heart Association 8.9 (2019): e012001.

Donnino, Michael W., et al. "Temperature management after cardiac arrest: an advisory statement by the advanced life support task force of the international liaison committee on resuscitation and the American Heart Association emergency cardiovascular care committee and the council on cardiopulmonary, critical care, Perioperative and Resuscitation." Circulation 132.25 (2015): 2448-2456.

REBEL EM
LITFL
EB Medicine
Mayo Clinic Florida TTM Guideline

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