Evaluation of the averaged parasympathetic tone activity and its dynamic variation to assess intraoperative nociception in relation to hemodynamic changes in dogs.

This study aimed to determine the performance of the averaged parasympathetic tone activity (PTAm) and its dynamic variation (ΔPTA) to assess intraoperative nociception in relation to heart rate (HR) and direct mean arterial pressure (MAP) in dogs undergoing laparoscopic ovariectomy. This prospective, observational, clinical study included 32 bitches. The PTAm, HR, MAP, and bispectral index (BIS) were assessed before (pre-stimulus), as well as 1 min and 2 min after, four surgical stimuli: insufflation, introduction of trocars, and removal of the left and right ovaries. A two-way ANOVA was performed to compare PTAm, HR, MAP, and BIS data across surgical stimuli. A ≥ 20% drop in PTAm or a ≥ 20% increase in HR and/or MAP regarding the pre-stimulus values was considered a PTAm-drop and/or a hemodynamic response, respectively. The performance of PTAm pre-stimulus, PTAm 1 min, and ΔPTA in predicting the hemodynamic response was assessed by calculation of the area under the receiver operating characteristic (ROC) curve. At insufflation, PTAm decreased after 1 (p = 0.010) and 2 (p = 0.045)min, and ΔPTA was different (p = 0.005) between dogs that presented hemodynamic response and dogs that did not. At PTAm-drop, MAP increased after 1 min (p = 0.001) and 2 min (p = 0.001) with respect to pre-stimulus value, whereas HR and BIS did not change. ROC curves showed a threshold value of PTAm pre-stimulus ≤51 to detect hemodynamic response (sensitivity 69%, specificity 52%). The PTAm and ΔPTA only assessed intraoperative nociception during insufflation. The PTAm pre-stimulus association to the hemodynamic response in anaesthetized dogs showed poor sensitivity and no specificity.

Parasympathetic Tone Changes in Anesthetized Horses after Surgical Stimulation, and Morphine, Ketamine, and Dobutamine Administration.

Autonomic nervous system (ANS) activity can modify cardiovascular parameters in response to nociceptive stimuli or drugs in anesthetized animals. The aim of this study was to determine if a surgical nociceptive stimulus and morphine, ketamine, and dobutamine administration would modify ANS activity observed as a change in the mean parasympathetic tone activity (PTAm) in anesthetized horses. In 20 anesthetized horses, heart rate (HR), mean arterial pressure (MAP), and PTAm were monitored before and 1, 3, and 5 min after surgical incision, and before and 10 min after the administration of morphine (0.2 mg/kg IV). If nystagmus or spontaneous ventilation was observed, ketamine (0.5 mg/kg IV) was given, and the three variables were registered before and 3 and 5 min afterward. If MAP reached ≤62 mmHg, a dobutamine infusion was administered, and the three variables were recorded before and 5 min after starting/increasing the infusion (0.25 µg/kg/min IV every 5 min). The three variables were registered before and 1, 3, and 5 min after a PTAm decrease of ≥20%, HR increase of ≥10%, or MAP increase of ≥20%. The PTAm decreased 3 min after the administration of ketamine and 1 min after a PTA event. The surgical incision, dobutamine, and morphine did not modify PTAm. The absence of changes in ANS activity after the nociceptive stimulus and lack of correlation between PTAm and HR or MAP suggest that PTAm is a poor indicator of sympathetic activation under the study conditions. Ketamine seems to affect ANS activity by decreasing PTAm.

Influence of general anaesthesia on the intravenous acetaminophen pharmacokinetics in Beagle dogs.

OBJECTIVE: To determine if general anaesthesia influences the intravenous (IV) pharmacokinetics (PK) of acetaminophen in dogs. STUDY DESIGN: Prospective, crossover, randomized experimental study. ANIMALS: A group of nine healthy Beagle dogs. METHODS: Acetaminophen PK were determined in conscious and anaesthetized dogs on two separate occasions. Blood samples were collected before, and at 5, 10, 15, 30, 45, 60 and 90 minutes and 2, 3, 4, 6, 8, 12 and 24 hours after 20 mg kg-1 IV acetaminophen administration. Haematocrit, total proteins, albumin, alanine aminotransferase, aspartate aminotransferase, urea and creatinine were determined at baseline and 24 hours after acetaminophen. The anaesthetized group underwent general anaesthesia (90 minutes) for dental cleaning. After the administration of dexmedetomidine (3 µg kg-1) intramuscularly, anaesthesia was induced with propofol (2-3 mg kg-1) IV, followed by acetaminophen administration. Anaesthesia was maintained with isoflurane in 50% oxygen (Fe'Iso 1.3-1.5%). Dogs were mechanically ventilated. Plasma concentrations were analysed with high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling. A Wilcoxon test was used to compare PK data between groups, and clinical laboratory values between groups, and before versus 24 hours after acetaminophen administration. Data are presented as median and range (p < 0.05). RESULTS: A two-compartmental model best described time-concentration profiles of acetaminophen. No significant differences were found for volume of distribution values 1.41 (0.94-3.65) and 1.72 (0.89-2.60) L kg-1, clearance values 1.52 (0.71-2.30) and 1.60 (0.91-1.78) L kg-1 hour-1 or terminal elimination half-life values 2.45 (1.45-8.71) and 3.57 (1.96-6.35) hours between conscious and anaesthetized dogs, respectively. Clinical laboratory variables were within normal range. No adverse effects were recorded. CONCLUSIONS AND CLINICAL RELEVANCE: IV acetaminophen PK in healthy Beagle dogs were unaffected by general anaesthesia under the study conditions. Further studies are necessary to evaluate the PK in different clinical contexts.

Determination of acute tolerance and hyperalgesia to remifentanil constant rate infusion in dogs undergoing sevoflurane anaesthesia.

OBJECTIVE: To determine if acute opioid tolerance (AOT) or opioid-induced hyperalgesia (OIH) could develop and limit the remifentanil-induced reduction in the sevoflurane minimum alveolar concentration (MAC). The response to mechanical nociceptive threshold (MNT) was evaluated and related to OIH. STUDY DESIGN: A crossover, randomized, experimental animal study. ANIMALS: A total of nine Beagle dogs. METHODS: The dogs were anaesthetized with sevoflurane in 50% oxygen. Baseline sevoflurane MAC was measured (MACb1). Remifentanil (0.3 µg kg-1 minute-1) or 0.9% saline constant rate infusion (CRI) was administered intravenously (IV). Sevoflurane MAC was determined 20 minutes after CRI was initiated (MACpostdrug1), 30 minutes after MACpostdrug1 determination (MACpostdrug2) and after 1 week (MACb2). The MNT was determined at baseline (before anaesthesia), 3 and 7 days after anaesthesia. An increase of MACpostdrug2 ≥0.25% compared to MACpostdrug1 was considered evidence of AOT. A decrease in MNT at 3 and 7 days or an increase in MACb2 or both with respect to MACb1 were considered evidence of OIH. RESULTS: Remifentanil CRI reduced sevoflurane MACpostdrug1 by 43.7% with respect to MACb1. MACpostdrug2 was no different from MACpostdrug1 with the saline (p = 0.62) or remifentanil (p = 0.78) treatments. No significant differences were observed in the saline (p = 0.99) or remifentanil (p = 0.99) treatments between MACb1 and MACb2, or for MNT values between baseline, 3 and 7 days. CONCLUSION AND CLINICAL RELEVANCE: In dogs, under the study conditions, remifentanil efficacy in reducing sevoflurane MAC did not diminish in the short term, suggesting remifentanil did not induce AOT. Hyperalgesia was not detected 3 or 7 days after the administration of remifentanil. Contrary to data from humans and rodents, development of AOT or OIH in dogs is not supported by the findings of this study.

Cardiorespiratory and anaesthetic effects of two continuous rate infusions of dexmedetomidine in alfaxalone anaesthetized dogs.

Six Beagles were used in this prospective randomised crossover experimental study. Dexmedetomidine was administered at 0, 1 or 2 µg/kg IV for group C, LDA and HDA, respectively. Animals were induced and maintained with alfaxalone at 0.07 mg/kg/min with a CRI dexmedetomidine dose of 0, 0.5 or 1 µg/kg/h for group C, LDA and HDA, respectively. Cardiorespiratory variables, arterial blood gases and depth of anaesthesia were recorded. The recovery times and quality of recovery were scored. Group HDA produced a greater increase in the depth of anaesthesia than LDA. However, with both protocols, CI was halved compared to normal values in dogs. The use of oxygen before and during the anaesthetic maintenance is advisable, mainly if dexmedetomidine is going to be use as a pre-medicant and maintenance agent. The quality of recovery was better in groups receiving dexmedetomidine, without causing an increase in recovery time.

Comparative study of select biochemical markers in cerebrospinal fluid of healthy dogs before and after treatment with nutraceuticals.

BACKGROUND: Several studies indicate that changes in cerebrospinal fluid (CSF) composition depend on the disease stage and reflect modification of brain energy metabolism (BEM). Also, it has been reported that a decline in cognitive functions may be mitigated by incorporating nutraceuticals in the diet. OBJECTIVE: Assuming the beneficial effect of nutraceuticals on BEM and oxidative damage, the aim of this study was to determine if the administration of a nutraceutical compound results in changes of select CSF biomarkers in healthy adult Beagle dogs. METHODS: Two separate CSF and blood samples were obtained from 11 healthy adult Beagle dogs, before and after 50 days of treatment with a veterinary combined nutraceutical. CSF analysis included a total nucleated cell count, total protein, glucose, sodium, chloride, potassium, pyruvate, and lactate concentrations, and calculation of lactate/pyruvate ratio. CBC and serum biochemistry were also performed. The Wilcoxon test was used to analyze the significance of the changes after nutraceutical treatment. RESULTS: All studied variables remained within reference intervals, before and after treatment. A significant increase in CSF sodium and glucose concentration, and a decrease in lactate levels, was observed after treatment (P < .05), and the lactate/pyruvate ratio was decreased after treatment (P = .05). In serum, sodium and chloride concentrations were significantly increased (P < .05), and creatinine concentration was significantly decreased (P < .05) after treatment. CONCLUSIONS: After 50 days of treatment with a nutraceutical compound, CSF glucose, sodium, and lactate concentrations, and L/P ratio were significantly different, suggesting an influence of nutraceuticals' administration on CSF composition.

Postoperative analgesic effects of dexketoprofen, buprenorphine and tramadol in dogs undergoing ovariohysterectomy.

The objective of this study was to compare the postoperative analgesic effects of dexketoprofen, tramadol, and buprenorphine in dogs undergoing ovariohysterectomy. Seventy-five adult female dogs were randomly assigned to receive an intravenous injection (IV) of 1mg/kg of dexketoprofen (D), 0.02 mg/kg of buprenorphine (B) or 2mg/kg of tramadol (T). Pain assessment was performed during 48 h after ovariohysterectomy using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale (CMPS-SF). Rescue analgesia was required in 43%, 21%, and 5% of dogs in the B, T, and D groups, respectively, with significant differences between B and D (p=0.010) groups. The DIVAS and CMPS-SF values of the B group were significantly higher than those of the T and D groups. The most common undesirable effect was dysphoria in dexketoprofen group. Tramadol and dexketoprofen provide superior postoperative analgesia compared with buprenorphine in dogs undergoing ovariohysterectomy.

Anaesthetic and cardiorespiratory effects of a constant-rate infusion of alfaxalone in desflurane-anaesthetised sheep.

A prospective, randomised, blinded controlled study was performed to determine the anaesthetic and cardiorespiratory effects of a constant-rate infusion (CRI) of alfaxalone in 12 sheep anaesthetised with desflurane, and undergoing experimental orthopaedic surgery. Sheep were sedated with dexmedetomidine (4 µg/kg, intravenously) and butorphanol (0.3 mg/kg, intravenously). Anaesthesia was induced with alfaxalone (1 mg/kg/minute to effect, intravenously) and maintained with desflurane in oxygen and alfaxalone 0.07 mg/kg/minute or saline for 150 minutes (range 150-166 minutes). The anaesthetic induction dose of alfaxalone, the desflurane expiratory fraction required for anaesthetic maintenance, cardiorespiratory measurements and blood-gases were recorded at predetermined intervals. Quality of sedation, anaesthetic induction and recovery were assessed. The alfaxalone induction dose was 1.7 mg/kg (1.2 to 2.6 mg/kg). The desflurane expiratory fraction was lower (22 per cent) in sheep receiving alfaxalone CRI (P=0). Also, heart rate (P=0), cardiac index (P=0.002), stroke index (P=0) and contractility (P=0) were higher, and systemic vascular resistance (P=0.002) was lower. Although respiratory rate tended to be higher with alfaxalone, there was no difference in PCO2 between the groups. Recovery times were significantly longer in sheep given alfaxalone (25.4 v 9.5 minutes) but recovery quality was similar. Alfaxalone reduced requirements of desflurane and maintained similar cardiorespiratory function, but recovery time was more prolonged.

[Development of a septic shock experimental model oriented at training. Application in the training of depuration techniques in the management of severe sepsis]. / Desarrollo de un modelo experimental de shock séptico orientado a la formación. Aplicación en el entrenamiento de técnicas de depuración en el manejo de la sepsis grave.

OBJECTIVE: To define a septic shock experimental model that can be used in for training in the early management of septic shock, specifically by extracorporeal depuration (ECD). DESIGN: A case-control experimental study. SETTING: Veterinary university hospital. SUBJECTS: Ten Beagle dogs (weight 12-15kg). INTERVENTIONS: Shock was induced using 1mg/kg Escherichia coli lipopolysaccharide (LPS) diluted in 20 mL saline infused in 10 minutes, with a subsequent follow-up at 6 hours. There was no intervention in 5 animals in order to define the natural course of the shock and 5 underwent high volume hemofiltration (HVHF, 100mL/kg/h) to define delay in response to treatment. VARIABLES: Pressures (arterial and pulmonary), hemodynamic parameters, gastric tonometry and respiratory function were recorded. RESULTS: The LPS effect was evidenced at 2 minutes of the infusion and the 10 animals showed severe shock at the end of the infusion. At 2-hours, changes between treated and non-treated animals were seen in cardiac output, systolic volume variability and mucous CO(2). Mean arterial pressure was significantly different at four hours. All non-treated subjects died during the 6-hour follow-up and all the treated animals survived for this period. Based on these results, we developed a workshop that has been used in five courses (www.ccmijesususon.com - www.crrtcordoba.com.es/), obtaining the previous results. CONCLUSIONS: Our shock model shows a predictable behavior, very short latency and a sufficiently rapid improvement in the treated animals for it to be applied in training workshops. It is useful for training in the high-volume hemofiltration (HVHF) and can be used for training in the early management of septic shock.

Relationship of bispectral index to hemodynamic variables and alveolar concentration multiples of sevoflurane in puppies.

The relationships between bispectral index (BIS), cardiovascular variables and minimum alveolar concentration (MAC) multiples of sevoflurane in puppies were determined. Five puppies were anesthetized with sevoflurane on two occasions. First, the individual sevoflurane MAC values were determined for each puppy. Secondly, dogs were anesthetized with sevoflurane at each of 5 MAC multiples, 0.75, 1, 1.25, 1.5 and 1.75 MAC administered in random order. Hemodynamic parameters and BIS data were collected for 20min. Somatic stimulus was then applied and the same parameters and data were collected for 6min. Correlation between BIS and end tidal sevoflurane and between BIS and hemodynamic parameters were studied. We found positive significant correlation in both cases. BIS is lower in puppies that in adults at the same alveolar anesthetic concentrations and sevoflurane appears to be a safe anesthetic in puppies.

Effect of medetomidine infusion on the anaesthetic requirements of desflurane in dogs.

The objective of this paper was to evaluate the effect of constant rate infusion of medetomidine on the anaesthetic requirements of desflurane in dogs. For this, six healthy dogs were studied. Measurements for baseline were taken in the awake, unsedated dogs, then each dog received intravenously (i.v.) three anaesthetic protocols: M (no medetomidine infusion), M0.5 (infusion of medetomidine at 0.5 microg/kg/h, i.v.) or M1 (infusion of medetomidine at 1 microg/kg/h, i.v.). All dogs were sedated with medetomidine (2 microg/kg, i.v.) and measurements repeated in 10 min. Induction of anaesthesia was delivered with propofol (3 mg/kg, i.v.) and maintained with desflurane for 90 min to achieve a defined surgical plane of anaesthesia in all cases. After tracheal intubation infusion of medetomidine was initiated and maintained until the end of anaesthesia. Cardiovascular, respiratory, arterial pH (pHa) and arterial blood gas tensions (PaO(2), PaCO(2)) variables were measured during the procedure. End tidal desflurane concentration (EtDES) was recorded throughout anaesthesia. Time to extubation, time to sternal recumbency and time to standing were also noted. Heart rate and respiratory rate were significantly decreased during sedation in all protocols compared to baseline values. Mean heart rate, mean arterial pressure, systolic arterial pressure, diastolic arterial pressure, respiratory rate, tidal volume, arterial oxygen saturation, end-tidal CO(2), pHa, PaO(2), and PaCO(2) during anaesthesia were similar for all protocols. EtDES for M (8.6 +/- 0.8%) was statistically higher than for M0.5 (7.6 +/- 0.5%) and M1 (7.3 +/- 0.7%) protocols. Infusion of medetomidine reduces desflurane concentration required to maintain anaesthesia in dogs.

Comparison of romifidine and medetomidine pre-medication in propofol-isoflurane anaesthetised dogs.

The objective of this paper was to evaluate romifidine as a pre-medicant in dogs prior to propofol-isoflurane anaesthesia, and to compare it with medetomidine. For this, eight healthy dogs were anaesthetised. Each dog received three pre-anaesthetic protocols: R40 (romifidine, 40 microg/kg, IV), R80 (romifidine, 80 microg/kg, IV) or MED (medetomidine, 10 microg/kg, IV). Induction of anaesthesia was delivered with propofol and maintained with isoflurane. The following variables were studied before sedative administration and 10 min after sedative administration: heart rate (HR), mean arterial pressure (MAP), systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) and respiratory rate (RR). During maintenance, the following variables were recorded at 5-min intervals: HR, MAP, SAD, DAP, arterial oxygen saturation (SpO(2)), end-tidal CO(2)(EtCO(2)), end-tidal concentration of isoflurane (EtISO) required for maintenance of anaesthesia and tidal volume (TV). Time to extubation, time to sternal recumbency and time to standing were also registered. HR and RR experimented a significantly decreased during sedation in all protocols respect to baseline values. Mean HR, MAP, SAP, DAP, SpO(2), EtCO(2), and TV during anaesthesia were similar for the three protocols. End tidal of isoflurane concentration was statistically similar for all protocols. Recovery time for R40 was significantly shorter than in R80 and MED. The studied combination of romifidine, propofol and isoflurane appears to be an effective drug combination for inducing and maintaining general anaesthesia in healthy dogs.

Dexmedetomidine or medetomidine premedication before propofol-desflurane anaesthesia in dogs.

The objective of this study was to evaluate dexmedetomidine as a premedicant in dogs prior to propofol-desflurane anaesthesia, and to compare it with medetomidine. Six healthy dogs were anaesthetized. Each dog received intravenously (i.v.) five preanaesthetic protocols: D1 (dexmedetomidine, 1 microg/kg, i.v.), D2 (dexmedetomidine, 2 microg/kg, i.v.), M1 (medetomidine, 1 microg/kg, i.v.), M2 (medetomidine, 2 microg/kg, i.v.), or M4 (medetomidine, 4 microg/kg, i.v.). Anaesthesia was induced with propofol (2.3-3.3 mg/kg) and maintained with desflurane. The following variables were studied: heart rate (HR), mean arterial pressure, systolic arterial pressure, diastolic arterial pressure, respiratory rate (RR), arterial oxygen saturation, end-tidal CO2, end-tidal concentration of desflurane (EtDES) required for maintenance of anaesthesia and tidal volume. Arterial blood pH (pHa) and arterial blood gas tensions (PaO2, PaCO2) were measured during anaesthesia. Time to extubation, time to sternal recumbency and time to standing were also recorded. HR and RR decreased significantly during sedation in all protocols. Cardiorespiratory variables during anaesthesia were statistically similar for all protocols. EtDES was significantly different between D1 (8.1%) and D2 (7.5%), and between all doses of medetomidine. Desflurane requirements were similar for D1 and M2, and for D2 and M4 protocols. No statistical differences were observed in recovery times. The combination of dexmedetomidine, propofol and desflurane appears to be effective for induction and maintenance of general anaesthesia in healthy dogs.