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Objective: This study investigated the performance among four cardiac output (CO) monitoring techniques in comparison with the reference method intermittent pulmonary artery thermodilution (iPATD) and their ability to diagnose fluid responsiveness (FR) during a modified passive leg raise (PLR M ) maneuver in isoflurane-anesthetized dogs undergoing acute blood volume manipulations. The study also examined the simultaneous effect of performing the PLR M on dynamic variables such as stroke distance variation (SDV), peak velocity variation (PVV), and stroke volume variation (SVV)., Study Design: Prospective, nonrandomized, crossover design., Study Animals: Six healthy male Beagle dogs., Methods: The dogs were anesthetized with propofol and isoflurane and mechanically ventilated under neuromuscular blockade. After instrumentation, they underwent a series of sequential, nonrandomized steps: Step 1: baseline data collection; Step 2: removal of 33 mL kg -1 of circulating blood volume; Step 3: blood re-transfusion; and Step 4: infusion of 20 mL kg -1 colloid solution. Following a 10-min stabilization period after each step, CO measurements were recorded using esophageal Doppler (ED CO ), transesophageal echocardiography (TEE CO ), arterial pressure waveform analysis (APWA CO ), and electrical cardiometry (EC CO ). Additionally, SDV, PVV, and SVV were recorded. Intermittent pulmonary artery thermodilution (iPATD CO ) measurements were also recorded before, during, and after the PLR M maneuver. A successful FR diagnosis made using a specific test indicated that CO increased by more than 15% during the PLR M maneuver. Statistical analysis was performed using one-way analysis of variance for repeated measures with post hoc Tukey test, linear regression, Lin's concordance correlation coefficient (ρc), and Bland-Altman analysis. Statistical significance was set at p  < 0.05., Results: All techniques detected a reduction in CO ( p  < 0.001) during hemorrhage and an increase in CO after blood re-transfusion and colloid infusion ( p  < 0.001) compared with baseline. During hemorrhage, CO increases with the PLR M maneuver were as follows: 33% for iPATD ( p  < 0.001), 19% for EC ( p  = 0.03), 7% for APWA ( p  = 0.97), 39% for TEE ( p  < 0.001), and 17% for ED ( p  = 0.02). Concurrently, decreases in SVV, SDV, and PVV values ( p  < 0.001) were also observed. The percentage error for TEE, ED, and EC was less than 30% but exceeded 55% for APWA. While TEE CO and EC CO slightly underestimated iPATD CO values, ED CO and APWA CO significantly overestimated iPATD CO values. TEE and EC exhibited good and acceptable agreement with iPATD. However, CO measurements using all four techniques and iPATD did not differ before, during, and after PLR M at baseline, blood re-transfusion, and colloid infusion., Conclusion and Clinical Relevance: iPATD, EC, TEE, and ED effectively assessed FR in hypovolemic dogs during the PLR M maneuver, while the performance of APWA was unacceptable and not recommended. SVV, SDV, and PVV could be used to monitor CO changes during PLR M and acute blood volume manipulations, suggesting their potential clinical utility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Paranjape, Henao-Guerrero, Menciotti and Saksena.)

Isoflurane is a commonly used inhalation anesthetic in species undergoing veterinary care that induces hypotension, impacting organ perfusion, making it imperative to minimize its occurrence or identify effective strategies for treating it. This study evaluated and compared the hemodynamic effects of DOB, NEP, VAS, and HES in twelve isoflurane-anesthetized Beagle dogs. The order of the first three treatments was randomized. HES was administered last. Data were collected before treatments (baseline) and after 10 min of a sustained MAP of <45 mmHg induced by a high end-tidal isoflurane concentration (T0). Once treatment was initiated and the target MAP was achieved (65 to 80 mmHg) or the maximum dose reached, data were collected after 15 min of stabilization (T1) and 15 min after (T2). A 15 min washout period with a MAP of ≥65 mmHg was allowed between treatments. The intravenous dosage regimens started and were increased by 50% every five minutes until the target MAP or maximum dose was reached. The dosages were as follows: DOB, 5-15 μg/kg/min; NEP, 0.1-2 μg/kg/min; VAS, 0.5-5 mU/kg/min; and HET, 6% 1-20 mL/kg/min. DOB improved CO, DO 2 , and VO 2 , but reduced SVR. VAS elevated SVR, but decreased CO, DO 2 , and VO 2 . HES minimally changed BP and mildly augmented CO, DO 2 , and VO 2 . These treatments failed to reach the target MAP. NEP increased the arterial BP, CO, MPAP, and PAWP, but reduced HR. Norepinephrine infusion at 0.44 ± 0.19 μg/kg/min was the most efficient therapy for correcting isoflurane-induced hypotension.

Numerous cardiac output (CO) technologies were developed to replace the 'gold standard' pulmonary artery thermodilution due to its invasiveness and the risks associated with it. Minimally invasive lithium dilution (LiD) shows excellent agreement with thermodilution and can be used as a reference standard in animals. This study evaluated CO via noninvasive electrical cardiometry (EC) and acquired hemodynamic variables against CO measured using LiD in six healthy, anesthetized dogs administered different treatments (dobutamine, esmolol, phenylephrine, and high-dose isoflurane) impacting CO values. These treatments were chosen to cause drastic variations in CO, so that fair comparisons between EC and LiD across a wide range of CO values (low, intermediate, and high) could be made. Statistical analysis included linear regression, Bland-Altman plots, Lin's concordance correlation coefficient (ρ c ), and polar plots. Values of p < 0.05 represented significance. Good agreement was observed between EC and LiD, but consistent underestimation was noted when the CO values were high. The good trending ability, ρ c of 0.88, and low percentage error of ±31% signified EC's favorable performance. Other EC-acquired variables successfully tracked changes in CO measured using LiD. EC may be a pivotal hemodynamic tool for continuously monitoring circulatory changes, as well as guiding and treating cardiovascular anesthetic complications in clinical settings.

Objective: To demonstrate if modified passive leg raise (PLR M ) maneuver can be used for volumetric evaluation of fluid responsiveness (FR) by inducing cardiac output (CO) changes during experimental induction and correction of hypovolemia in healthy anesthetized dogs. The effects of PLR M on plethysmographic variability index (PVI) and pulse pressure variation (PPV) were also investigated., Study Design: Prospective, crossover study., Animals: A total of six healthy anesthetized Beagle dogs., Methods: Dogs were anesthetized with propofol and isoflurane. They were mechanically ventilated under neuromuscular blockade, and normothermia was maintained. After instrumentation, all dogs were subjected to four stages: 1, baseline; 2, removal of 27 mL kg -1 circulating blood volume; 3, after blood re-transfusion; and 4, after 20 mL kg -1 hetastarch infusion over 20 minutes. A 10 minute stabilization period was allowed after induction of each stage and before data collection. At each stage, CO via pulmonary artery thermodilution, PVI, PPV and cardiopulmonary variables were measured before, during and after the PLR M maneuver. Stages were sequential, not randomized. Statistical analysis included repeated measures anova and Tukey's post hoc test, considering p < 0.05 as significant., Results: During stage 2, PLR M at a 30° angle significantly increased CO (mean ± standard deviation, 1.0 ± 0.1 to 1.3 ± 0.1 L minute -1 ; p < 0.001), with a simultaneous significant reduction in PVI (38 ± 4% to 21 ± 4%; p < 0.001) and PPV (27 ± 2% to 18 ± 2%; p < 0.001). The PLR M did not affect CO, PPV and PVI during stages 1, 3 and 4., Conclusions and Clinical Relevance: In anesthetized dogs, PLR M at a 30° angle successfully detected FR during hypovolemia, and identified fluid nonresponsiveness during normovolemia and hypervolemia. Also, in hypovolemic dogs, significant decreases in PVI and PPV occurred in response to PLR M maneuver., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In animals, invasive pulmonary artery thermodilution (PATD) is a gold standard for cardiac output (CO) monitoring, but it is impractical in clinical settings. This study evaluates the agreement between PATD and noninvasive electrical cardiometry (EC) for measuring CO and analyzes the other EC-derived hemodynamic variables in six healthy anesthetized dogs subjected to four different hemodynamic events in a sequential order: (1) euvolemia (baseline); (2) hemorrhage (33% blood volume loss); (3) autologous blood transfusion; and (4) 20 mL/kg colloid bolus. The CO measurements obtained using PATD and EC are compared using Bland-Altman analysis, Lin's concordance correlation (LCC), and polar plot analysis. Values of p < 0.05 are considered significant. The EC measurements consistently underpredict the CO values as compared with PATD, and the LCC is 0.65. The EC's performance is better during hemorrhage, thus indicating its capability in detecting absolute hypovolemia in clinical settings. Even though the percentage error exhibited by EC is 49.4%, which is higher than the standard (<30%), EC displays a good trending ability. Additionally, the EC-derived variables display a significant correlation with the CO measured using PATD. Noninvasive EC may have a potential in monitoring trends in hemodynamics in clinical settings.

Objective: To investigate the relationship between invasively measured stroke volume (SV) and (1) esophageal Doppler-derived indices such as stroke distance (StrokeD), flow time corrected (FTc), stroke distance variation (SDV), and peak velocity variation (PVV); and (2) arterial load (AL) variables during evaluation of fluid responsiveness (FR) in anesthetized dogs undergoing sudden hemodynamic shifts in blood volume., Animals: 6 healthy male dogs., Procedures: Dogs were anesthetized with isoflurane, ventilated mechanically, and instrumented to undergo sequential, nonrandomized experimental stages. The dogs transitioned from normovolemia (NORMO-BL) to hypovolemia (30% blood loss; HYPO-30), followed by autologous blood transfusion, and then to hypervolemia (colloid bolus). During each stage, SV was quantified using pulmonary artery thermodilution and its relationship with StrokeD, FTc, SDV, and PVV; and AL variables such as effective arterial elastance (Ea), dynamic arterial elastance (Eadyn), and total arterial compliance (Ca) were established., Results: As SV decreased significantly during HYPO-30 compared to NORMO-BL, there was a significant (P < .001) decrease in StrokeD, FTc, and Ca, with simultaneous increases in SDV, PVV, Ea, and Eadyn. Upon restoration of blood volume, these values stabilized closer to NORMO-BL. A significant (P < .001) correlation was observed between SV and StrokeD, FTc, Ea, Eadyn, and Ca., Clinical Relevance: Minimally invasive StrokeD, FTc, SDV, and PVV act as SV surrogates and help assess FR during different blood volume stages in healthy dogs. During hypovolemia-induced hypotension, Ea, Eadyn, and Ca may be able to guide therapeutic decisions favoring improvement in blood pressure and SV.

Objective: To determine the effect of fentanyl on the minimum alveolar concentration of isoflurane (MAC ISO ) and cardiovascular variables in dogs, and how the treatment of bradycardia affects them., Study Design: Prospective, randomized crossover-controlled trial., Animals: A total of six male Beagle dogs weighing 9.9 ± 0.7 kg (mean ± standard deviation) and aged 13 months., Methods: To each dog, two treatments were assigned on different days: fentanyl (FENTA) or fentanyl plus glycopyrrolate (FENTA glyco ) to maintain heart rate (HR) between 100 and 132 beats minute -1 . Determinations of MAC ISO were performed with 10 plasma fentanyl target concentrations ([Fenta] Target (0, 0.16, 0.32, 0.64, 1.25, 2.5, 5.0, 10.0, 20.0 and 40.0 ng mL -1 ) for FENTA and 5 [Fenta] Target (0, 1.25, 2.5, 5.0, 10.0 ng mL -1 )) for FENTA glyco . During each MAC ISO determination, cardiovascular variables [mean arterial pressure (MAP), HR and cardiac index (CI)] were measured, and systemic vascular resistance index (SVRI) calculated. Pharmacodynamic models were used to describe the plasma fentanyl concentration [Fenta]-response relationship for the effect on MAC ISO and cardiovascular variables. A mixed-model analysis of variance followed by Dunnett's or Tukey's test, and the Bonferroni adjustment were used for comparisons within and between each treatment, respectively. Significance was set as p < 0.05., Results: Fentanyl decreased MAC ISO by a maximum of 84%. The [Fenta] producing 50% decrease in MAC, HR and CI were 2.64, 3.65 and 4.30 ng mL -1 (typical values of population model), respectively. The prevention of fentanyl-mediated bradycardia caused no significant effect on MAC ISO , but increased HR, MAP and CI, and decreased SVRI when compared with isoflurane alone., Conclusions and Clinical Relevance: Fentanyl caused a plasma concentration-dependent decrease in MAC ISO , HR and CI and an increase in SVRI. Cardiovascular improvements associated with fentanyl in isoflurane-anesthetized dogs only occurred when the fentanyl-mediated bradycardia was prevented., (Copyright © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe the pharmacokinetics of buprenorphine in dogs following administration of a high-concentration formulation of buprenorphine., Study Design: Prospective, randomized, crossover study., Animals: A total of six healthy male intact Beagle dogs, aged 9-13 months and weighing 10.3 ± 1.4 kg (mean ± standard deviation)., Methods: Dogs were randomized to be administered buprenorphine (0.12 mg kg -1 ; Simbadol, 1.8 mg mL -1 ) via the intravenous (lateral saphenous) or subcutaneous (dorsal interscapular) route followed by the alternative route of administration after a 14 day interval. Blood was sampled before administration and at set times up to 72 hours after injection. Plasma buprenorphine concentration was measured using liquid chromatography-tandem mass spectrometry., Results: A three-compartment model with zero or biphasic rapid and slow first-order input in (intravenous or subcutaneous data, respectively) and first-order elimination from the central compartment best fitted the data. The rapid first-order input accounted for 63% of the dosage absorption. Typical values (% interindividual variability) for the three compartment volumes were 900 (33), 2425 (not estimated) and 6360 (28) mL kg -1 . The metabolic and two distribution clearances were 25.7 (21), 107.5 (74) and 5.7 (61) mL minute -1 kg -1 . The absorption half-life for the fast absorption phase was 8.9 minutes with a 0.7 (103) minute delay. The absorption half-life for the slow absorption phase was 347 minutes with a 226 (42) minute delay. Median (range) bioavailability calculated from noncompartmental analysis was 143 (80-239)%. Calculated terminal half-life was 963 minutes., Conclusions and Clinical Relevance: The high-concentration formulation of buprenorphine administered subcutaneously had a large volume of distribution and a rapid absorption phase followed by slower, delayed absorption. The high estimate of bioavailability should be interpreted with caution as values above 100% are most commonly related to experimental issues., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To compare pulmonary gas exchange, tissue oxygenation and cardiovascular effects of four levels of end-expiratory pressure: no positive end-expiratory pressure (ZEEP), positive end-expiratory pressure (PEEP) of maximal respiratory system compliance (PEEPmaxC rs ), PEEPmaxC rs  + 2 cmH 2 O (PEEPmaxC rs+2 ), PEEPmaxC rs  + 4 cmH 2 O (PEEPmaxC rs+4 ), in isoflurane-anesthetized dogs., Study Design: Prospective randomized crossover study., Animals: A total of seven healthy male Beagle dogs, aged 1 year and weighing 10.2 ± 0.7 kg (mean ± standard deviation)., Methods: The dogs were administered acepromazine and anesthesia was induced with propofol and maintained with isoflurane. Ventilation was controlled for 4 hours with ZEEP, PEEPmaxC rs , PEEPmaxC rs+2 or PEEPmaxC rs+4 . Cardiovascular, pulmonary gas exchange and tissue oxygenation data were evaluated at 5, 60, 120, 180 and 240 minutes of ventilation and compared using a mixed-model anova followed by Bonferroni test. p < 0.05 was considered significant., Results: Cardiac index (CI) and mean arterial pressure (MAP) were lower in all PEEP treatments at 5 minutes when compared with ZEEP. CI persisted lower throughout the 4 hours only in PEEPmaxC rs+4 with the lowest CI at 5 minutes (2.15 ± 0.70 versus 3.45 ± 0.94 L minute -1 m -2 ). At 180 and 240 minutes, MAP was lower in PEEPmaxC rs+4 than in PEEPmaxC rs , with the lowest value at 180 minutes (58 ± 7 versus 67 ± 7 mmHg). Oxygen delivery index (DO 2 I) was lower in PEEPmaxC rs+4 than in ZEEP at 5, 60, 120 and 180 minutes. Venous admixture was not different among treatments., Conclusion and Clinical Relevance: The use of PEEP caused a transient decrease in MAP and CI in lung-healthy dogs anesthetized with isoflurane, which improved after 60 minutes of ventilation in all levels of PEEP except PEEPmaxC rs+4 . A clinically significant improvement in arterial oxygenation and DO 2 I was not observed with PEEPmaxC rs and PEEPmaxC rs+2 in comparison with ZEEP, whereas PEEPmaxC rs+4 decreased DO 2 I., (Copyright © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Background: This is the first case report description, to our knowledge, of a cranial mediastinal mass (suspected thymoma) causing orthostatic hypotension in a dog., Case Presentation: A Labrador Retriever presented for urethral stent placement during cystoscopy secondary to transitional cell carcinoma diagnosis. During anesthesia, the patient had unexpected severe and poorly-responsive hypotension following a shift in position. Several days later, an intrathoracic mass was discovered, raising concerns that the position of the mass in relation to the great vessels and heart may have been the cause of the hypotension. The patient returned for a second stent placement, and computed tomography of the chest confirmed a cranial mediastinal mass, most suspected to be thymoma based on the results of cytology. The patient was kept in sternal recumbency, but when re-positioning to left lateral recumbency, there was a dramatic blood pressure drop that corrected with a return to sternal positioning., Conclusions: To our knowledge, orthostatic hypotension has not been described in relation to thymoma in dogs. Thymomas are rare; however, they may be associated with disease of autonomic dysfunction, such as myasthenia gravis, that may lead to orthostatic hypotension. This has been described within the human literature, and we hypothesize it was present in the currently described case. Concurrently, thymomas may grow to a substantial size and cause direct compression of the intrathoracic vasculature. As such, it should be on the differential list for poorly-responsive hypotension following a shift in body positioning under anesthesia.

Objective: To compare the pharmacokinetics of fentanyl at lower (LHR) or higher heart rate (HHR) in dogs anesthetized with isoflurane., Study Design: Prospective, randomized, crossover controlled trial., Animals: A group of six healthy 13-month-old male Beagle dogs weighing 9.9 ± 0.7 kg (mean ± standard deviation)., Methods: Dogs were allocated to two treatments: LHR (HR: 45-75 beats minute -1 ) and HHR (HR: 100-130 beats minute -1 ). Anesthesia was maintained with isoflurane and hydromorphone (0.1 mg kg -1 followed by 0.02-0.10 mg kg -1 hour -1 ) for both treatments. Glycopyrrolate was administered in HHR to maintain HR within the desired range. Afterwards, fentanyl (20 μg kg -1 ) was intravenously administered over 5 minutes. Arterial blood samples were collected for plasma fentanyl concentration measurement by liquid chromatography/mass spectrometry. The pharmacokinetics of fentanyl were compared between treatments and the differences were considered significant at p < 0.05., Results: A three-compartment model best fitted the changes in plasma fentanyl concentration. Clearance (CL; mL minute -1 kg -1 ) was 33.2 (24.0-48.0) and 61.3 (44.5-72.7), maximum concentration (ng mL -1 ) 33.6 (23.4-36.6) and 20.0 (16.7-28.0), apparent volume of the rapid peripheral compartment (mL kg -1 ) 436 (352-723) and 925 (499-1887), apparent volume at steady state (mL kg -1 ) 4064 (3453-6546) and 7195 (5077-8601), cardiac index (CI; mL minute -1 m -2 ) 2.83 (1.98-3.67) and 4.91 (3.22-6.09) and HR (beats minute -1 ) 68 (49-72) and 120 (102-129) for LHR and HHR, respectively, with significant differences between treatments. Significant correlations (0.92 and 0.90) were found between CI and CL, and between HR and CL, respectively., Conclusions and Clinical Relevance: The increase in HR and the resultant improvement in cardiac output increased fentanyl CL and volume of distribution, which resulted in a decrease in plasma fentanyl concentration in isoflurane-anesthetized dogs., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the effect of two doses of fentanyl upon chest wall rigidity of dogs anesthetized at equipotent doses of isoflurane [1.3 minimum alveolar concentration (MAC ISO ) of each dose of fentanyl]., Study Design: Prospective crossover randomized study., Animals: A group of eight male Beagle dogs, approximately 1 year old and weighing 12.1 ± 1.6 kg (mean ± standard deviation)., Methods: The dogs were anesthetized with isoflurane and instrumented for the measurement of esophageal pressure (P ESO ), flow (V˙) and volume (V). Chest wall elastance (E CW ) was estimated by multiple linear regression of the model. P ESO (t) = V˙(t) × R CW  + V(t) × E CW  + EEP ESO where t is time, R CW is chest wall resistance and EEP ESO is end-expiratory P ESO . Chest wall compliance (C CW ) was calculated as 1/E CW and normalized to the body weight of each dog (mL cmH 2 O -1 kg -1 ). Anesthesia was maintained at 1.3 MAC ISO for at least 15 minutes and C CW recorded (C CW-ISO ). The dogs were randomly assigned to the lower fentanyl dose [loading dose (33 μg kg -1 ) and infusion (0.2 μg kg -1 minute -1 )] or the higher fentanyl dose [loading dose (102 μg kg -1 ) and infusion (0.8 μg kg -1 minute -1 )]. After 60 minutes of fentanyl infusion, C CW was recorded for each dose (C CW-FENT ). During fentanyl infusion, the dogs were maintained at equipotent doses of isoflurane (1.3 MAC ISO for each fentanyl dose). A two-way analysis of variance followed by a Bonferroni test was used to compare C CW-ISO and C CW-FENT in both treatments and C CW-FENT between treatments. A p value <0.05 was considered significant., Results: Neither of the fentanyl doses decreased C CW and there was no difference in C CW-FENT between doses., Conclusions and Clinical Relevance: Fentanyl at the studied doses did not result in chest wall rigidity in dogs anesthetized with equipotent doses of isoflurane (1.3 MAC ISO )., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare the cardiopulmonary effects of low and high doses of fentanyl before and after the correction of bradycardia in isoflurane-anesthetized dogs., Study Design: Prospective, randomized crossover trial., Animals: Eight healthy male Beagle dogs weighing 11.1 ± 1.3 kg [mean ± standard deviation (SD)] and aged approximately 1 year., Methods: The dogs were anesthetized with isoflurane [1.3 × minimum alveolar concentration (MAC)] on two occasions and fentanyl was administered intravenously; either low-dose fentanyl, loading dose (33 μg kg -1 ) and infusion (0.2 μg kg -1 minute -1 ) or a high-dose, loading dose (102 μg kg -1 ) and infusion (0.8 μg kg -1 minute -1 ). Cardiopulmonary variables were measured at three time points in equipotent isoflurane concentrations (1.3 MAC): before fentanyl administration (ISO), during fentanyl-induced bradycardia (ISO-F) and after administration of glycopyrrolate normalized heart rate (ISO-F NHR ). Data are mean ± SD., Results: Heart rate and cardiac index (CI) decreased and systemic vascular resistance index (SVRI) increased at ISO-F in both treatments. Bradycardia and vasoconstriction at ISO-F were greater in high than in low-dose fentanyl (42 ± 7 versus 57 ± 15 beats minute -1 and 3457 ± 1108 versus 2528 ± 968 dyne second cm -5 m -2 ), respectively. Oxygen delivery index (DO 2 I) decreased only during high-dose fentanyl. CI and DO 2 I were higher in both treatments at ISO-F NHR than at ISO-F; however, they were higher only during the high-dose fentanyl than at ISO. SVRI was higher at ISO-F than at ISO and ISO-F NHR in both treatments, and was higher at ISO-F in the high than in the low-dose treatment., Conclusions and Clinical Relevance: An overall improvement in cardiovascular function of dogs anesthetized with equipotent isoflurane doses (1.3 MAC) was observed after the treatment of bradycardia only with the high-dose fentanyl., (Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To characterize the isoflurane-sparing effects of a high and a low dose of fentanyl in dogs, and its effects on mean arterial pressure (MAP) and heart rate (HR)., Study Design: Prospective, randomized crossover trial., Animals: Eight healthy male Beagle dogs weighing 12.1 ± 1.6 kg [mean ± standard deviation (SD)] and approximate age 1 year., Methods: Dogs were anesthetized using isoflurane and minimum alveolar concentration (MAC) was determined in duplicate by the bracketing method using an electrical stimulus on the tarsus. Animals were administered fentanyl: low dose (33 μg kg -1 loading dose, 0.2 μg kg -1  minute -1 ) or high dose (102 μg kg -1 loading dose, 0.8 μg kg -1  minute -1 ) and MAC was re-determined (MAC ISO-F ). Blood was collected for analysis of plasma fentanyl concentrations before administration and after MAC ISO-F determination. All values are presented as mean ± SD., Results: Isoflurane MAC (MAC ISO ) was 1.30 ± 0.23% in the low dose treatment, which significantly decreased to 0.75 ± 0.22% (average MAC reduction 42.3 ± 9.4%). MAC ISO was 1.30 ± 0.18% in the high dose treatment, which significantly decreased to 0.30 ± 0.11% (average MAC reduction 76.9 ± 7.4%). Mean fentanyl plasma concentrations were 6.2 and 29.5 ng mL -1 for low and high dose treatments, respectively. MAP increased significantly only in the high dose treatment (from 81 ± 8 to 92 ± 9 mmHg). HR decreased significantly in both treatments from 108 ± 25 to 61 ± 14 beats minute -1 with the low dose and from 95 ± 14 to 42 ± 4 beats minute -1 with the high dose., Conclusions and Clinical Relevance: Fentanyl administration resulted in a dose-dependent isoflurane MAC-sparing effect with bradycardia at both doses and an increase in MAP only at high dose. Further evaluation is needed to determine the effects of fentanyl on the overall cardiovascular function., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

OBJECTIVE To assess the effects of topically applied 2% dorzolamide hydrochloride-0.5% timolol maleate ophthalmic solution (DHTM) on incidence and severity of postoperative ocular hypertension (POH; ie, intraocular pressure [IOP] > 25 mm Hg) in dogs undergoing cataract extraction by phacoemulsification. DESIGN Randomized, masked, controlled study. ANIMALS 103 dogs (180 eyes). PROCEDURES Pertinent history, signalment, and ophthalmic examination findings were recorded. Dogs received 1 drop of DHTM or sham treatment solution (sterile, buffered, isotonic eye drops) in both eyes 14 hours and 2 hours before anesthetic induction and at the time of corneal incision closure (ie, end of surgery); IOPs were assessed by rebound tonometry 2, 4, 6, and 8 hours after surgery and between 7:30 and 8:00 am on the following day. Dogs with IOPs of 26 to 45 mm Hg received 1 drop of 0.005% latanoprost solution topically; the surgeon's treatment of choice was used for dogs with IOPs > 45 mm Hg. Incidence of POH and postoperative IOPs were compared between treatment groups. RESULTS DHTM treatment resulted in significantly lower incidence of POH than did sham treatment at the level of the dog (18/53 [34%] vs 31/50 [62%]) and the eye (24/94 [26%] vs 42/86 [48%]). Mean IOP did not differ between groups at the time of POH detection. The DHTM-treated eyes that developed POH were significantly more likely to have a 1-hour follow-up IOP < 25 mm Hg after latanoprost administration than were sham-treated eyes (19/25 [76%] vs 18/35 [51%]; OR, 3.87). CONCLUSIONS AND CLINICAL RELEVANCE Multidose perioperative administration of DHTM in dogs undergoing phacoemulsification reduced the incidence of POH and improved responsiveness of POH to latanoprost treatment.

Objective: To determine the relationship between tissue oxygen saturation (StO2) and oxygen delivery (D˙O2) during hypoxemia and hyperoxemia., Study Design: Prospective, randomized study., Animals: Eight purpose-bred Beagle dogs., Methods: Dogs were anesthetized with isoflurane, ventilated to eucapnia, and instrumented for thermodilution cardiac output, invasive mean arterial pressure (MAP), sartorius muscle StO2 and airway gas monitoring. Dogs were administered rocuronium to facilitate mechanical ventilation and esmolol to minimize anesthetic effects on cardiac output. Instrumentation and baseline data collection were at 0.21 fractional inspired oxygen (FIO2). Dogs were evaluated at high (0.40 then 0.95) and low (0.15 then 0.10) FIO2 sequences in random order with a 60 minute rest period at FIO2 0.21 between sequences. Target FIO2 was achieved by manipulating nitrogen and oxygen flow rates. Data collected at each FIO2, after a 10 minute period of stabilization, included heart rate (HR), MAP, cardiac index (CI) and StO2. Arterial oxygen content (CaO2) and oxygen delivery index (D˙O2I) were calculated at each FIO2. Data analysis included Pearson's correlation analysis and mixed-model anova (p < 0.05)., Results: There were no significant differences in HR, MAP or CI across all FIO2 values. Significant decreases occurred in mean ± standard deviation StO2 (90 ± 4% to 69 ± 18%; p = 0.0001), D˙O2I (458 ± 70 to 281 ± 100 mL minute(-1) m(-2); p = 0.0008) and CaO2 (13.2 ± 1.53 to 8.4 ± 2.05 mL dL(-1); p = 0.0001) from FIO2 0.21 to 0.10, but not at remaining FIO2 values. The correlation between StO2 and D˙O2I across all FIO2 values was strong (r = 0.97; p = 0.0013) and linear., Conclusions and Clinical Relevance: In this model of hypoxemia and hyperoxemia, the strong correlation between StO2 and D˙O2I suggests that StO2 can be used to estimate D˙O2., (© 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Object: Irreversible electroporation (IRE) is a novel nonthermal ablation technique that has been used for the treatment of solid cancers. However, it has not been evaluated for use in brain tumors. Here, the authors report on the safety and feasibility of using the NanoKnife IRE system for the treatment of spontaneous intracranial gliomas in dogs., Methods: Client-owned dogs with a telencephalic glioma shown on MRI were eligible. Dog-specific treatment plans were generated by using MRI-based tissue segmentation, volumetric meshing, and finite element modeling. After biopsy confirmation of glioma, IRE treatment was delivered stereotactically with the NanoKnife system using pulse parameters and electrode configurations derived from therapeutic plans. The primary end point was an evaluation of safety over the 14 days immediately after treatment. Follow-up was continued for 12 months or until death with serial physical, neurological, laboratory, and MRI examinations., Results: Seven dogs with glioma were treated. The mean age of the dogs was 9.3 ± 1.6 years, and the mean pretreatment tumor volume was 1.9 ± 1.4 cm(3). The median preoperative Karnofsky Performance Scale score was 70 (range 30-75). Severe posttreatment toxicity was observed in 2 of the 7 dogs; one developed fatal (Grade 5) aspiration pneumonia, and the other developed treatment-associated cerebral edema, which resulted in transient neurological deterioration. Results of posttreatment diagnostic imaging, tumor biopsies, and neurological examinations indicated that tumor ablation was achieved without significant direct neurotoxicity in 6 of the 7 dogs. The median 14-day post-IRE Karnofsky Performance Scale score of the 6 dogs that survived to discharge was 80 (range 60-90), and this score was improved over the pretreatment value in every case. Objective tumor responses were seen in 4 (80%) of 5 dogs with quantifiable target lesions. The median survival was 119 days (range 1 to > 940 days)., Conclusion: With the incorporation of additional therapeutic planning procedures, the NanoKnife system is a novel technology capable of controlled IRE ablation of telencephalic gliomas.

Objective: To compare the hemodynamic responses to orotracheal intubation following induction of anesthesia with propofol, ketamine-propofol, and ketamine-diazepam in premedicated dogs., Design: Prospective, randomized, masked study., Animals: 10 healthy adult Beagles., Procedures: Dogs were randomly allocated to be anesthetized twice, with a 1-week wash-out interval, by means of 2 of 3 possible protocols (propofol [4 mg/kg {1.8 mg/lb}, n = 6 dogs], ketamine [2 mg/kg {0.9 mg/lb}] and propofol [2 mg/kg; 7], or ketamine [5 mg/kg {2.3 mg/lb}] and diazepam [0.2 mg/kg {0.09 mg/lb}; 6]). After instrumentation, continuous heart rate, systolic arterial blood pressure, mean arterial blood pressure, diastolic arterial blood pressure, cardiac index, stroke volume index, and systemic vascular resistance were recorded. Fifteen minutes after premedication, dogs were anesthetized; all anesthetics were administered IV. After 5 minutes, orotracheal intubation was performed without the use of a laryngoscope. Data were collected prior to intubation (baseline), at intubation, and 30, 60, 90, 120, 150, and 180 seconds thereafter. Results were compared among the 3 groups and over time., Results: No differences among groups were observed for any variables studied. In all groups, arterial blood pressures were significantly decreased at various time points after intubation. A significant increase in systolic arterial blood pressure was observed between baseline and the 30-second time point in the ketamine-diazepam group. No significant differences were detected over time for the other variables in any group., Conclusions and Clinical Relevance: Intubation after anesthetic induction with ketamine-diazepam caused transitory hypertension, whereas intubation after induction with propofol or ketamine-propofol did not cause cardiovascular stimulation. In dogs in which hypertension is a concern, propofol or ketamine-propofol may be a better choice for induction prior to orotracheal intubation.

Objective: To evaluate the cardiorespiratory effects of IV administration of propofol (4 mg/kg), ketamine hydrochloride and propofol (2 mg/kg each; K-P), or ketamine hydrochloride (5 mg/kg) and diazepam (0.2 mg/kg; K-D) before and after induction of anesthesia (IoA) in dogs sedated with acepromazine maleate and oxymorphone hydrochloride., Animals: 10 healthy adult Beagles., Procedures: Each dog was randomly allocated to receive 2 of 3 treatments (1-week interval). For instrumentation prior to each treatment, each dog was anesthetized with isoflurane. After full recovery, acepromazine (0.02 mg/kg) and oxymorphone (0.05 mg/kg) were administered IV. Fifteen minutes later (before IoA), each dog received treatment IV with propofol, K-P, or K-D. Cardiorespiratory and arterial blood gas variables were assessed before, immediately after, and 5 minutes after IoA., Results: Compared with findings before IoA, dogs receiving the K-P or K-D treatment had increased cardiac output, oxygen delivery, and heart rate 5 minutes after IoA; K-P administration did not change mean arterial blood pressure or stroke volume and decreased systemic vascular resistance. Propofol decreased mean arterial blood pressure and systemic vascular resistance immediately after IoA but did not change heart rate, cardiac output, or oxygen delivery. All treatments caused some degree of apnea, hypoventilation, and hypoxemia (Pao2 < 80 mm Hg)., Conclusions and Clinical Relevance: In dogs, K-P treatment maintained mean arterial blood pressure better than propofol alone and increased heart rate, cardiac output, or oxygen delivery, as did the K-D treatment. Supplemental 100% oxygen should be provided during IoA with all 3 treatments.

Objective: To evaluate tissue oxygen saturation (Sto2) by use of near-infrared spectroscopy in experimental acute hemorrhagic shock and resuscitation in dogs., Animals: 14 healthy adult purpose-bred Beagles., Procedures: Dogs were anesthetized with isoflurane via facemask, anesthesia was maintained with propofol and rocuronium bromide, and dogs were mechanically ventilated to maintain normocapnia. Dogs were studied under normovolemia (baseline), hypovolemia with target mean arterial blood pressure < 40 mm Hg achieved and maintained steady for 10 minutes (hypovolemia T1), then 20 minutes later (hypovolemia T2), following resuscitation with shed blood (after transfusion), and after administration of 20 mL of hetastarch/kg (hypervolemia). Conditions were executed sequentially during a single anesthetic episode, allowing stabilization between states (10 minutes). Hemoglobin concentration, mean arterial blood pressure, arterial blood gas concentrations, cardiac index, oxygen delivery indexed to body surface area, and Sto2 were monitored., Results: From baseline to hypovolemia T1, there was a significant reduction in mean ± SD oxygen delivery index (619 ± 257 mL/min/m(2) to 205 ± 76 mL/min/m(2)) and Sto2 (94 ± 4.4% to 78 ± 12.2%). Following resuscitation, Sto2 (80 ± 8.5% vs 92 ± 6.45%) and oxygen delivery index (211 ± 73 mL/min/m(2) vs 717 ± 221 mL/min/m(2)) significantly increased, returning to baseline values. Hypervolemia had no effect on Sto2 or oxygen delivery index. A strong correlation (r = 0.97) was detected between mean oxygen delivery index and Sto2 across all time points., Conclusions and Clinical Relevance: Under the conditions of this study, there was a strong correlation between Sto2 and oxygen delivery, suggesting that Sto2 may be used to estimate oxygen delivery.

Objective: To identify ventilatory protocols that yielded good image quality for thoracic CT and hemodynamic stability in cats. Animals-7 healthy cats., Procedures: Cats were anesthetized and ventilated via 4 randomized protocols (hyperventilation, 20 seconds [protocol 1]; single deep inspiration, positive inspiratory pressure of 15 cm H(2)O [protocol 2]; recruitment maneuver [protocol 3]; and hyperventilation, 20 seconds with a positive end-expiratory pressure of 5 cm H(2)O [protocol 4]). Thoracic CT was performed for each protocol; images were acquired during apnea for protocols 1 and 3 and during positive airway pressure for protocols 2 and 4. Heart rate; systolic, mean, and diastolic arterial blood pressures; blood gas values; end-tidal isoflurane concentration; rectal temperature; and measures of atelectasis, total lung volume (TLV), and lung density were determined before and after each protocol., Results: None of the protocols eliminated atelectasis; the number of lung lobes with atelectasis was significantly greater during protocol 1 than during the other protocols. Lung density and TLV differed significantly among protocols, except between protocols 1 and 3. Protocol 2 TLV exceeded reference values. Arterial blood pressure after each protocol was lower than before the protocols. Mean and diastolic arterial blood pressure were higher after protocol 3 and diastolic arterial blood pressure was higher after protocol 4 than after protocol 2., Conclusions and Clinical Relevance: Standardization of ventilatory protocols may minimize effects on thoracic CT images and hemodynamic variables. Although atelectasis was still present, ventilatory protocols 3 and 4 provided the best compromise between image quality and hemodynamic stability.

Object: Nonthermal irreversible electroporation (NTIRE) is a novel, minimally invasive technique to treat cancer, which is unique because of its nonthermal mechanism of tumor ablation. This paper evaluates the safety of an NTIRE procedure to lesion normal canine brain tissue., Methods: The NTIRE procedure involved placing electrodes into a targeted area of brain in 3 dogs and delivering a series of short and intense electric pulses. The voltages of the pulses applied were varied between dogs. Another dog was used as a sham control. One additional dog was treated at an extreme voltage to determine the upper safety limits of the procedure. Ultrasonography was used at the time of the procedure to determine if the lesions could be visualized intraoperatively. The volumes of ablated tissue were then estimated on postprocedure MR imaging. Histological brain sections were then analyzed to evaluate the lesions produced., Results: The animals tolerated the procedure with no apparent complications except for the animal that was treated at the upper voltage limit. The lesion volume appeared to decrease with decreasing voltage of applied pulses. Histological examination revealed cell death within the treated volume with a submillimeter transition zone between necrotic and normal brain., Conclusions: The authors' results reveal that NTIRE at selected voltages can be safely administered in normal canine brain and that the volume of ablated tissue correlates with the voltage of the applied pulses. This preliminary study is the first step toward using NTIRE as a brain cancer treatment.

Nonthermal irreversible electroporation (NTIRE) is a new minimally invasive technique to treat cancer. It is unique because of its nonthermal mechanism of tumor ablation. Intracranial NTIRE procedures involve placing electrodes into the targeted area of the brain and delivering a series of short but intense electric pulses. The electric pulses induce irreversible structural changes in cell membranes, leading to cell death. We correlated NTIRE lesion volumes in normal brain tissue with electric field distributions from comprehensive numerical models. The electrical conductivity of brain tissue was extrapolated from the measured in vivo data and the numerical models. Using this, we present results on the electric field threshold necessary to induce NTIRE lesions (495-510 V/cm) in canine brain tissue using 90 50-mus pulses at 4 Hz. Furthermore, this preliminary study provides some of the necessary numerical tools for using NTIRE as a brain cancer treatment. We also computed the electrical conductivity of brain tissue from the in vivo data (0.12-0.30 S/m) and provide guidelines for treatment planning and execution. Knowledge of the dynamic electrical conductivity of the tissue and electric field that correlates to lesion volume is crucial to ensure predictable complete NTIRE treatment while minimizing damage to surrounding healthy tissue.