Intra-operative hypotension in anaesthetised horses

Hypotension is a relatively common complication during inhalational agent anaesthesia in horses, with a reported prevalence of 42% and 88% in horses undergoing anaesthesia for elective and abdominal surgery, respectively (Parviainen and Trim, 2000; Adami et al, 2020). Horses may be particularly susceptible to the negative inotropic and vasodilatory effects of inhalational agents (Grosenbaugh and Muir, 1998), which is reflected by the much lower tendency for hypotension to occur during total intravenous anaesthesia (Bettschart-Wolfensberger et al, 2005; Mama et al, 2005).

Hypotension has been defined as a mean arterial pressure (MAP) <70 mmHg (Voulgaris and Hofmeister, 2009) and most anaesthetists aim to maintain a MAP ≥70 mmHg in anaesthetised horses (Wagner, 2009). Intra-operative hypotension has been associated with prolonged time to standing (Voulgaris and Hofmeister, 2009), poorer recovery quality (Hector et al, 2020), poor survival in horses with acute abdominal disease (Parry et al, 1983) and increased incidence or severity of myopathy (Grandy et al, 1987; Dodman et al, 1988; Lindsay et al, 1989; Richey et al. 1990; Young and Taylor 1993; Duke et al, 2006).

Direct measurement of arterial blood pressure (ABP) is performed routinely in most horses undergoing general anaesthesia in the hospital setting, and is one of the most important parameters used in monitoring haemodynamic status (Corley, 2004). It is important to consider that while direct measurement of ABP is often taken as an indicator of tissue perfusion, this parameter does not always reflect blood flow and oxygen delivery (Tranquilli et al, 2007; Shauvliege and Gasthuys, 2013). Therefore, changes in peripheral and systemic vascular resistance (SVR) should also be considered when addressing hypotension during equine anaesthesia.

Causes of hypotension

Several factors can contribute to the development of intra-operative hypotension in horses. These may include administration of inhalational anaesthetic agents and some sedatives, controlled mechanical ventilation (CMV), recumbency position of the horse and systemic illness, which may be accompanied by hypovolaemia and/or decreased myocardial contractility.

Inhalational anaesthetic agents

The administration of inhalational anaesthetic agents produces a dose-related cardiovascular depression in horses (Steffey and Howland, 1980), resulting in arterial hypotension and impairment of skeletal muscle blood flow (Lee et al, 2002). Both isoflurane and sevoflurane produce dose-dependent hypotension resulting from a decrease in SVR or cardiac output or both (Steffey and Howland, 1980; Aida et al, 1996; Grosenbaugh and Muir, 1998; Raisis et al, 2000a). Vasodilation, particularly venodilation, is the primary cause of relative hypovolaemia which may be seen with the administration of inhalational anaesthetic agents and may be associated with increased venous compliance, decreased venous return, and reduced response to vasoactive substances (Noel-Morgan and Muir, 2018). The detrimental effect of inhalational agents on ABP can occur in either lateral or dorsal recumbency, but the effect may be greater in dorsal recumbency (Gasthuys et al, 1991). Anaesthetic agent-induced hypotension can impair blood flow to peripheral tissues, which may lead to an increased incidence of post-anaesthetic myopathy or lameness (Grandy et al, 1987; Richey et al, 1990; Young and Taylor 1993).

Acepromazine

The main cardiovascular effects of acepromazine are mediated by peripheral alpha (α)1-adrenoceptor blockade at the level of the peripheral arterioles, resulting in vasodilation, a decrease in vascular resistance, a decrease in ABP and a compensatory increase in heart rate (Muir and Mason 1993; Marroum et al, 1994; Merlo and Rota, 1999, Monteiro et al, 2007). In healthy horses, the administration of acepromazine (0.02–0.025 mg/kg intravenously (IV)) prior to isoflurane anaesthesia did not alter the effect of isoflurane or dobutamine on cardiovascular function, or influence the dobutamine infusion rate necessary to increase MAP (Monteiro et al, 2011; Schier et al, 2016). In another small prospective study, intramuscular (IM) administration of acepromazine (0.035mg/kg) did not affect HR, MAP, dobutamine requirements or arterial blood gas values in healthy horses under isoflurane anaesthesia in dorsal recumbency (Midon et al, 2021). Intramuscular rather than intravenous administration of acepromazine may help avoid a sudden decrease in blood pressure (Kalchofner et al, 2009).

However, in systemically compromised horses, where vascular tone may be altered and compensatory mechanisms compromised, the cardiovascular effects of acepromazine may be significant, so administration should be avoided in these patients. The undesirable effects of acepromazine administration can be particularly prominent and may become life-threatening in systemically compromised horses suffering from hypotension, hypovolaemia, anaemia, or dehydration (McKelvey and Hollingshead, 2003). Acepromazine should be avoided in horses with colic owing to the potential for the exacerbation of hypotension by virtue of the α1-adrenoceptor antagonist effect.

Controlled mechanical ventilation

During isoflurane anaesthesia, horses receiving controlled mechanical ventilation (CMV), had lower heart rates, systolic arterial pressure, stroke volume and cardiac output compared with spontaneous breathing (Edner et al, 2005). The effect that CMV imposes on the cardiovascular system can be, in part, explained by considering the differences between spontaneous respiration and CMV. During spontaneous respiration, gas flows into the lung down a pressure gradient generated by subatmospheric intrapleural pressure. However, during CMV, the opposite occurs and the positive pressure which is applied to the lungs is transmitted to intrathoracic structures, including the relatively thin-walled central veins, thereby reducing right atrial preload and, consequently, reducing cardiac output (Edner et al, 2005; Araos et al, 2020). Furthermore, positive pressure in the alveoli acts to compress adjacent capillaries which increases pulmonary vascular resistance, thereby increasing right ventricular afterload and further reducing cardiac output (Roos et al, 1961; Araos et al, 2020). When employing CMV, a certain drop in ABP is unavoidable when switching from spontaneous ventilation to CMV, therefore, hypotension should be considered as a potential complication (Moreno-Martinez et al, 2022). The magnitude and duration of the pressure applied, compliance of the lungs, and thorax and volume status can all magnify the effect of CMV on cardiac output (Araos et al. 2020). Hypovolaemic horses, such as those suffering from colic or haemorrhage, may be at greater risk of hypotension if CMV is applied (Noel-Morgan and Muir 2018) and for these reasons, direct ABP monitoring is warranted when CMV is used.

Recumbency position

Intra-operative recumbency position of the horse may influence venous return to the heart by virtue of the anatomical relationship between various abdominal organs and the caudal vena cava. Dorsal recumbency compared with lateral recumbency causes more pronounced hypotension (Gasthuys et al, 1991; Blissit et al, 2008) which may be associated with compromised venous return owing to the weight imposed on the caudal vena cava by the abdominal organs.

Systemic illness and colic

Many horses with colic are hypotensive to some extent, and for at least some of the time during general anesthesia (Boesch, 2013). Horses suffering with colic are frequently hypovolaemic and endotoxaemic as a result of intestinal damage, and may often present with significant circulatory derangement (Dugdale et al, 2007). The combination of relative and absolute hypovolaemia during anesthesia and surgery in physiologically compromised animals can be challenging to manage, since some animals may rapidly develop irreversible and refractory shock after the loss of relatively small amounts of blood (Noel-Morgan and Muir, 2018). Vasodilation, predominantly caused by venodilation, is an important cause of relative hypovolemia produced by anaesthetic drugs and can be exacerbated in systemically compromised, septic, hypothermic, or aged animals (Noel-Morgan and Muir 2018). Decreased systolic function and even myocardial damage, as evidenced by increased levels of cardiac troponin I, have been documented in horses with colic (Borde et al, 2011; Radcliffe et al, 2012).

Reduced circulating volume

Inadequate circulating volume results in reduced cardiac preload and thus reduced cardiac stroke volume (Corley, 2004). A reduction in circulating volume or absolute hypovolaemia may result from controlled or uncontrolled haemorrhage and implies loss of blood, plasma or water from the vascular compartment (Noel-Morgan and Muir 2018). Absolute hypovolaemia occurs when there is a decrease in blood volume relative to a normally-sized vascular space whereas relative hypovolaemia implies a normal, or possibly increased, blood volume that cannot fill the vascular compartment because the volume of the vascular compartment has increased (Noel-Morgan and Muir, 2018). Inadequate circulating volume is common in critically ill horses for many reasons (Corley 2004) and horses can lose large volumes of fluid into the gastrointestinal tract (Rose, 1981). The principal cause of relative hypovolemia is vasodilation, especially venodilation. Vasodilation during anesthesia may be a consequence of various factors such as drug effect and/or drug toxicity (sensitivity to anaesthetic drugs or anaesthetic overdose), impairment or loss of compensatory mechanisms, coexisting or induced metabolic acidosis, or concurrent traumatic or surgically-induced inflammation, sepsis, cardiogenic shock and hypothermia (Noel-Morgan and Muir 2018). Fluid therapy restores or increases the circulating volume and improves venous return to the heart. An increase in venous return leads to an increased stroke volume and helps to increase cardiac output and ultimately tissue blood flow (Corley, 2004).

Decreased myocardial contractility and cardiac output

Systemic inflammatory response syndrome (SIRS) and the complex cascade of events characterised by the release of a multitude of inflammatory cytokines can have a detrimental effect on cardiac myocytes, resulting in reduced cardiac contractility (Corley, 2004). The maintenance of adequate cardiac output and ABP are dependent upon a normal blood volume, vascular tone, venous return, heart rate, ventricular function, and multiple autoregulatory mechanisms (Noel-Morgan and Muir, 2018).

Treatment

There are several treatment options for the management of hypotension, including;

• Reduction in the delivered concentration of inhaled anaesthetic agents or other potentially hypotensive agents
• Increased intravenous fluid administration.
• Administration of inotropic drugs
• Administration of vasopressors (Wagner, 2009).

Reduction in the delivered concentration of inhaled anaesthetic agents.

When approaching the management of intra-operative hypotension, the delivered concentration of inhalational anaesthetic agent should be considered and reduced where possible. It is well-established that the volatile anaesthetic agents isoflurane and sevoflurane cause dose-dependent vasodilation. Reduction of the concentration of volatile anaesthetic is one of the general principles to prevent and treat cardiopulmonary depression (Gozalo-Marcilla et al, 2014).

Partial or supplemental intravenous anaesthesia

Implementation of partial or supplemental intravenous anaesthetic (PIVA/SIVA) techniques may reduce volatile agent requirements. The administration of α-2 adrenoreceptor agonists reduces volatile agent requirement, most likely by providing extra sedation and analgesia (Gozalo-Marcilla et al, 2015). For example, in one prospective clinical study, administration of xylazine by IV infusion following a bolus reduced the need for blood pressure support and decreased isoflurane requirements compared to isoflurane alone in horses undergoing elective surgery (Pöppel et al, 2015). However, the impact of α-2 adrenoreceptor agonists on cardiovascular function should be considered and the use of these drugs in compromised horses remains controversial (Gozalo-Marcilla et al, 2015). Intravenous administration of lidocaine has been shown to have MAC sparing effects, without negative cardiovascular effects, in both healthy horses (Dzikiti et al, 2003) and those with colic (Driessen, 2005). It is important to note that horses may be particularly sensitive to the negative cardiovascular effects of inhaled anaesthetic agents, such that even healthy horses that are lightly anaesthetised and moving can be hypotensive (Wagner, 2009). Implementation of PIVA or SIVA techniques in these horses may be beneficial.

Avoiding over-zealous controlled mechanical ventilation

Avoiding over-zealous CMV is important in order to minimise ventilator-induced hypotension. Hypercapnia is generally associated with improvement in cardiovascular function as an increase in circulating catecholamines has been associated with an increase in arterial carbon dioxide tension (PaCO₂) and improved haemody-namics (Weaver and Walley, 1975; Wagner et al, 1990).

In the event that ceasing controlled mechanical ventilation and allowing spontaneous ventilation is not feasible, consideration of ventilator settings may help minimise the detrimental cardiopulmonary effects of CMV and aid in the management of hypotension:

• Consider peak airway pressure values. It has been established that as airway pressures increase, stroke volume and cardiac output progressively decrease (Morgan et al, 1966)
• In horses end-inspiratory pressures of 25cmH2O produced greater cardiovascular depression than end-inspiratory pressures of 20 cmH2O or spontaneous ventilation (Mizuno et al, 1994)
• A respiratory rate of 8–10 breaths per minute has been suggested for CMV of healthy adult horses (Steffey, 1981)
• CMV in healthy horses undergoing elective surgery using isoflurane–medetomidine anaesthesia did not impair cardiovascular function when they were slightly hypoventilated maintaining mild hypercapnia (Kalchofner et al, 2009).

Intravenous fluid therapy

Ensuring adequate intravenous fluid administration is important to support circulating volume. Additional boluses of crystalloid or colloid fluids may improve circulating volume in horses with volume depletion. If fluid therapy is inadequate to restore tissue oxygen delivery, vasoactive agents may be used to support the cardiovascular system (Corley, 2004).

Myocardial contractility

Myocardial contractility can be improved in the horse by optimising preload, minimising the concentration of inhalational anaesthetic agent delivered by assessing anesthetic depth frequently and using a balanced anaesthetic technique, administering positive inotropic drugs or administering therapies for endotoxemia (Boesch et al, 2013).

Calcium supplementation

Calcium depletion may play a role in myocardial dysfunction in patients with sepsis, therefore, measurement of calcium and supplementation where necessary is indicated. Calcium can be used as an inotropic agent and has been shown to attenuate the cardiovascular depression caused by isoflurane, which may be particularly effective if the horse is hypocalcaemic (Grubb et al, 1999). One suggested approach for calcium supplementation is to administer 2 mg/kg per hour (approximately 50ml of 23% calcium borogluconate added to a 5L volume of intravenous crystalloid fluids and administered to a 500kg horse over 1 hour) (Hardy, 2009). Serum calcium should then be re-assessed and further treatment implemented where necessary.

Vasoactive drugs

The cardiovascular depressant effects of most anaesthetic agents often necessitate the use of supportive drugs like dobutamine, even in healthy horses (Dugdale et al, 2007). When considering the administration of inotrope or vasopressor therapy, all the available haemodynamic data should be considered (Corley, 2004).

Ideal properties of vasoactive drugs used in horses for the treatment of hypotension during general anaesthesia include:

• Short onset of action (Corley, 2004)
• Rapid metabolism (Corley 2004)
• Cost effectiveness
• IV route of administration to allow variable rate infusion.

These properties allow the agent to be titrated to effect, and because the underlying pathophysiology may rapidly change, helps to prevent harm by prolonged inappropriate treatment (Corley, 2004).

Dobutamine.

Dobutamine is a synthetic catecholamine which directly affects cardiac contractility by stimulating β₁-adrenoreceptors and increases blood pressure (Muir and McGuirk, 1985). Dobutamine has strong affinity for the β1-adrenoreceptors and weak affinity for β2- and α-adrenoreceptors (Corley, 2004). For the treatment of anaesthetic-induced hypotension, dobutamine is the initial vasoactive drug of choice (Ohta et al, 2013) and is the most commonly administered vasoactive agent used to treat hypotension during inhalation anaesthesia in horses (Fantoni et al. 2013). Dobutamine administration should be carefully titrated from a starting point of 0.5–1 µg/kg per minute IV in adult horses (Corley, 2004).

Advantages

Dobutamine increases cardiac stroke volume, which is the difference between end-diastolic and end-systolic ventricular volume (Corley 2004).

Dobutamine has a positive inotropic effect when used at low-to-moderate doses, and studies have shown that its administration results in an increased ABP and cardiac output in horses (Donaldson, 1988; Lee et al, 1998; Dugdale et al, 2007).

At dobutamine infusion rates 0.5-2 µg/kg per minute IV, the in-crease in MAP may be mainly attributable to the increase in stroke volume. This is supported by the finding that MAP increases almost in parallel with stroke volume in healthy horses (Ohta et al, 2013).

In an experimental study, dobutamine infusion at the higher rate of 3 µg/kg per minute IV resulted in a dose-dependent increase in MAP, cardiac output and heart rate, and a decrease in SVR (Dancker et al, 2018).

Dobutamine infusion (2.5 µg/kg per minute IV) enhanced cardiac systolic function in heathy horses under isoflurane-anaesthesia (Vitale et al, 2013).

Dobutamine infusion (0.5–3 µg/kg per minute IV) increased micro-perfusion of the gastrointestinal tract (Dancker et al, 2018).

Dobutamine better preserves blood flow to muscles than other vasoactive drugs (Valverde et al, 2006).

Concurrent administration of IV fluids may improve the effects of dobutamine on cardiac output in the event of reduced preload (Loughran et al, 2017). In healthy anaesthetised horses, the co-administration of dobutamine and IV fluids significantly increased femoral blood flow in both limbs, while administration of dobutamine alone did not (Loughran et al, 2017).

In anaesthetised foals, dobutamine infusion (2.5 µg/kg per minute IV) resulted in an increase in cardiac index which was attributed to an increase in stroke volume index, as heart rate changed very little. However, at the higher infusion dose (5 µg/kg per minute IV), the increase in cardiac index is attributed to both the increase in stroke volume index and heart rate (Craig et al, 2007). Similar findings were reported in healthy isoflurane anaesthetised foals receiving dobutamine infusions at 4 – 8µg/kg per minute IV where cardiac index and stroke volume index increased significantly, but the increase in heart rate was greater at higher infusion rates (Valverde et al, 2006).

It is important to note that in horses, inconsistent results have been reported after dobutamine administration, Although ABP consistently increases during dobutamine administration (Young et al, 1998; Raisis et al, 2000), increases in cardiac output are not always observed and furthermore, when increases in cardiac output are reported, it has been associated with either an increase in stroke volume or heart rate (Mizuno et al, 1994; Young et al, 1998).

Disadvantages

Dobutamine is known to increase myocardial oxygen consumption and sometimes induce tachycardia and ventricular arrhythmias (Vitale et al, 2013). Inotropes increase cardiac work and thus oxygen consumption, which may be important when oxygen delivery is marginal (Corley, 2004).

Dobutamine may exert a weak positive chronotropic effect as well as a potent inotropic effect. At higher dosages (7.5–10 µg/kg per minute IV), dobutamine infusion may result in an increased heart rate in adult horses (Vitale et al, 2013) and foals (Craig et al, 2007). The positive chronotropic effect of dobutamine was manifested at 2.5 and 10 μg/kg per minute IV, causing tachycardia and arrhythmias in two of six halothane-anaesthetised ponies (Lee et al, 1998).

Even at lower doses (0.5–2 μg/kg per minute IV), dobutamine infusion may be associated with a gradual increase in heart rate during surgery when using dobutamine to maintain MAP at an adequate level (Ohta et al, 2000).

At higher infusion doses (7.5 µg/kg per minute IV), dobutamine may cause cardiac arrythmias. In one study, arrhythmias were diagnosed in five of six (83.3%) horses. Two out of six horses (33%) developed sinus tachycardia (heart rate > 60 beats per minute), both at 5 and 7.5 µg/kg per minute IV infusion rates, while three of six (50%) showed supraventricular tachycardia at 7.5 µg/kg per minute IV (Vitale et al, 2013)

Potential mechanisms responsible for arrhythmogenesis are direct stimulation of ß1- and α₁-adrenoreceptors, resulting in in-creased automaticity, irregular patterns of ventricular activation, the development of early after depolarisation leading to ‘trigger activity’, and autonomic imbalance (Swanson et al, 1985).

Dobutamine administration in horses suffering with colic, where hypovolaemia and tachycardia may already be present, may be more likely to cause tachyarrhythmias than increase ABP, even at low-infusion rates (Robertson, 1999).

Dopamine

Dopamine is an endogenous catecholamine that is commonly used as a positive inotrope and vasopressor in veterinary practice (Oh et al, 2022). However its use in small animal anaesthesia has been much more extensively explored compared to equine anaesthesia where evidence for its use is sparse. Dopamine has a dose-dependent effect on dopaminergic, α_1-adrenergic, and β-adrenergic receptors (Dancker et al, 2018).

Advantages

Cardiac output was significantly increased at 15 and 30 mins following administration of dopamine (2.5 and 5 μg/kg per minute IV) in healthy anaesthetised horses (Trim et al, 1985).

Renal blood flow increased after IV dopamine infusion (2.5 and 5 μg/kg per minute) for 60 minutes in conscious healthy horses (Trim et al, 1989).

The activation of dopaminergic receptors is known to induce local vasodilation without significantly affecting systemic MAP (Oh et al, 2022). However, since dopamine has effects at different receptors, individual response may be unpredictable.

Disadvantages

In healthy anaesthetised horses, IV infusion of dopamine (1–5µg/kg per minute IV) reduced MAP and SVR but increased cardiac output and heart rate (Dancker et al, 2018).

Dopamine administration (1–5 µg/kg per minute IV) significantly decreased the microvascular blood flow at the stomach, small intestine and large intestine measurement sites in one experimental study (Dancker et al, 2018).

In healthy anaesthetised horses, dopamine increased cardiac output but decreased microvascular blood flow and tissue oxygen concentration, indicating that doses of dopamine (1–5 µg/kg per minute IV) may induce ischaemia in peripheral organs and tissues (Dancker et al, 2018).

High doses of dopamine (5 µg/kg per minute) significantly decreased oxygen saturation at the small and large intestinal sites (Dancker et al, 2018).

Supraventricular premature contractions occurred in one horse and episodes of tachycardia occurred in two horses during infusion of dopamine at 5 μg/kg per minute IV (Trim et al, 1985).

Dopamine infusion (5 µg/kg per minute IV) was accompanied by dysrhythmias in some conscious horses (Trim et al, 1989).

The reason that dopamine may decrease local perfusion, while at the same time increasing cardiac output and stroke volume, is not entirely clear. It is possible that at moderate to high dopamine infusion rates (2-5 μg/kg per minute IV), despite a modest increase in cardiac output, profound peripheral vasodilation may lead to a reduction in MAP below the critical perfusion pressure, which results in an inability to maintain local blood flow (Dancker et al, 2018). The clinical evidence for the use of dopamine infusion in horses remains sparse and further investigation is required before its use can be recommended during equine anaesthesia.

Vasopressors

Vasopressor agents (Table 1) act to increase vascular smooth muscle tone, principally in the arterioles. This increases the pressure gradient across a tissue capillary bed, allowing perfusion. However, resistance to flow is also increased. For this reason, it is important to carefully titrate vasopressor agents to achieve an optimum balance between perfusion pressure and flow (Corley, 2004).

Phenylephrine

Phenylephrine is a sympathomimetic amine that acts predominantly on α₁-adrenergic receptors with little or no agonism at ß-adrenergic and dopaminergic receptors (Corley 2004). The short half-life of phenylephrine means that it should be administered as a constant rate infusion (Corley 2004). To avoid excessive vasoconstriction due to the rapid increase in plasma concentration, low (0.25 μg/kg/min IV) to medium (0.5 μg/kg/min IV) infusion rates are recommended for clinical use (Ohta et al. 2013). Phenylephrine infusion may be prepared by adding 10–20 mg phenylephrine diluted in 1 L of 0.9% NaCl solution and administered slowly IV over 15 minutes or longer (Fantoni et al. 2013). Considering the long-lasting effect of phenylephrine on vascular tone and resistance, infusion should be ceased when MAP reaches the target value (Ohta et al. 2013). If phenylephrine is used as a vasopressor, it is recommended that it is used in conjunction with a ß-agonist, such as dobutamine (Corley 2004).

Advantages

Phenylephrine acts selectively at α₁-adrenoreceptors, thereby increasing blood pressure by increasing vascular resistance (Corley, 2012).

Phenylephrine has been reported to be effective in treating severe peripheral vasodilation in horses (Dugdale et al, 2007).

In normal adult horses, phenylephrine infusion resulted in increased MAP and increased SVR (Hardy et al, 1994).

At doses of 0.25–1 µg/kg per minute IV in sevoflurane anaesthetised horses, the increase in MAP was mainly attributable to the increase in SVR, which was associated with the direct vasoconstrictive effect of phenylephrine (Ohta et al, 2013).

Disadvantages

Phenylephrine infusion may increase MAP and SVR but causes a dose-dependent decrease in cardiac output and heart rate (Dancker et al, 2018).

Phenylephrine infusion decreases cardiac index (Fantoni et al, 2013). The decrease in cardiac output may be a result of a decrease in heart rate, as cardiac stroke volume was unchanged (Hardy et al, 1994).

Although phenylephrine can improve ABP, this may be at the expense of cardiac output. The vasoconstriction elicited by phenylephrine may have detrimental effects on tissue perfusion (Lee et al, 1998).

Phenylephrine infusion (0.5–3 µg/kg per minute IV) induced a strong vasopressor response with a significant increase in SVR which is likely to be mediated via α₁-adrenoreceptor activity.

Phenylephrine infusion (0.5–3 µg/kg per minute IV) resulted in a reduction in heart rate, most likely as a reflex response to the increased afterload (Dancker et al, 2018).

Phenylephrine administration increases myocardial oxygen demand in the face of increased cardiac afterload, and this may pre-dispose cardiac arrhythmias (Dugdale et al, 2007).

High doses of phenylephrine (3 µg/kg per minute IV) significantly decreased oxygen saturation at the stomach, small intestinal and large intestinal measurement sites in isoflurane-anaesthetised horses (Dancker et al, 2018). In a prospective clinical study, phenylephrine infusion (2 µg/kg per minute IV) resulted in reduced tissue oxygen delivery (Fantoni et al, 2013).

It is important to note that phenylephrine should not be used routinely, and its use is recommended only when other treatments have failed to improve hypotension (Ohta et al, 2013).

Noradrenaline

Noradrenaline is an endogenous catecholamine, acting as a sympathetic neural and humoral transmitter in most animal species (Adams, 2009). Noradrenaline has a strong agonist effect at α1- and α2-adrenergic receptors with affinity for ß1-adrenergic receptors and a minor effect at ß2-adrenergic receptors (Corley, 2004). The dose should be carefully titrated from a starting dose of 0.1 µg/kg per minute (Corley, 2004).

Advantages

Noradrenaline is primarily used for its intense vasoconstrictor effect in the haemodynamic management of horses under anaes-thesia, specifically when low ABP or decreased SVR is refractory to both fluid therapy and dobutamine (Corley, 2004; Craig et al, 2007).

Noradrenaline has an intense vasopressor effect that induces an increase in systolic and diastolic ABP, which translates into positive inotropic and chronotropic effects (Adams, 2009).

Noradrenaline infusion (0.1–0.5 µg/kg per minute IV) resulted in an increase in diastolic and systolic ABP in healthy anaesthetised horses without significant effect on cardiac output. Stroke volume increased and heart rate decreased at the higher infusion rate of 0.5 µg/kg per minute IV (Dancker et al. 2018).

Noradrenaline exerts a significant vasoconstrictive effect with-out appearing to compromise local blood flow or cardiac output at infusion rates 0.1–0.5 µg/kg per minute IV (Dancker et al, 2018).

Noradrenaline infusion (0.1–0.5 µg/kg per minute IV) led to no significant changes in local microvascular blood flow at small intestinal, large intestinal and stomach measurements sites in one experimental study (Dancker et al, 2018).

Disadvantages

In healthy anaesthetised foals, noradrenaline infusion (0.05–0.4 µg/kg per minute IV) caused a 58% increase in SVR and reduction in cardiac output, although the decrease in cardiac index was not significant (Craig et al, 2007).

In healthy adult anaesthetised horses, an increase in SVR at in-fusion rates of 0.2–0.5 µg/kg per minute IV may result in decreased tissue perfusion at sites such as the skin or muscle (Dancker et al, 2018).

Preload pressures increased by 30% in anaesthetised foals and this could be attributed to venoconstriction (Craig et al, 2007).

The use of noradrenaline warrants further investigation in a prospective clinical study, but results are promising, and its use might be indicated for patients with severe endotoxin-mediated peripheral vasodilation, where intravenous fluid therapy and inotropes do not allow sufficient control of ABP (Dancker et al, 2018).

Ephedrine

Ephedrine is a synthetic sympathomimetic amine that acts directly on α- and ß-adrenergic receptors and indirectly through the release of norepinephrine from sympathetic nerve endings (Daunt, 1990; Egger et al, 2009). Ephedrine exerts an equal magnitude of effects at α1, ß1 and ß2 adrenoreceptors at low-to-moderate doses but has predominant α1 effects at higher doses (Lee et al, 2002).

Advantages

In a small prospective clinical study, ephedrine (0.02 mg/kg per minute IV) increased MAP by increasing cardiac index and SVR (Fantoni et al, 2013). Increases in MAP after ephedrine bolus administration of 0.06 mg/kg IV were not associated with changes in heart rate in healthy anaesthetised horses (Hellyer et al, 1998).

In a small experimental study, ephedrine administration of 0.1 and 0.2 mg/kg IV was associated with minimal changes in SVR (Lee et al. 2002).

Ephedrine infusion (0.02mg/kg per minute IV) improved CO, which is likely to be a result of improved myocardial contractility as HR was unchanged in a prospective study of healthy anaesthetised horses (Fantoni et al, 2013).

In isoflurane anaesthetised horses undergoing elective surgery, ephedrine infusion (0.02 mg/kg/min IV) resulted in improved oxygen delivery and no changes in oxygen extraction compared to baseline (Fantoni et al, 2013).

Ephedrine administration (0.06mg/kg IV) had no significant effect on packed cell volume or total protein in healthy anaesthetised horses (Hellyer et al, 1998).

In a small prospective study, ephedrine (0.2 mg/kg IV) consistently increased cardiac index and intra-muscular blood flow in both forelimbs during halothane anaesthesia (Lee et al, 2002).

Disadvantages

Repeated administration or continuous infusion of ephedrine may result in depletion of presynaptic norepinephrine stores and tachyphylaxis.

After administration of 0.1 mg/kg IV ephedrine in halothane anaesthetised ponies, a reduction in arterial oxygen tension was seen (Lee et al, 2002). The reasons for this were not clear in the study but this finding may have been a result of the opening of intrapulmonary shunts (Lee et al, 2002).

In an experimental study, one pony developed supraventricular premature complexes after administration of a second bolus of ephedrine (0.2mg/kg IV), but no other adverse effects were seen (Lee et al, 2002). No arrythmias were seen after administration of a single ephedrine dose of 0.06mg/kg IV in healthy anaesthetised horses in another study (Hellyer et al, 1998).

Vasopressin

Vasopressin acts on V₁α receptors in the periphery to cause vasoconstriction, and on V2 receptors in the collecting tubule of the nephron to cause water resorption (Corley, 2004).

There is evidence to suggest that V1 agonists may be unsuitable for use in horses that have not been adequately fluid resuscitated or are maintained on conservative fluid therapy regimens (Corley 2004). Current evidence indicates that vasopressin administration is not recommended in foals owing to a failure to increase cardiac index and oxygen delivery (Valverde et al, 2006).

Monitoring response to treatment

Therapeutic interventions that result in a reduction in heart rate toward or within the normal range are likely to be beneficial (Corley, 2004). Maintenance of normotension (MAP >70 mmHg) in anaesthetised horses without precipitating tachycardia is encouraging and may reflect effective management, although clinicians should be aware that vasoconstriction may inhibit peripheral tissue perfusion.

Urine output can be a useful guide to end-organ perfusion and may be a more useful indicator of cardiovascular status than ABP alone (Corley, 2004). This can easily be measured during general anaesthesia in horses.

Blood lactate concentrations can also be a useful guide to the adequacy of tissue oxygen delivery and can help to guide haemodynamic therapy (Corley, 2004).

Summary

It is common knowledge that anaesthetised horses may frequently require treatment for arterial hypotension (Donaldson, 1988), but a range of management options are available. Addressing the underlying mechanism contributing to the development of hypotension is important for its effective management, but multiple factors may be implicated and response to treatment can vary between patients and in clinical situations.

KEY POINTS

• Hypotension is a common complication during inhalational agent anaesthesia in horses.
• Most anaesthetists would strive to maintain mean arterial pressure > 70mmHg during general anaesthesia in horses where possible.
• Treatment or management options for hypotension include; reduction in delivered concentration of inhalational agent where possible, adequate intravenous fluid therapy, avoidance of over-zealous controlled mechanical ventilation, administration of vasoactive agents including dobutamine, noradrenaline, phenylephrine or ephedrine.
• Identification of the underlying cause of hypotension may aid in its effective treatment and management, however, this may not always be straight forward in different clinical situations.