Brachycephalic airway syndrome in dogs is characterized by anatomic abnormalities that include stenotic nares, aberrant nasal conchae, elongated soft palate, everted laryngeal saccules, laryngeal collapse, hypoplastic trachea of various severities, and bronchial collapse; the syndrome also often causes upper airway obstruction.1–7 Clinical signs associated with these abnormalities can include various degrees of dyspnea, snoring, stridor, exercise intolerance, regurgitation, vomiting, cyanosis, syncope, and collapse. In a survey,8 91% of owners of brachycephalic dogs reported that their dogs had stridor while sleeping, 100% reported stridor during exercise, and 68% reported an increase in inspiratory effort during exercise.
Arterial blood gas results for mesocephalic or dolichocephalic dogs have been compared with those of brachycephalic dogs, revealing that the overall Paco2 was significantly higher (mean ± SD, 40.2 ± 3.3 mm Hg for brachycephalic dogs and 33.0 ± 2.1 mm Hg for nonbrachycephalic dogs) and Pao2 was significantly lower (76.8 ± 15.2 mm Hg for brachycephalic dogs and 94.0 ± 12.6 mm Hg for nonbrachycephalic dogs) in brachycephalic dogs.9 In addition, English Bulldogs, a brachycephalic breed, can have prolonged periods of arterial oxygen saturation < 90% during sleep.10
Brachycephalic airway syndrome may also predispose affected dogs to vomiting and regurgitation, which may lead to aspiration pneumonia. Severity of gastrointestinal signs is associated with severity of respiratory signs such as stertor, exercise intolerance, and cyanosis in French Bulldogs, another brachycephalic breed.11
Given the aforementioned anatomic abnormalities and clinical signs, anesthesia is believed to pose a greater risk to brachycephalic versus other dog breeds owing to airway blockage and decreased oxygenation. Common practice is to leave brachycephalic dogs intubated for as long as possible following anesthesia because of these concerns.12 To the authors' knowledge, no studies have been conducted to evaluate whether brachycephalic dogs are more prone than nonbrachycephalic dogs to develop perianesthetic complications during routine surgeries. The purposes of the study reported here were to determine whether brachycephalic dog breeds were more likely to develop perianesthetic complications than nonbrachycephalic breeds and to identify other risk factors for complications. Our hypothesis was that brachycephalic dogs would be at a higher risk of perianesthetic complications than nonbrachycephalic dogs.
Materials and Methods
Animals
Medical records of The Ohio State University Veterinary Medical Center were electronically searched to identify brachycephalic dogs (exposed cohort) and nonbrachycephalic dogs (unexposed cohort) that had undergone general anesthesia for routine surgery or advanced imaging between January 1, 2012, and December 31, 2012. Dogs were included if they had been assigned an ASA status between I and III prior to surgery. Dogs were excluded if they had been assigned an ASA status of IV or V, had undergone emergency surgery, or underwent only radiation therapy.
Once all eligible brachycephalic dogs had been identified, 1 eligible nonbrachycephalic dog was selected to match each included brachycephalic dog on the basis of surgical procedure performed or, if no exact procedure match was available, on the basis of similar procedure invasiveness. As a second, third, and fourth priority, dogs were also matched by age, body weight, and sex, respectively, whenever possible.
Data collection
Information was obtained from the medical records regarding dog breed, age, sex, and body weight; surgical procedure performed; ASA status; drugs administered throughout the procedure (ie, specific sedatives, opioids, induction anesthetic agents, maintenance agent, and additional drugs); whether episodes of hypotension (systolic arterial blood pressure < 80 mm Hg or mean arterial blood pressure < 60 mm Hg) and bradycardia (heart rate < 60 beats/min) were recorded, the duration of each episode, and the nature of interventions performed; and whether hypothermia (rectal or esophageal temperature < 35.6°C [96.1°F]) was recorded. Information regarding recorded peri- and postanesthetic complications such as hypertension, vomiting or regurgitation, VPCs, and dysphoria was also obtained, as were durations of anesthesia, surgery, and positive-pressure ventilation (if provided). The postanesthetic period was defined as the time from discontinuation of inhalant anesthetic to discharge from the hospital. Information regarding postanesthetic complications was also obtained from discharge instructions.
Procedures were grouped in 3 broad categories: noninvasive, minimally invasive, and invasive. Noninvasive procedures included imaging (CT or MRI), dental hygiene procedures, wound management, and endoscopy. Minimally invasive procedures included ophthalmic surgeries, orthopedic surgeries, ovariohysterectomy and orchiectomy, mass removal surgeries, tail or digit amputations, and cardiological coiling or ballooning. Invasive procedures included intra-abdom-inal surgeries other than ovariohysterectomy, such as portosystemic shunt ligation, exploratory celiotomy, and gastrointestinal biopsy; neurologic surgeries (eg, ventral slot or hemilaminectomy procedures); and upper airway surgeries, such as arytenoid lateralization and procedures to correct brachycephalic airway syndrome. Procedures were also categorized by responsible hospital service (ie, orthopedic, soft tissue, dentistry, ophthalmology, radiology, or multiple services).
Statistical analysis
Logistic regression was performed by use of statistical softwarea to compare the odds of 3 outcomes—intra-anesthetic, postanesthetic, and perianesthetic (both intra-anesthetic and postanesthetic) complications—between brachycephalic and nonbrachycephalic dogs, controlling for other factors. A forward-selection model building approach was used to select from the variables brachycephalic status; procedure invasiveness; dog age, sex, and body weight; attending hospital service; ASA status; type of administered sedative, opioid, induction agent, and maintenance agent; duration of anesthesia; and presence of hypothermia during anesthesia (yes or no). Any variable with a univariable model P value of ≤ 0.20 was considered in the multivariable analysis.
Hypotension and bradycardia were classified as anesthetic complications, and in the multivariable model for postanesthetic complications, hypotension and bradycardia were included as independent variables. If multiple anesthesia procedures were performed for a single patient, only 1 procedure was included for analysis to avoid correlated data. Coefficients in the final multivariable models for each of the 3 outcomes were exponentiated to generate ORs. The null hypothesis that the OR was equal to 1 was tested by computation of the likelihood ratio X2 statistic. Odds ratios for which the 95% CI excluded 1 were considered significant.
Results
Animals
A total of 486 (243 brachycephalic and 243 nonbrachycephalic) dogs were considered for inclusion in the study. Twenty (8.2%) dogs in each group were excluded because they had undergone ≥ 2 procedures requiring anesthesia during 2012, leaving 223 dogs in each group. Thirteen brachycephalic dog breeds were represented, including Boxer (n = 45), English Bulldog (41), Shih Tzu (31), Pug (29), Boston Terrier (21), Mastiff (15), French Bulldog (14), American Bulldog (10), Chinese Shar-Pei (5), Lhasa Apso (5), Brussels Griffon (3), Pekingese (2), and Dogue de Bordeaux (2).
Outcomes
Perianesthetic (intra- and postanesthetic) complications were recorded for 49.1% (n = 219) of all 446 dogs, intra-anesthetic complications for 40.4% (180), and postanesthetic complications for 8.7% (39). These complications were recorded for 49.8% (n = 111), 49.3% (110), and 13.9% (31) of the 223 brachycephalic dogs, respectively, and 48.4% (108), 48.9% (109), and 3.6% (8) of the 223 nonbrachycephalic dogs, respectively.
The most common postanesthetic complication was aspiration pneumonia, which was recorded for 9 (4.0%) brachycephalic dogs and no nonbrachycephalic dogs. Other complications included regurgitation (7 [3.1%] brachycephalic dogs); dysphoria (1 [0.4%] brachycephalic and 4 [1.8%] nonbrachycephalic dogs); prolonged recovery (3 [1.3%] brachycephalic and 3 [1.3%] nonbrachycephalic dogs); stertorous breathing (3 [1.8%] brachycephalic and 1 [0.4%] nonbrachycephalic dogs); death (2 [0.9%] brachycephalic dogs); vomiting, anemia requiring blood transfusion, cranial or facial edema, hematuria or urinary tract infection, or inappetence (1 [0.4%] brachycephalic dog each); and VPCs (1 [0.4%] nonbrachycephalic dog). Of the 9 dogs with aspiration pneumonia, 4 had thoracic radiography performed prior to anesthesia with no radiographic or clinical signs of aspiration pneumonia detected. Four dogs had radiography performed only after the anesthetic event. One dog had aspiration pneumonia diagnosed on the basis of thoracic radiographic findings before the anesthetic event. Postoperative thoracic radiographs were obtained for this dog 24 hours after surgery, revealing worsening of the aspiration pneumonia.
Factors associated with outcome
No associations with any evaluated outcome were identified for sedatives, opioids, hypothermia, or anesthetic maintenance agents used or dog age. Factors identified through multivariable modeling as significantly associated with intra-anesthetic complications included brachycephalic status, body weight, duration of anesthesia, reproductive status, and attending hospital service (Table 1). In this model, brachycephalic dogs were 1.57 times as likely to have an intra-anesthetic complication as were nonbrachycephalic dogs. For each 30-minute increase in duration of anesthesia, the odds of an intra-anesthetic complication increased by 0.6% (OR = 1.01). Sexually intact females were approximately twice as likely to have an intra-anesthetic complication as were castrated males. The odds of a complication decreased by 2.0% for every 1-kg (2.2-lb) increase in body weight (OR = 0.98). Dogs treated by the orthopedic service were 44.0% less likely to have a complication than were those treated by the soft tissue or dentistry services (OR = 0.56).
Results of multivariable logistic regression modeling to identify factors associated with intra-anesthetic complications in dogs undergoing routine surgery or advanced imaging (n = 446; 223 brachycephalic and 223 nonbrachycephalic dogs).
Factor | OR (95% CI) | P value |
---|---|---|
Brachycephalic (vs nonbrachycephalic) | 1.57 (1.05–2.34) | 0.03 |
Body weight (kg) | 0.98 (0.97–0.99) | 0.01 |
Anesthetic duration (every 30 min) | 1.01 (1.00–1.01) | 0.003 |
Reproductive status | ||
  Castrated male | 1.00 | Referent |
  Sexually intact female | 2.1 (0.02–4.32) | 0.04 |
  Spayed female | 0.89 (0.02–4.32) | 0.63 |
  Sexually intact male | 1.20 (0.67–2.15) | 0.54 |
Attending hospital service | ||
  Soft tissue or dentistry | 1.00 | Referent |
  Orthopedics | 0.56 (0.32–0.98) | 0.04 |
  Ophthalmology | 0.86 (0.47–1.59) | 0.64 |
  Radiology | 0.60 (0.31–1.16) | 0.13 |
  Multiple services | 0.58 (0.15–2.15) | 0.41 |
Associations were considered significant when the 95% CI for a given OR excluded 1. An OR > 1 indicates an increased risk of the outcome relative to the risk in the referent group, and OR < 1 indicates a decreased risk.
Factors identified through multivariable modeling as significantly associated with perianesthetic (intra-anesthetic and postanesthetic) complications included brachycephalic status, body weight, duration of anesthesia, and attending hospital service (Table 2). In this model, brachycephalic dogs were approximately twice as likely to have a perianesthetic complication as were nonbrachycephalic dogs (OR = 2.06). For each 30-minute increase in the duration of anesthesia, the odds of a perianesthetic complication increased by 18.0% (OR = 1.18). Dogs treated by the orthopedic or radiology services were less likely to have a complication than those treated by the soft tissue service. The odds of a perioperative complication decreased by 2% with every 1-kg increase in body weight (OR = 0.98).
Results of multivariable logistic regression modeling to identify factors associated with perianesthetic (intra-anesthetic and postanesthetic) complications in the dogs of Table 1.
Factor | OR (95% CI) | P value |
---|---|---|
Brachycephalic (vs nonbrachycephalic) | 2.06 (1.38–3.07) | < 0.001 |
Body weight (kg) | 0.98 (0.97–1.00) | 0.01 |
Anesthetic duration (per 30-min interval) | 1.18 (1.04–1.33) | 0.01 |
Attending hospital service | ||
  Soft tissue | 1.00 | Referent |
  Dentistry | 0.62 (0.22–1.72) | 0.36 |
  Orthopedics | 0.49 (0.03–0.86) | 0.01 |
  Ophthalmology | 0.65 (0.35–1.21) | 0.18 |
  Radiology | 0.45 (0.23–0.87) | 0.03 |
  Multiple services | 1.04 (0.25–4.35) | 0.96 |
See Table 1 for key.
Factors identified through multivariable modeling as significantly associated with postanesthetic complications included brachycephalic status, ASA status, invasiveness of surgery, and anesthetic induction agent used (Table 3). Brachycephalic dogs had approximately 4 times the odds of a postanesthetic complication relative to nonbrachycephalic dogs (OR = 4.33). The odds of postanesthetic complication increased with increasing ASA status. Dogs that underwent an invasive procedure were approximately 5 times as likely to have a postanesthetic complications as were dogs that underwent a noninvasive procedure (OR = 5.21). In addition, use of ketamine plus a benzodiazepine for anesthetic induction was approximately 4 times as likely to be followed by a postanesthetic complication as use of propofol with or without lidocaine (OR = 4.45).
Results of multivariable logistic regression modeling to identify factors associated with postanesthetic complications in the dogs of Table 1.
Factor | OR (95% CI) | P value |
---|---|---|
Brachycephalic (vs nonbrachycephalic) | 4.33 (1.85–10.15) | 0.001 |
ASA status | ||
  I | 1.00 | Referent |
  II | 2.59 (0.99–6.70) | 0.05 |
  III | 3.79 (1.32–1.08) | 0.01 |
Type of surgery | ||
  Noninvasive | 1.00 | Referent |
  Minimally invasive | 0.99 (0.33–2.90) | 0.99 |
  Invasive | 5.21 (1.88–14.50) | 0.002 |
Type of anesthetic induction agent used | ||
  Propofol with or without lidocaine | 1.00 | Referent |
  Propofol plus ketamine | 1.31 (0.41–1.19) | 0.65 |
  Ketamine plus benzodiazepine | 4.4S (1.50–13.12) | 0.007 |
  Other induction agent | 2.0a (0.21–20.75) | 0.53 |
See Table 1 for key.
Discussion
Brachycephalic dogs are commonly brought to the authors' hospital for surgery to treat brachycephalic airway syndrome. Brachycephalic dogs are also referred for routine surgeries because veterinarians and owners presume that a brachycephalic dog is at a higher risk of adverse outcomes from anesthesia, although this has never been conclusively demonstrated. A survey13 of owners of dogs with severe brachycephaly revealed that following brachycephalic airway surgery, dogs had fewer life-threatening respiratory-related events in their home environment than before surgery. Such events included choking fits, which decreased in incidence from 60% to 5%, and collapse, which decreased in incidence from 27% to 3%. However, only 7 dogs included in that study13 had a history of brachycephalic airway surgery.
Respiratory distress due to upper airway obstruction and overheating due to dysfunctional thermoregulation are among the most life-threatening circumstances for brachycephalic dogs, and these factors account for much of the deterioration in their quality of life.8 These signs are also a concern for brachycephalic dogs in a hospital setting. Pain or fear-induced tachypnea, with a consequent increase in work of breathing, can lead to a substantial increase in negative pressure within the airway.12 This negative pressure can then cause or exacerbate airway collapse or obstruction, and ineffective ventilation can soon lead to hypoxia and even negative-pressure pulmonary edema. In addition, the high prevalence of gastrointestinal signs (mostly vomiting and regurgitation) in brachycephalic dogs, including but not limited to gastroesophageal reflux, distal esophagitis, and diffuse pyloric hyperplasia, may lead to a higher risk of possible aspiration than the risk for dogs without these signs.11 Therefore, brachycephalic dogs will often receive gastroprotectants, antinausea medications, and prokinetics in the perianesthetic period to reduce the risk of regurgitation and aspiration pneumonia.
Withholding of food for 24 hours and sedative administration prior to anesthesia have been proposed to reduce the risk of regurgitation and aspiration pneumonia in brachycephalic dogs.14 In addition, prophylactic gastrointestinal medication administration (proton-pump inhibitors, prokinetics, antinausea medications) to brachycephalic dogs undergoing upper airway surgery may be helpful in preventing complications like aspiration pneumonia.11 One study15 showed improvement of gastrointestinal signs without complete resolution after brachycephalic airway surgery. Another study16 revealed improvement of gastrointestinal signs after brachycephalic airway surgery; however, medical management of gastrointestinal signs had no significant long-term effect, and improvement was achieved with surgery alone. A 24-hour food withholding period prior to anesthesia was not beneficial in that study.16
Brachycephalic dogs were at a higher risk than nonbrachycephalic dogs of developing complications in the perianesthetic period in the present study, but even more so in the postanesthetic period specifically. Brachycephalic conformation was significantly associated with outcome in all 3 models, with the greatest association observed for complications during the postanesthetic period. Brachycephalic dogs are likely at a higher risk of complications following rather than during anesthesia because respiratory obstruction can occur after extubation.
Death was the most severe complication in the present study, and this as well as other types of perianesthetic complications appeared more common in brachycephalic dogs than in nonbrachycephalic dogs. Dysphoria and VPCs were the only 2 complications that were more common in nonbrachycephalic dogs. In general, brachycephalic dogs are prone to a higher resting vagal tone than nonbrachycephalic dogs and therefore more prone to sinus bradycardia,17 which should put them at a lower risk for VPCs.
Anesthetized brachycephalic dogs should remain intubated until they are awake,12 which helps to improve breathing because the airway is kept open. In the authors' experience, endotracheal tubes are well tolerated by most brachycephalic dogs, even when dogs are fairly awake following anesthesia. Brachycephalic dogs with airway obstruction had significantly shorter expiratory-to-inspiratory ratios than control dogs in another study,18 which further supports the Hoareau hypothesis of a high resistance to flow on inspiration. Thus, increasing the oxygen flow by providing an adequate airway opening with the endotracheal tube decreases respiratory effort.
Invasive (vs noninvasive) procedures were associated with increased risk of postanesthetic complications in the study reported here. Our data suggested a higher rate of complications in brachycephalic dogs during the intra-anesthetic and perianesthetic periods with increasing duration of anesthesia. Prolonged surgery is significantly related to complication rates in humans.19 In a previous study20 involving anesthetized cats and dogs, procedure duration and type of anesthetic induction and maintenance agents used were associated with anesthetic-related death.
Sexually intact females were at higher risk of intra-anesthetic complications than males in the present study; however, the reason for this remains unclear. To the authors' knowledge, this finding has not been reported previously.
Although many dogs were included in the present study, the design was observational in nature and not a randomized controlled trial. It would be worthwhile to investigate whether specific anesthetic agents may minimize the odds of perianesthetic complications in brachycephalic dogs. In addition, information on other potential risk or protective factors, such as body condition score, was unavailable. Therefore, although an association was identified between body weight and intra- or perianesthetic complications, it remains unknown whether this association could have been attributable to body condition or to breed size. Further investigation is warranted into the potential association between body condition score and anesthetic-related complications in brachycephalic dogs.
Invasive procedures and higher ASA status, together with brachycephalic dog breed, accounted for higher risks of a broad range of postanesthetic complications in the study reported here. At the time of our study, we were unaware of any reported studies regarding associations between perianesthetic complications and procedure invasiveness in brachycephalic dogs. Noninvasive procedures included those such as CT or MRI, whereas invasive procedures included exploratory celiotomy or gastrointestinal surgery, which can lead to blood loss or functional ileus. The duration of postoperative ileus was briefer with less invasive procedures (eg, laparoscopic cholecystectomy) than with more invasive procedures (eg, open cholecystectomy) in a previous study21 involving humans.
High ASA status has also been associated with a higher risk of death in dogs and cats.22 We intentionally excluded dogs with an ASA status ≥ IV from the present study to decrease the impact of systemic abnormalities on outcome, and this choice may have accounted for the finding that the ASA status had a lower OR for postanesthetic complications than the brachycephalic breed. Despite the exclusion of dogs with a high ASA status and dogs that underwent emergency procedures, both deaths observed in our study involved brachycephalic and not nonbrachycephalic dogs. One brachycephalic dog died of cardiac arrest during anesthetic induction with propofol and had been anesthetized for intravitreal gentamycin injection. The other brachycephalic dog died 4 days after undergoing a Billroth II procedure; this patient stopped breathing during morning treatments and then had cardiac arrest.
In general, brachycephalic dogs were often classified as ASA status II for no other reason than the brachycephaly. Although care was taken to ensure that most nonbrachycephalic dogs had the same or worse ASA status as their matched brachycephalic counterpart, the odds of developing complications remained higher for brachycephalic dogs.
We also found that dogs that received ketamine and a benzodiazepine as anesthetic induction agents were at higher risk of postanesthetic complications than dogs for which propofol with or without lidocaine was used. This finding was unexpected given that both ketamine and benzodiazepines cause minimal to no respiratory depression23 and are considered appropriate for dogs with airway disease or dysfunction. The induction and recovery phases of anesthesia for brachycephalic dogs can be dangerous, but the maintenance phase is generally straightforward because the laryngeal opening is protected by an endotracheal tube.12
Brachycephalic dogs were 1.57 times as likely to have intra-anesthetic complications and 4.33 times as likely to have postanesthetic complications as were nonbrachycephalic dogs in the present study. The etiology of perianesthetic complications is likely multifactorial, and additional studies should be performed to identify anesthetic practices that reduce the risk of perianesthetic complications in brachycephalic dogs.
Acknowledgments
Presented in abstract form at the American College of Veterinary Surgeons Surgery Summit, Indianapolis, Ind, October 2017.
The authors thank Kathleen Bailey, Heather Cruea, Theresa Hand, Gladys Karpa, Mary Beth Morrow, Amanda Spires, Robyn Victorine, and Dan Wallon for data collection and patient care.
ABBREVIATIONS
ASA | American Society of Anesthesiologists |
CI | Confidence interval |
VPC | Ventricular premature contraction |
Footnotes
Stata, version 13, StataCorp LP, College Station, Tex.
References
1. Trader R. Nose operation. J Am Vet Med Assoc 1949;114:210–211.
2. Oechtering TH, Oechtering GU & Nöller C. Structural characteristics of the nose in brachycephalic dog breeds analysed by computed tomography. Tierarztl Prax 2007;35:177–187.
3. Farquharson J, Smith KW. Resection of the soft palate in the dog. J Am Vet Med Assoc 1942;100:427–430.
4. Leonard HC. Eversion of the lateral ventricles in dogs; five cases. J Am Vet Med Assoc 1957;131:83–84.
5. Leonard HC. Collapse of the larynx and adjacent structures in the dog. J Am Vet Med Assoc 1960;137:360–363.
6. Suter PF, Colgrove DJ, Ewing GO. Congenital hypoplasia of the canine trachea. J Am Anim Hosp Assoc 1972;8:120–127.
7. De Lorenzi D, Bertoncello D & Drigo M. Bronchial abnormalities found in a consecutive series of 40 brachycephalic dogs. J Am Vet Med Assoc 2009;235:835–840.
8. Roedler FS, Pohl S, Oechtering GU. How does severe brachycephaly affect dog's lives? Results of a structured preoperative owner questionnaire. Vet J 2013;198:606–610.
9. Hoareau GL, Jourdan G, Mellema M, et al. Evaluation of arterial blood gases and arterial blood pressures in brachycephalic dogs. J Vet Intern Med 2012;26:897–904.
10. Hendricks JC, Kline LR, Kovalski RJ, et al. The English Bulldog: a natural model of sleep-disordered breathing. J Appl Physiol 1987;63:1344–1350.
11. Poncet CM, Dupre GP, Freiche VG, et al. Prevalence of gastrointestinal tract lesions in 73 brachycephalic dogs with upper respiratory syndrome. J Small Anim Pract 2005;46:273–279.
12. Grubb T. Anesthesia for patients with respiratory disease and/or airway compromise. Top Companion Anim Med 2010;25:120–132.
13. Pohl S, Roedler FS, Oechtering GU. How does multilevel upper airway surgery influence the lives of dogs with severe brachycephaly? Results of a structured pre- and postoperative owner questionnaire. Vet J 2016;210:39–45.
14. Hendricks JC. Brachycephalic airway syndrome. Vet Clin North Am Small Anim Pract 1992;22:1145–1153.
15. Haimel G, Dupre GP. Brachycephalic airway syndrome: a comparative study between Pugs and French Bulldogs. J Small Anim Pract 2015;56:714–719.
16. Poncet CM, Dupre GP, Freiche VG, et al. Long-term results of upper respiratory syndrome surgery and gastrointestinal tract medical management in 51 brachycephalic dogs. J Small Anim Pract 2006;47:137–142.
17. Doxey S & Boswood A. Differences between breeds of dog in a measure of heart rate variability. Vet Rec 2004;154:713–717.
18. Bernaerts F, Talavera J, Leemans J, et al. Description of original endoscopic findings and respiratory functional assessment using barometric whole-body plethysmography in dogs suffering from brachycephalic airway obstruction syndrome. Vet J 2010;183:95–102.
19. Kroenke K, Lawrence VA, Theroux JF, et al. Operative risk in patients with severe obstructive pulmonary disease. Arch Intern Med 1992;152:967–971.
20. Brodbelt D. Perioperative mortality in small animal anaesthesia. Vet J 2009;182:152–161.
21. Schippers E, Ottinger AP, Anurov M, et al. Intestinale motilität nach laparoskopischer vs. konventioneller cholezystektomie. Langenbecks Arch Chir 1992;377:14–18.
22. Bille C, Auvigne V, Libermann S, et al. Risk of anaesthetic mortality in dogs and cats: an observational cohort study of 3546 cases. Vet Anaesth Analg 2012;39:59–68.
23. Haskins SC, Farver TB, Patz JD. Cardiovascular changes in dogs given diazepam and diazepam-ketamine. Am J Vet Res 1986;47:795–798.