History

A 9-year-old 513-kg (1,128-lb) Thoroughbred gelding (horse 1) with a history of bilateral forelimb lameness localized to the feet of approximately 2 years' duration underwent general anesthesia to facilitate MRI of both front feet. A complete physical examination at the time of admission did not reveal any evidence of systemic abnormalities. Food, but not water, was withheld overnight.

Prior to anesthesia, the horse had a heart rate of 36 beats/min, respiratory rate of 16 breaths/min, and rectal temperature of 37.3°C (99.2°F). A 14-gauge catheter was aseptically placed in the right jugular vein and secured with a suture. The horse was premedicated with xylazine (0.6 mg/kg [0.27 mg/lb], IV), and its mouth was rinsed with water to remove any accumulated particulate matter. Anesthesia was induced with midazolam (0.1 mg/kg [0.045 mg/lb], IV) and ketamine (2.2 mg/kg [1.0 mg/lb], IV), and an endotracheal tube (internal diameter, 26 mm) was inserted. The horse was then hoisted onto a purpose-built aluminum table with a 10-inch foam pad and positioned in left lateral recumbency with the dependent limbs pulled forward and the nondependent legs in a neutral position relative to the body, parallel to each other. The head was placed on a table with 1-inch-thick padding that was specifically designed for use with canine patients during MRI. The height of this table was not adjustable, and the table was the same height as the MRI gantry. As a result, the head of the horse was no more than 4 inches above or below the midline when the aluminum table was raised to image the dependent forefoot or lowered to image the nondependent forefoot. Anesthesia was maintained with isoflurane in oxygen delivered via a circle system with an MRI-compatible large animal anesthesia machine.^a Mechanical ventilation was instituted at a rate of 6 breaths/min and tidal volume of approximately 15 mL/kg (6.8 mL/lb). Lactated Ringer's solution was administered IV during anesthesia (10 mL/kg/h [4.5 mL/lb/h]). A 20-gauge catheter was placed in the right transverse facial artery for direct measurement of arterial blood pressure. Additional monitoring with an MRI-compatible multiparameter monitor^b included ECG and pulse oximetry. Mean arterial blood pressure was maintained > 70 mm Hg with IV administration of dobutamine at rates between 2.5 and 10 μg/kg/min (1.1 and 4.5 μg/lb/min). An arterial blood sample was obtained for blood gas analysis 60 minutes after induction of anesthesia. Results included pH of 7.284 (reference range, 7.32 to 7.44), Pao₂ of 351.4 mm Hg (reference range, 100 to 500 mm Hg), Pa2co₂ of 75.6 mm Hg (reference range, 38 to 46 mm Hg), and HCO2₃⁻ of 36.2 mmol/L (reference range, 20 to 28 mmol/L), indicating respiratory acidemia and hypoventilation with metabolic compensation. Electrolyte and lactate concentrations were within reference limits. After these results were obtained, the tidal volume delivered by the ventilator was increased to approximately 18 mL/kg (8.2 mL/lb). A second arterial blood sample for blood gas analysis was obtained 60 minutes later. Results included pH of 7.471, Pao₂ of 395.4 mm Hg, Paco₂ of 38.6 mm Hg, and HCO₃⁻ of 28.4 mmol/L, indicating correction of hypoventilation. After the MRI procedure was concluded, the horse was weaned from the ventilator. Anesthesia was discontinued, and the horse was moved to a padded recovery stall and placed on an inflatable pillow. Total anesthesia time was 170 minutes. The horse was extubated and administered romifidine (0.02 mg/kg [0.009 mg/lb], IV) and acepromazine (0.01 mg/kg [0.0045 mg/lb], IV). When the horse first began making movements, the air pillow was deflated and the horse was allowed to recover unassisted. The horse rolled into sternal recumbency 22 minutes after extubation and assumed a standing position 25 minutes later. Recovery was considered uneventful. The horse was led out of the recovery stall and back to its stall in the ward. When the horse arrived at its stall, the handler noticed that the horse's face was asymmetric and that the left masseter muscle was larger than the right (Figures 1 and 2). The swelling was hot and firm, and palpation of the swelling elicited signs of pain. However, the horse was able to move its mouth and prehend food normally.

On the same day, a 9-year-old 586-kg (1,289-lb) Oldenburg mare (horse 2) with a history of right fore-limb lameness localized to the foot of approximately 3 months' duration underwent general anesthesia to facilitate MRI of both front feet. A complete physical examination at the time of admission did not reveal any evidence of systemic abnormalities. Food, but not water, was withheld overnight. Prior to induction of anesthesia, the horse had a heart rate of 32 beats/min, respiratory rate of 16 breaths/min, and rectal temperature of 37.6°C (99.7°F). Anesthetic induction, maintenance, and monitoring and positioning of horse 2 were similar to those described for horse 1. Lactated Ringer's solution was administered at a rate of 10 mL/kg/h, IV, and mean arterial blood pressure was maintained > 70 mm Hg with IV administration of dobutamine at rates between 2.5 and 10 μg/kg/min. An arterial blood sample was obtained for blood gas analysis 90 minutes after induction of anesthesia. Results included pH of 7.574, Pao₂ of 514.3 mm Hg, Paco₂ of 25.4 mm Hg, and HCO₃⁻ of 23.7 mmol/L, indicating respiratory alkalemia and hyperventilation. Electrolyte and lactate concentrations were within reference limits. In response, the tidal volume delivered by the ventilator was reduced to approximately 12 mL/kg (5.5 mL/lb). A second arterial blood sample was obtained for blood gas analysis 60 minutes later. Results included pH of 7.449, Pao₂ of 485.2 mm Hg, Paco₂ of 42.6 mm Hg, and HCO₃⁻ of 29.8 mmol/L, indicating correction of hyperventilation. After the MRI procedure was concluded, the horse was weaned from the ventilator. Anesthesia was discontinued, and the horse was moved to a padded recovery stall and placed on an inflatable pillow in a similar manner as described for horse 1. Total anesthesia time for horse 2 was 180 minutes. The horse was extubated and administered romifidine (0.02 mg/kg, IV) and acepromazine (0.02 mg/kg, IV), and when the horse first began making movements, the air pillow was deflated and the horse was allowed to recover unassisted. The horse moved directly to a standing position 61 minutes after extubation, without first rolling into sternal recumbency. Recovery of horse 2 was also considered uneventful, but when the anesthetist entered the recovery stall to lead the horse out, the horse was noted to have swelling of the left masseter muscle similar to that described for horse 1. The horse was led back to its stall in the ward. Both horses underwent complete physical examinations, and no other areas of muscle swelling or discomfort were noted.

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Photograph of a 9-year-old Thoroughbred gelding that developed EPAM after undergoing general anesthesia for MRI. Notice the enlarged left masseter muscle (arrows).

Citation: Journal of the American Veterinary Medical Association 240, 1; 10.2460/javma.240.1.40

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Front view of the same horse as in Figure 1. Notice the facial asymmetry, with enlargement of the left side of the face (arrows).

Citation: Journal of the American Veterinary Medical Association 240, 1; 10.2460/javma.240.1.40

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Venous blood samples were obtained from each horse and submitted for plasma biochemical analysis. Results for horse 1 included CK activity of 3,473 U/L (reference range, 71 to 300 U/L) and AST activity of 528 U/L (reference range, 150 to 294 U/L); all other measured values were within reference limits. Results for horse 2 included CK activity of 1,353 U/L and AST activity of 484 U/L; all other measured values were within reference limits.

Question

What is the most likely cause of the left-sided facial swelling in these 2 horses? What precautions should be taken to prevent this problem from developing in the future in horses undergoing general anesthesia for MRI?

Answer

The most likely cause of the facial swelling in these 2 horses was EPAM resulting from decreased perfusion, ischemia, and reperfusion injury of the left masseter muscle groups secondary to inadequate padding of the head during anesthesia. To reduce the chances of future episodes of masseter muscle swelling, the canine table used for these horses should have additional padding added to it or its use be discontinued.

Treatment and Outcome

The treatment plan for both horses consisted of anti-inflammatory and analgesic medications to reduce the swelling and discomfort associated with myopathy. Both horses were closely monitored to ensure that they were able to eat and drink, and provisions were made to administer fluids IV if there were concerns about hydration. However, after the horses were observed for several hours, it was clear that both were able to eat and drink and that IV fluid therapy was not needed. Initial anti-inflammatory and analgesic treatments for horse 1 consisted of phenylbutazone (2.5 mg/kg, IV) and ice packing of the affected muscle. Initial anti-inflammatory and analgesic treatments for horse 2 consisted of flunixin meglumine (1.1 mg/kg [0.5 mg/lb], IV) and ice packing of the affected muscle. The difference in drug selection for the 2 horses was due to clinician preference.

The following morning, both horses were eating and drinking normally and passing manure of normal consistency and amount. The swollen areas on both horses had reduced in size but had not completely resolved in either horse. Anti-inflammatory and analgesic treatment was continued in both horses and consisted of application of 10 mL of dimethyl sulfoxide gel and a 5-inch ribbon of 1% diclofenac sodium topical cream^c to the affected area twice daily for 1 day. The horses were discharged the following day with minimal swelling of the area.

Discussion

Equine postanesthetic myopathy occurs in horses after general anesthesia and can result in skeletal muscle necrosis. Most commonly, muscle groups on the dependent side of horses positioned in lateral recumbency are affected; however, muscle groups on the nondependent side can also be involved.¹ In horses positioned in dorsal recumbency, the epaxial and gluteal muscles are most commonly affected.¹ Affected muscles include the quadriceps, gluteal, triceps, biceps femoris, neck, masseter, carpal flexor, and vastus lateralis muscles.^2–5 In a multicenter study,⁶ EPAM was the cause of death in 7% of horses that died within 7 days after being anesthetized for reasons other than colic. Factors contributing to EPAM include large body mass, long duration of recumbency, inadequate padding, improper positioning, intraoperative hypotension, and hypoxemia.¹ In both horses described in the present report, inadequate padding was thought to be the cause of EPAM.

A diagnosis of EPAM can be made on the basis of clinical signs and results of serum or plasma biochemical analyses and histologic analysis of muscle biopsy specimens. Clinical signs range in severity and include difficult recovery, inability to stand, swollen and painful muscles, severe lameness, sweating, tachycardia, muscle fasciculation, and myoglobinuria.¹ Serum and plasma biochemical abnormalities include increases in CK and AST activities as a result of compromised integrity of the skeletal muscle sarcoplasm. Creatine kinase is a cytosolic enzyme with highest activity in skeletal muscle. It has a half-life of < 2 hours, and measured activities return to normal within 2 to 3 days after cessation of myonecrosis.⁷ Creatine kinase activity can be used to monitor ongoing muscle damage. Aspartate aminotransferase is found mainly in hepatic and skeletal muscle tissue, and AST activity is not as specific for muscle injury. Muscle damage results in increases in AST activity as a result of changes in muscular permeability. Aspartate aminotransferase has a half-life of 7 to 10 days, and increases in serum or plasma AST activity persist longer than increases in serum or plasma CK activity and are not as valuable for monitoring ongoing muscle damage.⁸ Histologic examination of muscle biopsy specimens can differentiate EPAM from other equine muscle diseases.⁹ However, in the horses described in the present report, EPAM was diagnosed on the basis of clinical signs and high CK and AST activities alone.

The pathophysiology of EPAM is thought to be related to altered blood flow, decreased perfusion, and ischemic injury to muscle.¹ Two mechanisms are believed to contribute and can occur independently or simultaneously. First, external pressure from the horse's body weight on capillary beds exceeds perfusion pressure, resulting in capillary bed collapse. Second, hypotension results in inadequate blood pressure to perfuse muscle, resulting in decreased oxygen delivery and local tissue hypoxia. In either case, hypoperfusion of the capillary bed leads to increased permeability, edema, and inflammation. Inflammatory cytokines extend the damage to surrounding tissues. Pain pathways are also activated. Reperfusion injury occurs when blood flow is restored and results in swollen, edematous muscle and, potentially, compartment syndrome, which is self-perpetuating and can result in compressive muscle death unless the pressure is relieved.^1,8 Injuries associated with EPAM are not limited to the skeletal muscle. Secondary pathological changes include renal tubule damage and acute renal failure secondary to myoglobin pigment nephropathy, laminitis, muscle wasting, and fibrosis.⁸ Hypotension was not thought to contribute to EPAM in the horses described in the present report because neither horse was hypotensive during the procedure; however, the padding under the heads of the 2 horses was inadequate and probably contributed to capillary bed compression.

Treatment of horses with EPAM includes supportive care, volume resuscitation, and anti-inflammatory and analgesic medications.^1,8 Affected horses should be encouraged to stand, and horses can be assisted with head and tail ropes or full body slings.¹⁰ In severely affected horses, the authors have used multiple fasciotomies to decrease intracompartmental pressure, which allowed affected horses to stand. Affected horses that do not stand within 4 to 8 hours after the end of anesthesia have a poor prognosis.

In horses with EPAM, volume expansion and diuresis can be achieved with IV administration of crystalloid fluids. Fluid rates of 10 to 20 mL/kg/h (4.5 to 9.1 mL/lb/h) can be administered initially and then reduced to 4 to 5 mL/kg/h (1.8 to 2.3 mL/lb/h) to restore circulating volume, correct electrolyte abnormalities, and promote dilution of myoglobin and diuresis.⁸ Diuresis should continue until pigmenturia has resolved and fluid and electrolyte balance have been restored. Mildly affected horses, such as the 2 described in the present report, may not require IV volume replacement as long as hydration is maintained and gross pigmenturia is not observed.

Anti-inflammatory medications are indicated to reduce swelling and ongoing muscle damage and alleviate pain in horses with EPAM. Topical diclofenac paste was used in the 2 horses described in the present report; however, it is unknown whether this formulation has beneficial effects in affected horses. Horses with gross pigmenturia should have renal function closely monitored if NSAIDs are used. The use of corticosteroids in horses with EPAM remains debatable. Acute myopathy associated with corticosteroid treatment has been identified in critically ill human patients.¹¹

Horses with EPAM may require additional analgesic medications, such as butorphanol or morphine, which can be used as intermittent injections or infusions.¹² Lidocaine infusions may be used to provide analgesia and treat reperfusion injury.^13,14

Other treatments that may have benefit include mannitol infusion, dantrolene administration, application of ice packs and cool water baths, administration of dimethyl sulfoxide IV or topically, and supplementation with vitamin E and selenium.^1,8,15,16 Stall rest is recommended initially with EPAM, followed by gradually increasing physical activity.

Time to recover from EPAM is variable, and horses may develop muscle fibrosis and contracture.⁸ Extent of recovery can be evaluated with serial physical examinations, evaluations of CK and AST activities, and ultrasound examinations of affected muscle.¹⁷

Techniques for prevention of EPAM should be included in the anesthetic plan for horses.¹ Horses should be placed on adequately padded surfaces when anesthetized. Equine surgical table foam padding ranging in thickness from 8 to 12 inches is available.^d Padding should be large enough for the entire body of the horse and provide contoured support. Additional smaller pads can be used to support the limbs, head, and neck. For horses in lateral recumbency, the dependent limbs should be pulled forward to decrease compression of the triceps and quadriceps muscles and the nondependent limbs should be positioned parallel to each other and should not be maintained in an excessively flexed or extended position for a long period of time. Horses in dorsal recumbency should be placed squarely on their backs. Sternal recumbency should be avoided because it is associated with a high incidence of EPAM even when horses are on well-padded surfaces.⁵

Inhalant anesthetics are potent vasodilators and decrease muscle blood flow, cardiac output, and mean arterial blood pressure. Adequate mean arterial blood pressure is necessary to provide regional blood flow to organs and tissue beds. Consequently, there is a strong correlation between hypotension and EPAM.¹⁸ It is recommended that mean arterial blood pressure in anesthetized horses be maintained > 70 mm Hg.^1,19 Hypotension can be treated with IV administration of crystalloid fluids and infusion of dobutamine at rates ranging from 2 to 20 μg/kg/min (0.9 to 9.1 μg/lb/min). Administering ketamine or lidocaine to allow the delivered inhalant anesthetic concentration to be reduced can improve blood pressure.^20,21 The use of isoflurane rather than halothane may reduce the incidence of EPAM because muscle blood flow has been shown to be higher in horses anesthetized with isoflurane.²² It is unknown whether sevoflurane would provide the same benefits as isoflurane.

Limiting anesthetic duration can decrease the incidence of EPAM. Prolonged anesthesia increases the risk of death in horses, and anesthetic times > 3 hours increase that risk by a factor of 4.8.²³

In summary, EPAM can be a serious complication of general anesthesia in horses. It can be treated with supportive care and anti-inflammatory medications; however, some horses do not recover. The incidence of EPAM can be minimized by maintaining appropriate arterial blood pressure, providing adequate padding, ensuring proper patient body positioning, and minimizing anesthetic and recumbency time.