The OCR is a physiologic phenomenon whereby manipulations of the eye and associated tissues or an increase in intraocular pressure results in sudden bradycardia.1 The ophthalmic branch of the trigeminal nerve (cranial nerve V) is the afferent branch of this reflex arc. It carries sensory signals from the orbit to the reticular formation within the CNS. The vagus nerve (cranial nerve X) mediates the efferent parasympathetic signaling of the OCR. The OCR has been described in humans,1–3 dogs,4,5 and other species.5,6 Inherent protective mechanisms limit the severity of vagal stimulation such as vagal escape and vagal fatigue; however, such mechanisms may fail in anesthetized dogs given that anesthetics are known to blunt at least part of the sympathetic responses.7
Heart rate and blood pressure are important determinants of cardiac output. Maintenance of heart rate and blood pressure within reference limits is fundamental during anesthesia to ensure adequate tissue perfusion and prevent organ damage secondary to tissue hypoxia. If unrecognized and left untreated, an OCR can lead to severe hypotension secondary to bradycardia and result in hypoperfusion and tissue hypoxia. An OCR may also result in asystole and death,8 which emphasizes the importance of vigilant patient monitoring during general anesthesia.
Evidence from the human and veterinary medical literature suggests that administration of anticholinergic drugs (atropine or glycopyrrolate)9,10 or RNBs with local anesthetics6 may prevent an OCR from occurring.11 In veterinary species, RNBs provide adequate perioperative analgesia and reduce the need for postoperative analgesic administration.12 The infratemporal approach to RNB has been described as one of the easiest methods to provide adequate retrobulbar cone anesthesia and reduce the need for systemic administration of neuromuscular blocking agents.13 However, RNBs have been associated with potential complications, including ineffective blockade, retrobulbar hematoma, intrathecal injection, inadvertent IV injection, respiratory depression, and, rarely, sudden death.
Although anticholinergic drugs can be administered to treat intraoperative bradycardia,14 whether these drugs should be routinely administered prior to ophthalmic surgery remains controversial in both human and veterinary medicine because such drugs have a wide range of effects with the potential to cause important adverse effects.2,15 Anticholinergic drugs can cause severe tachycardia in dogs,16 resulting in an increase in myocardial oxygen demand and decrease in coronary perfusion, potentially leading to myocardial ischemia and hypoxia. These drugs can also cause gastrointestinal ileus and decrease lower esophageal sphincter tone, thereby increasing the risk of regurgitation and aspiration pneumonia.17
To the authors’ knowledge, the prevalence of an OCR occurring or the effectiveness of anticholinergic drugs or RNBs in preventing an OCR from occurring in dogs during enucleation has not been reported. The aim of the retrospective study reported here was to determine the prevalence of and covariates associated with an OCR occurring in a heterogeneous population of dogs during enucleation. The hypothesis was that preoperative administration (vs no administration) of RNBs or anticholinergic drugs would be associated with a lower prevalence of OCR in dogs undergoing enucleation.
Materials and Methods
Animals
Paper medical records of client-owned dogs evaluated at the veterinary teaching hospitals of the University of Pennsylvania and Université de Montréal between January 1, 2010, and June 30, 2015, were reviewed to identify dogs that underwent enucleation during that period. Dogs that had incomplete records or irregular hemodynamic data owing to trauma or administration of vasoactive drugs were excluded from the study.
Medical records review
Data collected from the medical record of each dog included age and body weight at the time of hospital admission, breed, reproductive status, reason for enucleation (diagnosis), types and doses of administered anesthetic drugs (with particular attention to preoperative administration of anticholinergic drugs within 30 minutes before surgery began), and whether an RNB was performed before enucleation. Durations of anesthesia and surgery were also recorded. Dogs with a recorded breed were classified as brachycephalic if they were among the following breeds included in the study: American Staffordshire Terrier, Bichon Frise, Boston Terrier, Bulldog, Cane Corso, Chihuahua, Coton de Tulear, Cairn Terrier, French Bulldog, Havanese, Lhasa Apso, Maltese, Pekinese, Pomeranian, Pug, Shih Tzu, and Chinese Shar-Pei.
Enucleation
In nonemergent situations, food was withheld from dogs for at least 8 hours prior to induction of anesthesia for the enucleation. Sedative and anesthetic drugs were chosen by the board-certified veterinary anesthesiologist in charge of anesthetic management. Anesthetized dogs were endotracheally intubated and connected to a circular coaxial rebreathing circuit with inhalant anesthetics delivered in oxygen. Anesthetic monitoring included noninvasive blood pressure monitoring with a Doppler ultrasonic or oscillometric device, pulse oximetry, capnography, esophageal temperature measurement, and lead II ECG. Mechanical ventilation was instituted only if dogs developed hypoventilation. Enucleations consisted of excision of the globe following resection of the ophthalmic nerve and adjacent tissues.
OCR
An OCR was arbitrarily defined as having occurred if a sudden decrease of ≥ 30% in heart rate from the baseline value was observed. Baseline heart rate was calculated as the mean of heart rates recorded over the 15-minute period that immediately preceded the OCR up to and excluding the point the sudden decrease was noted. A diagnosis of OCR was ruled out for dogs that had received treatments known to cause bradycardia (ie, opioids, fluid boluses, or α2-adrenoceptor agonists) immediately before a sudden decrease in heart rate was noted.
Statistical analysis
All statistics were computed with the aid of statistical software.a The Anderson-Darling test was used to assess data normality. Normally distributed continuous data (age and durations of anesthesia and surgery) are reported as mean ± SD. Nonnormally distributed continuous data (body weight) are reported as median (range).
Binomial logistic regression was performed to assess whether putative risk factors (ie, age, body weight, brachycephalic status [yes vs no], and preoperative anticholinergics or RNB administration [yes vs no]) were associated with the prevalence of OCR. Values of P ≤ 0.05 were considered significant.
Results
Animals
A total of 159 dogs underwent enucleation during the study period. Of these dogs, 14 were excluded because of incomplete records or irregular hemodynamic data, resulting in 145 dogs (91 from the University of Pennsylvania and 54 from the Université de Montréal veterinary teaching hospitals) being included in the study.
Mean ± SD age was 6.7 ± 3.7 years, and median (range) body weight was 10.1 kg (22.2 lb; range, 0.9 to 72.0 kg [2.0 to 158.4 lb]). Sixty-six (45.5%) dogs were spayed females, 56 (38.6%) were castrated males, 13 (9.0%) were sexually intact males, and 10 (6.9%) were sexually intact females. Dog breeds or types represented by ≥ 2 dogs included mixed-breed dog (n = 19 [13.1%]), Pug (13 [9.0%]), Shih Tzu (12 [8.3%]), Labrador Retriever (12 [8.3%]), Boston Terrier (11 [7.6%]), Cocker Spaniel (9 [6.2%]), Chihuahua (5 [3.4%]), Yorkshire Terrier (4 [2.8%]), Jack Russell Terrier (4 [2.8%]), Miniature Pinscher (4 [2.8%]), Siberian Husky (4 [2.8%]), Pekinese (3 [2.1%]), Lhasa Apso (3 [2.1%]), Fox Terrier (2 [1.4%]), Maltese (2 [1.4%]), Chinese Shar-Pei (2 [1.4%]), Tibetan Spaniel (2 [1.4%]), Beagle (2 [1.4%]), Rat Terrier (2 [1.4%]), Poodle (2 [1.4%]), and French Bulldog (2 [1.4%]). Fifty-two of the 126 (41.3%) dogs with a recorded breed, excluding mixed-breed dogs, were categorized as brachycephalic.
Enucleation procedure
For the 121 dogs for which it could be determined, the most common diagnoses that prompted enucleation were glaucoma (n = 59 [48.8%]), ocular neoplasia (17 [14.0%]), perforated corneal ulcer (15 [12.4%]), and proptosis (14 [11.6%]). Mean ± SD durations of anesthesia and surgery were 107 ± 40 minutes and 55 ± 30 minutes, respectively.
Generally, dogs were premedicated with a μ-opioid receptor agonist or partial agonist (most common opioids in decreasing order of use: hydromorphone, methadone, oxymorphone, butorphanol, and morphine; n = 142 [97.9%]) without or with acepromazine (61 [42.1%]) or dexmedetomidine (14 [9.7%]), a benzodiazepine (midazolam or diazepam; 78 [53.8%]), or lidocaine (8 [5.5%]). Seventeen (11.7%) dogs also received an anticholinergic drug (atropine or glycopyrrolate, IM), and 82 (56.6%) dogs received an RNB, which was performed with bupivacaine alone or equal amounts of bupivacaine and lidocaine.
Anesthesia was induced by IV administration of various doses of propofol (n = 113 [77.9%]), alfaxalone (10 [6.9%]), ketamine (9 [6.2%]), or etomidate (3 [2.1%]). Anesthesia was maintained with isoflurane (n = 140 [96.6%]), propofol plus a constant rate infusion of fentanyl (2 [1.4%]), or sevoflurane (1 [0.7%]). Information regarding anesthetic induction and maintenance agents was missing for 10 and 2 dogs, respectively.
OCR
Overall, 7 of the 145 (4.8%) dogs had an OCR observed and 138 (95.2%) had no OCR observed during the enucleation procedure. Two dogs in the OCR group had a diagnosis of proptosis, and 1 each had a diagnosis of glaucoma, desmetocele, traumatic eye puncture, or corneal ulcer. For 1 dog in the OCR group, the diagnosis that prompted enucleation was missing from the medical record.
No difference (P = 0.56) in mean age was identified between dogs that had an (8.0 ± 3.6 years) or had no (7.1 ± 4.8 years) OCR observed during the enucleation procedure. Median body weight of dogs that had an OCR was 8.3 kg (18.3 lb; range, 0.9 to 10.4 kg [2.0 to 22.9 lb]) and of dogs that had no OCR was 10.3 kg (22.7 lb; range, 1.7 to 72.0 kg [3.7 to 158.4 lb]).
Overall, 1 of 7 dogs in the OCR group and 0 of 119 dogs in the no-OCR group were brachycephalic (P = 0.10). A significantly (P = 0.04) greater proportion of dogs in the OCR group (6/7) did not receive an RNB prior to surgery, compared with the proportion of dogs in the no-OCR group that did not receive an RNB (57/138; OR, 0.12; 95% confidence interval, 0.01 to 1.00).
Only 1 of 7 dogs in the OCR group received an anticholinergic drug (atropine at 20 μg/kg [9.1 μg/lb], IM) before surgery, whereas 16 of 138 dogs in the no-OCR group received atropine (n = 5; 5 to 10 μg/kg [2.3 to 4.5 μg/lb], IM) or glycopyrrolate (11; 5 to 10 μg/kg, IM). No significant (P = 0.64) association was identified between preoperative administration of anticholinergic drugs and the prevalence of OCR (OR, 1.45; 95% confidence interval, 0.31 to 6.76).
Discussion
Results of some studies18,19 suggest that RNBs with local anesthetics are unreliable for preventing an OCR from occurring in humans. On the other hand, RNBs are reportedly effective at preventing an OCR from occurring in horses.6 Findings of the present study suggested that RNBs may help prevent an OCR from occurring in dogs undergoing enucleation. This advantage complements other known benefits associated with the use of local anesthetics, such as less need for systemic analgesic administration during and after surgery. However, both the benefits and disadvantages of RNBs should be considered owing to the associated risk of eye perforation and retrobulbar hematoma formation. Although cardiac arrest can occur following RNB administration in cattle,20 this complication has not been reported in dogs. Various approaches to RNBs have been described for dogs, and the supratemporal technique provides a distribution of injectate similar to that achieved with the inferior temporal approach, but with fewer complications.21
In the present study, administration of anticholinergic drugs as part of premedication prior to enucleation had no association with the prevalence of OCR occurring during surgery. Atropine (50 μg/kg [22.7 μg/lb]) or glycopyrrolate (10 μg/kg) administered IM to dogs 20 minutes before anesthetic induction results in an increased heart rate for at least 90 minutes, compared with the heart rate in placebo-treated dogs.22 The maximum dose of atropine used as a part of pre-medication did not exceed 20 μg/kg in our study, and this may have resulted in a briefer duration of effect than previously observed.23 Administration of anticholinergic drugs 30 minutes before surgery begins should prevent intraoperative vagal reflexes from occurring for as long as 1 hour after anesthetic induction. Given the brief duration of enucleation, it was unlikely that the OCR observed in the 1 dog that received atropine prior to enucleation could be explained by the waning effect of such drugs. A randomized controlled clinical trial would be required to determine the effectiveness of anticholinergic drugs in preventing an OCR from occurring in dogs during enucleation procedures.
In the present retrospective study, the prevalence of OCR during the procedure was 4.8%. The extent of the decrease in heart rate is known to differ depending on which afferent neural pathway is stimulated.24 Early experiments revealed a high response rate of dogs to nasal electric stimulations, resulting in bradycardia.4 Therefore, differences between the results of the present study and those of that experimental study4 as well as reported findings for humans may be attributable to the nature of the stimulus (electric vs surgical stimulation) causing the OCR. The arbitrary definition of OCR used in the present study might have resulted in an underestimation of prevalence.
In humans undergoing general anesthesia, age is an important factor in the prevalence of OCR. For example, OCR episodes appear most commonly in, but not strictly in, anesthetized children.1 However, in the present study, young age could not be explored as a risk factor for OCR because, with the exception of 1 dog, all patients were > 6 months of age. Another factor hypothesized to be associated with the prevalence of OCR in dogs was brachycephalic conformation, given the widespread belief that brachycephalic dogs have higher parasympathetic tone than dolicocephalic dogs.24 However, OCR was not more common in brachycephalic dogs than it was in dolichocephalic dogs in our study.
The results obtained in the present study were limited by the retrospective study design. Analysis was based on data collected from the paper medical records of 2 veterinary teaching hospitals. In some instances, drug doses were not recorded, nor were details about specific techniques used to perform RNBs. Consequently, the contribution of specific anesthetic drug regimens in the development of OCR could not be assessed. Drugs commonly used for general anesthesia can produce perioperative bradycardia. Opioids may have parasympathomimetic effects and induce bradycardia, particularly following bolus administration or IV infusion.25,26 Constant rate infusions of opioids can slow myocardial impulse conduction at the atrioventricular node, resulting in atrioventricular blocks of varying degrees.27 Opioid-induced bradycardia readily responds to treatment with anticholinergic drugs such as atropine or glycopyrrolate. In veterinary medicine, α2-adrenoceptor agonists are commonly used for their sedative and analgesic properties. These drugs produce marked peripheral vasoconstriction with hypertension and reflex bradycardia. Administration of anticholinergic drugs to hypertensive patients following administration of α2-adrenoceptor agonists would be contraindicated because this could be expected to increase myocardial work and oxygen demand.28
Surgical technique and surgeon dexterity may be other important factors in the likelihood of patients having an OCR. Whether enucleation had been performed by experienced board-certified veterinary ophthalmologists or surgeons or by individuals in training was not recorded in the anesthetic record. A case report29 exists of a dog that underwent cleft palate repair and had several episodes of severe bradycardia and asystole owing to prolonged tongue traction, and this finding suggests that duration of stimulation could be an important factor in the development of bradycardia. It follows that surgeon experience may also impact whether an OCR occurs because such experience may impact the degree and duration of traction on orbital tissues, although this possibility has not been evaluated in veterinary medicine to the authors’ knowledge.
Overall, findings of the present study suggested that an RNB, in addition to providing perioperative analgesia, may help prevent the OCR from occurring in dogs during enucleation, whereas premedication with anticholinergic drugs may not. Neither brachycephalic conformation nor age was associated with the prevalence of OCR. No attempt was made to evaluate whether hypotension might be temporally or causally associated with OCR. Additionally, the long-term clinical effects of OCR were not evaluated, although no deaths were noted. Therefore, the clinical relevance of OCR in dogs remains unknown.
Acknowledgments
No third-party funding or support was received in connection with this study or the writing or publication of the manuscript. The authors declare that there were no conflicts of interest.
ABBREVIATIONS
| OCR | Oculocardiac reflex |
| RNB | Retrobulbar nerve block |
Footnotes
MiniTab for Windows, version 17, Minitab Inc, State College, Pa.
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