The Role of Vasopressors in the Management of Circulatory Failure

Educational Objectives

The goal of this program is to improve the management of circulatory failure. After hearing and assimilating this program, the clinician will be better able to:

1. Recognize etiologies of circulatory failure.

2. Choose appropriate vasopressors for the treatment of
circulatory failure.

Summary

Definition of circulatory failure: multiple definitions generally related to failure of circulation; frequently cardiac in origin; other causes include lack of volume or circulatory resistance; final common pathway lack of supply of nutrients (eg, oxygen) or removal of metabolic products (eg, lactate)

Shock: syndrome of impaired oxygenation and perfusion of tissue; mechanisms include absolute or relative decrease in delivery of oxygen, ineffective perfusion of tissues, and ineffective utilization of delivered oxygen

Signs and symptoms: include abnormal mental status and hypotension; hypotension considered deviation from patient’s baseline blood pressure; additional signs include tachypnea, tachycardia, cold and clammy skin, oliguria, metabolic acidosis, high anion gap, and hyperlactatemia

Causes of high anion gap: causes include methanol, uremia (chronic renal failure), diabetic ketoacidosis, alcohol-induced acidosis, starvation, some medications, infection, infusion of iron, inborn errors of metabolism (eg, Cori B hyperlactatemia; liver of patients with Cori B inadequate for conversion of lactate); increased lactate, ethylene glycol, salicylates, carbon monoxide, other inhaled agents or toxins, cyanide, congenital heart disease, antibiotics (especially aminoglycosides), theophylline, and toluene

Classification of shock: hypovolemic, cardiogenic, distributive, and obstructive

Etiologies: hypovolemic — hemorrhagic and nonhemorrhagic; cardiogenic — myopathic, dysrhythmic, and mechanical valvular; distributive — adrenal crisis (lack of cortisol), sepsis, systemic inflammatory response syndrome, toxic shock, end-stage liver disease, and anaphylaxis; obstructive — pulmonary embolism, cardiac tamponade, and tension pneumothorax

Resuscitation: consider airway, breathing, and circulation; blood pressure equals cardiac output multiplied by systemic vascular resistance; cardiac output equals stroke volume multiplied by heart rate; factors include preload, pump, and afterload; ensure adequate repletion of preload (30 mL/kg ideal body weight); administer fluid as rapidly as needed; not all patients require full 30 mL/kg; administer sufficient quantity to address problem

Cannon and Rosenblueth receptors: β1 — chronotropic, dromotropic, and inotropic effects; α1 — vasoconstriction; α2 — works on mixed smooth muscle only (not cardiac muscle); β2 — associated with relaxation of smooth muscle; can lead to hypotension in excess; V1 — vasopressin-type receptors; discovered in early 2000s; G proteins; cause contraction of smooth muscles

Vasopressors: effect predominantly α at high doses; reduction of total amount of agent administered may ameliorate problems; vasopressors act across continuum of effects; each agent has dose-dependent effects; balance desired effects with adverse drug reactions; tailor choice of agent to perceived deficit (eg, preload, pump, afterload); adequate resuscitation required before tailoring of preload; vasoactive therapies serve as bridge to improve perfusion of end organs

Choice of vasopressors: norepinephrine generally preferred catecholamine; epinephrine initial vasopressor of choice for septic, cardiogenic, and hypovolemic shock; side effects include dysrhythmias (eg, tachycardia) and increased lactate; speaker considers dopamine second- or third-line agent only (does not provide benefit for renal perfusion); most vasopressors pure α agents at pharmacologic doses

Dobutamine: agent of choice for cardiogenic shock; only add-on option for septic shock

Vasopressin: should not be titrated; long time required for onset of effect; add-on agent (not first line); requires caution in patients with myocardial depression

Milrinone: short-term alternative (causes tachyphylaxis)

Strategies: clinical trials of inotropy and heart failure showed poorer survival in patients treated with pure vasoconstrictors (eg, norepinephrine); some evidence suggests use of analogues of vasopressin in appropriate dosages associated with better rate of survival; selected vasotherapy in appropriate settings likely to benefit some patients; vasoactive therapy seems beneficial for vasodilatory shock; some cardiac evidence favors noncatecholamines

Agents: norepinephrine — first-line agent; maximum dose 100 µg/min; vasopressin — second-line agent; should not be titrated; some promise of improved outcome in pure cardiogenic shock; manipulation of specific adrenergic receptors not additive

Combinations: employed in “desperate situations” but survival rare; use of 2 catecholamines plus vasopressin portends poor outcome unless readily correctable cause for shock identified and treated; 4 vasopressors almost uniformly fatal

Readings

Avni T et al: Vasopressors for the treatment of septic shock: systematic review and meta-analysis. PLoS One 2015;10(8):e0129305; Belletti A et al: The effect of inotropes and vasopressors on mortality: a meta-analysis of randomized clinical trials. Br J Anaesth 2015 Nov;115(5):656-75; Belletti A et al: Non-adrenergic vasopressors in patients with or at risk for vasodilatory shock: a systematic review and meta-analysis of randomized trials. PLoS One 2015;10(11):e0142605; Cecconi M et al: Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med 2014 Dec;40(12):1795-815; Jentzer JC et al: Pharmacotherapy update on the use of vasopressors and inotropes in the intensive care unit. J Cardiovasc Pharmacol Ther 2015 May;20(3):249-60; Morozowich ST et al: Pharmacologic agents for acute hemodynamic instability: recent advances in the management of perioperative shock- a systematic review. Ann Card Anaesth 2015 Oct-Dec;18(4):543-54; Nguyen HB et al: Comparative effectiveness of second vasoactive agents in septic shock refractory to norepinephrine. J Intensive Care Med 2017 Aug;32(7):451-9; Tarvasmaki T et al: Current real-life use of vasopressors and inotropes in cardiogenic shock — adrenaline use is associated with excess organ injury and mortality. Crit Care 2016 Jul 4;20(1):208.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Naylor was recorded at the Survey of Current Issues in Surgical Anesthesia, held November 27 to December 1, 2017, in Naples, FL, and presented by the Cleveland Clinic Anesthesiology Institute. For information about upcoming CME opportunities from the Cleveland Clinic, please visit www.ccfcme.org. The Audio Digest Foundation thanks the speakers and sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

AN601401

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.