History

A 5-month-old 209-kg (460-lb) Quarter Horse colt was referred for treatment of bilateral contractures of the deep digital flexor tendons of the forelimbs. On initial examination, the foal was bright, alert, and responsive. Rectal temperature was 38.3°C (101.1°F), pulse rate was 86 beats/min, and respiratory rate was 26 breaths/min. No physical abnormalities other than bilateral contractures of the deep digital flexor tendons of the forelimbs were identified. Results of a CBC were unremarkable other than slightly low PCV (29.6%; reference range, 32% to 53%), slightly high fibrinogen concentration (500 mg/dL; reference range, 100 to 400 mg/dL), and moderate anisocytosis. A serum biochemical panel was not performed. The foal was scheduled for surgery the following day.

On the day of surgery, a 14-gauge, 5.25-inch catheter was placed in the right external jugular vein. Procaine penicillin (4 × 10⁶, IM), tetanus toxoid (1 mL, IM), and phenylbutazone (400 mg, IV) were given 1 hour prior to anesthetic induction. The foal was premedicated with xylazine hydrochloride (200 mg, IV), and anesthesia was induced with ketamine hydrochloride (500 mg, IV) and diazepam (7.5 mg, IV). Attempts to insert 18- and 20-mm (internal diameter) endotracheal tubes were unsuccessful. Therefore, a 16-mm (internal diameter) cuffed Murphy endotracheal tube was inserted.

The foal was positioned in left lateral recumbency, and the endotracheal tube was attached to a large animal anesthetic breathing circuit that had been primed with sevoflurane (5%) in oxygen (2.3 L/min). Intermittent positive-pressure ventilation was instituted at a rate of 8 breaths/min with an inspiratory pressure of 20 cm of H₂O and tidal volume of 2.5 L. Lactated Ringer's solution (4.6 L/h, IV) was administered to maintain circulating blood volume. An arterial cannula was placed in the right dorsal metatarsal artery and connected to a pressure transducer that was zeroed at the point of the shoulder. After 5 minutes, the delivered concentration of sevoflurane was reduced to 4%; mean arterial pressure during this period ranged from 65 to 90 mm Hg. After 15 minutes, the delivered concentration of sevoflurane was further reduced to 3.5%. End-tidal partial pressure of CO₂ (P^ETCO₂) ranged from 45 to 55 mm Hg. Twenty-four minutes after induction of anesthesia, an arterial blood sample was submitted for blood gas analysis^a (Table 1).

Forty minutes after induction of anesthesia, slight flexion of the foal's neck was observed, and the anesthetic plane was assumed to be insufficient. Therefore, butorphanol (2 mg, IV) was administered. However, no improvement was seen, and the foal began to have slight muscle twitches involving all 4 limbs. Administration of 3 sequential doses of ketamine (25 mg, IV) approximately 7 to 10 minutes apart did not result in any improvement, and the muscle twitches became progressively more pronounced. Even after administration of diazepam (2 mg, IV), the muscle twitches became worse, and PETCO₂ increased to 50 to 55 mm Hg.

Fifty-seven minutes after induction of anesthesia, a second arterial sample was submitted for blood gas analysis (Table 1). Two more boluses of ketamine (25 mg, IV) were administered, and the 16-mm endotracheal tube was replaced with a 20-mm (internal diameter) tube in an attempt to help decrease PaCO₂. Once the endotracheal tube was replaced, intermittent positive-pressure ventilation was reinstituted at a rate of 8 breaths/min with an inspiratory pressure up to 30 cm of H₂O and tidal volume of 3 L.

While the endotracheal tube was being replaced, a third arterial blood sample was obtained and submitted for blood gas analysis (Table 1). The foal continued to have muscle twitching; therefore, anesthesia was discontinued. The anesthetic period had lasted 80 minutes.

Question

What is the anesthetic complication in this foal?

Answer

Analysis of the third arterial blood sample obtained 74 minutes after anesthetic induction revealed substantial increases in serum potassium concentration and PaCO₂. These findings in conjunction with the clinical signs were consistent with an episode of hyperkalemic periodic paralysis.

At the time the diagnosis of hyperkalemic periodic paralysis was made, administration of lactated Ringer's solution was discontinued, and 5% dextrose (500 mL) with 10% calcium gluconate (15 mL) was administered IV. During recovery from anesthesia, a second bolus (500 mL) of 5% dextrose was administered. The foal showed excitement during recovery, and strong muscle contractures were seen. The foal attempted to stand multiple times with assistance before being able to remain standing. Time to standing was 35 minutes.

After the foal had recovered from anesthesia, acetazolamide (500 mg, PO, q 12 h) and small amounts of coastal hay were given. A serum biochemical panel performed shortly after anesthetic recovery revealed high glucose (307 mg/dL; reference range, 58 to 134 mg/dL), creatinine (2.3 mg/dL; reference range, 1.1 to 2 mg/dL), and phosphorus (5.4 mg/dL; reference range, 1.7 to 3.9 mg/dL) concentrations; low calcium concentration (10.9 mg/dL; reference range, 11 to 13 mg/dL); and high creatine kinase activity (2,068 U/L; reference range, 73 to 450 U/L). Serum potassium concentration was within reference limits (4.1 mmol/L; reference range, 3.0 to 4.2 mmol/L).

The day after surgery, the foal had an episode of generalized muscle fasciculations and swaying and was treated with 5% dextrose (2 L) and 0.9% NaCl solution (1 L) with calcium gluconate (15 mL), IV. The generalized muscle fasciculations and swaying lasted approximately 45 minutes. Beginning the evening of the day after surgery, the foal was fed oats (0.75 lb), sweet feed (1 handful), and corn syrup (60 mL) twice daily, in addition to coastal hay and PO administration of acetazolamide. The surgery was rescheduled for 4 days later.

Five days after the first anesthetic episode, results of blood gas analysis of an arterial blood sample were within reference limits (Table 2). Procaine penicillin (4 million units, IM), phenylbutazone (400 mg, IV), and tetanus toxoid (1 mL, IM) were administered, and the foal was premedicated with xylazine (150 mg, IV). Anesthesia was induced with ketamine (460 mg, IV) and diazepam (23 mg, IV), and a 20-mm (internal diameter) endotracheal tube was placed. The endotracheal tube was attached to a large animal anesthetic breathing circuit that had been primed with sevoflurane (5%) in oxygen (2.5 L/min). Intermittent positive-pressure ventilation was instituted at a rate of 8 breaths/min with an inspiratory pressure of 24 cm of H₂O and tidal volume of 3 L. Crystalloid fluids (0.9% NaCl solution with 2.5% dextrose and 50 mEq of calcium gluconate/L) were administered IV to support circulating blood volume and protect against hyperkalemia. An arterial blood sample was collected 16 minutes after induction of anesthesia (Table 2). Blood glucose concentration at this time was 190 mg/dL.

Thirty minutes after induction of anesthesia, the delivered concentration of sevoflurane was reduced to 3%. Additional arterial blood samples were submitted for blood gas analysis 35 and 54 minutes after induction of anesthesia (Table 2). Forty-five minutes after induction of anesthesia, a bolus of butorphanol (3 mg, IV) was administered in response to high mean arterial blood pressure (80 mm Hg) that was thought to be pain related. Mean arterial blood pressure was 65 mm Hg 3 to 5 minutes later. The horse was taken to the recovery room 80 minutes after induction of anesthesia. In the recovery room, the foal was given butorphanol (5 mg, IM) and oxygen was insufflated (10 L/min) in the endotracheal tube. A single bolus of xylazine (20 mg, IV) was administered. After 30 minutes, the foal stood successfully with little struggle or ataxia.

Discussion

Possible causes of muscle rigidity or fasciculation in an anesthetized horse include hyperkalemic periodic paralysis, various alterations in serum electrolyte concentrations, seizures, anesthetic myositis, and malignant hyperthermia.^1,2 Hyperkalemic periodic paralysis was considered the most likely cause in the foal described in the present report on the basis of results of blood gas analyses, the lack of response to diazepam administration, and the fact that rectal temperature was only slightly high.

Hyperkalemic periodic paralysis was first reported in 1986.³ The cause is an autosomal dominant genetic defect in the sodium-potassium pump that causes the cell membrane to be overly permeable to sodium.^3–7 Nearly 0.4% of all American Quarter Horses are either homozygous or heterozygous for the genetic defect causing hyperkalemic periodic paralysis.^3,6-8 The disease is most common in male, heavily muscled Quarter Horses shown in halter shows.^6–10 Although most common in American Quarter Horses, it may also be seen in Quarter Horse crosses, Appaloosas, and American Paint Horses.^3,6-9 A definitive diagnosis of hyperkalemic periodic paralysis can be made by means of a PCR assay.^3,4,6-8 All affected horses are related to the Quarter Horse sire Impressive.^5–7

Clinical signs of hyperkalemic periodic paralysis include spasm or paralysis of the pharyngeal or laryngeal muscles, high serum potassium concentration (> 5.5 mmol/L), muscle fasciculation, prolapse of the third eyelid, muscle weakness, cardiac arrhythmias, involuntary collapse, and death.^3–6,8–11 There are multiple reports^4,9 of affected horses that are unable to stand or have prolonged periods of paralysis after anesthesia. Hyperkalemic periodic paralysis should be suspected in young foals that have excessive respiratory tract noise or discharge milk from their nares.⁸ The foal described in the present report was a young, male, heavily muscled Quarter Horse.

The difficulties encountered with endotracheal intubation during the initial anesthetic episode in the foal described in the present report were most likely a result of laryngeal spasm that occurred at the time of anesthetic induction. Because of xylazine's arrhythmogenic properties, a smaller dose was administered during the second anesthetic episode, and the dose of diazepam was increased to assist with muscle relaxation and intubation.

Episodes of hyperkalemic periodic paralysis are often triggered by stress, such as occurs with a change in diet, infection, an irregular training or exercise regimen, trailering, pregnancy, chilling, physical restraint, surgery, withholding of food prior to anesthesia, and anesthesia itself.^3,4,6,8,11 Certain alterations that can occur as a result of anesthesia, such as high serum potassium concentration, acidosis, high PaCO₂, and low body temperature, can also trigger an episode.^3,6,8 Certain drugs, such as potassium penicillin, ketamine, succinylcholine, and halothane, can also trigger or exacerbate an episode and, therefore, should be used with caution in horses with the underlying condition.⁸ The foal described in the present report was exposed to many of these factors prior to and during the initial anesthetic episode.

In horses with hyperkalemic periodic paralysis, treatment with acetazolamide or hydrochlorothiazide for 2 days prior to elective surgery can decrease the likelihood of an episode by promoting urinary excretion of potassium.^3,4,6,8,10 Acetazolamide has the added benefit of causing insulin release, which will also decrease serum potassium concentration.^3,7 Phenytoin may also be used to treat horses with hyperkalemic periodic paralysis, but is reserved for horses in which acetazolamide is ineffective because of the high cost of phenytoin and the high risk of adverse effects associated with its use.^7,8

In periods between episodes, horses with hyperkalemic periodic paralysis typically have serum potassium concentrations well within reference limits, so care should be taken to avoid inducing hypokalemia.^8,12 During anesthesia, horses with hyperkalemic periodic paralysis should be given fluids free from potassium, such as isotonic saline solution or 5% dextrose, to help prevent hyperkalemia.^6–8,10,12 Administration of 5% dextrose has the added benefit of causing insulin release, which promotes intracellular movement of potassium.^7,8,10,12 During episodes of hyperkalemic periodic paralysis, this effect can be augmented through administration of NPH insulin.^4,7 However, calcium gluconate should also be administered IV during an episode because calcium gluconate antagonizes hyperkalemia-induced depolarization and protects the heart against arrhythmias.^3,4,6-8,10 Acidemia causes an extracellular shift of potassium to buffer the hydrogen ions and, thus, can provoke or exacerbate an episode of hyperkalemic periodic paralysis. Therefore, during anesthesia, normoventilation or even slight hyperventilation should be achieved to decrease the likelihood of respiratory acidosis. If metabolic acidosis is present, sodium bicarbonate may be infused to help maintain a normal or even slightly alkalotic blood pH.^4,6,7

Monitoring of a horse with hyperkalemic periodic paralysis during anesthesia should include serial blood gas analyses and determinations of blood pH and serum glucose and electrolyte concentrations. Electrocardiography is mandatory to help detect an episode of hyperkalemic periodic paralysis because tall T waves, small P waves, and widening of the QRS complex are often the first signs of an episode.^3,4,8,10,11 Because chilling can also provoke an episode, body temperature should be monitored. Capnography should be used to ensure that hypercapnia is prevented.

Recovery should be as calm and nonstressful as possible. A dark, quiet, well-padded room will decrease stimulation. Good pain relief is essential, as well as oxygen supplementation.⁸ Allowing the horse to remain intubated as long as possible will help to protect the airway should the horse have laryngeal spasms during recovery. Small doses of sedatives may be necessary to facilitate a smooth transition from inhalant anesthesia to recovery.

Prior knowledge that a horse has hyperkalemic periodic paralysis can facilitate preanesthetic planning. In horses in which status is unknown, close monitoring during anesthesia will help identify an episode quickly and allow for rapid treatment. In hindsight, immediate recognition of the episode of hyperkalemic periodic paralysis during the initial anesthetic period in the horse described in the present report would have prevented administration of additional doses of ketamine, which were contraindicated. As was the case for this foal, horses with hyperkalemic periodic paralysis can be safely anesthetized, given proper anesthetic preparation and management.