1 CVS Drugs-1

Cardiovascular Drugs for Anesthesia

Speaker: Dr. Brighton T. Dzikiti, PhD, MSC, BVSc

Affiliation: Anesthesiology Department of Clinical Science, Contributions from Dr. J Maney

Lecture Objectives

• Familiarity with Essential Concepts:

  • Basic cardiovascular physiology related to cardiac output (CO) and tissue perfusion: Understand how CO influences oxygen delivery to tissues and the importance of maintaining adequate perfusion during anesthesia.

  • Basic receptor physiology: Grasp the role of different receptors in cardiovascular function and drug interactions.

  • Drug mechanisms of action: Review pharmacodynamics of key cardiovascular agents used in anesthetic practice.

  • Physiological effects of drugs: Examine how pharmacologic agents impact cardiovascular parameters.

  • Indications for drugs in anesthetized patients: Identify clinical scenarios that warrant specific drug interventions in anesthesia.

  • Practical Ability: Enhance skills in selecting appropriate treatments tailored to unique patient clinical situations.

Strategies for Treating Hypotension

• Administer vasopressors when necessary to maintain adequate blood pressure levels.

• Use fluid resuscitation as an initial approach to restore intravascular volume and improve circulation.

• Monitor hemodynamic parameters closely to assess the effectiveness of interventions and adjust treatment accordingly. Consider patient-specific factors such as age, comorbidities, and the underlying cause of hypotension to tailor treatment plans effectively.

Initial Steps:

• Evaluate Patient:

  • Adjust the vaporizer settings if the patient appears too deep for the stimulation level.

  • If the patient is light, consider administering a MAC-sparing agent (such as an opioid) to help lower anesthetic requirements before making further adjustments.

  • If the patient presents with bradycardia and hypotension, promptly administer an anticholinergic agent to counteract vagal effects.

Fluid Administration:

• Fluid Therapy:

  • Administer crystalloid and/or colloid fluid boluses based on the severity of hypotension and ongoing losses to restore circulating volume and improve perfusion.

Persistent Hypotension Options:

• Vasopressors and Inotropes:

  • Consider initiating vasopressor therapy and inotropic agents to support blood pressure and myocardial performance when fluid therapy is insufficient.

Cardiovascular Drug Classes

Key Categories:

• Anticholinergics: Used to manage bradycardia and related issues.

• Antiarrhythmics: Drugs tailored for correcting arrhythmias in anesthetized patients.

• Vasopressors/Inotropes:

  • Adrenergic agonists: Effective agents for increasing vascular tone and improving cardiac output.

  • Vasopressin: Important non-adrenergic agent that can help in cases of vasodilatory shock.

Cardiovascular Physiology Review

• Understanding the role of blood pressure regulation and cardiac function in different physiological states.

• Mechanisms of action for various vasopressors and their impacts on hemodynamics.

• Norepinephrine: A potent alpha-adrenergic agonist that increases systemic vascular resistance and enhances cardiac output, making it a first-line treatment for septic shock.

• Epinephrine: A non-selective adrenergic agonist that increases heart rate and myocardial contractility, commonly used in cardiac arrest and anaphylaxis.

• Dopamine: A precursor to norepinephrine that can have dose-dependent effects on heart rate and blood pressure; at low doses, it primarily acts on dopaminergic receptors to increase renal blood flow, while higher doses stimulate beta-adrenergic receptors to enhance cardiac output.

• Vasopressin: An antidiuretic hormone that causes vasoconstriction and increases blood pressure by acting on V1 receptors, often used in conjunction with other vasopressors in critical care settings.

• Phenylephrine: A selective alpha-1 adrenergic agonist used primarily as a decongestant and to increase blood pressure in hypotensive patients; it is often administered in surgical settings to maintain hemodynamic stability.

• Norepinephrine: A potent vasopressor and neurotransmitter that primarily stimulates alpha-1 adrenergic receptors to cause vasoconstriction, thereby increasing systemic vascular resistance and blood pressure; it also has some beta-1 adrenergic activity to enhance cardiac contractility.

Goal: Optimize Oxygen Delivery to Tissues (DO2)

• Key Factors in DO2:

  • Cardiac output (CO): The volume of blood the heart pumps per minute.

  • Hemoglobin (Hb) Content: The amount of oxygen-carrying hemoglobin present in the blood.

  • Oxygen saturation of Hb (SaO2): The percentage of hemoglobin saturated with oxygen.

  • Formula: DO2 = CO x CaO2 (blood O2 content) ~ CO x Hb x SaO2.

Cardiac Output (CO) Equation

• Formula:

  • CO = Heart Rate (HR) x Stroke Volume (SV).

• Stroke Volume Influencers:

  • Key factors affecting stroke volume include preload (the degree of ventricular stretch), afterload (the resistance the heart must overcome to eject blood), and contractility (the heart's intrinsic ability to pump).

  • An increase in preload or contractility tends to enhance CO, while an increase in afterload can diminish it.

Drug Targets for Optimizing Cardiac Output

• Manipulating Variables:

  • Heart Rate: Adjust using anticholinergics and antiarrhythmics since low HR can decrease CO, while excessively high or irregular HR can lead to compromised cardiac output as well.

  • Contractility: Inotropic agents are utilized when contractile strength is inadequate, significantly affecting CO.

  • Afterload/Preload: Carefully adjust afterload with vasopressors since anesthetics commonly induce vasodilation, impacting cardiovascular stability.

Anticholinergics

Definition:

• Competitive antagonists at muscarinic acetylcholine receptors (antimuscarinic).

• Also antagonized by neuromuscular blocking drugs (NMBDs) at nicotinic receptors.

Effects:

• Decrease parasympathetic tone: This results in effective parasympatholytic effects.

• Increase heart rate (chronotropy) and conduction speed through the AV node (dromotropy), counteracting conditions such as bradycardia.

Muscarinic Receptors and Their Effects

• M1: Found in CNS, salivary glands, and stomach (related to H+ secretion).

• M2: Present in heart, CNS, and airway smooth muscle (slows HR).

• M3: Located in CNS, salivary glands, stomach, airway smooth muscle, and vascular endothelium (associated with actions like salivation and bronchoconstriction).

Indications for Anticholinergics

When to Use:

• Indicated in cases of bradycardia due to increased vagal tone resulting from conditions such as:

  • Intubation procedures.

  • Vomiting episodes.

  • Manipulation of gastrointestinal or hepatobiliary structures.

  • Opioid administration postoperatively.

  • Specific breeds that are brachycephalic and prone to respiratory distress.

Adverse Effects of Anticholinergics

• Gastrointestinal:

  • Including increased viscosity of saliva, ileus, and colic (particularly concerning in horses and ruminants).

  • There may be reduced pressure in the lower esophageal sphincter leading to reflux potential.

• CNS Effects:

  • Sedation can commonly occur.

• Respiratory:

  • Bronchodilation is often a noted effect, offering potential benefits in specific circumstances.

• Ophthalmic:

  • Effects include mydriasis (notable with atropine); however, contraindicated in glaucoma as it can complicate pupil evaluation in resuscitation scenarios.

Paradoxical Bradycardia

Mechanism:

• The blockade of presynaptic inhibitory M1 receptors may lead to increased release of ACh, a phenomenon more likely at lower doses.

Symptoms:

• This reaction may generate initial bradycardia or atrioventricular block within a minute post-injection, warranting monitoring and prompt management.

Anticholinergics: Atropine

Administration:

• Routes include IV, IM, SQ, and intratracheal.

• Dosage:

  • For bradycardia: Administer 0.5 mg IV every 3-5 minutes as needed, up to a total of 3 mg.

  • For organophosphate poisoning: Administer 1-2 mg IV initially, with repeated doses as necessary.

  • For anaphylaxis: Administer 0.3-0.5 mg IM every 5-15 minutes as needed, depending on the severity of the reaction.

  • For cardiac arrest: Administer 1 mg IV/IO every 3-5 minutes during resuscitation efforts, with a total maximum dose of 3 mg.

  • For asthma exacerbations: Administer 0.3-0.6 mg nebulized every 20 minutes for up to three doses, or 0.01-0.03 mg/kg subcutaneously.

  • For severe cases, consider continuous nebulization at 0.5-1 mg/hour, monitoring the patient closely for any adverse reactions.

Onset:

• Approximately 1 minute when administered IV.

Duration:

• Typically lasts 30-60 minutes.

Notable Effects:

• While relatively effective, can induce marked tachycardia and crosses both the blood-brain barrier and placenta, necessitating caution in specific cases.

Anticholinergics: Glycopyrrolate

Administration:

• Routes include IV, IM, and SQ.

Onset:

• Varies from 1–5 minutes when given IV.

Duration:

• Approximately 2-3 hours.

Notable Effects:

• Potential for mild-to-moderate tachycardia is present, but unlike atropine, it does not cross the placenta or the blood-brain barrier; however, the slower onset makes it unsuitable for immediate emergencies.

Antiarrhythmic Drugs Overview

Class IB: Lidocaine

• Mechanism: A sodium channel blocker primarily indicated for treating ventricular arrhythmias (VPCs, ventricular tachycardia).

• Administration: Short-acting; typically given as a bolus followed by a CRI (constant rate infusion).

• Treatment Criteria: Indications for treatment include hypotension, inadequate perfusion, R-on-T phenomena, presence of multiform VPCs, or a rapid heart rate exceeding 180 bpm.

Antiarrhythmic Drugs

• Class II: Beta-blockers (Esmolol, Atenolol):

  • Effective for managing severe sinus or supraventricular tachycardia and occasionally utilized during anesthesia under specific clinical conditions (e.g., pheochromocytoma in dogs, hyperthyroidism in cats).

  • Notably, Esmolol is commonly utilized due to its rapid onset and short duration of action, making it ideal for modulating acute tachycardias.

Adrenergic Receptors Review

Pressors/Inotropes:

• The majority of these agents act on adrenergic receptors, excluding vasopressin.

• α-1 and α-2: Primarily induce vasoconstriction, affecting systemic vascular resistance.

• β-receptors:

  • β-1: Focus on increasing inotropy (contractility) and chronotropy (heart rate).

  • β-2: Cause vasodilation and bronchodilation, particularly relevant during respiratory distress or asthmatic events.

Vasopressors/Inotropes: Adverse Effects

Overstimulation Risks:

• α Overstimulation:

  • May lead to vasoconstriction, decreased peripheral perfusion, and elevated central perfusion, all of which can increase the cardiac workload significantly.

• β-1 Overstimulation:

  • Often results in tachyarrhythmias and increased myocardial oxygen demands, potentially leading to ischemia.

• β-2 Overstimulation:

  • Causes excessive vasodilation which may lower preload, resulting in inadequate heart filling.

Vasopressor & Inotrope Drugs List

Common Medications:

• Adrenergic: Mixed agents include Dopamine, Ephedrine, Norepinephrine, Epinephrine.

• Primary β (Inotropes): Dobutamine (and Isoproterenol).

• Primary α: Phenylephrine, particularly noted for its selective α1 effects.

• Non-adrenergic: Vasopressin, which has a unique mechanism distinct from adrenergic agents.

Inotropes: Dopamine

• Mechanism: Exhibits dose-dependent receptor agonism.

• Low Dose (0.5-3 mcg/kg/min): Primarily acts via dopamine receptor agonism.

• Medium Dose (3-10 mcg/kg/min): Engages β-adrenergic agonism leading to increased inotropy and chronotropy.

• High Dose (>10 mcg/kg/min): Activates both β- and α-adrenergic pathways to increase inotropy while facilitating vasoconstriction.

• Administration: Takes advantage of a short half-life and is commonly utilized as a CRI in cases with hypotension in canine and feline patients.

Inotropes: Dobutamine

• Effects: Functions primarily as a positive inotrope via β1 agonism, offering secondary positive chronotropic effects at higher dosages.

• Administration: Like Dopamine, it has a short half-life and is used as a CRI; it is particularly used for managing hypotension in horses undergoing inhalation anesthesia and in RUSVM donkeys as well.

Vasopressors: Ephedrine

• Action: Serves as a mixed agonist primarily affecting α receptors for vasoconstriction mixed with some β1 and β2 effects that confer positive inotropy.

• Considerations: Notable risk of reflex bradycardia which can arise from vasoconstrictive actions, there is also potential CNS stimulation that may elevate MAC requirements during anesthesia.

• Duration: Action lasts around 20-30 minutes, and effectiveness may diminish with repeated doses.

Vasopressors: Phenylephrine

• Administration: Administered IV as CRI due to its short-acting nature.

• Mechanism: Selective α-1 agonist that induces vasoconstriction, effectively raising blood pressure.

• Risks: Can diminish cardiac output and tissue perfusion if myocardial contractility is poor; its vasoconstrictor effects may lead to splenic contraction, thus useful in cases of nephrosplenic entrapment in horses.

Vasopressors: Norepinephrine

• Mechanism: Acts as a mixed agonist, primarily α for vasoconstriction which also increases preload, and β1 for improving contractility.

• Clinical Use: Regarded as the first-line treatment for septic shock in human medicine and is ideally suited for cases requiring immediate pressor support. It is also short-acting and delivered via CRI.

Vasopressors: Epinephrine

• Mechanism: A non-selective agonist impacting α, β1, and β2 pathways.

• Indications: Often indicated during cardiopulmonary resuscitation or in anaphylactic shock scenarios; caution is warranted due to the potential for arrhythmogenic results, particularly ventricular fibrillation.

Vasopressors: Isoproterenol

• Mechanism: A potent β1 and β2 agonist.

• Effects: Enhances contractility and heart rate via β1 stimulation while providing bronchodilation due to β2 effects.

• Clinical Use: Frequently indicated for 3rd degree AV block management (b1 effect) along with providing therapeutic bronchodilation (b2 effect); short half-life and typically administered as a CRI.

Vasopressin (ADH)

• Mechanism: Functions as a non-adrenergic sympathomimetic agent that induces vasoconstriction through V1 receptors.

• Indications: Valuable in cases of refractory shock or unresponsive hypotension when administered as a CRI; however, caution is necessary as it can lead to significant vasoconstriction, risking tissue ischemia and may synergize with epinephrine in CPR scenarios.

Strategies for Treating Hypotension

• Address Underlying Causes:

  • Determine if reduced contractility is present; in such cases, initiate treatment with inotropic agents.

  • In cases of vasodilation, implement vasoconstrictors to restore hemodynamic stability.

Case Examples Framework

Objectives:

• Analyze cardiac output, stroke volume (considering preload, contractility, afterload), heart rate, systemic vascular resistance, and arterial blood pressure through pharmacotherapy interventions (chromatropes, inotropes, vasodilators, maintenance fluids, vasopressors).

Case 1 Summary

• Patient: 2 y.o F Beagle undergoing an OHE surgery.

• Premeds: Acepromazine, hydromorphone.

• Induction: Propofol, maintained on isoflurane.

• Observations: 20 minutes into surgery - T=99.5°F, P=45, R=12, Doppler BP=75 mmHg.

• Diagnosis/Treatment Challenge: Underlying causes and interventions are being assessed based on parameters presented.

• Potential causes for hypotension include hypovolemia, anesthetic depth, or cardiac issues.

• Interventions may involve fluid therapy, adjusting anesthetic levels, or administering cardiovascular support medications. Further monitoring of vital signs is essential to determine the effectiveness of these interventions and to guide additional treatment strategies. Continuous assessment of the patient's response to treatment will help identify any need for more aggressive measures or adjustments in the therapeutic approach.

Case 2 Summary

• Patient: 12 y.o MN GSD presented with hemoabdomen secondary to splenic hemangiosarcoma.

• Before Induction: ECG evaluation showed MAP = 55 mmHg indicating significant hypotension.

• Diagnosis/Treatment Challenge: Analytical approach to address hypotensive status with effective pharmacotherapy.

• Initiated fluid resuscitation with crystalloids to stabilize blood pressure.

• Administered vasopressor agents to improve mean arterial pressure and ensure adequate organ perfusion.

• Continued monitoring of vital signs and laboratory parameters to assess response to treatment and adjust therapy as needed.

• Consideration of additional interventions such as inotropic support if hypotension persists despite initial management.

Case 3 Summary

• Patient: 18 y.o TB gelding weighing 525 kg diagnosed with suspected strangulating bowel obstruction (colic).

• Pre-anesthetic Treatment: 1L hypertonic saline and 10L Norm-R administered.

• Intra-op Direct MAP Reading: 62 mmHg denoting ongoing hypoperfusion requiring treatment.

• Diagnosis/Treatment Challenge: Establishing appropriate management strategies tailored to restore hemodynamic stability.

Case 4 Summary

• Patient: 5-month-old F DSH for OHE surgery.

• Premeds: Acepromazine, hydromorphone, ketamine.

• Induction: Ketamine/Diazepam, maintained on isoflurane (currently light depth indicated).

• Observations: 20 minutes into surgery - T=99.0°F, P=140, R=15, Doppler BP=70 mmHg.

• Diagnosis/Treatment Challenge: Further analysis required to gauge treatment efficacy and refine strategy.

Conclusion

• University: Ross University School of Veterinary Medicine

• Q&A: Open for questions from participants.