History

A 9-year-old 6.8-kg (15.0-lb) castrated male cat with acute onset of dyspnea of 24 hours’ duration was evaluated as part of an emergency consultation at the Veterinary Teaching Hospital at Washington State University. Approximately 3 months previously, the referring veterinarian identified left-sided ventricular hypertrophy on thoracic radiography and a presumptive diagnosis of feline asthma was made. The cat was also previously treated for eosinophilic bronchitis secondary to confirmed Mycoplasma infection. The cat's presumptive asthma signs were treated as needed with albuterol and terbutaline. On physical examination, the cat was bright, alert, and responsive and laboratory values for CBC and serum biochemistry profile were within reference limits. On thoracic auscultation, there was a grade II/VI heart murmur and the lung sounds were harsh in all fields. There was mild abdominal effort during breathing, which progressed to dyspnea and open mouth breathing as the cat became more distressed during the physical examination. The cat was placed in an oxygen cage (oxygen concentration, 38% to 40%) and given furosemide (2.2 mg/kg [1 mg/lb], IM) prior to being transported to the radiology suite for thoracic radiography and echocardiography. A severe, diffuse, patchy pulmonary interstitial pattern was identified radiographically, and left ventricular hypertrophy and enlargement of the main pulmonary artery were identified on the echocardiogram. These findings suggested that asthma or primary pulmonary disease could be contributing to the cat's respiratory distress, and bronchoalveolar lavage (BAL) under general anesthesia was scheduled for the following day. The patient was returned to the oxygen cage and kept overnight for observation. Food, but not water, was withheld overnight in preparation for anesthesia the next morning.

Prior to induction of general anesthesia, the cat had a heart rate of 200 beats/min, respiratory rate of 36 breaths/min, and rectal temperature of 38.2°C (100.8°F). The cat was premedicated with butorphanol (0.3 mg/kg [0.13 mg/lb], IM), and 15 minutes later, a 22-gauge catheter was aseptically placed in the right cephalic vein. Oxygen was administered for 10 minutes via face mask prior to the induction of anesthesia with propofol (5 mg/kg [2.2 mg/lb], IV [total dose, 30 mg]) until an adequate depth of anesthesia (light plane of surgical anesthesia) was achieved (adequate muscle relaxation, slow and regular ventilation, absence of swallowing reflex, and sluggish palpebral reflex). Prior to endotracheal intubation, 0.1 mL of lidocaine injectable solution (0.3 mg/kg) was instilled topically on the arytenoid cartilages via a syringe and a 20-gauge IV catheter. A cuffed endotracheal tube (internal diameter, 4.5 mm) was inserted into the trachea, and oxygen was administered via a nonrebreathing Bain circuit at a rate of 2 L/min. Propofol was administered in small increments (0.2 to 0.3 mL, IV) as needed to maintain a light plane of anesthesia. The cat was placed in sternal recumbency to facilitate performance of the BAL. Lactated Ringer solution (10 mL/kg/h [4.5 mL/lb/h]) was administered IV during anesthesia. An ultrasonic Doppler flow detector^a probe was positioned over the dorsal pedal artery on the left hind limb and a No. 2 size cuff with an aneroid manometer was positioned on the crural region above the tarsus to measure systolic arterial blood pressure. Additional monitoring with a multiparameter monitor included ECG (lead II) and pulse oximetry,^b with the probe placed on the interdigital web of the cat's forelimb.

After instrumentation for monitoring was complete and the cat was stable under anesthesia (heart rate, 155 beats/min; respiratory rate, 15 breaths/min; oxygen saturation, 97%; systolic arterial blood pressure as measured by Doppler ultrasonography, 85 mm Hg), 2 manual breaths were administered by squeezing the Bain system reservoir bag (peak airway pressure, 15 cm H₂O), during which resistance to positive pressure ventilation and excursions of the thorax were assessed as normal, and the cat was disconnected from the breathing circuit. For BAL, a catheter adapter^c was attached to a red rubber urinary catheter and passed through the endotracheal tube and 1 bolus (20 mL) of room temperature (approx 22°C), sterile, nonbacteriostatic saline (0.9% NaCl) solution was instilled into the lungs and then immediately aspirated into a sterile syringe. At completion of the BAL procedure (duration, approx 2 minutes), the cat was not breathing. The breathing circuit was immediately reconnected, and 2 positive pressure breaths (peak inspiratory pressure, 15 cm H₂O) were again delivered by manual squeezing of the reservoir bag. However, profound resistance was noted when the bag was squeezed and no thoracic excursions occurred. Endotracheal tube obstruction with foreign material possibly dislodged during BAL was suspected. The endotracheal tube was removed and examined, but no obstruction was evident. During inspection of the tube, the cat continued to receive oxygen via a tight-fitting face mask but, because it was still not breathing, the oxygen saturation as measured by pulse oximetry decreased to 80% and the cat became cyanotic (ie, blue mucous membranes). The endotracheal tube was rein-troduced into the trachea with the help of a guide wire (patient at a medium depth and light plane of surgical anesthesia), and 2 positive pressure manual breaths were attempted, but the resistance to lung inflation was still present. At this time, the sound from the Doppler monitor rapidly decreased in intensity, becoming silent shortly thereafter, and the cat's heart rate decreased from 120 to 50 beats/min in < 1 minute, followed by absence of a palpable peripheral pulse or heart beat on auscultation. The ECG tracing showed normal sinus rhythm and, in < 1 minute, bradycardia, then asystole. Because these changes were indicative of cardiopulmonary arrest, thoracic compressions (100 compressions/min), attempted manual positive pressure ventilation (10 breaths/min; peak inspiratory pressure, 15 cm H₂O), and advanced life support were initiated. The cat received a dose of epinephrine (0.01 mg/kg [0.005 mg/lb], IV) and atropine (0.04 mg/kg [0.018 mg/lb], IV) for cardiovascular support. Because of the resistance to lung expansion, albuterol (180 μg [2 puffs] delivered through the endotracheal tube) was administered. Approximately 2 minutes after initiation of cardiopulmonary resuscitation, audible blood flow was heard from the Doppler monitor, sinus rhythm was observed on the ECG, the mucous membranes were pale pink, and the cat started breathing spontaneously. Manual positive pressure breaths were delivered without excessive resistance. Within 5 minutes after the cardiopulmonary arrest, the ECG tracing showed a normal heart rhythm with a rate of 200 beats/min, normal oxygen saturation as measured by pulse oximetry (> 95%), capillary refill time < 2 seconds, pink mucous membranes, and a respiratory rate of approximately 25 breaths/min with normal thoracic excursions. The cat received another dose of albuterol (180 μg) via the endotracheal tube and a dose of terbutaline (0.01 mg/kg, IM) after 5 minutes of spontaneous breathing and was extubated 15 minutes after the initiation of cardiopulmonary resuscitation.

The cat recovered without further complications and was placed in an oxygen cage for close observation in the intensive care unit. It continued to improve throughout the day and was placed back into a normal cage later that evening. The patient was discharged 2 days after the BAL procedure without further incident. The cytologic interpretation from the BAL fluid was eosinophilic bronchitis, and results of bacteriologic culture were positive for Mycoplasma sp; thus, feline asthma was the presumptive diagnosis.

Question

What was the cause of the cardiopulmonary arrest in this cat? Was the presumptive preexisting respiratory disease a precipitating factor? Was general anesthesia a complicating factor? Did the BAL procedure contribute?

Answer

In this patient, an inability to ventilate, with resultant hypoxemia, led to cardiopulmonary arrest. The inability to ventilate was presumed to be secondary to severe bronchoconstriction resulting from lower airway hyperresponsiveness associated with preexisting feline asthma, exacerbated by general anesthesia and the BAL procedure.

Discussion

In cats, asthma is believed to be triggered by inhaled allergens, with young to middle-aged cats most commonly affected.¹ The disease is characterized by inflammation of the lower airways. Clinical signs range from intermittent cough to severe respiratory distress and are attributable to airway obstruction caused by bronchial inflammation, with subsequent smooth muscle constriction, epithelial edema, and mucous gland hypertrophy and hyperactivity.^1,2 None of the described clinical signs are pathognomonic for asthma, and there are no simple blood tests to aid diagnosis.³ Many of the observed signs can also occur with primary cardiac or pulmonary disease. To differentiate asthma from cardiac or pulmonary disease, additional diagnostic tests may include thoracic radiography, bronchoscopy with BAL, or endotracheal wash, with the latter 2 tests requiring general anesthesia. Because asthma was suspected in this cat, BAL under general anesthesia was scheduled.

Airway dysfunction can be exacerbated by general anesthesia. Anesthesia may cause inability to cough, impairment of the mucociliary clearance apparatus, decreased pharyngeal muscle tone, altered diaphragmatic function, and an increase in the amount of fluid layering the airway wall, all of which increase airway resistance and impair respiratory function.⁴ Direct stimulation of the airway, as may be induced by laryngoscopy, tracheal intubation, administration of cold inspired oxygen with inhalation anesthetics, and tracheal extubation, may induce bronchoconstrictive reflexes.⁵ In human patients, the overall incidence of bronchospasm during general anesthesia has been reported to generally be low, ranging between 0.17% and 4.2%,⁶ but incidence of bronchospasm may be as high as 9% in anesthetized asthmatic patients, occurring most commonly following endotracheal intubation.⁷

In human medicine, there are specific protocols and guidelines for anesthetizing asthmatic patients.^4,6,8,9 Although there are no specific anesthetic protocols for feline patients with suspected asthma, there are some recommendations regarding treatment and management prior to anesthesia and an anesthetic protocol can be developed on the basis of knowledge of the effect of anesthetic drugs on the respiratory system. Preoxygenation for 3 to 5 minutes is recommended to reduce the risk of hemoglobin desaturation and hypoxemia during anesthetic induction. Preoxygenation is especially beneficial if a prolonged or difficult intubation is expected or if the patient is already dependent on supplemental oxygenation. However, it may be contraindicated if restraint and placement of an oxygen mask agitate the patient.¹⁰

Patients should be handled quietly and calmly and sedated prior to induction of anesthesia. An optimal premedication drug would relieve anxiety, eliminate endotracheal tube–mediated laryngospasm, decrease respiratory effort, and ideally avert the induction of bronchospasm, while avoiding oversedation and respiratory depression. No ideal drug or drug combination would meet all of these criteria, but acceptable options for premedication include opioids, acepromazine, benzodiazepines, and α₂-adrenergic receptor agonists. For the cat described in the present report, we chose butorphanol, an agonist-antagonist opioid. Opioids can provide calming and pain relief, and opioid-mediated effects are reversible, enhancing their safety. Opioid-mediated respiratory depression can be a considerable concern in human patients,^9–11 but is generally a minor concern in most veterinary patients because animals appear more tolerant of many opioid-mediated adverse effects, including respiratory depression.¹² Opioids also cause suppression of the cough reflex,¹³ thereby decreasing the exacerbation of bronchoconstriction by cough-inducing techniques, such as endotracheal intubation. In cats, opioids can cause excitement rather than sedation; however, butorphanol generally produces mild sedation in this species. Acepromazine is commonly used for patients with respiratory dysfunction because it causes minimal to no adverse effects on ventilatory function.¹³ Acepromazine does cause relaxation of the muscles in the pharyngeal region, which may increase upper airway resistance, and the drug has a long duration of action, which may delay recovery.¹³ Benzodiazepines, such as midazolam or diazepam, cause minimal to no respiratory depression and do not alter bronchial tone in human patients¹⁴ but are unlikely to provide adequate sedation when used alone in anxious patients; however, midazolam can be administered IM with an opioid or other mild sedative such as dexmedetomidine or a tranquilizer like acepromazine, and may provide enough calming to proceed with anesthetic induction. α₂-Adrenergic receptor agonists such as dexmedetomidine cause anxiolysis and sympatholysis, with minimal adverse effects on respiratory and pulmonary function. Dexmedetomidine causes drying of respiratory secretions in human patients,⁸ and low doses of dexmedetomidine appear to protect against bronchoconstriction in dogs.¹⁵ With any of these drugs, sedation can also cause mild respiratory depression, such that respiratory function should be monitored following drug administration.

Following sedation, anesthesia should be rapidly induced with an IV protocol and intubation should not be attempted until the patient is at a fairly deep anesthetic plane. A light plane of anesthesia can result in difficulty intubating and subsequent airway hyperreactivity responses due to mechanical irritation (eg, with laryngoscopy, endotracheal intubation, and BAL). Manipulation of the airway or surgical stimulation at this stage increases the risk of bronchospasm.¹⁶ Thus, we suggest that the choice of anesthetic induction drug is not as critical as achieving a suitable depth of anesthesia before rapid intubation. Acceptable options for anesthetic induction include propofol, alfaxalone, and ketamine. Propofol was chosen for the patient described in the present report because it can easily be titrated to effect, facilitating delivery of the lowest possible dose that allows intubation. Dose is important because propofol does cause dose-dependent respiratory depression; however, it may protect against intubation-induced bronchoconstriction.¹⁷ Ketamine decreases airway resistance secondary to sympathomimetic bronchodilatory properties,^9,18 relaxes the bronchiolar musculature, and prevents bronchoconstriction induced by histamine, decreasing the risk of bronchospasm during anesthetic induction. These effects could be related to a direct effect on bronchial muscle as well as potentiation of catecholamines.⁹ However, ketamine increases bronchial secretions, preserves the cough reflex, and maintains upper airway skeletal muscle tone and upper airway reflexes (ie, sneezing, swallowing, coughing, laryngeal closure in response to stimulation), all of which may be considered adverse effects in patients with compromised airway function; these effects are more common with the IM administration of ketamine.^9,18,19 Alfaxalone,^d which received FDA approval in 2012, can induce transitory dose-dependent respiratory depression, with apnea being the most common adverse effect.²⁰ Lidocaine administered IV immediately prior to induction of anesthesia by means of IV propofol or ketamine can attenuate the coughing and bronchoconstriction reflex and the response to airway irritation that may occur during endotracheal intubation or suction.⁸ This technique would have been a useful addition to our protocol. In most patients with airway disease, anesthetic induction via face mask with any inhalation anesthetic is slow and not recommended. Anesthetic induction with desflurane via face mask is particularly dangerous in human patients with asthma because this drug may cause airway hyperreactivity, increased secretions, coughing, laryngospasm, and bronchospasm,^9,21 and these effects may also occur in cats.

For maintenance of anesthesia, isoflurane or sevoflurane is a reasonable choice, considering their bronchodilating properties and ability to decrease airway reactivity.^9,22 Sevoflurane has the added benefit of attenuation of histamine-induced bronchospasm; also, it may produce the least airway irritation among the currently available volatile anesthetics.^9,22 However, inhalation anesthesia and oxygen administration were not possible for the cat described in the present report because the bronchoscopy and BAL procedure required the use of a fiberscope size that did not allow passage via the necessary small-caliber endotracheal tube (internal diameter, 4.5 mm). As such, the patient had to be extubated and administered oxygen via flow-by at the nostrils. Anesthesia was maintained with administration of boluses of propofol (0.5 to 1 mg/kg [0.22 to 0.45 mg/lb], IV), titrated to maintain an adequate depth of anesthesia (medium depth and light plane of surgical anesthesia), as determined by response to the procedure, return of palpebral reflex, and increases in heart rate, respiratory rate, and blood pressure.

A smooth, gradual recovery minimizes the risk of postoperative bronchospasm. When the patient is awake and has appropriate airway reflexes, extubation can occur.⁹ However, stimulation of the larynx in recovery can induce bronchoconstriction such that extubation should occur before swallowing reflexes return. This is referred to as deep extubation (tracheal extubation while still deeply anesthetized) and is fairly common, especially in human pediatric anesthesia. This technique does have some risks because bronchospasm may still occur, as can regurgitation with subsequent aspiration due to the unprotected airway.¹⁰ Prior to the anesthetic complication in our patient, our plan had been to allow the cat to recover from anesthesia with oxygen supplementation in a darkened, quiet room and to perform deep extubation if possible.

Finally, in the patient of the present report, the BAL procedure likely played a major role in the cardiopulmonary arrest. Bronchoalveolar lavage is usually considered a safe procedure in human and veterinary patients and is routinely performed on an outpatient basis. Complications of BAL in dogs and cats with preexisting lung disease but without dyspnea are reportedly rare.²² However, BAL may have adversely affected respiratory function, and BAL-induced hypoxemia, hypoxia,^23,24 tachypnea, and decreased tidal volume because of ventilation-perfusion abnormalities due to retained saline solution and loss of surfactant may occur.²³ Direct stimulation of the airway induced by the BAL catheter, introduction of fluid into the lower airways, and airway suctioning may induce bronchoconstrictive reflexes.⁵ Bronchospasm or worsening of clinical signs occurred in 14 of 273 (5.1%) asthmatic human patients during BAL,²⁵ compared with only 1 of 57 (1.8%) patients with chronic obstructive pulmonary disease.²⁶ There is 1 report¹⁰ of severe bronchoconstriction after BAL in a dog with eosinophilic airway disease. When the bronchoconstrictive episode was suspected, the dog was reanesthetized and treated with injectable dexamethasone, aminophylline, and atropine.¹⁰ To our knowledge, severe bronchoconstriction as a potential complication of BAL has not been reported in cats.

In the patient of this report, once the bronchoconstriction episode occurred, the cat became very hard to ventilate; evidence of hypoxemia occurred very quickly (decreased oxygen saturation and cyanosis), which led to rapid deterioration in cardiopulmonary function and cardiopulmonary arrest; and cardiopulmonary resuscitation was initiated immediately. Standard cardiopulmonary resuscitation drugs (atropine and epinephrine) were administered, as were drugs specifically used to treat the presumed bronchoconstriction. Terbutaline (a long-acting drug that is indicated for the long-term management of clinical signs that have been and are difficult to control) and albuterol (a short-acting drug to be administered as needed, for rescue management of symptoms) are β₂-adrenergic receptor agonist drugs and are widely used in human and veterinary medicine for the treatment of bronchospasm. These drugs were chosen because they have been found to effectively treat or prevent general anesthesia–induced bronchospasm.^4,5,8,9,27 In human patients, the concurrent administration of albuterol and systemic corticosteroids before endotracheal intubation was found to significantly improve respiratory function as well as markedly reduce the risk of postoperative bronchospasm in 1 study.²⁸ Albuterol prevented the increase in airway resistance associated with endotracheal intubation in children with asthma during sevoflurane anesthesia.²⁹ Thus, pretreatment with these drugs may also be beneficial in asthmatic cats.

In the management of the impending cardiopulmonary arrest, the cat of the present report was treated with atropine and epinephrine. Both drugs also possess bronchodilatory properties and likely aided in resumption of adequate ventilation. Atropine at therapeutic doses decreases airway secretions and increases airway diameter. This mechanism is via blockade of the muscarinic receptor 3 (parasympathetic nervous system).³⁰ Epinephrine acts on the smooth muscles of the bronchi and generates relaxation by means of epinephrine-induced activation of β₂-adrenergic receptors.³¹ The cat was reevaluated by the Internal Medicine Service at the Washington State University Veterinary Teaching Hospital 3 months after hospital discharge for increased respiratory effort, open mouth breathing, and a respiratory rate of 180 breaths/min. The air quality in the area had been poor over the previous few weeks because of large fires in a nearby part of the state, and an acute episode of asthma was suspected. The patient was admitted and placed in an oxygen cage (oxygen concentration, 38% to 40%), and dexamethasone sodium phosphate (0.15 mg/kg [0.068 mg/lb], IV) and albuterol (90 μg, 1 puff) were administered. The next morning, once the cat was stabilized, thoracic radiographs were obtained. The cat was kept overnight for observation and was discharged the next day having achieved complete resolution of respiratory distress. At the last recheck examination, the cat was still on medication (theophylline, fluticasone, and albuterol) and had mild, sporadic flare-ups of asthma.

In summary, general anesthesia for small animal patients with a history of suspected asthma should be approached with an understanding of the possible complications that can occur, especially if diagnostic procedures involving direct stimulation of the airway are scheduled. A plan to prevent or minimize any likely complications in these patients should be in place prior to the procedure as well as to treat those that may occur. Opioids or sedatives should be administered to facilitate endotracheal intubation, and a deep plane of anesthesia should be achieved prior to intubation. Oxygen supplementation with vigilant monitoring consisting of pulse oximetry, ECG, and blood gas analysis (if available) is recommended.³² Pretreatment with anti-inflammatory and bronchodilating drugs may be warranted. Even with careful preparation, equipment and personnel to implement full resuscitative measures including advanced life support should be readily available when anesthetizing asthmatic patients.