Effect of heart rate on the pharmacokinetics of fentanyl in dogs anesthetized with isoflurane and hydromorphone.

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.

The effect of two doses of fentanyl on chest wall rigidity at equipotent doses of isoflurane in dogs.

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 (MACISO) 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 (PESO), flow (V˙) and volume (V). Chest wall elastance (ECW) was estimated by multiple linear regression of the model. PESO(t) = V˙(t) × RCW + V(t) × ECW + EEPESO where t is time, RCW is chest wall resistance and EEPESO is end-expiratory PESO. Chest wall compliance (CCW) was calculated as 1/ECW and normalized to the body weight of each dog (mL cmH2O-1 kg-1). Anesthesia was maintained at 1.3 MACISO for at least 15 minutes and CCW recorded (CCW-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, CCW was recorded for each dose (CCW-FENT). During fentanyl infusion, the dogs were maintained at equipotent doses of isoflurane (1.3 MACISO for each fentanyl dose). A two-way analysis of variance followed by a Bonferroni test was used to compare CCW-ISO and CCW-FENT in both treatments and CCW-FENT between treatments. A p value <0.05 was considered significant. RESULTS: Neither of the fentanyl doses decreased CCW and there was no difference in CCW-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 MACISO).

Ultrasound-guided catheterization of the femoral artery in a canine model of acute hemorrhagic shock.

OBJECTIVE: To describe a technique for gaining ultrasound-guided access to the femoral artery in an experimental model of acute hemorrhagic shock in anesthetized dogs. CASE SERIES SUMMARY: Five healthy, purpose-bred adult male intact Beagles were enrolled in a respiratory mechanics study under general anesthesia. Upon completion of the primary study a hypovolemic state was induced by blood removal to achieve a mean arterial pressure ≤ 55 mm Hg. Dogs were positioned in dorsal recumbency with the hind limb extended caudally. An ultrasound probe was applied to the medial aspect of the hind limb and positioned in the transverse orientation so that the femoral artery was visualized in its short axis. The artery was identified by lack of compression and presence of visible pulsation. The probe was rotated 90° into the longitudinal orientation such that the artery was visualized in its long axis. Under ultrasound guidance a 19-gauge introducer needle was advanced into the lumen of the femoral artery. Using a modified Seldinger technique the needle was removed and a catheter was placed in the femoral artery. Correct placement of the catheter was verified by observation of the characteristic arterial blood pressure waveform. Upon completion of the study dogs were humanely euthanized. The femoral artery was successfully catheterized in 4/5 dogs and a hematoma was reported in 1/5 dogs. NEW OR UNIQUE INFORMATION PROVIDED: Ultrasound-guided femoral artery catheterization is feasible on anesthetized dogs with concurrent acute hemorrhagic shock.

High-Frequency Irreversible Electroporation for Intracranial Meningioma: A Feasibility Study in a Spontaneous Canine Tumor Model.

High-frequency irreversible electroporation is a nonthermal method of tissue ablation that uses bursts of 0.5- to 2.0-microsecond bipolar electric pulses to permeabilize cell membranes and induce cell death. High-frequency irreversible electroporation has potential advantages for use in neurosurgery, including the ability to deliver pulses without inducing muscle contraction, inherent selectivity against malignant cells, and the capability of simultaneously opening the blood-brain barrier surrounding regions of ablation. Our objective was to determine whether high-frequency irreversible electroporation pulses capable of tumor ablation could be delivered to dogs with intracranial meningiomas. Three dogs with intracranial meningiomas were treated. Patient-specific treatment plans were generated using magnetic resonance imaging-based tissue segmentation, volumetric meshing, and finite element modeling. Following tumor biopsy, high-frequency irreversible electroporation pulses were stereotactically delivered in situ followed by tumor resection and morphologic and volumetric assessments of ablations. Clinical evaluations of treatment included pre- and posttreatment clinical, laboratory, and magnetic resonance imaging examinations and adverse event monitoring for 2 weeks posttreatment. High-frequency irreversible electroporation pulses were administered successfully in all patients. No adverse events directly attributable to high-frequency irreversible electroporation were observed. Individual ablations resulted in volumes of tumor necrosis ranging from 0.25 to 1.29 cm3. In one dog, nonuniform ablations were observed, with viable tumor cells remaining around foci of intratumoral mineralization. In conclusion, high-frequency irreversible electroporation pulses can be delivered to brain tumors, including areas adjacent to critical vasculature, and are capable of producing clinically relevant volumes of tumor ablation. Mineralization may complicate achievement of complete tumor ablation.

Cardiovascular and respiratory effects of two doses of fentanyl in the presence or absence of bradycardia in isoflurane-anesthetized dogs.

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-FNHR). 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 (DO2I) decreased only during high-dose fentanyl. CI and DO2I were higher in both treatments at ISO-FNHR 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-FNHR 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.

Isoflurane minimum alveolar concentration sparing effects of fentanyl in the dog.

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 (MACISO-F). Blood was collected for analysis of plasma fentanyl concentrations before administration and after MACISO-F determination. All values are presented as mean ± SD. RESULTS: Isoflurane MAC (MACISO) 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%). MACISO 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.

Evaluation of tissue hemoglobin saturation (StO2) using near-infrared spectroscopy during hypoxemia and hyperoxemia in Beagle dogs.

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.

Evaluation of tissue oxygen saturation with near-infrared spectroscopy during experimental acute hemorrhagic shock and resuscitation in dogs.

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.