/  Part I.5 – Anesthesia and Care of the Large Animal for Survival Studies: Sheep



Anesthesia and Care of the Large Animal for Survival Studies: Sheep

Cheryl Blaze BVSc PhD MBA

A. Introduction

Ruminant physiology and anatomy present special challenges for general anesthesia. The rumen is the first and largest of the four stomachs and the herbivorous diet means that bacterial fermentation is the initial process of digestion. Only the fourth stomach produces acid and this is a relatively small organ. Volatile fatty acids and gas, primarily carbon dioxide and methane, are produced in large quantities in the rumen and during anesthesia bacteria continue to produce gas and acids.

Fasting is essential for 12-18 hours and water should be withheld for 6-12 hours. Even with this duration of fasting the rumen does not empty completely and there remains the risk of regurgitation and potential aspiration of ruminal contents into the lungs. Drugs administered during anesthesia depress the CNS and produce relaxation of sphincters, the cardia and the esophageal muscle. Decreased intra-thoracic pressure can also predispose to regurgitation and this may be caused by respiratory obstruction, e.g. during the intubation procedure. The enormous weight and volume of the gut press against the diaphragm and restrict breathing, especially if the animal is in dorsal (supine) recumbency. This causes various degrees of hypoventilation and V/Q mismatch with the potential for hypoxemia.

In studies using pregnant animals, e.g. fetal research, careful attention must be paid to the metabolic status of the ewe as ketosis can develop quickly in late pregnancy. The ewe will become depressed and recumbent and there will be increased urine and blood ketones, blood urea nitrogen and free fatty acids and decreased blood glucose and potassium (1,2). This condition should be treated immediately it is recognized. Fasting is still necessary before anesthesia to limit the risk of regurgitation and aspiration but the animal must be administered a slow intravenous infusion of 5% dextrose and also receive B vitamins and calcium if indicated. Blood glucose monitoring should be done on a regular basis during the fasting period and throughout surgery. A complete description of pregnancy ketosis is beyond the scope of this author’s experience and further information on the management of this condition can be found in veterinary texts (1,2).

Another risk with anesthesia of sheep is the development of tympany from ongoing bacterial fermentation that can impede ventilation. Other factors that can cause tympany are the use of anticholinergics (depress vagal tone to the gut and therefore cause atony) and general depression caused by anesthetic drugs. Ina conscious animal volume receptors in the rumen help promote eructation and removal of gas. However these are inhibited if covered by fluid or foam3 and during anesthesia this could occur simply because of the position of the animal. Placement of a stomach tube is not usually very successful for removal of gas because the ruminal end of the tube will not necessarily be in the gas pocket. Even if this did occur, the gas may not be able to move downhill along the tube to exit the animal. In dire cases, a trochar may be required to remove the gas.

Ruminants normally produce saliva in large volumes and this continues during anesthesia. Salivary composition varies with the gland of origin but generally is rich in urea, phosphorus, potassium and other electrolytes (4). During anesthesia these are lost if saliva production continues for many hours. Saliva should be directed away from the mouth to reduce the risk of it collecting in the oropharynx and moving down the trachea to slide past the cuff of the endotracheal tube. Saliva can be serous, mucous, or mixed depending on the gland of origin. The parotid glands produce serous saliva and the buccal, palatine and pharyngeal glands produce mucous saliva. Mixed saliva is produced by the submaxillary, sublingual and labial glands.

There are some differences of opinion on the use of anticholinergics as part of an anesthesia protocol in ruminants and it is useful to understand the physiology of saliva production so that an informed decision can be made. The autonomic nervous system acts synergistically in production of saliva. Parasympathetic stimulation increases blood flow and saliva production and the sympathetic system contracts the myoepithelial cells (“basket cells”) surrounding the ducts and expels saliva. Anticholinergics appear to block the production of serous saliva but not mucous saliva and so the saliva that is produced after anticholinergic administration is more viscid. This would be a detriment if saliva became inhaled into the airway. Another disadvantage of these drugs is that they depress normal gut movement – although it is unclear at what dosage this occurs. Ruminal atony may result from anesthesia with these drugs. However in some cases it is helpful to reduce the flow of saliva and in these cases anticholinergics are a useful adjunct to anesthesia. An example may be a sheep in which several intubation attempts are required, a problem that progressively becomes worse as saliva starts to fill the oral cavity, especially after ketamine induction. Saliva can drain down the trachea and in these cases a single dose of anticholinergic may make this part of the procedure much easier, allowing faster control of the airway.

B. Physical Examination

Most animals are purchased as Specific Pathogen Free. The word “specific” is used loosely. There are some pathogens that may be harbored by the animal and some sheep diseases are zoonotic5,6. Care must be taken to ensure that personnel are protected if the disease status of the animal is uncertain and especially if any personnel are immune-compromised. The attending veterinarian should always be consulted if there is any concern about the health status of animals to be purchased.

Table 1 lists normal vital signs for sheep and Tables 2, 3 and 4 list hematology and chemistry values. Note that normal body temperature is higher than for some other species so a decrease in temperature during surgery may not be appreciated as being of concern when in fact it could indicate significant hypothermia. The heart can be ausculted or “listened to” best at the fourth intercostal space located just posterior to the left elbow in a standing sheep. Special note should be taken of respiratory system as the stress of transport to the research facility can allow sub-clinical disease to become clinically apparent. This could be manifest as coughing or nasal discharge. The eyes should be bright and clear. The pupil is brick shaped and changes to a circular shape only when deeply anesthetized or if muscle relaxants are administered.

Table 1. Normal vital signs for resting adult sheep.

table 1

Table 2. Erythrocyte parameters in sheep. (25-27)

table 2

Table 3. Leukocyte parameters, plasma protein and fibrinogen in sheep. (25-27)

table 3

Table 4. Serum chemistry in sheep. (25-27)

table 4

C. Preparation of Equipment

A breathing circuit including a 3 L rebreathing bag designed for adult humans is suitable for a sheep. The anesthetic circuit and ventilator should be pressure checked to 25-30 cm H2O to ensure there are no leaks and the endotracheal tube cuffs should be inflated and left undisturbed for 10-15 minutes to ensure there are no slow leaks. The most suitable size of tube is 8 to 10 mm ID. Damage to the cuffs by sharp molars may occur during intubation so it is wise to have two or three tubes ready for use in case one has to be discarded. A stylet is useful for guiding the tube through the glottis and KY jelly or other lubricant should be used on the cuffs. A laryngoscope with a long straight blade and a bright light is essential as well as a tie or rope for holding the jaws open for intubation and for tying the tube in place. Note that if one-lung ventilation is being considered the commercially available one-lung endotracheal tubes for adult humans are too short for the long airway of a sheep that measures approximately 32 cm from incisors to carina. It will be necessary to use an endobronchial blocker that may also be barely adequate.

A peripheral nerve stimulator is essential if the sheep is to be paralyzed. Infusion pumps and printouts of varying infusion rates for the animal should be prepared and an anesthetic record form prepared. Label all syringes with the names of drugs to be used. A bland eye ointment will protect the corneas from scratches, desiccation, spray solutions, etc. Suction apparatus should be available for managing the salivation that continues during anesthesia.

D. Pre-Medication

Pre-medication allows for reduced doses of induction agent and inhalant but in ruminant species it could potentially predispose to regurgitation. Generally speaking the pure mu agonist opioids cause excitement in ruminants but the agonist/antagonist butorphanol can be used for sedation via the kappa opioid receptors. Diazepam or midazolam can be added to butorphanol for a synergistic effect but when used alone may cause some dysphoria. As discussed above anticholinergics may be useful but for personnel experienced at intubation they may not be necessary. Alpha 2 agonists such as xylazine are not appropriate as pre-medicants for cardiovascular research because of hypertension, bradycardia, significant depression of cardiac output and sensitization of the myocardium to arrhythmias (7). Xylazine has been reported to cause pulmonary edema in sheep (8). Other effects of xylazine are hyperglycemia, hypoinsulinemia (9,10), polyuria, gut atony, an oxytocin-like effect on the pregnant uterus (11) and profuse salivation.

Intramuscular injection can be done into the lumbar muscles parallel to the spine at the pelvic level. Alternatively the intravenous route can be used if a catheter is already in place with a reduction in the dose rate to approximately half the IM dose.

Table 5 lists dose rates of drugs for premedication, induction, maintenance and postoperative analgesia.

Table 5. Drug doses for anesthesia of sheep. (28-30)

table 5

E. Intravenous Catheter Placement

The jugular vein is easy to catheterize once the wool has been shorn and the skin wiped clean of lanolin and other oils. The sheep should be restrained with the head and neck held almost vertical and to one side to allow easier visualization of the vein. The skin is thick so it is useful to create a hole in the skin with a needle of larger gauge than that of the catheter, taking care not to pierce the vein. This will make it easier to slide the catheter through the skin. The long flexible neck means that it is relatively easy for the catheter to be accidentally dislodged from the vein so it is essential to use a long catheter, approximately five inches long and 16-18 gauge. The catheter can be secured to the skin with skin glue and then sutured when the sheep is anesthetized. The thick skin is difficult to suture and this would be painful for a conscious sheep.

On rare occasions when a jugular vein is not available, a mammary vein may be used, e.g. in a pregnant animal.

Sheep also have a cephalic vein on the antero-medial aspect of the forelegs and these veins can accommodate 18-20 gauge catheters approximately three inches long. This is not the most suitable choice for the first catheter placement as the skin is very thick in this region and the catheter may become dislodged easily when the sheep is lifted and moved after induction. If a second catheter is required, e.g. if blood transfusion is anticipated, the lateral saphenous vein on the hindlimb can be used as an accessory site once the sheep is anesthetized. This is located just above the hock (Fig. 1) and an 18-20 gauge catheter is suitable.

figure 1Figure 1. Location of lateral saphenous vein on hindlimb.

F. Induction and Intubation

The most common drug protocol for induction of healthy sheep is ketamine added to diazepam or midazolam. The drugs can be mixed in the same syringe and given to effect. It is preferable to have extra drug drawn up because intubation can be a frustrating process. A disadvantage of this protocol is the salivation caused by ketamine.

Propofol is generally not suitable because apnea may occur, especially with rapid injection. The short duration of propofol is a disadvantage if repeated doses are necessary to allow intubation and hypoxemia will result fairly rapidly if intubation attempts are prolonged.

For animals with moderate to severe cardiovascular compromise etomdiate and midazolam are a better choice for induction. A disadvantage of etomidate in septic and critically ill humans is adrenocortical suppression (12,13) although this has not been studied in sheep. Depending on the duration and extent of the procedure to be done and the status of the animal at the time, steroid cover may be indicated if etomidate is chosen (Table 6).

Table 6. Steroids, antibiotics and ancillary drugs for sheep.

table 6

Avoid struggling at induction. A rapid and smooth induction will facilitate intubation and control of the airway. Ensure an adequate depth of anesthesia before intubating. The process of intubation is stimulating to the pharyngeal area and may provoke regurgitation.

Note that in sheep the left apical bronchus branches from the trachea above the tracheal bifurcation (Fig. 2) and if an excessively long endotracheal tube is used it could potentially block that lobe from ventilation. However this is unlikely complication because of the length of the neck compared to the length of most endotracheal tubes that are commercially available.

figure 2Figure 2. Latex mold of part of sheep airway showing the left apical bronchus arising approximately 5 cm proximal to the carina.

Intubation is generally difficult because of the long narrow jaws that do not open very wide and the thickened dorsum of the tongue that impedes a clear view of the glottis (Fig. 3). Fortunately sheep do not develop laryngospasm. The safest way to intubate is to have the animals in sternal (prone) recumbency with an assistant holding the jaws open with a strong rope or cord. Because of the length of the mandible a long blade and a bright light on the laryngoscope are essential. Usually the laryngoscope blade is held to the side of the mouth to allow more room for the tube. The molars have very sharp edges and the tube cuff is easily damaged. A stylet can be used inside the tube to enter the glottis and act as a guide for the tube but care must be taken not to traumatize surrounding soft tissues (Fig. 4).

figure 3aFigure 3a. Frontal view of sheep mandible and tongue illustrating the difficulty in viewing the glottis.

figure 3bFigure 3b. Lateral view of sheep mandible showing the thickened dorsum of the tongue.

figure 4Figure 4. Intubation with stylet inside endotracheal tube advanced to act as a guide through the glottis.

ALWAYS have a spare tube ready, with the cuff checked. After intubation inflate the cuff and determine whether it is functional. Damage to the cuff necessitates removal of the tube and reintubation with another tube that has an intact cuff. Sheep do not have upper incisor or canine teeth so the tube should be fixed in place by a tie that is secured behind the head rather than around the jaw. The correct placement of the tube in the trachea should be confirmed by capnography.

Fiberoptic equipment (Fig. 5) can be used for intubation and allows for direct visualization of the oropharyngeal structures and reliable insertion of the tube into the trachea. Not all research facilities will have this available.

figure 5Figure 5. Location for placement of a Doppler probe and cuff on the limb of a sheep. The hair/wool should be clipped before securing the probe.

Regurgitation during intubation

If regurgitation occurs it is imperative to immediately cease attempts to intubate and hang the head down so that the material can drain out of the mouth. The mouth should be washed out quickly with water to remove ingesta and the tube should also be washed. If there is a very large amount of regurgitated material, or if aspiration is suspected, it is preferable to allow the animal to recover and postpone the procedure, but there may be occasions when surgery cannot be postponed. In these cases, once the mouth is clean the intubation procedure should continue as quickly as possible and the cuff inflated. If regurgitation does not cease for some time, the intubation attempt should be delayed further and the animal given more induction drugs if necessary to restore an adequate depth of anesthesia. Intubation should only be continued if regurgitation has ceased and the mouth and pharyngeal area are seen to be clean, so that ingesta is not inadvertently introduced into the airway with the tube. Prophylactic antibiotic therapy may be indicated but this would be dictated by the extent of regurgitation, the research protocol, the principal investigator and the attending veterinarian.

Positioning and padding

It is useful to have a padded stretcher available, allowing the animal to fall onto it to avoid having to move the sheep around once anesthetized. Position the animal as carefully as possible, avoiding sudden jerking movements that can cause movement of fluid out of the rumen through the relaxed sphincters. The stretcher can then be lifted onto the surgery table.

Use padding such as a rolled towel under the neck to elevate the mid-neck region and allow the head to tilt in a nose-down position. This ensures that if fluid or ingesta move cranially from the rumen, the material must first travel uphill and then down to the pharyngeal area to exit the mouth. There is some controversy over whether a stomach tube is useful. A large bore stomach tube can be placed to direct any ingesta away from the mouth. A tube placed through the cardia could promote movement of ingesta out of the rumen, but the advantage of a tube is that if regurgitation does occur the fluid is directed out of the mouth. However a tube will not necessarily prevent aspiration. A large bore suction catheter should be used regularly during anesthesia to remove saliva that accumulates in the oropharynx.

Protection of the eyes with eye lubricant is essential to avoid any possibility of a corneal scratch. If a facial or neck area requires surgical preparation, the eyes should also be protected from clipped wool and disinfecting solutions. Nerve damage can be avoided by using padding under the face and forelimb and by pulling the lowermost forelimb forward if the sheep is in lateral recumbency. Also, positioning the uppermost hindlimb so that it is parallel to the table or floor will reduce the likelihood of ischemia of the limbs (pressure on the femoral vessels) or nerve damage. Ruminants are not usually plagued by myositis although nerve damage can certainly occur with poor positioning or padding. When in dorsal recumbency the legs should not be tied tightly to the table as ischemic necrosis of the extremities may occur. Ideally the hindlimbs should be supported by padding on the lateral sides (between the sheep and the table) to avoid excessive stretch of the ligaments surrounding the hip joints Adbudction of the hindlimbs is not a natural pose for sheep and excessive strain on ligaments can be a source of morbidity such as pain, stiffness and difficulty walking on recovery.

G. Maintenance and Monitoring

Inhalant agents

These are the drugs of choice for maintenance of anesthesia but have no analgesic properties. Isoflurane is the most commonly used agent because of its rapid action and relatively low cost. An appropriate vaporizer setting is 1.5% to 2.5% with a flow rate of oxygen at 15-20 mL/kg/minute. The vaporizer setting can be decreased soon after analgesic infusions have commenced. Similarly, sevoflurane is initially provided at 2.5% to 3.5% and decreased when analgesics are added. Halothane is no longer available commercially in the United States. It is the inhalant with the greatest propensity to sensitize the myocardium to arrhythmias and is not a good choice for cardiothoracic surgery.

If a variable FIO2 is required for anesthesia the carrier gas should be medical air/oxygen and not nitrous oxide/oxygen. Ruminants will have pockets of air in their gastrointestinal tract regardless of the duration of fasting and these can rapidly increase in volume if nitrous oxide is used. Apart from the risk of tympany and its effect on ventilation, the minimum alveolar concentration (MAC) values for nitrous oxide in many non-human species (approximately 200 or more (14)) is significantly greater than the value for man (104+/-115) and this indicates that nitrous oxide would have minimal anesthetic effect in a sheep.

The tidal volume should be set at 10-15 ml/kg with a peak inspiratory pressure not exceeding 25 cm H2O. Respiratory rate should be set at 12-16 breaths per minute. A positive end expiratory pressure (PEEP) valve at 2.5 or 5 cm H2O may be required if hypoxemia develops or if the inherent PEEP value of the ventilator appears to be insufficient.

Muscle relaxants

These drugs provide only relaxation and no analgesia or anesthesia. Because laryngospasm is not a hazard in sheep anesthesia and intubation can be difficult it is unwise and unnecessary to use muscle relaxants for intubation. A paralyzed animal that proves to be difficult to intubate can rapidly desaturate and die while intubation is being attempted. For monitoring neuromuscular block suitable nerves are the peroneal, ulnar and facial nerves. For cardiovascular surgery the facial nerve is probably most suitable as movement in response to nerve stimulation offers the least distraction to the surgical team. The electrodes are placed across the dorsal buccal branch of the facial nerve at a point 3 cm ventral to the medial canthus of the eye (16). A square wave stimulus lasting 0.2 to 0.3 milliseconds is most commonly used with a stimulator that can provide a supramaximal stimulus and single twitch, train of four and tetanic stimulation. These variable patterns allow more complete assessment of partial blockade that might exist even after antagonism at the end of the procedure.

During maintenance of anesthesia of a paralyzed sheep it is imperative to monitor signs of anesthetic depth to ensure that the animal is not conscious and paralyzed. Because eye reflexes are lost the best method is to monitor heart rate and blood pressure for any spikes with surgical stimulation or any other unexpected increases. Lacrimation is not a consistent feature of awareness in sheep.


Analgesics should be included in the anesthetic protocol and in the author’s experience constant rate infusions of fentanyl, lidocaine and ketamine provide excellent analgesia with minimal effect on cardiovascular parameters. These can be infused via a syringe pump or added to the balanced electrolyte solution used for fluid therapy during surgery. If the latter option is chosen a separate electrolyte solution without added analgesics should be used for any fluid bolus that might be required to avoid an overdose of the analgesic drugs. Apart from the analgesic properties of these drugs there is a reduction of MAC allowing a lower percentage of inhalant to be used, thereby helping to maintain acceptable blood pressure.

Before anesthesia it is useful to create a computer chart of the dose range for each drug based on the animal’s body weight so that changes to the infusion rate can be made easily without having to make a calculation each time. Once the body weight is input the formula will calculate the flow needed for each drug at each dose rate for that particular animal.

Intercostal nerve blocks are beneficial and can be easily performed before surgery and repeated postoperatively to manage pain caused by a chest tube. Posterior to each rib are the artery, vein and nerve in this order. Bupivacaine at 1.5 mg/kg as a total dose can be divided into equal volumes to block two intercostal nerves on either side of the intercostal space where the incision is to be made (lateral chest wall) or where the chest tube exits. This is not as practical for a sternotomy because the length of the incision crosses many nerves and the dose of bupivacaine required for all the nerves would be excessive.


Epidural injection of analgesics can be done in small ruminants but there are some considerations that must be recognized. This technique is more suited to surgery on the abdomen or hindquarters of the animal and it is unclear to what extent epidural analgesia is helpful for thoracic surgery. The most effective drugs to use would be local anesthetics but the resultant paralysis creates much more work for animal care attendants and there is a risk of urinary infection and the potential for injury as the animal slowly regains motor strength and struggles. Cardiovascular collapse is also a risk if the injection is inadvertently done into the subarachnoid space. The most commonly used drugs for epidural injection in sheep are the alpha-2 agonists (xylazine, etc.), which have adverse effects on the cardiovascular system and therefore are not suitable for cardiovascular research. Opioids have not been investigated thoroughly for sheep epidural injection.

H. Determinants

Heart rate

Heart rate is normally in the range of 80-100 and is somewhat responsive to changes in depth of anesthesia. A significant increase is a good indication of awareness in a paralyzed animal. Steadily increasing heart rate may indicate increasing hypercarbia if other signs of anesthesia are unchanged and could also be a response to blood loss.

Electrocardiography (ECG)

If arrhythmias such as premature ventricular contractions develop during anesthesia first ascertain whether the cause could be something simple that is relatively easy to reverse. For example painful stimuli, hypercarbia, excessive depth of anesthesia, or hypoxemia can contribute to arrhythmias. With cardiac surgery one could expect arrhythmias to develop due to direct stimulation of the myocardium and in this case 2% lidocaine is useful as a bolus at 2 mg/kg IV or sometimes sprinkled lightly directly onto the heart. An infusion may be necessary for ongoing treatment of arrhythmia at a rate of 75-85 mg/kg/minute.

Arterial blood pressure

This is usually fairly high during anesthesia, unlike non-ruminant species and varies with depth of anesthesia. A mean value of 90-100 is normal in sheep and hypotension during anesthesia is unusual and means that anesthesia is too deep, or the sheep is hypothermic or hypovolemic. Blood pressure can be measured indirectly by a Doppler ultrasonic probe and cuff or by oscillometry using a cuff around a limb. For indirect measurement the Doppler crystal can be placed posterior to the feet above the common digital arteries, just above the dew claws and the cuff placed around the limb a few inches above this (Fig. 6). The width of the cuff should be as close as possible to 40% of the circumference of the limb.

For direct measurement a peripheral artery can be catheterized and connected via a transducer to an amplifier for a digital reading of systolic, diastolic and mean blood pressures. The auricular artery on the dorsal spine of the pinna is easily accessible and can be quickly catheterized with a 20 gauge catheter once the wool is shaved. The common digital arteries just dorsal to the dewclaws are useful pulse points but very difficult to catheterize because of the proximity of the hard dew claws and the sharp angle that has to be negotiated for threading the catheter once the vessel is penetrated. The femoral and carotid arteries are other pulse points but the carotid artery requires a cut-down for catheterization. A catheter in the femoral artery can be inserted percutaneously but this may not be a convenient location for sampling during the surgical procedure. These locations require very firm pressure for several minutes after removal of the catheter.

Inotropes and pressors for cardiovascular support

Cardiac output and contractility can be supported if necessary by infusions of inotropes and/or pressors. Dobutamine, a β agonist, will improve cardiac output primarily by increasing contractility. Ephedrine, an α and β sympathomimetic drug, will increase contractility and systemic vascular resistance but there may be some tachyphylaxis with repeated use. Dopamine can be used in sheep but tachycardia at higher doses can limit its usefulness for treating hypotension.

Arterial oxygenation

The gold standard for PaO2 measurement is an arterial blood gas sample which can be obtained easily from a catheter inserted into the auricular artery. A guide to oxygenation can be obtained from a pulse oximeter which is useful for continuous calculation of hemoglobin oxygen saturation. This can be applied before or immediately after induction. The lip or tongue are the most commonly used sites but some sheep have pigmented mucous membranes and the tongue can be quite slippery from saliva. Occasionally the pinna can be used but the thickness of the tissue may preclude reliable readings. The vulva or prepuce are alternative sites.

Arterial blood gas

For most domesticated species arterial blood gas values are similar although herbivores tend to be slightly alkalemic while carnivores are slightly academic. It is not unusual for the base excess in a sheep to be +4 to +6. Typical values for a sheep being ventilated with isoflurane and an inspired oxygen fraction (FIO2) of 0.98 would be PaCO2 of 36-40 mm Hg and PaO2 in the range 450-550 mm Hg. Some V/Q mismatch is to be expected in sheep for reasons discussed in the introduction and the use of a PEEP valve may be indicated. If significant hypoxemia is noted investigate whether aspiration may have occurred (check the oropharynx for fluid accumulation) or whether the ventilator settings may be providing an excessive tidal volume. Depressed cardiac output caused by excessive tidal volume, especially in the presence of tympany, can cause hypoxemia.


This is a valuable tool at induction for ensuring correct placement of the endotracheal tube and also during anesthesia for monitoring ventilation. Capnography can warn of various problems such as inspiratory or expiratory obstruction, venous air embolism, pulmonary embolism, bronchospasm, circuit or cuff leak, malfunctioning exhalation valve, hypothermia, rebreathing and a significant decrease in cardiac output.

Intravenous fluids

For surgery of long duration a balanced electrolyte solution such as Ringer’s lactate is preferable to sodium chloride because of the steady loss of electrolytes in the saliva. The flow rate of IV fluids is generally 10ml/kg/hour but may need to be adjusted to allow for blood loss. A pressure bag should be available for rapid fluid replacement if indicated. Changes in central venous pressure (CVP) will indicate the need for fluid replacement. If blood loss is significant a colloid solution should be used in conjunction with the crystalloid solution to retain oncotic pressure in the vasculature. This is usually done once the value of total plasma protein is approximately 4g/dL or lower. Hydroxyethylstarch solutions (e.g. Hetastarch® or Voluven®) can be administered at 5ml/kg as a bolus with repeated doses as needed up to a maximum of 20ml/kg/day (Hetastarch®) or 50 ml/kg/day (Voluven®). Great care should be taken not to exceed an appropriate volume and it is wise to measure the colloid oncotic pressure at the end of the procedure. A disadvantage of colloid solutions is the risk of allergic reaction and the effect on coagulation parameters if used in large quantities, although voluven is less likely to create these problems (17).

Blood groups, blood volume and blood transfusion

In cardiovascular research with long term studies there is sometimes the need for blood transfusion during or immediately after surgery to maintain optimum health of the animals. For acute hemorrhage during surgery auto-transfusion is the optimum method of maintaining tissue perfusion and oxygenation but transfusion of blood from a donor sheep may be required. Some facilities keep a donor animal for this purpose. Normal blood volume of sheep is 7% of body weight so for the average sheep of 40 kg with a blood volume of 2.8 liters a 10% loss is 280 milliliters. Keep in mind that hematocrit can be as low as 27 and still be within the normal range for this species. However the hematocrit should be compared with the baseline value for that animal so that the need for blood or blood products can be assessed appropriately.

There are eight blood groups described in sheep, EAA, EAB, EAC, EAD, EAM, EAR, EAF30 and EAF41 (18). There is high variability of blood groups between individuals so cross matching is not usually practical. It is generally safe to transfuse whole blood without matching beforehand, especially since research sheep are young and healthy when purchased and would not have required transfusion prior to this. Erythrocytes of sheep are more fragile than those of humans (19) and reports of survival time of erythrocytes in sheep plasma vary from 64-94 days (20) to 125 days (21) to 70-153 days (22), to 140-150 days (23). These variations are likely caused by the different methods of measurement as well as other factors.

Although buccal mucosal bleeding time is a common clinical test of primary clotting function in dogs and cats, lip bleeding time is more commonly used in large animal species. Bleeding time in sheep is reported as 5.8 +/-1.4 min (19).

Central venous pressure (CVP)

This is easy to measure via a Swan Ganz catheter or a regular jugular catheter and the value should be 5-10 cm H2O. The value will guide the rate of fluid replacement.

Urine flow

For prolonged procedures a Foley catheter in the urinary bladder allows measurement of urine volume, which should be 1mL/kg/hour. Values for urine volume, CVP and arterial blood pressure will guide decisions on fluid therapy during the procedure.

Hematology and chemistry

Values for PCV, TP, blood glucose and lactate should be measured periodically, e.g. every two hours. Glucose is required for muscle contraction and brain function and hypoglycemia will contribute to hypotension, decreased cardiac contractility and a prolonged anesthetic recovery. A dextrose infusion can be instituted to correct hypoglycemia. The usual concentration is 2.5% but 5% may be required in severe cases. The osmolality of the solution depends on the solvent and the solution with the closest match to the osmolality of extracellular fluid (280) is 2.5% dextrose in 0.45% saline. Increased lactate indicates insufficient tissue perfusion which results in muscle pain that will affect the quality of anesthetic recovery.

Body temperature

Anesthesia normally causes a loss of body temperature and this is compounded by removal of the wool coat and an open chest as well as the cold dry gas provided for ventilation. A decreasing body temperature means that less anesthetic agent is required and recovery can be prolonged. A fluid warmer for the intravenous fluid line to the sheep can afford some protection but will not make a significant impact on the loss of body heat.

Eye position

In a spontaneously breathing sheep the globe may move to a ventral or ventro-medial position at a surgical plane but sheep do not demonstrate any significant changes in eye position with different planes of anesthesia. The palpebral reflex in many species is a good indicator of light anesthesia but is less reliable in sheep. A dilated pupil in a spontaneously breathing sheep indicates excessive anesthetic depth and imminent death. With muscle relaxant use the pupil will be dilated and the globe centrally located and in this case the palpebral reflex is lost.

Esophageal motility

This occurs during all but the deepest planes of anesthesia and should not alarm the anesthesiologist. The esophagus is composed of skeletal muscle innervated by the vagus via single neuron pathways. This means that there are no autonomic ganglia and therefore the nervous impulses are not prevented by anticholinergics. Movement of the esophagus is inhibited by muscle relaxants but in a spontaneously breathing sheep occasional movement does not indicate light anesthesia.

Use of a wound soaker (diffusion) catheter

Towards the end of surgery when closure is beginning a wound soaker (diffusion) catheter should be interposed in the tissue layers to allow infusion of local anesthetic post-operatively. This is a good method of controlling postoperative pain and allows for a faster return to normal activity and appetite. There are different types commercially available in various sizesa,b and local anesthetic can be infused for two to three days either by syringe pump or by the balloon incorporated in the catheter design. If lidocaine is used as a constant rate infusion the dose to use is 2 mg/kg/hour with a flow rate set at 5ml/hour. To accomplish this in an adult sheep lidocaine commercially available as a 2% solution should be diluted to 1.5%. Remove 187 ml from a 250 ml bag of normal saline and replace with 187 ml of 2% lidocaine. The resultant concentration of lidocaine will be 1.5%. In the author’s experience this provides very good local analgesia without causing seroma formation. The thickness of tissue on the chest wall is not great and a seroma may develop if the flow rate is too high. An alternative to a lidocaine infusion is bupivacaine injected into the catheter every 6 hours (Table 5).

I. Recovery

This is the part of anesthesia where problems may develop that can jeopardize the entire day’s work. Often it is due to inattention to the animal once it has recovered because of other tasks required at the end of the day. Losing an animal at this stage is demoralizing and expensive and can cause questions to be raised by the institution’s Animal Care and Use Committee. For best results it is advisable to assign staff for the express purpose of monitoring the animal for several hours after the end of surgery. The attending veterinarian is an important resource for all investigators and should be consulted if any doubt arises about animal care, especially for the postoperative period.

Once the procedure is complete the inhalant should be turned off and oxygen flow maintained for at least five minutes. The pharynx should be suctioned to remove any residual saliva. Ruminants should be placed in sternal recumbency for recovery, e.g. by being propped up against a wall with hay bales or some other support. This allows eructation of gas and rapid head-down tilt should regurgitation occur at this stage (not common). The endotracheal tube should remain in place till the animal is making vigorous swallowing movements. As the tube is removed the cuff should be left partially inflated so that any secretions or fluid that may have entered the trachea can be removed with the tube. Ruminants do not develop laryngospasm as do some other species and so removing the tube with a partially inflated cuff does not create a problem. The cuff may be damaged by the molars during extubation.

Two important causes of morbidity and mortality after cardiovascular surgery are insufficient reversal of neuromuscular blockade and residual pneumothorax. Ensuring that neuromuscular blockade is fully reversed is a first step especially since only temporary antagonism in sheep has been reported (24). If the sheep cannot hold its head up after extubation residual neuromuscular block should be suspected and evaluated and additional antagonist can be administered if indicated. Other causes of weakness are hypokalemia, hypocalcemia, hypoglycemia, hypothermia and moderate to severe anemia. These conditions are easy to assess and treat.

Evacuation of the chest is equally important and the animal’s ventilatory status should be very closely monitored in the early recovery phase. In some cases continuous suction may be required for a time. The arterial catheter should remain in place for several hours with regular flushing to allow blood gas sampling to continue. It must be securely fastened to the skin (skin glue or suture) and sealed with a luer lock cap. A pulse oximeter can give early warning of hypoxemia but can be frustrating to use as many sheep have pigmented lips or pinnae creating an unreliable reading and saliva creates a slippery surface from which the probe can dislodge easily. An unreliable reading can also result from peripheral vasoconstriction caused by hypothermia, pain, or anxiety.

Providing oxygen postoperatively may be indicated in some cases and this is achieved by placing a Foley catheter into each nasal passage and connecting them to a humidified source of oxygen at a flow rate of 2-3 L/minute.

A third possible cause of morbidity and mortality is awareness during a long and painful surgical procedure and this indicates the need to provide humane care for the animal during surgery with careful monitoring by personnel who are not distracted by other tasks. Intolerable stress to the animal can be the cause of early postoperative death.

Basic values to monitor are hematocrit, plasma protein, lactate, blood glucose, body temperature and if indicated colloid oncotic pressure. A complete chemistry and electrolyte panel and an arterial blood gas sample should be run if the sheep does not appear to be recovering well. Always ensure that struggling is not caused by residual pneumothorax. Lung sounds should be monitored for wheezing that could indicate bronchoconstriction caused by aspiration. The total volume of intravenous fluids administered should be calculated. Rumen sounds should return within a few hours of anesthesia and a good indication that a sheep is recovering well is an interest in food.

A problem that may occur if surgery was done in the neck area, e.g. carotid artery, is inflammation that affects the vagus nerve. The result of this is gut atony, leading to inappetance, depression and tympany. To treat this complication and to provide analgesia an anti-inflammatory drug should be used such as phenylbutazone, carprofen, or flunixin meglumine (Table 5).

Postoperative analgesia is very important for a smooth recovery. A sign of pain in ruminants is grinding of teeth and this must be recognized early so that intervention can occur. The use of a diffusion catheter for local anesthetic infiltration along the incision site is an excellent method of controlling postoperative pain and the catheter can remain in place for 3-4 days. Intercostal nerve blocks can be repeated to block nerves on either side of the dermatome where the chest tube exits the chest. If the sheep appears to be uncomfortable buprenorphine can be injected IV and the ketamine, lidocaine and fentanyl infusions can be continued at reduced rates for approximately 12 hours postoperatively (Table 5). Apart from the humane aspect of providing analgesia, it is extremely important to recognize that a comfortable sheep will recover more quickly and be a more reliable research subject than a struggling sheep that is in pain.


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