Medical Pharmacology Chapter 43:  Adult Cardiac Procedures

Cardiovascular Anesthesia: Choice of Agents and Related Issues

• Overview:

  •  Probably no single "ideal" anesthetic for patients with coronary vascular disease

  •  Anesthetic choice, as assessed by large, randomized clinical trials, does not appear to influence outcome, i.e. perioperative myocardial infarction incidence (MI incidence = about 4%; mortality = approximately 2%-3%)

• Rationale for anesthetic choice:

  • Nature and extent of pre-existing cardiac disease/dysfunction

  • Pharmacology of the individual drug(s)

  •  Examples:

    •  Case I -- patient has severe congestive heart failure + evidence of significant loss of myocardial muscle mass due to previous infarction

      • Anesthetic choice should favor agents which have relatively less myocardial depressants characteristics 

    •  Case II -- patient has angina which occurs only on significant exertion; otherwise the patient appears healthy

      • Anesthetic choice would favor a volatile agent which would tend to reduce myocardial oxygen demand (myocardial depressant)

  • Most patients would benefit most likely from some degree of myocardial depression induced by the anesthetic agent (with attendant reduction in myocardial oxygen demand); however, patients with very limited myocardial reserve are at risk for congestive heart failure caused by the anesthetic.

Fast Track Recovery

• Changes in anesthetic, perfusion techniques, and surgical approaches: reduced ICU stays: Economic and Clinical factors

• Definition: "fast-track" recovery:

  • Early postoperative awakening and extubation

  • Reduced ICU stay

  • Shortened hospitalization time

• Early extubation-multiple approaches for the cardiac surgical patient

  • Protocols that favor early extubation

    1. Volatile anesthetics + low dose narcotics

    2. Total intravenous (IV) anesthesia with short-acting agents (e.g.,alfentanil (Alfenta), propofol (Diprivan), midazolam (Versed))

    3. Combination of opiates, sufentanil (Sufenta) and morphine, instilled intrathecally prior to induction (with appropriate anesthetic techniques, early extubation (within eight hours) is possible)

Opioids

• Major advantages:

  •  Minimal or no myocardial depression

  •  No change in automaticity (some increase in vagal activity)

  •  Stable hemodynamics, no enhanced sensitivity to catecholamines

  •  Heart rate reduction (except for the opioid meperidine (Demerol) which has an anticholinergic property)

  •  Opioids do not interfere with intraoperative use of autonomic/cardiovascular drugs

  •  Absence of organ toxicity

  •  Assists with postoperative management of pain (analgesia)

  •  Cardiac, renal, CNS autoregulation of blood flow maintained

  •  Limited intraoperative moment-to-moment adjustments

  •  Good patient tolerance to the presence of  an endotracheal tube, nasogastric tube, and/or airway suctioning

•  Disadvantages:

  •  Hypertension/tachycardia during surgical stimulation (for cardiac surgery, these effects could be expected during sternotomy and aortic manipulation)

  •   Bradycardia/Hypotension when opioids are combined with benzodiazepines/other sedatives, during induction

  •  Muscular rigidity during induction (may occur also during emergence)

  •  Awareness may not be noted by intraoperative personnel, if patient is totally paralyzed

  •  Recall of intraoperative activity may occur unless an amnestic agent is also administered

  •  Extended recovery time possible (noting here particularly spontaneous ventilation) -- Less likely with careful dosage selection of opioid and other CNS depressants agents-- (exception remifentanil (Ultiva) common extremely short-acting fentanyl (Sublimaze) derivative which is rapidly hydrolyzed by tissue esterases)

  •  Limited ability to titrate with high-dose procedures

• Use of a "primary opioid" technique: in a patient with significant/severe myocardial dysfunction

• With normal ventricular function, opioids would likely be combined with other anesthetics or vasoactive drugs

• Planned extubation time: major factor in selection of opioid dosage and specific opioid to be used.

• Opioid actions that indirectly affect cardiac status

  •  Bradycardia-- vagus nerve activation

  •  Arterial and venous dilatation due to sympathetic reflex selective suppression (manifestation -- orthostatic hypotension)

  •  Histamine release (particularly for morphine, meperidine (Demerol) and other chemically similar agents)

  •  Indirect actions:  readily managed; do not prevent large opioid dosages for anesthesia application

    • Management of Opioid Effects

      •  "Cholinomimetic" effects -- antagonized by anticholinergic agents, e.g. glycopyrrolate (Robinul), atropine -- use of these agents avoided or limit opioid-induced bradycardia

      •  Hemodynamic (hypotensive) effects:

        • Normovolemic patient, supine, with slow opioid IV infusion for example with morphine 5 mg/minute: minimal hypotension would be seen

        •  Histamine effects can be prevented by histamine₁ and histamine₂  receptor blocking drugs

        •  Hypotensive effects also respond to:

          • Legs-up position

          • IV infusion of fluids

          • Vasoactive drugs such as phenylephrine (Neo-Synephrine) (alpha-adrenergic agonist)

            • Ephedrine is indicated in the management of hypotension secondary to bradycardia and vasodilation

• Characteristics of a commonly used opioid, fentanyl (Sublimaze)

  • Dosage, when used as a single agent: 20-50 ug/kg (starting) + 2-3 micrograms/minute subsequently

  • Consequence:

    1. Very significant analgesia

    2. Sleep

    3. unconsciousness

  • Similar large dosages of morphine, meperidine (Demerol) and similar agents are avoided due to side effects associated with these large dosages

• More about disadvantages associated with high-dosage opioid use:

  • Typically  opioid elimination is SLOW (Exception: remifentanil (Ultiva) (rapidly hydrolyzed by tissue esterases))

    •  Consequences of slow opioid elimination:

      1.  Prolonged times for consciousness recovery

      2.  Prolongation of time to spontaneous ventilation

      3.  Note that prolonged recovery, in this context, may be advantageous since mechanical ventilation support will be continued into the postoperative time-frame, which may last several hours or overnight -- in patients with cardiovascular disorder, the use of narcotic antagonists, e.g. naloxone (Narcan); naltrexone (ReVia) is relatively contraindicated

  • Positive-pressure ventilation is impeded by opioids, which induced apnea and skeletal muscle rigidity

    • In patients breathing pure oxygen prior to anesthesia induction, rigidity which prevents positive-pressure ventilation is not an immediate emergency

      • Rationale:

        1.  If lungs are filled with oxygen, oxyhemoglobin desaturation will be prolonged (due apneic oxygenation) -- typically ample time for rigidity to subside

        2. CO₂ tension rises slowly during this period

      • When rigidity subsides, it is important to correct hypercarbia probably, thus relieving elevated PA pressures and possible systemic hypotension.

    •  Forcing positive-pressure ventilation during opioid-induced rigidity tends to impede cardiac function by reducing venous return, secondary to increased intrathoracic pressure

    •  To relieve opioid-induced rigidity: a fully paralyzing muscle relaxant dose, given IV, will reverse the rigidity within 1-2 minutes

    •  Opioid-related rigidity can occur both during induction and emergence

    •  Reduction in rigidity intensity: small dose of muscle relaxants (reversal by fully, paralyzing doses)

    •  Rigidity, varied in presentations, may resemble seizures; however, in humans seizure is probably not produced even with the very highest doses of fentanyl (Sublimaze)

  •   Intraoperative Awakening

    •  Occurring in response to painful stimuli

    •  Associated with reduced drug concentration

    •  Significant problem because:

      1. Paralyzed patient will not be able to indicate somatic signs of awakening

      2. Autonomic nervous system and/or hemodynamic changes are not reliable indicators of patients' awakening

    • Approaches which reduce likelihood of patient intraoperative awareness

      1.  Adequate administration of preanesthetic agents or intraoperative anesthetic supplementation  (for example addition of a benzodiazepine)

      2.  Opioid Dose titration (titrating  to effect, than maintenance by IV infusion of drug)

      3.  Using muscle relaxants only if needed and only at the minimum dosage required

      4.  Anesthetist awareness of inadequate anesthesia signs

    •  Signs of inadequate anesthesia include:

      •   Somatic signs, which may be difficult to result in the presence of muscle relaxants

        • increased electromyographic activity

        • coughing,  bucking on endotracheal tube

        • movement (particularly when correlated with noxious/painful stimulation which may include manipulation of endotracheal tube, skin incision, sternotomy, electrocautery of skin or periosteum)

      •   Sympathetic nervous system signs:

        • Tearing

        • Sweating

        • Mydriasis -- may be confounding in the presence of some autonomic nervous system drugs

      •   Hemodynamic effects-observation of hemodynamic changes may be made more difficult by drug therapy or by cardiovascular disease itself

        • Increased blood-pressure associated with painful stimulation

        • Increased heart rate associated with painful stimulation (increased heart rate is observed less frequently than an increase in BP)

      •   EEG -- index of CNS electrical activity

        • Presence of "arousal" patterns in the electroencephalogram

        • Evoked potential recovery (e.g. auditory)

    • Intraoperative awareness-solution to the problem:

      • Primary anesthetist responsibility: maintain patient's unconsciousness for the duration of the procedure

        •  The use of an amnestic drug such as midazolam (Versed) or scopolamine is not a substitute for insuring patient unconsciousness

        •  It is possible that intraoperative awakening leads later to sleep disturbances, anxiety attacks, and other unpleasant effects during the postoperative time frame

Intravenous (IV) Sedative-Hypnotics

• Overview

  • A reduced opioid approach involves adjuvants, typically a short-acting sedative administered by IV infusion, e.g. midazolam (Versed) or propofol (Diprivan)

  • Favorable characteristics:

    • Administration can be continued postoperatively in the ICU setting

    • "Fairly rapid" awakening

  • Analysis of two protocols:

    • (1) propofol (Diprivan) infusion in combination with low-dose fentanyl (Sublimaze) with (2) high-dose fentanyl (Sublimaze) in a subset of cardiac surgical patients with low myocardial output

    • Conclusion:

      • (a) Propofol (Diprivan)/reduced-dose fentanyl (Sublimaze) patients awakened earlier with earlier extubation possible.

      • (b) No adverse effect on myocardial contractility

• Midazolam (Versed) is often used to supplement opioid anesthesia -- and heart because of relatively minimal, non-dose-dependent cardiovascular effects

• Etomidate (Amidate):

  • Maintenance of reflex responsiveness

  • Maintenance of sympathetic nervous tone

  • Relatively limited use due to concerns about steroid synthesis inhibition

• Propofol (Diprivan):

  • Vasodilation effect

  • Slight negative chronotropic effect

  • Advantages: rapid control of patient responds to noxious stimulation; short recovery time

• Thiopental (Pentothal):  similar overall to propofol (Diprivan) with a longer recovery time

• Interaction of Sedative-Hypnotics and Opioids:

  1. Hypnotics reduce opioid dosage requirements

     •  Recovery time length may not be shortened

     •  Without concommittant reduction of sedative-hypnotic and opioid dosages, prolonged recovery times may be observed (greater than that associated with either drug alone)

  2. Opioid-mediated Ventilatory/respiratory depression and sleep: Important synergistic interaction

     •  Significant concern (dangerous) in the immediate post-operative time (reduction in noxious stimulation associated with surgery; stimulation which promotes respiration)

     •  Patient may be monitored with less vigilance and early signs of respiratory depression may be missed

  3. Combination of opioids at anesthetic dosages with sedative-hypnotics can precipitate a hypotensive response during induction

     •  Low-dose (< 75 ug fentanyl (Sublimaze); 20 ug sufentanil (Sufenta))administration of an opioid following induction with a hypnotic can produce significant systemic hypertension, which responds to sympathomimetic vasopressor drugs

     •  Advantage of combining a hypnotic and an opioid, insuring unconsciousness, during intraoperative periods of total paralysis, is that resulting hypotension may be really controlled

       • For very critically ill patients who may not tolerate even mild hypotension, the combination of opioid-sedative-hypnotics should be avoided

  4. Effective management of sudden, arousal in response to noxious simulation may involve a drug that produces a rapid CNS response. CNS agents are preferable to vasodilators/sympatholytics because the somatic and/or sympathetic responses may be associated with pain awareness.

     •  Thiopental (Pentothal) (50-150 mg)

     •  Propofol (Diprivan) (25-75 mg)

     •  Alfentanil (Alfenta) (15-50 ug/kg)

     •  Remifentanil (Ultiva) (0.5-2 ug/kg)

Nitrous Oxide (NO)

• Overview:

  •  Supplemental for both intravenous anesthetics and potent inhaled agents

  •  May be the primary anesthetic used with muscle relaxants

• Cardiac surgical application concerns:

  •  Mild, but potentially detrimental effects in patients with compromised cardiac function

  •  NO:

    • Decreases cardiac output

    • Increases systemic vascular resistance (afterload)-this effect on vascular resistance occurs when nitrous oxide is given alone or in combination with opioids

  • Occasionally, NO-induced hypertension and reduced myocardial contractility are sufficient to mandate discontinuation of the agent -- cardiac function typically recovers within minutes (this rapid recovery allows ready testing of patients tolerance to NO)

  • A particular concern has been the observation that in patients with coronary vascular disease, NO may induce ischemia in the region supplied by a "critically" stenotic artery and, as a result, induce regional myocardial dysfunction-- this ischemic NO effect has not been observed in coronary bypass surgery when NO is used to supplement fentanyl (Sublimaze) anesthesia

  •  Other detrimental effects:

    • NO expands air-filled spaces (including air emboli)-spaces which may occur in cardiac chambers or in saphenous vein grafts. -this characteristic has led some to suggest that nitrous oxide should not be used in operations involving extracorporeal circulation

      • If, during a procedure, arterial air embolism is suspected, NO use should be discontinued

    • NO should not be used with pneumothorax, unless a functioning thoracotomy tube has been inserted

    • Some NO advantages (e.g. rapid onset/recovery) are also observed with more current inhaled agents such as desflurane (Suprane) and sevoflurane (Sevorane, Ultane).  These agents do not exhibits expansion in air-filled volumes

    • NO may potentiates truncal rigidity caused by opioids

Inhalational Agents

• Overview:

  • The use inhalational agents in cardiac surgery involves a balancing between desirable features and disadvantages

• Advantages of  inhalation anesthetics

  • Fulfill objectives of anesthesia:

    •  causes unconsciousness

    •  muscle relaxation

    •  rapid ventilatory function recovery (allowing early tracheal extubation postoperatively)

  •  Dose-related  reduction in ventricular work/oxygen consumption

  •  Easily reversible

  •  Amnesia

  •  Titratable myocardial depression

  •  Attenuation of autonomic (sympathetic) response to surgical stimulation and cardiopulmonary bypass

•  Disadvantages of inhalation anesthetics

  •  Myocardial depression-excessive under some conditions

  •   Hypotension, secondary to either vasodilation or reduced by myocardial contractility

  •  Incomplete suppression of sympathetic responses to noxious/painful stimulation

  •  Absence of postoperative analgesia (i.e., sub-anesthetic concentrations do not provide analgesia)

  •  Post-operative shivering, secondary to peripheral vasodilation -- would be accompanied by increased oxygen demand because of excessive heat loss

• In cardiovascular surgery, the combination of volatile anesthetics and narcotics optimizes advantages of both, while reducing the likelihood of untoward systemic responses

• Tailoring of inhalational agents to the patient's needs:  examples:

  • Patient has a high systemic vascular resistance (high afterload, which necessarily increases myocardial oxygen requirements by increasing ventricular wall tension): Appropriate inhalational agent = possibly isoflurane (Forane) which produces vasodilation

  • Patient exhibits cardiac hypertrophy (hypertrophic cardiomyopathy):  Appropriate inhalational agent  = possibly enflurane (Ethrane), taking advantage of that drug's myocardial depressant effect

    •  Hypertrophic cardiomyopathy is usually asymmetrical (affecting only one side) --

      • Myocardial dysfunction occurs because of:

        • Reduced (narrowed) ventricular outflow

        • Reduced ventricular chamber size

        • Valvular dysfunction

      •  Factors that worsen hypertrophic cardiomyopathy -- factors which increased myocardial contractility, e.g.

        • Sympathetic nervous system simulation (stress)

        • Medications, for example digoxin (Lanoxin, Lanoxicaps)

        • Reduced blood return which may occur in dehydration or following excessive diuretic use

      •  Forms of the disease:

        • Idiopathic hypertrophic subaortic stenosis: inherited, autosomal dominant; incidence = about 1 out of 10,000 individuals

        • Acquired hypertrophic cardiomyopathy secondary to high blood pressure (hypertensive hypertrophic cardiomyopathy)

* Drawings courtesy of The Cardiomyopathy Association

• General comments:

  •  Isoflurane (Forane): significant coronary vasodilator (other volatile anesthetics also, but to a reduced extent):  dose-dependent effect; clinically significant at 1 MAC or greater

    • Coronary steal: with specific, regional coronary stenosis, isoflurane (Forane)-mediated dilation of other coronary vessels tend to cause blood shunting away from stenotic arteries

    • Because of coronary steal, isoflurane (Forane) should be used in limited dosages, noting that it is rarely used alone at high concentrations for general anesthesia, but rather in combination with other agents.  

  •  Desflurane (Suprane) and Sevoflurane (Sevorane, Ultane): faster recovery compared to older, volatile anesthetics

    •  Faster recovery may not be advantageous in the context of  postcardiac patients, since more sedation may be required in the ICU before attainment of hemodynamic stability and before extubation which occurs, in the case of early extubation, about 4-6 hours post surgery

• More about Inhalational Agents

  • Volatile agents in patients with good cardiac performance:

    • Isoflurane (Forane) (and halothane (Fluothane), infrequently used in adult patients): effective as primary anesthetics

    • Desflurane (Suprane) and sevoflurane (Sevorane, Ultane): similar properties (hemodynamic) to  isoflurane (Forane)

      • Very rapid onset

      • Rapid recovery

    • Particularly useful in patients with coronary vascular disease but with normal ventricular function

Myocardial Performance

• Patient grouping based on cardiac performance:

  • Good: 

    •  Ejection fraction > 0.5; 

    •  Normal cardiac index (2.5 liters/min/m²)

    •  Normal stroke volume index (40-60 mL/beats/m²)

  •  Poor:

    •  Ejection fraction < 0.3 OR

    •  Low cardiac index (< 2.0 liters/min/m² with normal/elevated preload)

    •  Mechanical abnormalities such as valvular heart disease

  •  Other factors to consider include:

    •  Response to stress, hypertension

    •  Ventricular wall motion abnormalities-may not be sufficient to be reflected in abnormal cardiac performance indices; however, may be indicative of underlying problems which will be evident  intraoperatively

• Anesthetics Use in myocardial dysfunction: Note the importance of dose-related dependencies

  •  Example: a drug may be contraindicated, because of excessive myocardial depression, if used as the primary anesthetic agent; however, when used in combination with another drug, it may be useful

    • Full anesthetic isoflurane (Forane) dose: possibly unacceptable attenuation of cardiac performance

    • Reduced anesthetic isoflurane (Forane) dose: acceptable and allows better management of systemic responses to noxious/painful stimulation

Cardiac Drugs

• Cardiovascular system-related agents, useful to manage  intraoperative developments related cardiac surgery

  • Oligouria (reduced urine output)

  • Hypo- and hyperkalemia (abnormal potassium levels can induce myocardial arrhythmias)

  • Pulmonary hypertension

  • Myocardial ischemia

  • Arrhythmias

  • Hypotension

  • Hypertension

  • Metabolic acidosis/cardiac failure

Premedication for Cardiovascular Surgery

• Overview-rationale for preanesthetic medication

  •  Reduce pain which may be associated with vascular cannulation (without producing cardiac/ventilatory depression)

  •  Amnesia

  •  Anxiolytic effects

  • These objectives are similar to those for other surgeries; however, doses may be affected in accord with the specifics of the cardiovascular disease, the presence of other co-existing diseases as well as the presence of other chronic drug treatments

• Premedication Examples:

  • Patient condition: coronary vascular disease, but with normal or least adequate left ventricular resting function; no pulmonary insufficiency

    • Medications -- generally heavily premedicated before surgery using:

      • An opioid

      • A sedative-hypnotic agent

      • Example #1:

        •  Diazepam (Valium) (0.1-0.2 mg/kg, orally (sip of water)) -- timing = 1-2 hours before transfer to the operating room

        •  Morphine: 0.1 mg/kg intramuscular injection -- timing = 30 minutes before transfer to the operating room

      • Example  #2:

        •  Lorazepam (Ativan) 25-50 ug/kg orally -- timing = 1-2 hours before transferred to the operating room

        •  IV fentanyl (Sublimaze) 0.5-1 ug/kg administered as needed following the first IV  cannulation

      • These sequences provide amnesia (diazepam (Valium); lorazepam (Ativan))

      • Larger doses of longer-acting agents provide an advantage for long-duration surgery;  note the absence of cardiac depression with these agents (respiratory depression: minimal; however the patient may be encouraged to take the occasional deep breath to avoid atelectasis and hypercarbia) 

        • During anesthesia/surgery preparation-- it may be useful for the patient to breathe oxygen-enriched air

  •  Patient condition: Valvular heart disease; impaired resting ventricular function; reduce/minimal cardiac reserve

    • Medications -- reduced amounts (higher dosages may be risky)

      • Already compromised cardiopulmonary function may be further impaired by drug-induced slight  additional myocardial depression

    • Example:

      • Morphine (0.05 - 0.08 mg/kg intramuscular +/-scopolamine (0.002-0.003 mg/kg) -- timing 1 hour or less before  the operation

        • Scopolamine:

          • Advantages: sedation, antiemetic properties, amnestic properties

          • Disadvantages: antisialagogue effects may be disturbing to the patient; postoperative confusion (particularly in the elderly)

    • Other drugs: Given that the patient has coronary vascular disease, beta-adrenergic blocking drugs may be helpful

      • Oral β-adrenergic blocker administration 1-2 hours before the procedure may lessen risk of myocardial ischemia and sequelae

        • Tachycardia suppression

        • Decrease likelihood of hypertension and arrhythmias

      • Nitroglycerin: therapeutic/prophylactic

Other medications

• Calcium channel blockers

  • For patients on calcium channel blockers, continued use of the agents may be preferable:

    • Rationale:

      • The calcium channel blocker was probably given to manage angina, hypertension, or arrhythmias.  If the drug was efficacious in these applications, it would be an advantage to continue the use of the blocker during the surgery when surgical conditions might provoke these cardiac abnormalities

      • The anesthetist would be prepared to manage a side effect of calcium channel blockade word to occur during the procedure (these side effects could be reasonably expected to include systemic hypotension and atrioventricular conduction blockade (recall that the main depolarizing ion at the AV node is calcium, hence calcium channel blockade could slow AV conduction))

• Appropriate to take first-daily dose of the following classes of agents (particularly if the surgery scheduled for late morning)

  • Long-acting nitrates

  • Adrenergic receptor antagonists

  • Calcium channel antagonists

  • Possibly antiarrhythmic agents, including digoxin (Lanoxin, Lanoxicaps), especially for patients predisposed to atrial arrhythmias with high ventricular following rates (note that digitalis glycosides decrease AV conduction, secondary to increased vagal tone; reduced may be conduction protects the ventricles in the presence of atrial  tachyarrhythmias)

• Clonidine (Catapres): controversial in  this setting:

  •  Possible reduction in intraoperative opioid requirement with shortening of post-operative ventilation requirements

  •  Possible problems with low systemic blood pressures (reduce systemic vascular resistance) -- this problem may be sufficiently serious to require intraoperative vasopressor support for patients chronically receiving clonidine (Catapres)

• Angiotensin converting enzyme inhibitors (ACE inhibitors)

  •  During cardiopulmonary bypass, low BP/refractory response to vasopressors may be caused by ACE inhibitors

  •  Drug discontinuation on the surgical day is reasonable; however hypertension may still require inner operative management using vasopressors, e.g. phenylephrine (Neo-Synephrine) (0.5-1 mg); or norepinephrine (Levophed)

• Peptic ulcer/esophageal reflux medication: appropriate preanesthetic medication

  •  Combination of oral  antacids and antisecretory drugs such as glycopyrrolate (Robinul) cimetidine (Tagamet) -- rationale = reduction  of mucosal damage/symptoms perioperatively

• Glaucoma medication:

  •  Continued use of pilocarpine (Pilocar) eyedrops for narrow angle glaucoma

  •  Normal dosage regimen should be continued during the perioperative.

  •  Systemic anticholinergic agents may be used providing topical miotic treatment is maintained

• Intraoperative management of insulin-dependent diabetes

  • Primary objective: monitor perioperatively serum glucose (maintain between 100-250 mg/dL)

  •  Cardiopulmonary bypass may pose significant challenges for appropriate  blood glucose maintenance

  •  Factors contributing to insulin resistance (leading to significant hyperglycemia)

    •  Sympathetic nervous system/endocrine stress response to cardiopulmonary bypass

    •  Administration of sympathomimetic agents

    •  Resolution: 

      • May require bolus insulin administration at high concentration to avoid physiological consequences of severe hyperglycemia, including hyperosmolar coma, CNS ischemic damage, excessive diuresis

    •  Intraoperative management-one approach²

      • Regular insulin infusion 2-5 U/hr for diabetic patients (with or without insulin dependencies) throughout the operation

      • Hourly glucose level determination (administration note 10-20 g glucose is serum glucose decreases to below 100 mg/dL

      • Adjust insulin infusion rate up using intravenous bolus administration of 10-20 units of regular insulin, if needed, after cardiopulmonary bypass to provide a serum glucose range of 100-200 mg/dL.

Management of Intraoperative ischemia

• Overview: Multiple methods are available for managing intraoperative ischemia; interventions are often implemented at the same time

  • Hemodynamic abnormalities:

    1. Reduce tachycardia if present

    2. Correct for hypotensive or hypertensive states

  • ß-adrenergic receptor blockade

    • Rationale: reduction in myocardial oxygen requirement secondary to negative chronotropic (reduced rate) and negative inotropic (reduced contractility) 

    • In patients with unstable (vasospastic or Prinzmetal's) angina: reduction in ischemia and myocardial infarction

    • Cautious use in patients with impaired pulmonary function (e.g. beta-adrenergic blockers are typically contraindicated in asthma because sympathetic,ß-adrenergic receptor-mediated tone causes bronchodilation, which is obviously desirable); also cautious use in patients with significant left ventricular function deficits, even though ß-adrenergic receptor blockers may be helpful in patients with mild/moderate congestive heart failure

  • Nitroglycerin (intravenous)

    • Mainstay of medical treatment for the ischemic myocardium

    •  Nitroglycerin reduces preload (particularly important with high filling pressures and arterial pressure)

    •  Hypotensive states and sympathetic nervous system reflex-mediated tachycardia may occur

  • Heparin

    • Pathologic thrombosis -- important etiology in myocardial ischemia

    •  Heparin:

      1. Reverses ischemia

      2. May prevent myocardial muscle damage (infarction)

    •  Note that in cardiopulmonary bypass (CPB): patients are usually heparinized in advance; however, immediate anticoagulation before CPB would be indicated for pre-bypass myocardial ischemia

• Heparin Review

  • Composition:

    • Sulfated mucopolysaccharides (heterogenous)

  • Mechanism of Action:

    1. Binds to endothelial cell surface membrane.

    2. Heparin activity dependent on: plasma protease inhibitor antithrombin III

       • Antithrombin III -- inhibitor of clotting factors proteases (forming 1:1 stable complexes)

       • Complex forming reactions normally slow -- accelerated by three orders of magnitude (1000 times) by heparin

       • Following antithrombin-protease complex formation, heparin is released; available for binding to other antithrombin molecules

         •  A heparin high-molecular-weight (HMW) fraction has higher affinity for antithrombin compared to other fractions

         •  A heparin low-molecular-weight (LMW) fraction has a lower affinity for antithrombin but inhibits factor Xa (activated)

  • Toxicity:heparin

    • Major adverse/toxic effect: bleeding

      • Risk managed by attention to:

        1. Patient selection

        2. Dosage control

        3. Monitoring of partial thromboplastin time (PTT)

      •  Factors predisposing to hemorrhage:

        • Elderly

        • Renal failure patients

    •  Long-term heparin use-- increased incidence of:

      • Osteoporosis

      • Spontaneous fractures

    •  Transient thrombocytopenia: frequency = 25%

    •  Severe thrombocytopenia: frequency = 5%

    •  Paradoxical thromboembolism ® heparin-induced platelet aggregation

    •  Patients on heparin:

      • Thrombocytopenia that causes bleeding: probably due to heparin

      • New thrombus: may be due to heparin

      • If thromboembolic disease may be heparin-induced:® discontinue heparin

  • Contraindications:heparin

    •  Heparin hypersensitivity

    •  Hematologic disease:

      • Hemophilia, thrombocytopenia, purpura,

    •  Cardiovascular:

      • Severe hypertension, intracranial hemorrhage, infective endocarditis

    •  Active tuberculosis

    •  Gastrointestinal tract

      • Ulcerative lesions

      • Visceral carcinoma

    •  Advanced hepatic/renal dysfunction

    •  Threatened abortion

    •  Related to medical procedures:

      • After brain, spinal cord or eye surgery

      • Lumbar puncture/regional anesthesia blocks

  •  Reversal of Heparin Effects:

    1. Drug discontinuation

    2. Use specific antagonist, e.g. protamine sulfate (note!- excess protamine also has an anticoagulant effect)

• Calcium Channel Blockers (management of  intraoperative ischemia continued)

  •  Especially effective in management of intraoperative ischemia secondary to vasospastic (Prinzmetal's) angina

  •  Effective for angina induced by hypertension (recall that hypertension can induce ischemia by increasing myocardial oxygen requirements secondary to the increased wall tension (afterload))

  •  Effectiveness of calcium channel antagonists in managing myocardial ischemia interoperability depends on concurrent use of other interventions, including the use of ß-adrenergic receptor antagonists and anticoagulation

•  Cardiopulmonary bypass (CPB)

  • Hemodynamically unstable patients with myocardial ischemia should be placed on CPB assumed as possible

    • Rationale-

      1. On CPB the heart is allowed to "rest", significantly reducing oxygen demand with maintenance of coronary vascular perfusion pressure 

      2. While on the bypass the patient may be given other drugs such as ß-adrenergic receptor antagonists without the risk of cardiovascular instability

• Intra-aortic balloon pump

  •  Appropriate for ischemia which is not manageable by drugs

  •  Rationale:

    • Reduces myocardial oxygen demand (wall tension) by decreasing resistance to left ventricular ejection

    • Improves coronary vascular perfusion by increasing diastolic pressures

  •  Circumstances for use:

    • Preoperatively-these patients have persistent symptoms (should not delay CPB for the hemodynamically unstable patient)

    • Use during the procedure:-for patients with ischemia refractory even after CPB

• Patient myocardial performance evaluation following  revascularization (coronary artery bypass grafting)

  • Adequacy of grafting may be assessed following CPB through the use transesophageal ultrasound (TEE ultrasound), which may detect abnormal ventricular wall motion (hypokinetic regions)

  •  A "problem" graft may be due to a surgical technical problem or even vasospasm (internal mammary artery) -- which may respond to calcium channel  antagonist treatment or to the use of vasodilators

  • Other post-bypass grafting ischemia episodes may occur because of air embolization (especially in the right coronary artery)-rate country can or failure secondary to this event may require returning to CPB with high coronary perfusion pressure and administration of nitroglycerin (vasodilator).

• ¹Primary Reference:  Ross, AF, Gomez, MN. and Tinker, JH Anesthesia for Adult Cardiac Procedures in  Principles and Practice of Anesthesiology (Longnecker, D.E., Tinker, J.H. Morgan, Jr., G. E., eds)  Mosby, St. Louis, Mo., pp. 1659-1698, 1998.

• ²Primary Reference: Shanewise, JS and Hug, Jr., CC, Anesthesia for Adult Cardiac Surgery, in Anesthesia, 5th edition,vol 2, (Miller, R.D, editor; consulting editors, Cucchiara, RF, Miller, Jr.,ED, Reves, JG, Roizen, MF and Savarese, JJ) Churchill Livingston, a Division of Harcourt Brace and Company, Philadelphia, pp. 1753-1799, 2000.

• ³Primary Reference: Wray Roth, DL, Rothstein, P and Thomas, SJ Anesthesia for Cardiac Surgery, in Clinical Anesthesia, third edition  (Barash, PG, Cullen, BF, Stoelting, R.K, eds), Lippincott-Raven Publishers, Philadelphia, pp. 835-865, 1997