Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses.

Background: Matrix type transdermal buprenorphine patches have not been investigated in horses and may provide an effective means of providing continuous pain control for extended period and eliminating venous catheterization. Objective: Assessment of the physiological variables (heart rate, respiratory rate, body temperature) and thermal nociceptive threshold testing, and describing the pharmacokinetic profile of transdermal buprenorphine matrix-type patch (20 µg h-1 and 40 µg h-1 dosing) in healthy adult horses. Study design: Randomised experimental study with a Latin-square design. Methods: Six adult healthy horses received each of the three treatments with a minimum 10 day washout period. BUP0 horses did not receive a patch (control). BUP20 horses received one patch (20 µg h-1) applied on the ventral aspect of the tail base resulting in a dose of 0.03-0.04 µg kg-1 h-1. BUP40 horses received two patches placed alongside each other (40 µg h-1) on the tail base resulting in a dose of 0.07-0.09 µg kg-1 h-1. Whole blood samples (for determination of buprenorphine concentration), physiological variables and thermal threshold testing were performed before (0 h) and at 2, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, and 96 h after patch application. The patches were removed 72 h following placement and were analyzed for residual buprenorphine content. Results: Between the three groups, there was no change in physiological variables across timepoints as compared to baseline (p > 0.1). With the higher dose, there was a significant increase in thermal thresholds from baseline values from 2 h until 48 h and these values were significantly higher than the group receiving the lower patch dose for multiple timepoints up to 40 h. 40 µg h-1 patch led to consistent measurable plasma concentrations starting at 2 h up to 96 h, with the mean plasma concentrations of > 0.1 ng/ml from 4 h to 40 h. Conclusions: 20 µg h-1 and 40 µg h-1 patch doses were well tolerated by all horses. At higher dose, plasma buprenorphine concentrations were more consistently measurable and blunted thermal thresholds for 48 h vs. 32 h with 20 µg h-1 dosing as compared to control.

Performance of four cardiac output monitoring techniques vs. intermittent pulmonary artery thermodilution during a modified passive leg raise maneuver in isoflurane-anesthetized dogs.

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 (PLRM) maneuver in isoflurane-anesthetized dogs undergoing acute blood volume manipulations. The study also examined the simultaneous effect of performing the PLRM 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 (EDCO), transesophageal echocardiography (TEECO), arterial pressure waveform analysis (APWACO), and electrical cardiometry (ECCO). Additionally, SDV, PVV, and SVV were recorded. Intermittent pulmonary artery thermodilution (iPATDCO) measurements were also recorded before, during, and after the PLRM maneuver. A successful FR diagnosis made using a specific test indicated that CO increased by more than 15% during the PLRM 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 PLRM 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 TEECO and ECCO slightly underestimated iPATDCO values, EDCO and APWACO significantly overestimated iPATDCO 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 PLRM 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 PLRM maneuver, while the performance of APWA was unacceptable and not recommended. SVV, SDV, and PVV could be used to monitor CO changes during PLRM and acute blood volume manipulations, suggesting their potential clinical utility.

Evaluation of Electrical Cardiometry for Measuring Cardiac Output and Derived Hemodynamic Variables in Comparison with Lithium Dilution in Anesthetized Dogs.

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 (ρc), 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, ρc 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.

Agreement of cardiac output measurements by esophageal Doppler and transesophageal echocardiography with intermittent pulmonary artery thermodilution during pharmacologic manipulation of hemodynamics in anesthetized dogs.

OBJECTIVE: To compare cardiac output (CO) measurements by transesophageal echocardiography (TEECO) and esophageal Doppler monitor (EDMCO) with pulmonary artery thermodilution (PATDCO) in anesthetized dogs subjected to pharmacological interventions. The effect of treatments on EDM-derived indexes was also investigated. ANIMALS: 6 healthy male dogs (10.8 ± 0.7 kg). METHODS: Dogs were anesthetized with propofol and isoflurane, mechanically ventilated, and monitored with invasive mean arterial pressure (MAP), end-tidal isoflurane concentration (ETISO), PATDCO, TEECO, EDMCO, and EDM-derived indexes. Four treatments were administered to all dogs by randomization. Baseline data were collected before each treatment: (1) dobutamine infusion; (2) esmolol infusion; (3) phenylephrine infusion; and (4) ETISO > 3%. Data were collected after 10-minute stabilization and after 30 minutes of washout between treatments. Statistical tests were pairwise t test, Bland-Altman analysis, Lin's concordance correlation (ρc), and polar plot analysis with P < .05 set as significance. RESULTS: The mean ± SD relative bias (limits of agreement) for TEECO was 0.35 ± 25.2% (-49.1% to 49.8%) and for EDMCO was -27.2 ± 22.5% (-71.4% to 17%) versus PATDCO. The percent error for TEECO and EDMCO was 27.6% and 44.1%, respectively. The ρc value was 0.82 for TEECO and 0.66 for EDMCO. TEECO and EDMCO showed good trending ability. EDM-derived indexes displayed significant changes specific to the drug administered (P < .001). CLINICAL RELEVANCE: For minimally invasive CO monitoring, TEE may provide more favorable performance than EDM in clinical settings; however, EDM-derived indexes yield valuable hemodynamic information that reliably follows trends in CO, thus supporting critical decision-making in canine patients.

Agreement between Electrical Cardiometry and Pulmonary Artery Thermodilution for Measuring Cardiac Output in Isoflurane-Anesthetized Dogs.

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.

Volumetric evaluation of fluid responsiveness using a modified passive leg raise maneuver during experimental induction and correction of hypovolemia in anesthetized dogs.

OBJECTIVE: To demonstrate if modified passive leg raise (PLRM) 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 PLRM 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 PLRM 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, PLRM 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 PLRM did not affect CO, PPV and PVI during stages 1, 3 and 4. CONCLUSIONS AND CLINICAL RELEVANCE: In anesthetized dogs, PLRM 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 PLRM maneuver.

Esophageal Doppler-derived indices and arterial load variables provide useful hemodynamic information during assessment of fluid responsiveness in anesthetized dogs undergoing acute changes in blood volume.

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.

Transpulmonary ultrasound dilution is an acceptable technique for cardiac output measurement in anesthetized pigs.

OBJECTIVE: To evaluate cardiac output (CO) measurements using transpulmonary ultrasound (TPUD) technology and compare results with those of the gold standard, pulmonary arterial catheter thermodilution (PACTD), in 6 healthy anesthetized pigs during acute hemodynamic changes caused by manipulation of the blood volume. ANIMALS: 6 healthy male Landrace pigs. PROCEDURES: Over a period of 1 week, pigs were anesthetized with isoflurane, mechanically ventilated, and underwent instrumentation in dorsal recumbency. They were subjected to sequential experimental states during which the blood volume was manipulated so that the animals transitioned from normovolemia to hypovolemia (20% and 40% of blood volume depletion), back to normovolemia (autologous blood transfusion), and then to hypervolemia (following colloid bolus). During each volume state, CO measurements were compared between TPUD and PACTD. RESULTS: The mean ± SD relative bias between TPUD and PACTD was 7.71% ± 21.2% with limits of agreement -33.9% to 49.3%, indicating TPUD slightly underestimated CO values, compared with values obtained with PACTD. The mean ± SD of the bias between the 2 methods was 0.13 ± 0.5 L/min. Only 5 of 36 (13.9%) TPUD CO measurements had an absolute value of relative bias > 30%. The percentage error calculated for TPUD was 29.4%. CLINICAL RELEVANCE: Results suggested that TPUD measurements have acceptable agreement with PACTD measurements. Moreover, TPUD exhibits promising potential in being used interchangeably with PACTD for future hemodynamic research involving swine as species of interest.