Evaluation of transanesthetic complications comparing epidural versus analgesic continuous infusion in dogs submitted to neurosurgeries

Neurosurgeries have become more frequent in veterinary hospitals, however, there are some questions regarding anesthetics protocols and analgesic techniques. Thus, patient analgesia and hemodynamic stability play a key role in pre, post, and perioperative moments favoring an adequate recovery. This study aimed to evaluate the transanesthetic complications reported on anesthetic records of dogs submitted to hemilaminectomies in the university veterinary hospital of the Federal University of Santa Maria (UFSM) between January 2016 and August 2017, and compare three different analgesic protocols most commonly used in the routine for this surgery. In addition, transanesthetic parameters for each dog were equally recorded in five-minute intervals: cardiac frequency (FC), respiratory frequency (f) blood oxygen saturation (SpO2), mean artery pressure (PAM), temperature and end tidal CO2 (EtCO2). The patients were divided into three groups: Group M: animals receiving epidural analgesia with morphine 0.1mg/kg diluted in 0.26 ml/kg of saline solution 0.9%; Group FLK: bolus of fentanyl 2 μg/kg, lidocaine 1 mg/kg, and ketamine 1 mg/kg followed by infusion of fentanyl 0.1 μg/kg/min, lidocaine 50 μg/kg/min and ketamine 10 μg/ kg/min; and Group F: bolus of fentanyl 2 μg/kg followed by infusion of fentanyl 0.1 μg/kg/min. ANOVA was used to evaluate the anesthetic protocols complications, followed by Tukey’s post-hoc test with a significance level of 5% (p <0.05), comparing the mean of each parameter. Among the anesthetic complications that were found hypotension, bradycardia and hypercapnia were the most frequent. When 22.22% of the patients presented hypotension more evident on the first 10 minutes of anesthesia, 22.22% presented bradycardia, requiring the use of atropine (0.022 mg/kg) and 83.33% had hypercapnia on at least one of the times (EtCO2 > 45mmHg). With this study, it was observed that the use of continuous infusions of FLK, fentanyl, and epidural analgesia with morphine, in the used doses, were effective and safe in the dogs submitted to neurosurgeries, however, it was noticed that the use of morphine caused a greater reduction in temperature during the intraoperative period.


Introduction
Neurosurgeries are becoming increasingly constant on veterinarian hospitals routine, thus knowledge of adequate anesthetic protocols for these procedures are required. General anesthesia is essential for a surgical procedure on patients, furthermore, trans and postoperative analgesia, and maintenance of stable anesthesia is very important for animal welfare, in order to avoid morbidity and mortality during surgery (Godoi et al., 2009).
Patients with neurologic abnormalities have a need for greater anesthetic control, therefore neurologic function must be preserved at its maximum, to prevent hypoxia, hypercapnia, respiratory and cardiovascular instability (Cornick, 1992). During anesthetic procedures, it has been used multimodal analgesia, which means a drug association with distinct analgesic properties in order to block the pain from different pharmacodynamic mechanisms (Muir III et al., 2003).
This study aimed to evaluate the transanesthetic complications reported on anesthetic records of dogs submitted to hemilaminectomies in the university veterinary hospital of the Federal University of Santa Maria (UFSM) and compare three different analgesic protocols most commonly used in the routine for this surgery. In addition, the retrospective evaluation of the significance of variability from the following parameters: cardiac frequency (FC), respiratory frequency (f) blood oxygen saturation (SpO2), mean artery pressure (PAM), temperature and end tidal CO2 (EtCO2). Then compare the same parameters amongst dogs that were submitted to hemilaminectomy, and anesthetized with morphine epidurally administered, with continuous infusion of fentanyl or association of fentanyl, lidocaine, and ketamine (FLK). with heart rate (HR), respiratory frequency (f), blood oxygen saturation (SpO2), mean arterial pressure (MAP), temperature, and end-tidal CO2 (EtCO2). Furthermore, only medical records from patients anesthetized with the same induction protocol: propofol (Propovan ® ) 4 mg/kg IV plus diazepam (Diazepam ® ) 0.5 mg/kg IV, without pre-anesthetic medication and that were maintained in general anesthesia with isoflurane (Isoforine ® ) at 1.5% in spontaneous ventilation. Every patient received as support therapy dipyrone 25 mg/kg (Febrax ® ), cefalotine 30 mg/kg (Cefalotina Sódica ® ) and transoperative fluid therapy with Ringer Lactate (Ringer Com Lactato ® ) at a rate of 5 mL/kg/h.

Data analysis
Anesthetic protocols were analyzed by ANOVA, followed by Tukey's post-hoc test comparing the mean of each variable (HR, f, SpO2, EtCO2, temperature, MAP) from animals anesthetized on Groups M, FLK, and F throughout anesthesia (5-minutes interval). T0 was considered the time in which the patient was induced and a P-value of <0,05 was considered statistically significant for all comparisons made.

Results
It was analyzed a total of 67 medical records of dogs submitted to hemilaminectomy, but only 34 were filled, and 18 fit the protocols to be evaluated in this study.
Temperature presented a significant difference when compared to M to FLK and M to F, thus patients from Group M had greater body temperature reduction, even though they showed a higher mean temperature. The remaining variants displayed no difference in none of the three protocols.

Discussion
It is important to give special attention to pain control and management to ensure animal welfare and provide better recovery conditions for patients that were submitted to surgery or traumatized. Many strategies can be employed for pain treatment, therefore the professional must choose previously what drugs available will be used, always considering the patient, surgical procedure, and level of pain to which animal will be exposed (Fantoni & Cortopassi, 2009).
Contrasting with the results found by Godoi et al. (2009) where 26 from 54 animals submitted to neurosurgery were females and the predominant breed was Dachshund (22 dogs); this study showed a higher prevalence of males and crossbreeds. According to the same author, mean time of surgery on patients that were submitted to hemilaminectomy was 2 hours and 34 minutes (Godoi et al., 2009) which is way above mean time of anesthesia (1 hour and 55 minutes) for the same surgical procedure on the patients from this study.
Morphine is a prototype opiate analgesic that acts on μ, κ, and δ receptors. It is relatively hydrophilic and very useful for analgesia of dogs, cats, equines, and rodents. Regarding the adverse effects, there is a potential risk of histamine release and vomiting (Lamont & Mathews, 2013). Epidural administration of morphine has been employed with good results for pain management, like this study, without observation of adverse effects mentioned above. There are differences in opioids pharmacodynamics for CNS receptors among animal species, but in general, epidural analgesia is mediated by activation of μ -1, μ -2, κ and δ receptors (Valadão et al., 2002).
Epidural access in small animals is performed usually on the lumbosacral site (L7-S1) (Godoi et al., 2009), hence this region is chosen to administrate analgesia with morphine on animals from Group M. However, it is possible to access the epidural site at any intervertebral space from the lumbar spine (Klaumann & Otero, 2013). Regarding dogs and cats, it is preconized a total volume of epidural injection of 0.2 mL/kg but does not exceed 6 mL for animals weighing more than 30 kg. It was used distinct volumes from different drugs where the amount administered was between 0.13 and 0.36 mL/kg without the occurrence of adverse effects (Valverde, 2008).
The use of different drugs in continuous infusion techniques produces several benefits on balanced anesthesia, such as a minor requirement from the inhaled anesthetic and better pain control. The most commonly used in these protocols are local anesthetics, dissociative drugs, and opioids, which can be administered isolated or in association (Cerejo et al., 2013). Moreover, these analgesic agents act on different stages of a painful process, such as transduction, transmission, and integration, blocking nociception in different points, therefore this pharmacological synergy favors drug biotransformation and also allows its dose reduction (Muir III et al., 2003).
Fentanyl is a synthetic opioid agonist of μ receptors. When compared to morphine, fentanyl is 100 times stronger and more lipophilic, this drug has a fast onset and a short-term action. The administration of IV bolus of fentanyl (1 -5 μg/kg) followed by continuous infusion (1 -5 μg/kg/hour) provides suitable sedation and post-surgical analgesia (Gremião et al., 2018).
Ketamine has been often administered as part of a balanced anesthetic protocol due to its analgesic features, mainly when is used at subanesthetic dosages. This drug also reduces anesthetic requirements, maintaining hemodynamics parameters stable, and its analgesic property is attributed to the antagonistic PUBVET v.15, n.02, a747, p.1-6, Fev., 2021 effect on N-methyl-D-aspartate (NMDA) spinal cord receptors. Besides, ketamine also acts on opioid and muscarinic receptors (Carregaro et al., 2010).
Lidocaine has a local analgesic effect when used on continuous infusions and its use has been largely discussed in past years. It acts as preventing sympathetic responses that occur by surgical stimulus and reduces intraoperative use of opioids without promoting significant hemodynamic instabilities. The use of lidocaine on continuous infusion at 50 ug/kg/min reduced 18.7% of isoflurane and the absence of cardiovascular side effects on healthy dogs (Carregaro et al., 2010).
Hypotension and hypoventilation were complications related by Cerejo et al. (2013), which hypotensive episodes responded to vasopressor drugs or fluid therapy bolus, similarly to our study. According to the same author, there was an increase in end-tidal CO2 (> 50 mmHg) on 7.5% of evaluated dogs, differing from this paper with higher rates of animals with hypercapnia and absence of mechanic ventilation.
Apnea and cardiac arrhythmia (atrioventricular block and ventricular tachycardia) were also related in animals receiving FLK infusion (Cerejo et al., 2013), however, in this study, no animals exhibited these complications. Compared with other studies, where 25% of animals anesthetized with isoflurane for neurosurgeries showed bradycardia (Godoi et al., 2009), our study showed no difference in our evaluations (22.22%).
Heat loss from animals may occur by radiation, convection, conduction, skin evaporation, expired air, animal wastes (urine and feces), and CO2 release, thus, the use of surgical solutions, trichotomy, cold environment, and metabolism depression by anesthesia are important factors of body temperature decrease (Yazbek, 2010). The hypothalamus thermoregulator system is also affected by opioid administration (Biazzotto et al., 2006). Animals from the morphine group received antisepsis with alcohol-iodine-alcohol for peridural puncture and also had surgical antisepsis with chlorhexidine digluconate solution 1%, followed by chlorhexidine digluconate alcoholic solution 0.5 %, being exposed to subsequent processes of heat loss by evaporation, therefore this is a hypothesis to explain a significant temperature reduction.

Conclusions
In this study we observed that continuous infusion of FLK, fentanyl, and epidural analgesia with morphine were safe and effective on dogs submitted to neurosurgeries, however, it was demonstrated that the use of morphine caused a significant temperature reduction on transoperative, being necessary caution to avoid hypothermia. Also, hypercapnia results were significant, because it was more frequent than related from other authors, emphasizing the importance of mechanic ventilation for neurosurgeries. Thus, we conclude that more studies evaluating other parameters, such as cardiac output, central venous pressure, and hemogasometry are required.