Dosis sola facit venenum ("The dose alone makes the poison"), Paracelsus, 1493 to 1541.

Administration of sedative or anesthetic drugs is, in fact, a form of poisoning. It is aimed at causing minimal impairment of function other than loss of consciousness. Some damage to other normal functions, however, is inevitable. Although modern anesthesia is relatively safe, mortality rates increase dramatically in the presence of systemic disease.^1,2 Understanding the special requirements of each patient can improve preoperative preparation and the prioritization of perioperative monitoring techniques.

The healthy cardiovascular system can increase its function 3-fold when stressed. However, this reserve may be depleted by a disease process or by advanced age, as is the case in many cardiac patients. A critical insult may ultimately trigger a lethal cascade. It is therefore best to try to anticipate what can go wrong in the perioperative period, tailor the list of such expectations to the patients' specific condition (e.g., signalment, diagnosis, severity, chronicity, stability, comorbidities, ASA score, nature of the planned procedure), and to take appropriate preparatory measures, well in advance, for any potential contingency. The importance of planning in advance and meticulous perioperative monitoring cannot be overemphasized.

Anaesthesia of Cats and Dogs with Cardiac Disease

Different anesthetics have different cardiovascular effects, and different cardiac diseases may cause different modes of failure. It is essential to understand the pathophysiology of each disease, the cardiovascular side effects of each anesthetic drug, and their interactions.

Many practitioners are reluctant to anesthetize patients with a murmur, yet not all heart diseases are alike and they certainly do not carry the same risks. It is therefore imperative to reach a complete cardiac diagnosis rather than to settle for a "diagnosed" murmur as reason enough to avoid general anesthesia, especially when non-elective procedures are considered. Conditions like valvar regurgitation or stenosis exemplify this:

Myxomatous valve degeneration. Most aging dogs with a loud apical, plateau-shaped, systolic murmur have atrioventricular valve regurgitation, which typically goes along with a hyperkinetic ventricular contraction. This is why the most worrisome trait of most anesthetic agents, namely a negative inotropic effect, should not necessarily pose a high risk in most of these patients.

Semilunar valve stenosis. Likewise, when a loud, systolic, crescendo-decrescendo murmur is best heard over the heart base, congenital semilunar stenosis in dogs, or hypertrophic obstructive cardiomyopathy (HOCM) in cats, is more likely. In such cases the negative inotropic effect of anesthesia may actually be a blessing, just like that of the typically recommended oral pharmacotherapy for these obstructive conditions: a weaker contraction will decrease the tarns-obstruction pressure gradient and thus reduce myocardial oxygen consumption, minimizing the risk of anesthesia-related myocardial ischemia and arrhythmogenesis. By the same token, ketamine should be avoided in such patients due to its positive inotropic effect.

Prior to anesthesia, congestive heart failure, arrhythmia or conduction anomalies should be controlled. The therapy the animal is receiving and the time it was administered or discontinued should be considered, as it may have side effects relevant to the procedure (e.g., azotemia or hypotension). Hypertensive patients treated with amlodipine should often continue receiving it perioperatively.

Apart for careful selection of drugs, attention must be given to precise calculation and administration of fluid therapy, especially in patients with left-sided heart disease, as volume overload may occur easily with only little warning, leading to life threatening pulmonary edema. Moreover, even in cardiac patients with renal comorbidities, the ability to regulate plasma volume, vascular tone, acid-base, and electrolyte levels is already impaired, and each of these may actually deteriorate because of, rather than in spite of, aggressive fluid administration.^3,4 Ideally, monitoring must ascertain the presence of stable homeostasis and to promptly identify and treat developing trends of hypotension, dehydration, azotemia, electrolyte or acid-base imbalance, hypoxia, tachypnea, hypoventilation, arrhythmia, hypervolemia, coagulopathy, urinary output, and hyper- or hypothermia. Thermoregulation must be aggressive to avoid increased oxygen consumption due to panting or shivering (which increases oxygen demand, further taxing the cardiopulmonary system),⁵ and to avoid hyperthermia, especially in brachycephalic dogs. Pain might increase the sympathetic tone enough to have deleterious effects on cardiac function, requiring effective pain control even prior to its onset.

Anaesthesia of Patients with Atrioventricular Valve Regurgitation

Decreases in heart rate cause a greater fraction of the stroke volume to regurgitate into the atrium, while a mild increase in heart rate may improve the forward flow at the expense of regurgitation fraction, as will arteriolar-dilating anesthetics.

Preanesthetic Sedation

Whereas an anesthetic protocol which mildly decreases the force of myocardial contraction and vascular resistance may be beneficial, extreme bradycardia should be avoided. Pethidine and oxymorphone are opioids that mildly decrease contraction and mildly increase heart rate, while morphine and fentanyl will preserve cardiac function and give better analgesia when necessary, but may cause too severe a bradycardia, which would warrant anticholinergic support. A very low dose (i.e., 0.02 mg/kg or less) of acepromazine (ACP) may provide adequate tranquilization. However, ACP, a dopamine antagonist, reduces the efficacy of dopamine as a vasopressor in isoflurane-anesthetized dogs.⁶ High ACP doses will cause hypotension, which may lead to tissue ischemia with end-organ failure. Dramatic hypotension will require treatment that increases vascular resistance or intravascular volume, which, if excessive, may elicit pulmonary edema.

Induction

Induction can be performed with conservatively dosed propofol or thiopental. Etomidate maintains relatively normal cardiovascular function and is considered a good choice in severe valvular insufficiency.

Maintenance with Inhaled Anesthetics

Maintenance with inhaled anesthetics may be a good choice for these patients but a balanced protocol with an opioid or benzodiazepine constant rate infusion (CRI) may be necessary to minimize their dose, and inotropic and arrhythmogenic side effects.

Although right-sided congestive heart failure (CHF) develops less acutely, it is essential to avoid volume overload with severe tricuspid insufficiency, as this may ultimately lead to the development or worsening of ascites, and/or, more importantly, pleural effusion with impaired respiration. Severe anesthetic-related venodilation (via "pooling") or intermittent positive pressure ventilation may decrease venous return (preload), which can help underload the right ventricle, but can also decrease cardiac output. Hypoxemia and hypercapnea lead to pulmonary precapillary vasoconstriction (i.e., increase pulmonary vascular resistance), and thus increase right atrial pressure with a resultant risk of right-sided CHF.

Monitoring right atrial filling pressure is performed quite simply with direct measurement of the central venous pressure (CVP) and may be important in patients with severe tricuspid regurgitation, especially if pulmonary hypertension is identified.

Anaesthetizing Patients with Cardiomyopathy

Dilated cardiomyopathy (DCM) therapy is aimed at improving myocardial contraction and decreasing both preload and afterload. Using pimobendan, a positive inotrope and an arteriolar dilator, is the current standard. It should not be discontinued as it may attenuate the myocardial depression caused by anesthetics.

A benzodiazepine-opioid combination is a good choice for sedation of pets with DCM. Of the opioids, pethidine should be avoided as it is a strong negative inotrope. Acepromazine may add sedation when necessary and decreases afterload by arteriolar dilation, but at high doses may also cause excessive and prolonged hypotension. Alpha-2-agonists are contraindicated in patients with DCM due to bradycardia, conduction disturbances, myocardial depression, and arrhythmogenicity. Propofol and thiopental, despite having a short duration of action, may depress myocardial contraction dramatically. Ketamine as a positive inotrope and etomidate as a minor cardiovascular depressant are a reasonable combination for induction in DCM patients. The main disadvantage of ketamine is potential excitation, increasing oxygen demand, which, especially in the already compromised myocardium, potentially triggers myocardial ischemia with life-threatening ventricular arrhythmia. Adequate sedation, therefore, is essential.

Inhaled maintenance anesthetics cause a dose-dependent depression of myocardial contraction and should be used judiciously. To avoid high concentrations a balanced protocol is advised, for example with a CRI of low-dose ketamine, a benzodiazepine, and an opiate.

Due to the decreased cardiac output and anesthetic-induced myocardial and vascular tone depression, it is essential to monitor blood pressure and clinical parameters of tissue perfusion. If hypotension develops, positive inotropes (e.g., dobutamine or medium-dose dopamine, or even both) should be administered and careful use of vasopressors (e.g., higher-dose dopamine or phenylephrine) may also be indicated. Fluid supplementation should be done very carefully as volume overload may cause left-sided CHF. Central venous pressure monitoring can aid regulation of fluid therapy rate and duration. Due to potential pulmonary edema, perioperative oxygen saturation should be frequently monitored, well into recovery. Arterial blood gas should be considered in high-risk patients both prior to induction (and prior to preoxygenation) and at least once or twice intraoperatively, to identify trends of deterioration before they become catastrophic and irreversible. Intravenous diuretics should always be readily available for such developments, at a precalculated dose.

Anaesthesia of Patients with Hypertrophic Cardiomyopathy (HCM)

As in other cardiomyopathies, a decreasing ventricular compliance gradually builds high diastolic pressures even with low filling volumes, leading to elevation of left atrial and pulmonary venous pressures that may trigger pulmonary edema. This risk is especially important in HCM cats with a documented gallop. When accompanied by a dynamic left ventricular outflow tract obstruction (HOCM), the risk may be exacerbated by positive inotropes, excessive arteriolar dilation, hypovolemia (e.g., following overzealous diuretic therapy), or excessive tachycardia.

An opioid-benzodiazepine combination (e.g., butorphanol and midazolam, or morphine and midazolam, according to the amount of analgesia necessary) offers a good choice for premedication. Acepromazine offers good tranquilization but also causes vasodilation which may overly decrease preload. Therefore, if ACP is being used, doses should be low (e.g., 0.02 mg/kg or less). Alpha 2 agonists initially cause vasoconstriction and bradycardia and may therefore be beneficial. However, their delayed effects involve vasodilation and a decrease in both preload and systemic blood pressure. Therefore, when these drugs are considered (for example for fractious cats), doses used should be minimal, and monitoring of cardiovascular function should be frequent and continue well into recovery. Ketamine should not be used in patients with HCM as it increases heart rate, cardiac oxygen consumption, and possibly arrhythmogenicity, and may exacerbate left ventricular outflow tract obstruction in cats with HOCM, with resultant life-threatening hypotension. Volatile-gas induction in an induction cage, with adequate sedation, can also be considered.

Animals with HCM should receive only judicious fluid supplementation at a rate only enough to maintain adequate filling pressures, but overload should be avoided; monitoring CVP can help fine-tune intravenous fluid administration rate and duration.

A summary of cardiovascular effects of some of the common anesthetic drugs

References

1.  Brodbelt D. Feline anesthetic deaths in veterinary practice. Top Companion Anim Med. 2010;25(4):189–194.

2.  Bille C, Auvigne V, Libermann S, Bomassi E, Durieux P, Rattez E. Risk of anaesthetic mortality in dogs and cats: an observational cohort study of 3546 cases. Vet Anaesth Analg. 2012;39(1):59–68.

3.  Vollmar AM. Immunoreactive N-terminal fragment of proatrial natriuretic peptide, ANP (1–98), in plasma of healthy dogs and dogs with impaired volume regulation: a comparison with the C-terminal ANP (99–126). Res Vet Sci. 1991;50(3):264–268.

4.  Vollmar AM, Reusch C, Kraft W, Schulz R. Atrial natriuretic peptide concentration in dogs with congestive heart failure, chronic renal failure, and hyperadrenocorticism. Am J Vet Res. 1991;52(11):1831–1834.

5.  Entezariasl M, Isazadehfar K. Dexamethasone for prevention of postoperative shivering: a randomized double-blind comparison with pethidine. Int J Prev Med. 2013;4(7):818–824.

6.  Monteiro ER, Teixeira Neto FJ, Castro VB, Campagnol D. Effects of acepromazine on the cardiovascular actions of dopamine in anesthetized dogs. Vet Anaesth Analg. 2007;34(5):312–321.