Cardiovascular effects of increasing dosages of norepinephrine in healthy isoflurane-anesthetized New Zealand White rabbits

ObjectiveTo characterize the cardiovascular effects of increasing dosages of norepinephrine (NE) in healthy isoflurane-anesthetized rabbits.Study designProspective experimental study.AnimalsA total of nine female ovariohysterectomized New Zealand White rabbits weighing 3.4 ± 0.2 kg (mean ± standard deviation).MethodsRabbits were premedicated intramuscularly with buprenorphine (0.05 mg kg^–1) and midazolam (0.5 mg kg^–1). Anesthesia was induced with intravenous propofol and maintained with a 1.1 × minimum alveolar concentration of isoflurane for this species to induce hypotension. Rabbits were administered NE infusions at three doses: low, 0.1 μg kg^–1 minute^–1; medium, 0.5 μg kg^–1 minute^–1; and high doses, 1 μg kg^–1 minute^–1 for 10 minutes each in that order. Cardiovascular variables including heart rate (HR), cardiac output (CO) by lithium dilution technique and systolic (SAP), mean (MAP) and diastolic (DAP) invasive arterial blood pressures measured in the auricular artery were recorded at baseline, 10 minutes after the start of the infusion of each NE treatment and 10 minutes after NE was discontinued. A linear mixed model and a type III anova with Tukey’s post hoc comparison was performed (p < 0.05).ResultsSignificant increases in SAP (28% and 90%), MAP (27% and 90%) and DAP (33% and 97%) were measured with medium and high dose treatments, respectively (p < 0.001), with no changes in CO. HR decreased and stroke volume increased significantly with high dose treatment (by 17% and 15%, respectively; p < 0.05). No arrhythmias were noticed with NE treatments.Conclusions and clinical relevanceThe infusion of NE at 0.5–1.0 μg kg^–1 minute^–1 is a potentially effective treatment for hypotension in healthy isoflurane-anesthetized New Zealand White rabbits.     

Effects of norepinephrine and a combined norepinephrine and dobutamine infusion on systemic hemodynamics and indices of renal function in normotensive neonatal thoroughbred foals

BACKGROUND: Norepinephrine is a potent vasopressor that increases arterial blood pressure but may have adverse effects on renal blood flow. The combination of norepinephrine and dobutamine may lead to improved renal perfusion compared to an infusion of norepinephrine alone. The effects of these drugs in the normotensive neonatal foal have not been reported. HYPOTHESIS: Norepinephrine increases arterial blood pressure. Adding dobutamine to a norepinephrine infusion will change the renal profile during the infusions without changing the arterial blood pressure. ANIMALS: Eight conscious Thoroughbred foals were used in this study. METHODS: Each foal received norepinephrine (0.1 microg/kg/min), combined norepinephrine (0.1 microg/kg/min) and dobutamine (5 microg/kg/min), and a control dose of saline in a masked, placebo-controlled study. Heart rate, arterial blood pressure (direct), and cardiac output (lithium dilution) were measured, and systemic vascular resistance, stroke volume, cardiac index, and stroke volume index were calculated. Urine output, creatinine clearance, and fractional excretion of sodium, potassium, and chloride were measured. RESULTS: Norepinephrine and a combined norepinephrine and dobutamine infusion increased arterial blood pressure and systemic vascular resistance and decreased heart rate and cardiac index as compared to saline. The combination resulted in higher arterial pressure than norepinephrine alone. There was no significant difference in urine output, creatinine clearance, or fractional excretion of electrolytes with either infusion as compared to saline. CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that norepinephrine and a combined norepinephrine and dobutamine infusion cause unique hemodynamic effects without affecting indices of renal function, and this effect warrants further investigation.     

Cardiovascular effects of dose escalating of norepinephrine in healthy dogs anesthetized with isoflurane

ObjectiveTo evaluate the systemic cardiovascular effects of dose escalating administration of norepinephrine in healthy dogs anesthetized with isoflurane.Study designExperimental study.AnimalsA total of six adult laboratory Beagle dogs, 10.5 (9.2–12.0) kg [median (range)].MethodsEach dog was anesthetized with isoflurane at an end-tidal concentration of 1.7%, mechanically ventilated and administered a continuous rate infusion of rocuronium (0.5 mg kg^–1 hour^–1). Each dog was administered incremental dose rates of norepinephrine (0.05, 0.125, 0.25, 0.5, 1.0 and 2.0 μg kg^–1 minute^–1), and each dose was infused for 15 minutes. Cardiovascular variables were recorded before administration and at the end of each infusion period.ResultsNorepinephrine infusion increased mean arterial pressure (MAP), cardiac output (CO) and oxygen delivery in a dose-dependent manner. Systemic vascular resistance did not significantly change during the experiment. Stroke volume increased at the lower dose rates and heart rate increased at the higher dose rates. Oxygen consumption and lactate concentrations did not significantly change during infusions.ConclusionsIn dogs anesthetized with isoflurane, norepinephrine increased MAP by increasing the CO. CO increased with a change in stroke volume at lower dose rates of norepinephrine. At higher dosage, heart rate also contributed to an increase in CO. Norepinephrine did not cause excessive vasoconstriction that interfered with the CO during this study.Clinical relevanceNorepinephrine can be useful for treating hypotension in dogs anesthetized with isoflurane.     

Effects of intravenous butorphanol on cardiopulmonary function in isoflurane-anesthetized alpacas

OBJECTIVE: To determine the effects of intravenous (IV) butorphanol on the cardiopulmonary system and on the bispectral index (BIS) in isoflurane-anesthetized alpacas. STUDY DESIGN: Randomized, blinded cross-over experimental trial. ANIMALS: Eight healthy, young (3 +/- 1 SD years) adult female alpacas weighing 64 +/- 9 SD kg. METHODS: Alpacas were anesthetized with isoflurane by mask followed by tracheal intubation and maintenance of anesthesia with isoflurane in oxygen and intermittent positive pressure ventilation. Animals were assigned to two treatments, butorphanol (0.1 mg kg(-1), IV) and saline (0.01 mL kg(-1), IV) in a randomized manner allowing a 2-week interval between treatments. Cardiovascular variables included systolic, diastolic, and mean arterial blood pressure, heart rate, pulmonary arterial pressure, pulmonary arterial occlusion pressure (PAOP), central venous pressure, cardiac output, and pulmonary temperature (TEMP). Cardiac index, systemic vascular resistance (SVR), and pulmonary vascular resistance (PVR) were calculated. Bispectral index was also measured. Arterial and mixed venous blood samples were collected for blood gas analysis. All variables were recorded at baseline (time 0) and at 5, 10, 15, 30, 45 and 60 minutes following injection and were analyzed by using repeated-measures ANOVA (p < 0.05). PAOP, PVR, and BIS were analyzed by paired t-tests. RESULTS: Butorphanol decreased SVR at all times when compared with the baseline, but no difference was detected between treatments. TEMP decreased with time in both treatments, but they were not different from each other. Other cardiovascular, BIS, and blood gas variables were not different between groups. CONCLUSION AND CLINICAL RELEVANCE: We conclude that butorphanol had minimal effects on the cardiovascular system of the alpacas, causing a mild decrease in SVR.     

Effects of dobutamine on cardiovascular function and oxygen delivery in standing horses

Dobutamine is routinely used to improve cardiovascular function in anaesthetized horses. However, dobutamine in conscious horses is insufficiently investigated. Ten research horses that were already instrumented for a preceding trial were included into the study. Cardiovascular variables were recorded and blood samples taken after instrumentation (Baseline), before starting dobutamine and after 10 min of dobutamine infusion (2 µg kg⁻¹ min⁻¹). A significant increase in systemic blood pressure, mean pulmonary artery pressure and right atrial pressure, and a decrease in heart rate were observed with dobutamine compared with baseline measurements. Arterial and mixed venous haemoglobin and oxygen content, as well as mixed venous partial pressure of oxygen increased. No significant changes in cardiac output, stroke volume, systemic vascular resistance, arterial partial pressure of oxygen, or oxygen consumption, delivery and extraction ratio were detected. Concluding, dobutamine increased systemic blood pressure without detectable changes in stroke volume, cardiac output or systemic vascular resistance in conscious horses.     

Effects of norepinephrine and combined norepinephrine and fenoldopam infusion on systemic hemodynamics and indices of renal function in normotensive neonatal foals

Background: Norepinephrine increases arterial blood pressure but may have adverse effects on renal blood flow. Fenoldopam, a dopamine-1 receptor agonist, increases urine output in normotensive foals. The combination of norepinephrine and fenoldopam may lead to improved renal perfusion compared with an infusion of norepinephrine alone. The combined effects of these drugs have not been reported in the horse.
Hypothesis: Norepinephrine will alter the hemodynamic profile of foals without affecting renal function. Addition of fenoldopam will change the renal profile during the infusions without changing the hemodynamic profile.
Animals: Five conscious pony foals.
Methods: Each foal received norepinephrine (0.3 μg/kg/min), combined norepinephrine (0.3 μg/kg/min) and fenoldopam (0.04 μg/kg/min), and a control dose of saline in a masked, placebo-controlled study. Heart rate (HR), arterial blood pressure (direct), and cardiac output (lithium dilution) were measured, and systemic vascular resistance (SVR), stroke volume, cardiac index (CI), and stroke volume index were calculated. Urine output, creatinine clearance, and fractional excretion of electrolytes were measured.
Results: Norepinephrine and a combined norepinephrine and fenoldopam infusion increased arterial blood pressure, SVR, urine output, and creatinine clearance and decreased HR and CI compared with saline. The combination resulted in higher HR and lower arterial blood pressure than norepinephrine alone.
Conclusions and Clinical Importance: Norepinephrine might be useful for hypotensive foals, because in normal foals, this infusion rate increases SVR without negatively affecting renal function (creatinine clearance increased). Fenoldopam does not provide additional benefit to renal function. These findings warrant further investigation.     

The effects of maternal plasma dobutamine levels on fetal oxygenation in anaesthetized sheep

Objective To measure the effects of dobutamine infusion on fetal oxygenation during isoflurane anaesthesia in pregnant ewes. Study design Prospective randomized experimental study. Animals Seven clinically normal adult pregnant Rambouillet‐Dorset cross ewes with fetuses of 117–122 days gestational age. Methods The ewes were anaesthetized with ketamine (2 mg kg^?1) IM, and isoflurane (F_E′ISO 2.0%) in oxygen. After instrumentation and stabilization, dobutamine was infused at 4 µg kg^?1minute^?1 for 60 minutes and 10 µg kg^?1minute^?1 for 60 minutes in random order, separated by a 20‐minute washout period. Catheters were placed in the maternal and fetal carotid arteries; these were used for continuous blood pressure measurement and intermittent blood sampling. Results Maternal mean systemic carotid arterial pressure was 60 mm Hg prior to dobutamine infusion. After 5 minutes of dobutamine infusion, fetal oxygen saturation increased (p < 0.05) from 0.62 (0.17–0.71, minimum–maximum) to 0.72 (0.28–0.78) at a dose of 4 µg kg^?1minute^?1 and to 0.70 (0.20–0.73) at a dose of 10 µg kg^?1minute^?1. These increases were maintained during the infusion and were not significantly different between doses. Maternal oxygen saturation remained constant at 1.0 before and during all infusions. Although maternal heart rate and blood pressure increased (p < 0.05) by 90% and 25%, respectively, with dobutamine, this stimulant effect was not evident in the corresponding fetal variables. Maternal haemoglobin concentration increased 30% (p < 0.05) with each infusion. Conclusions Dobutamine at 4 µg kg^?1minute^?1 increases fetal oxygenation that is not improved by a dose of 10 µg kg^?1minute^?1. This increase is largely due to an increase in maternal haemoglobin concentration that, in turn, increases oxygen delivery to the placenta. Clinical relevance The use of dobutamine to treat hypotension in pregnant sheep during isoflurane anaesthesia improves fetal oxygenation. This may be true in other species.     

The effect of moderate hypovolemia on cardiopulmonary function in dogs

Objective: To collate canine cardiopulmonary measurements from previously published and unpublished studies in instrumented, unsedated, normovolemic and moderately hypovolemic dogs. Design: Collation of data obtained from original investigations in our research laboratory. Setting: Research laboratory, School of Veterinary Medicine. Subjects: Sixty‐eight dogs. Interventions: Subjects were percutaneously instrumented with an arterial catheter and a thermodilution cardiac output catheter. A femoral artery catheter was percutaneously placed for blood removal. Measurements and main results: Body weight, arterial and mixed‐venous pH and blood gases, arterial, pulmonary arterial, pulmonary artery occlusion, and central venous blood pressure, cardiac output, and core body temperature were measured. Body surface area, bicarbonate concentration, standard base excess, cardiac index (CI), stroke volume, systemic and pulmonary vascular resistance, left and right ventricular work and stroke work indices, left and right rate‐pressure product, alveolar PO₂, alveolar–arterial PO₂ gradient, arterial and mixed‐venous and pulmonary capillary oxygen content, oxygen delivery, oxygen consumption, oxygen extraction, venous admixture, arterial and venous blood carbon dioxide content, arterial–venous carbon dioxide gradient, carbon dioxide production were calculated. In 68 dogs, hypovolemia sufficient to decrease mean arterial blood pressure (ABPm) to an average of 62 mmHg, was associated with the following changes: arterial partial pressure of carbon dioxide (PaCO₂) decreased from 40.0 to 32.9 mmHg; arterial base deficit (BDa) increased from ?2.2 to ?6.3 mEq/L; lactate increased from 0.85 to 10.7 mm /L, and arterial pH (pHa) did not change. Arterial partial pressure of oxygen (PaO₂) increased from 100.5 to 108.3 mmHg while mixed‐venous PO₂ (PmvO₂) decreased from 49.1 to 34.1 mmHg. Arterial and mixed‐venous oxygen content (CaO₂ and CmvO₂) decreased from 17.5 to 16.5 and 13.8 to 9.6 mL/dL, respectively. The alveolar–arterial PO₂ gradient (A‐a PO₂) increased from 5.5 to 8.9 mmHg while venous admixture decreased from 2.9% to 1.4%. The ABPm decreased from 100 to 62 mmHg; pulmonary arterial pressure (PAPm) decreased from 13.6 to 6.4 mmHg; and pulmonary arterial occlusion pressure (PAOP) decreased from 4.9 to 0.1 mmHg. CI decreased from 4.31 to 2.02 L/min/m². Systemic and pulmonary vascular resistance (SVRI and PVRI) increased from 1962 to 2753 and 189 to 269 dyn s/cm⁵, respectively. Oxygen delivery (DO₂) decreased from 787 to 340 mL/min/m² while oxygen consumption (VO₂) decreased from 172 to 141 mL/min/m². Oxygen extraction increased from 20.9% to 42.3%. Conclusions: Moderate hypovolemia caused CI and oxygen delivery to decrease to 47% and 42% of baseline. Oxygen extraction, however, doubled and, therefore, oxygen consumption decreased only to 82% of baseline.     

Hemodynamic effects of dexmedetomidine in isoflurane-anesthetized cats

ObjectiveTo characterize the hemodynamic effects of dexmedetomidine in isoflurane-anesthetized cats.Study designProspective experimental study.AnimalsSix healthy adult female cats weighing 4.6 ± 0.8 kg.MethodsDexmedetomidine was administered intravenously using target-controlled infusions to maintain nine plasma concentrations between 0 and 20 ng mL^?1 in isoflurane-anesthetized cats. The isoflurane concentration was adjusted for each dexmedetomidine concentration to maintain the equivalent of 1.25 times the minimum alveolar concentration, based on a previous study. Heart rate, systemic and pulmonary arterial pressures, central venous pressure, pulmonary artery occlusion pressure, body temperature, and cardiac output were measured at each target plasma dexmedetomidine concentration. Additional variables were calculated. Arterial and mixed-venous blood samples were collected for blood gas, pH, and (on arterial blood only) electrolyte, glucose and lactate analysis. Plasma dexmedetomidine concentration was determined for each target. Pharmacodynamic models were fitted to the data.ResultsHeart rate, arterial pH, arterial bicarbonate concentration, mixed-venous PO₂, mixed-venous pH, mixed-venous hemoglobin oxygen saturation, cardiac index, stroke index, and venous admixture decreased following dexmedetomidine administration. Arterial blood pressure, central venous pressure, pulmonary arterial pressure, pulmonary arterial occlusion pressure, packed cell volume, PaO₂, PaCO₂, arterial hemoglobin concentration, mixed-venous PCO₂, mixed-venous hemoglobin concentration, ionized calcium concentration, glucose concentration, rate-pressure product, systemic and pulmonary vascular resistance indices, left ventricular stroke work index, arterial oxygen concentration, and oxygen extraction increased following dexmedetomidine administration. Most variables changed in a dexmedetomidine concentration-dependent manner.Conclusion and clinical relevanceThe use of dexmedetomidine as an anesthetic adjunct is expected to produce greater negative hemodynamic effects than a higher, equipotent concentration of isoflurane alone.     

Combined effects of dexmedetomidine and vatinoxan infusions on minimum alveolar concentration and cardiopulmonary function in sevoflurane-anesthetized dogs

ObjectiveTo evaluate the effects of combined infusions of vatinoxan and dexmedetomidine on inhalant anesthetic requirement and cardiopulmonary function in dogs.Study designProspective experimental study.MethodsA total of six Beagle dogs were anesthetized to determine sevoflurane minimum alveolar concentration (MAC) prior to and after an intravenous (IV) dose (loading, then continuous infusion) of dexmedetomidine (4.5 μg kg^–1 hour^–1) and after two IV doses of vatinoxan in sequence (90 and 180 μg kg^–1 hour^–1). Blood was collected for plasma dexmedetomidine and vatinoxan concentrations. During a separate anesthesia, cardiac output (CO) was measured under equivalent MAC conditions of sevoflurane and dexmedetomidine, and then with each added dose of vatinoxan. For each treatment, cardiovascular variables were measured with spontaneous and controlled ventilation. Repeated measures analyses were performed for each response variable; for all analyses, p < 0.05 was considered significant.ResultsDexmedetomidine reduced sevoflurane MAC by 67% (0.64 ± 0.1%), mean ± standard deviation in dogs. The addition of vatinoxan attenuated this to 57% (0.81 ± 0.1%) and 43% (1.1 ± 0.1%) with low and high doses, respectively, and caused a reduction in plasma dexmedetomidine concentrations. Heart rate and CO decreased while systemic vascular resistance increased with dexmedetomidine regardless of ventilation mode. The co-administration of vatinoxan dose-dependently modified these effects such that cardiovascular variables approached baseline.Conclusions and clinical relevanceIV infusions of 90 and 180 μg kg^–1 hour^–1 of vatinoxan combined with 4.5 μg kg^–1 hour^–1 dexmedetomidine provide a meaningful reduction in sevoflurane requirement in dogs. Although sevoflurane MAC-sparing properties of dexmedetomidine in dogs are attenuated by vatinoxan, the cardiovascular function is improved. Doses of vatinoxan >180 μg kg^–1 hour^–1 might improve cardiovascular function further in combination with this dose of dexmedetomidine, but beneficial effects on anesthesia plane and recovery quality may be lost.     

Evaluation of a new oscillometric blood pressure monitor in isoflurane-anesthetized dogs

Objective This study was conducted to evaluate the performance of a new veterinary oscillometric noninvasive blood pressure (NIBP) monitor in anesthetized dogs. Study design Assessment was made to determine how closely indirect measurements were associated with direct measurements, and if there were statistically significant differences between the measurements by site. Animals Six mongrel dogs weighing 27.8 ± 2.9 kg. Methods Dogs were anesthetized with thiopental and maintained with isoflurane, which was delivered with controlled ventilation. Direct pressure measurements were obtained via a percutaneously placed arterial catheter. A range of systolic arterial pressures (SAP) were achieved by changing the isoflurane concentrations. Sites of cuff placement for indirect measurements were identified as metacarpus, metatarsus, and anterior tibial. Results At pressures below 80 mm Hg, indirect systolic measurements averaged 4 ± 3 mm Hg, higher than the direct values. At normal and high levels, indirect systolic measurements underestimated direct values by 18 ± 6 and 23 ± 6 mm Hg, respectively. Diastolic and mean pressure measurements followed the same trend, with indirect values being lower than the direct arterial pressures. Systolic, diastolic and mean arterial pressure measurements differed by cuff‐placement site. Conclusions When analyzed by site and level, indirect systolic and mean arterial blood pressures during hypotension were essentially the same as direct pressures. However, at pressures within the normal or high range, indirect measurements underestimated the direct pressures. Clinical relevance Noninvasive blood pressure measurements with a new oscillometric monitor provided an excellent means of detecting arterial hypotension in anesthetized dogs. The metatarsal site for cuff placement was slightly better than the metacarpal or anterior tibial site, considering that the regression line was closest to complete equality between the indirect and direct measurements for SAP.     

Agreement between noninvasive oscillometric and invasive blood pressure measurements in isoflurane-anesthetized guinea pigs (Cavia porcellus)

ObjectiveTo assess the agreement between an oscillometric device and invasive blood pressure (IBP) measurements in anesthetized healthy adult guinea pigs.Study designProspective experimental study.AnimalsA total of eight adult Hartley guinea pigs.MethodsAll animals were anesthetized; a carotid artery was surgically exposed and catheterized for IBP measurements. A size 1 cuff placed on the right thoracic limb was connected to an oscillometric device for noninvasive blood pressure (NIBP) assessment. Concurrent pairs of systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures were recorded simultaneously with both methods every 3 minutes for 30 minutes. Agreement between IBP and NIBP measurements was determined using the Bland–Altman method, considering the recommended standards for the validation of NIBP measurement devices proposed by the American College of Veterinary Internal Medicine (ACVIM).ResultsThe bias and the 95% limits of agreement were: –14 (–31 to 3) mmHg, –2 (–14 to 10) mmHg and –1 (–13 to 11) mmHg for SAP, DAP and MAP, respectively.Conclusions and clinical relevanceThe oscillometric device used in this study to measure NIBP did not meet ACVIM criteria for validation. It showed good agreement for DAP and MAP but not for SAP measurements. Considering the small size of these animals and the resulting difficulty in performing percutaneous arterial catheterization, this device might be a useful tool to assess MAP and DAP during anesthetic procedures in adult guinea pigs.     

The cardiopulmonary effects of severe blood loss in anesthetized horses

Objective To characterize the acute cardiopulmonary effects of severe hemorrhage in anesthetized horses. Study design Prospective experimental study. Animals Three geldings and six mares, aged 14.4 ± 2.7 years, weighing 486 ± 41 kg (range: 425–550 kg). Methods Horses were anesthetized using xylazine, guaifenesin, ketamine and halothane or isoflurane. Cardiovascular variables, hematocrit, total solids, capillary refill time (CRT) and color of mucous membranes were measured as blood was collected from the carotid artery into sterile plastic bags. Arterial blood gas analysis was also performed. Results The average amount of blood collected from these horses was (mean ± SD) 53 ± 4.8 mL kg^?1 bodyweight (range: 23–32 kg) over 39 ± 4 minutes. Hematocrit decreased from 38 ± 3 to 32 ± 2% after induction of anesthesia and did not change significantly over the period of blood loss. Total solids decreased significantly after induction of anesthesia, and over the period of blood loss. Systolic, mean, diastolic and pulse pressures decreased as blood was lost. Heart rate did not change significantly. Capillary refill time increased from 1.6 ± 0.4 seconds to 4.8 ± 1.3 seconds as blood loss increased. Mucous membrane color deteriorated progressively. Arterial PO₂ decreased significantly over the period of blood loss. Conclusions Hematocrit and heart rate do not change significantly during acute severe hemorrhage in the anesthetized horse. Arterial blood pressure, pulse pressure and PaO₂ decrease as blood loss increases. Changes in mucous membrane color and CRT also occur as blood loss increases. Clinical relevance During severe hemorrhage in the inhalant‐anesthetized horse, both heart rate and hematocrit remain unchanged. Blood pressure decreases and changes in arterial PO₂ correlate most strongly with volume of blood lost.     

Dexmedetomidine low dose followed by constant rate infusion and antagonism by atipamezole in isoflurane-anesthetized cats: an echocardiographic study

Objective

To investigate the effects of a low dose of dexmedetomidine (DEX) followed by constant rate infusion (CRI) and reversal with atipamezole on systolic and diastolic functions in isoflurane-anesthetized healthy cats.

Pharmacokinetics and cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys (Macaca mulatta)

OBJECTIVE: To determine pharmacokinetics and selected cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys. ANIMALS: 6 adult male rhesus monkeys. PROCEDURE: Fentanyl (8 mg/kg of body weight, IV) was administered to 6 monkeys anesthetized with isoflurane. End-tidal isoflurane concentration and esophageal temperature were kept constant, and ventilation was mechanically assisted. Heart rate, rhythm, aortic blood pressure, and blood pH, gas, and fentanyl concentrations were determined before and for 8 hours after administration of fentanyl. Pharmacokinetics of fentanyl were derived by use of noncompartmental methods based on statistical moment theory. RESULTS: Heart rate and mean arterial pressure decreased transiently following fentanyl administration. Maximal decreases were observed 5 to 15 minutes after administration. Arterial pH, Paco2, and Pao2 ranged from 7.46 +/- 0.04 to 751 +/- 0.05 units, 29.2 +/- 3 to 34.6 +/- 4.4 mm Hg, and 412.6 +/- 105.3 to 482.9 +/- 71.2 mm Hg, respectively. The clearance, volume of distribution area, volume of distribution steady state, mean residence time, area under the curve, elimination rate constant, and half-life were 32.5 +/- 2.48 ml/kg/min, 9.04 +/- 1.91 L/kg, 70 +/- 1.2 L/kg, 218.5 +/- 35.5 min, 0.247 +/- 0.019 mg/ml/min, 0.004 + 0.001/min, and 192.0 +/- 33.5 min, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Transient but potentially clinically important decreases in heart rate and mean arterial pressure were observed following fentanyl administration. Distribution and clearance data were similar to those reported for dogs and humans.     

Effects of dobutamine, norepinephrine, and vasopressin on cardiovascular function in anesthetized neonatal foals with induced hypotension

OBJECTIVE: To determine the effects of dobutamine, norepinephrine, and vasopressin on cardiovascular function and gastric mucosal perfusion in anesthetized foals during isoflurane-induced hypotension. ANIMALS: 6 foals that were 1 to 5 days of age. PROCEDURES: 6 foals received 3 vasoactive drugs with at least 24 hours between treatments. Treatments consisted of dobutamine (4 and 8 Sang/kg/min), norepinephrine (0.3 and 1.0 Sang/kg/min), and vasopressin (0.3 and 1.0 mU/kg/min) administered IV. Foals were maintained at a steady hypotensive state induced by a deep level of isoflurane anesthesia for 30 minutes, and baseline cardiorespiratory variables were recorded. Vasoactive drugs were administered at the low infusion rate for 15 minutes, and cardiorespiratory variables were recorded. Drugs were then administered at the high infusion rate for 15 minutes, and cardiorespiratory variables were recorded a third time. Gastric mucosal perfusion was measured by tonometry at the same time points. RESULTS: Dobutamine and norepinephrine administration improved cardiac index. Vascular resistance was increased by norepinephrine and vasopressin administration but decreased by dobutamine at the high infusion rate. Blood pressure was increased by all treatments but was significantly higher during the high infusion rate of norepinephrine. Oxygen delivery was significantly increased by norepinephrine and dobutamine administration; O2 consumption decreased with dobutamine. The O2 extraction ratio was decreased following norepinephrine and dobutamine treatments. The gastric to arterial CO2 gap was significantly increased during administration of vasopressin at the high infusion rate. CONCLUSION AND CLINICAL RELEVANCE: Norepinephrine and dobutamine are better alternatives than vasopressin for restoring cardiovascular function and maintaining splanchnic circulation during isoflurane-induced hypotension in neonatal foals.     

The hemodynamic effects of medetomidine continuous rate infusions in the dog

ObjectiveTo characterize the hemodynamic effects of continuous rate infusions (CRI) of medetomidine administered at doses ranging from 0 to 3 μg kg^?1 hour^?1.Study designProspective, blinded, randomized experimental trial.AnimalsSix adult purpose-bred mongrel dogs.MethodsAnesthesia was induced with sevoflurane for placement of arterial and venous catheters. Dogs recovered from anesthesia after which baseline hemodynamic measurements were obtained via lithium dilution cardiac output (CO) determination, with subsequent measurements via pulse power analysis to provide continuous CO determinations. Medetomidine, 1, 2, or 3 μg kg^?1 hour^?1 or a volume equivalent placebo, was administered via CRI for 60 minutes. Systolic, mean, and diastolic arterial pressure, heart rate (HR), CO and stroke volume were measured and stroke index (SI), cardiac index (CI), total peripheral resistance (TPR), and total peripheral resistance index (TPRI) were calculated at 3, 7, 10, 20, 30, 45, 60, 90, and 120 minutes from the start of the infusion.ResultsIncrease in dose decreased SI by 25%, 19%, and 30%, HR by 33%, 57%, and 60%, CI by 50%, 65%, 70% and increased TPRI by 109%, 235%, and 222% from baseline to the 60-minute measurement for the 1, 2, and 3 μg kg^?1 hour^?1 doses, respectively. HR, TPRI, and CI all showed significant differences over the duration of the study from the placebo treatment.ConclusionsMedetomidine CRI produces clinically relevant changes in CO, TPR, and HR. The demonstrated decrease in CO is largely because of bradycardia and the degree of cardiovascular depression appears to be dose-dependent. These findings are consistent with previously described hemodynamic changes with single bolus administration of medetomidine.Clinical relevanceLow-dose medetomidine CRIs produce clinically relevant hemodynamic depression at doses as low as 1 μg kg^?1 hour^?1 and should be used cautiously in dogs.     

Use of ephedrine and dopamine in dogs for the management of hypotension in routine clinical cases under isoflurane anesthesia

OBJECTIVE: To determine the cardiovascular responses of ephedrine and dopamine for the management of presurgical hypotension in anesthetized dogs. STUDY DESIGN: Prospective, randomized, clinical trial. ANIMALS: Twelve healthy client-owned dogs admitted for orthopedic surgery; six per group METHODS: Prior to surgery, 58 anesthetized dogs were monitored for hypotension [mean arterial pressure (MAP) <60 mmHg] that was not associated with bradycardia or excessive anesthetic depth. Ephedrine (0.2 mg kg(-1), IV) or dopamine (5 microg kg(-1) minute(-1), IV) was randomly assigned for treatment in 12 hypotensive dogs. Ten minutes after the first treatment (Tx(1)-10), ephedrine was repeated or the dopamine infusion rate was doubled. Cardiovascular assessments taken at baseline, Tx(1)-10, and 10 minutes following treatment adjustment (Tx(2)-10) were compared for differences within and between treatments (p < 0.05). RESULTS: Ephedrine increased cardiac index (CI), stroke volume index (SVI), oxygen delivery index (DO(2)I), and decreased total peripheral resistance (TPR) by Tx(1)-10, while MAP increased transiently (<5 minutes). The second ephedrine bolus produced no further improvement. Dopamine failed to produce significant changes at 5 microg kg(-1) minute(-1), while 10 microg kg(-1) minute(-1) increased MAP, CI, SVI significantly from baseline, and DO(2)I compared with Tx(1)-10. The improvement in CI, SVI, and DO(2)I was not significantly different between treatments at Tx(2)-10. CONCLUSIONS AND CLINICAL RELEVANCE: In anesthetized hypotensive dogs, ephedrine and dopamine improved cardiac output and oxygen delivery. However, the pressure-elevating effect of ephedrine is transient, while an infusion of dopamine at 10 microg kg(-1) minute(-1) improved MAP significantly by additionally maintaining TPR.     

The effect of hyoscine on dobutamine requirement in spontaneously breathing horses anaesthetized with halothane

OBJECTIVE: To determine whether hyoscine has a sparing effect on the volume of dobutamine required to maintain mean arterial pressure (MAP) at 70 mmHg in horses anaesthetized with halothane. STUDY DESIGN: Prospective, randomized, controlled clinical trial. ANIMALS: Twenty adult horses weighing 507 +/- 97 kg (mean +/- SD), aged 10 +/- 5 years. MATERIALS AND METHODS: Pre-anaesthetic medication in all horses was intramuscular (IM) acepromazine (40 mug kg(-1)) and intravenous (IV) detomidine (0.02 mg kg(-1)). Anaesthesia was induced with ketamine (2.2 mg kg(-1) IV) and diazepam (0.02 mg kg(-1) IV), and maintained with halothane in oxygen. Horses breathed spontaneously. Flunixin (1.1 mg kg(-1) IV) was given to provide analgesia. Heart rate, ECG, invasive arterial pressure, respiratory rate, percentage end-tidal carbon dioxide, percentage end-tidal halothane and partial pressure of oxygen and carbon dioxide in arterial blood and blood pH were monitored. Dobutamine was infused by an infusion pump to maintain MAP at 70 mmHg. Horses were randomly assigned to receive saline or hyoscine (0.1 mg kg(-1)) IV 30 minutes after induction. The heart rate, MAP and volume of dobutamine infused over 30-minute periods were measured and analysed statistically using a one-way anova. RESULTS: After administration of hyoscine, heart rate increased for 10 minutes (p < 0.01) and MAP for 5 minutes (p < 0.01). There was no difference in the volume of dobutamine infused over 30 minutes between horses given hyoscine or saline, although there was a wide individual variation in dobutamine requirements. No side effects of hyoscine were seen. CONCLUSIONS: The increase in heart rate and blood pressure that occurs after 0.1 mg kg(-1) hyoscine is given IV in anaesthetized horses, is of short duration and does not significantly alter the amount of dobutamine required to maintain arterial pressure over the next 30 minutes. Clinical relevance The short duration of action of 0.1 mg kg(-1) hyoscine IV may limit its usefulness for correction of hypotension in horses anaesthetized with halothane. Further work is necessary to investigate the effects of higher or repeated doses or constant rate infusions of hyoscine.