History

A 1.3-year-old castrated male British Shorthair cat with a history of chronic lameness and diagnosed with bilateral femoral capital fracture was referred for bilateral femoral head and neck excision. The cat was not receiving any medication.

On presurgical examination, the cat was bright and responsive and had a body condition score of 6/9, body weight of 5.83 kg, heart rate (HR) of 120 beats/min (reference range, 160 to 180 beats/min), respiratory rate (RR) of 24 breaths/min (reference range, 15 to 30 breaths/min), and a rectal temperature of 37.7 °C (reference range, 36.7 to 38.9 °C). The oral mucous membranes were pink and moist. Findings on thoracic auscultation were unremarkable. The cat was classified as having had an American Association of Anesthesiologists risk classification of 2.

A 22-gauge catheter was placed in a cephalic vein, and the cat was premedicated with methadone (0.2 mg/kg, IV) and medetomidine (0.005 mg/kg, IV). Five minutes later, the cat received flow-by administered 100% O₂ (2 L/min) for 5 minutes before induction of general anesthesia with ketamine (0.5 mg/kg, IV) followed by alfaxalone (1 mg/kg, IV). The cat was intubated with a 5-mm-internal-diameter silicone endotracheal tube that was then connected to a nonrebreathing anesthetic system for delivery of 1.1% to 1.5% (vaporizer setting) isoflurane in O₂ (2 to 2.5 L/min). A multiparametric monitor (iMEC10; Shenzhen Mindray Bio-Medical Electronics) was used to monitor the cat's ECG, noninvasive blood pressure (NIBP) measured with oscillometry, O₂ saturation of hemoglobin measured with pulse oximetry (Spo₂), and RR measured with capnography. Fluid therapy with a crystalloid solution (Vetivex Hartmann's Solution; Dechra; 4 mL/kg/h) was started. Five minutes after the onset of inhalational anesthesia, the cat had an HR of 120 beats/min, RR of 5 breaths/min, Spo₂ of 99%, and systolic, diastolic, and mean NIBPs of 125, 80, and 105 mm Hg, respectively.

Twenty-five minutes after anesthetic induction, and immediately after the cat had been repositioned from left to right lateral recumbency to finalize clipping of the surgical area, the cat's HR suddenly decreased to 34 beats/min; sinus rhythm was maintained. The cat's systolic, diastolic, and mean NIBP measurements concomitantly decreased to 90, 40, and 60 mm Hg, respectively; however, within 60 seconds after this measurement, no NIBP measurements could be obtained. Femoral pulses were weak; HR and RR remained unchanged. A Doppler ultrasonic flow detector was applied over both palmar metacarpal and femoral arteries; however, no peripheral pulse could be detected. The cat was treated with glycopyrrolate (0.01 mg/kg, IV), atipamezole (0.025 mg/kg, IM), and a bolus of crystalloid fluid (10 mL/kg, IV, over 10 minutes), which resulted in increased HR (160 beats/min) within 5 minutes; however, the NIBPs were still unmeasurable, femoral pulses could not be detected by either palpation or the use of a Doppler ultrasonic flow detector, and no measurement of Spo₂ could be obtained. In the meantime, end-tidal CO₂ concentration (ETco₂) decreased from 48 to 20 mm Hg (reference range, 35 to 45 mm Hg) followed by respiratory arrest. Isoflurane administration was immediately discontinued, and manual ventilation was initiated at a rate of 8 to 10 breaths/min. When cardiopulmonary-cerebral resuscitation was about to be initiated, an initially weak but progressively improving femoral pulse was palpable. The cat's ETco₂ concomitantly increased to 25 to 28 mm Hg. The cat was allowed to recover from anesthesia. Recovery was smooth, with spontaneous breathing (RR, 40 breaths/min) approximately 5 minutes after the discontinuation of isoflurane and tracheal extubation 5 minutes thereafter. The procedure was postponed to allow for investigation of the cat's cardiovascular status.

A week later, an echocardiographic examination was performed by an experienced cardiologist who ruled out preexisting heart conditions and found clinically normal cardiac rhythm and heart structure and function. The cat's surgery was scheduled for later that same day.

Findings on presurgical examination were similar to those on the previous presurgical examination; HR was 160 beats/min, and RR was 36 breaths/min. After placement of a 22-gauge catheter in the left cephalic vein, the cat was premedicated with methadone (0.2 mg/kg, IV). Anesthesia was induced with IV administration of midazolam (0.2 mg/kg) and alfaxalone (2 mg/kg), the cat was intubated, and anesthesia, perioperative fluid therapy, and patient monitoring were performed as described for the cat's previous anesthetic event. However, immediately after induction, the cat's HR decreased from 160 to 120 beats/min; in consideration of the recent clinical history, the cat was treated with glycopyrrolate (0.01 mg/kg, IV) and crystalloid fluid bolus (5 mL/kg), even though the cat's systolic, diastolic, and mean NIBP measurements (110, 65, and 80mm Hg, respectively) had not decreased. This treatment increased the cat's HR to 158 beats/min.

An epidural injection of morphine sulfate (0.1 mg/kg) and 0.5% bupivacaine (1 mg/kg) was administered at the level of the lumbosacral junction with the cat in sternal recumbency. Fifteen minutes after epidural anesthesia, the cat was repositioned from sternal to right lateral recumbency to allow the preparation of the surgical field. Immediately afterward, there were sudden drops in the cat's HR (from 155 to 125 beats/min), NIBP measurements (systolic, 112 to 95 mm Hg; diastolic, 65 to 35 mm Hg; and mean, 80 to 56 mm Hg), and ETco₂ (f44 to 13 mm Hg); RR remained unchanged (15 breath/min). Atropine (0.02 mg/kg, IV) was administered, and within approximately 5 minutes, the cat's vital signs normalized (HR was 140 beats/min; systolic, diastolic, and mean NIBPs were 115, 35, and 80 mm Hg, respectively; ETco₂ was 45 mm Hg). As a measure to prevent further cardiovascular depression, isoflurane was titrated to effect during preparation for surgery to maintain a light plane of anesthesia, characterized by a slight palpebral reflex. The isoflurane vaporizer setting ranged from 1.1% to 1.2% in the preparation room. During transfer to the operation theater, the cat remained on the same trolley, and patient positioning was not changed; however, because the cat had spontaneous movements during transfer, the isoflurane vaporizer setting was increased to 2% (end-tidal isoflurane concentration was 1.2%).

Measurements for the cat's cardiovascular and respiratory variables remained within reference limits until the cat was repositioned from right lateral to sternal recumbency on the operating table approximately 40 minutes after atropine administration. At that point, decreases again occurred in HR (from 135 to 100 beats/min), NIBP measurements (systolic, from 105 to 80 mm Hg; and mean, 80 to 70 mm Hg), and ETco₂ (from 44 to 25 mm Hg); diastolic blood pressure and RR remained unchanged (35 mm Hg and 25 breaths/min). The same dose of atropine was repeated, and the cat's HR, NIBP measurements, and ETco₂ returned to within reference limits for 20 minutes. The same dose of atropine was repeated, and dopamine (5 μg/kg/min, IV, constant rate infusion) was also initiated. Afterward, the cat's HR and NIBP measurements remained within reference limits for the duration of the anesthetic procedure, which lasted 200 minutes. Recovery was smooth and uneventful.

Question

What likely caused or triggered the sudden-onset, potentially life-threatening bradycardia and hypotension in this cat? Could the conditions have been prevented?

Answer

Considering the cat's young age, clinically normal results on echocardiography, and no evidence of underlying comorbidities other than the orthopedic condition for which it was undergoing surgery, we hypothesized that a vasovagal response¹ caused the potentially life-threatening events. Bradycardia and hypotension responded to and could have been prevented with anticholinergics. This further supported our hypothesis that an increased vagal tone was at the origin of the episodes of cardiovascular and respiratory depression that occurred.

During the first episode of cardiovascular and respiratory depression, glycopyrrolate was chosen as treatment because the rapid escalation and severity of the events were not anticipated. However, in retrospect, it should be emphasized that administration of atropine, possibly accompanied by early discontinuation of isoflurane and initiation of cardiac compression, may have been a more appropriate clinical choice. Treatment and prevention were more targeted and effective during the second anesthetic event, as the case-specific knowledge achieved when the cat was first anesthetized helped us to anticipate a similar complication during the second anesthetic event.

Discussion

Vasovagal response is a generic expression used to describe the development of arteriolar dilatation and concomitant bradycardia leading to hypotension and, in awake subjects, loss of consciousness.² The sudden decrease in HR is caused by increased vagal activity, and arteriolar dilation is usually the result of sudden cessation or reduction of sympathetic tone.³ During general anesthesia, many factors (eg, hemorrhage, postural change, aortocaval compression, loco-regional nerve blockades, and pelvic and ophthalmic surgery) may trigger a vasovagal response.^4,5 In humans, the most common cause of vasovagal response is the Bezold-Jarisch reflex (BJR).⁴

The BJR is a complex neurocardiogenic reflex characterized by a triad including bradycardia, vasodilation, and often hypopnea. It occurs upon stimulation of cardiopulmonary mechano- and chemoreceptors and is mediated by vagal afferent nerves.⁴ Myocardial ischemia, infarction, and coronary stenosis are recognized causes of BJR in humans⁶; however, purely mechanical causes have also been implicated.⁷ Of these, a sudden decrease in ventricular filling with subsequent altered activation of the cardiac mechanoreceptors was hypothesized as a trigger mechanism in an anesthetized horse that developed cardiac arrest during transport to a recovery stall.⁸ Alternatively, 180° postural changes may produce a similar mechanical stimulation, as reported in a dog undergoing general anesthesia.⁹ In the cat of the present report, there was consistently a close temporal association between the observed cardiovascular impairment and repositioning; therefore, it is reasonable to hypothesize that BJR could have caused, or contributed to, the described life-threatening events.

An individual or breed predisposition to BJR and, therefore, vasovagal response should be considered. This cat was a British Shorthair, which is a brachycephalic cat breed. It would be reasonable to assume that, because the BJR is vagally mediated, individuals with a high vagal tone may be predisposed. It has been demonstrated that breed-related factors in dogs contribute to the balance between sympathetic and parasympathetic afferent activity; as a result, brachycephalic dog breeds are likely to show exaggerated respiratory sinus arrhythmia^10,11 and are more susceptible to bradycardia because of their increased basal vagal tone.¹² It is reasonable to speculate that the brachycephalic cat of the present report (vs a nonbrachycephalic cat) also may have been more susceptible to bradycardia and vasodilation.

Other factors (namely the administration of inhalant anesthetic, methadone, epidural block, and glycopyrrolate) could have contributed to the cat's episodes of acute cardiovascular depression. Isoflurane produces a range of physiologic alterations, including decreased systemic and pulmonary vascular resistances, venodilation, bradycardia, and decreased myocardial contractility, which can be exacerbated by the concomitant administration of opioids.^13,14 Isoflurane-induced cardiovascular and respiratory depression is dose dependent and, in cats, is minimal at alveolar concentrations of isoflurane of 1.3%, but clinically impactful when alveolar concentration isoflurane was increased to 2%.¹⁵ Twice during the second anesthetic event of the cat of the present report, bradycardia and hypotension occurred shortly after either the beginning of inhalational anesthesia or a relevant increase in vaporizer setting from 1.2% to 2%. A sudden onset of vasodilation in response to isoflurane may have caused a sudden decrease in venous return, which could have triggered an inverse Bainbridge reflex, characterized by bradycardia aimed at compensating for a reduced rate of diastolic ventricular filling. In humans, inverse Bainbridge reflex can occur after epidural anesthesia; however, any factor causing decreased systemic vascular resistances (eg, inhalational anesthesia) could potentially elicit it.¹⁶

One of the 3 episodes of acute cardiovascular and respiratory depression for the cat of the present report occurred 15 minutes after epidural anesthesia. In addition to an inverse Bainbridge reflex, epidural injection of 0.5% bupivacaine has caused decreases in HR and RR in cats but with minimal changes observed at a dose of 1 mg/kg,¹⁷ as used in the cat of the present report.

The first episode of acute cardiorespiratory compromise for the cat of the present report occurred immediately after glycopyrrolate administration. Owing to a transient blockade of the presynaptic muscarinic subtype-2 receptors, which function to inhibit the release of acetylcholine from the parasympathetic nerve ending as part of a negative-feedback mechanism, both atropine and glycopyrrolate can cause a transient, acute acetylcholine release in the synaptic cleft, producing a brief parasympathomimetic action^18,19 before the targeted anticholinergic effects are established. Glycopyrrolate could therefore have contributed to or aggravated the first episode of bradycardia and hypotension in this cat.

During epidural anesthesia, increased inhalational agent delivery or administration of glycopyrrolate could have contributed to cardiovascular and respiratory compromise. However, the only event that was consistently associated with sudden-onset bradycardia was the change in patient positioning. Therefore, we hypothesized that positional changes to this cat's recumbency were the main determinant of its vasovagal response.

In conclusion, life-threatening cardiovascular and respiratory depression occurred in a healthy cat anesthetized for routine surgery, possibly as a result of increased vagal tone and postural changes during the clinical procedures. Close and continuous monitoring of physiologic variables was essential for the early detection of the observed cardiovascular complications. Treatment and prevention of bradycardia and associated hypotension with anticholinergics resulted in the successful management of this cat.