Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs.

OBJECTIVE: To examine the accuracy of plethysmography variability index (PVI) as a noninvasive indicator of fluid responsiveness in hypovolaemic dogs. STUDY DESIGN: Prospective experimental study. ANIMALS: Six adult healthy sevoflurane-anaesthetized Beagle dogs. METHODS: Dogs were anaesthetized with 1.3-fold their individual minimum alveolar concentration of sevoflurane. The lungs were mechanically ventilated after neuromuscular blockade with vecuronium bromide. Cardiopulmonary variables including mean arterial blood pressure (MAP), central venous pressure (CVP), transpulmonary thermodilution cardiac output (TPTDCO), stroke volume (SV), perfusion index (PI), pulse pressure variation (PPV), stroke volume variation (SVV) and PVI were determined during six stages of graded venous blood withdrawal (5 mL kg-1 increments) and six stages of graded blood infusion (5 mL kg-1 increments). The cardiopulmonary variables were analysed using paired t test or Wilcoxon signed rank test. Correlations between PPV and SVV or PVI were analysed by linear regression. The accuracy of PPV, SVV and PVI for predicting fluid responsiveness was examined by using receiver operating characteristic curve analysis. A value of p < 0.05 was considered statistically significant. RESULTS: Blood withdrawal resulted in significant increases in PPV and PVI and decreases in MAP, CVP, TPTDCO, SV and PI. Blood infusion resulted in significant increases in MAP, CVP, TPTDCO, SV and PI and decreases in PPV and PVI. PPV and PVI showed a relevant correlation (p < 0.001, r2 = 0.62) and threshold values of PPV ≥ 16% (sensitivity 71%, specificity 82%) and PVI ≥ 12% (sensitivity 78%, specificity 72%) for identifying fluid responsiveness. SVV did not change. CONCLUSIONS AND CLINICAL RELEVANCE: Noninvasive measurement of PVI predicted fluid responsiveness with moderate accuracy equal to PPV in sevoflurane-anaesthetized mechanically ventilated dogs. Provisional threshold values for identification of fluid responsiveness were PPV ≥ 16% and PVI ≥ 12%. Clinical trials are needed to confirm these threshold values in dogs.

A review of equine anesthetic induction: Are all equine anesthetic inductions "crash" inductions?

Horses are the most challenging of the common companion animals to anesthetize. Induction of anesthesia in the horse is complicated by the fact that it is accompanied by a transition from a conscious standing position to uncconconscious recumbency. The purpose of this article is to review the literature on induction of anesthesia with a focus on the behavioral and physiologic/pharmacodynamic responses and the actions and interactions of the drugs administered to induce anesthesia in the healthy adult horse with the goal of increasing consistency and predictability.

Dynamic detection and reversal of myocardial ischemia using an artificially intelligent bioelectronic medicine.

Myocardial ischemia is spontaneous, frequently asymptomatic, and contributes to fatal cardiovascular consequences. Importantly, myocardial sensory networks cannot reliably detect and correct myocardial ischemia on their own. Here, we demonstrate an artificially intelligent and responsive bioelectronic medicine, where an artificial neural network (ANN) supplements myocardial sensory networks, enabling reliable detection and correction of myocardial ischemia. ANNs were first trained to decode spontaneous cardiovascular stress and myocardial ischemia with an overall accuracy of ~92%. ANN-controlled vagus nerve stimulation (VNS) significantly mitigated major physiological features of myocardial ischemia, including ST depression and arrhythmias. In contrast, open-loop VNS or ANN-controlled VNS following a caudal vagotomy essentially failed to reverse cardiovascular pathophysiology. Last, variants of ANNs were used to meet clinically relevant needs, including interpretable visualizations and unsupervised detection of emerging cardiovascular stress. Overall, these preclinical results suggest that ANNs can potentially supplement deficient myocardial sensory networks via an artificially intelligent bioelectronic medicine system.

Effect of 50% and maximal inspired oxygen concentrations on respiratory variables in isoflurane-anesthetized horses.

BACKGROUND: The purpose of this study was to compare the effects of 0.5 fraction of inspired oxygen (FiO2) and >0.95 FiO2 on pulmonary gas exchange, shunt fraction and oxygen delivery (DO2) in dorsally recumbent horses during inhalant anesthesia. The use of 0.5 FiO2 has the potential to reduce absorption atelectasis (compared to maximal FiO2) and augment alveolar oxygen (O2) tensions (compared to ambient air) thereby improving gas exchange and DO2. Our hypothesis was that 0.5 FiO2 would reduce ventilation-perfusion mismatching and increase the fraction of pulmonary blood flow that is oxygenated, thus improving arterial oxygen content and DO2. RESULTS: Arterial partial pressures of O2 were significantly higher than preanesthetic levels at all times during anesthesia in the >0.95 FiO2 group. Arterial partial pressures of O2 did not change from preanesthetic levels in the 0.5 FiO2 group but were significantly lower than in the >0.95 FiO2 group from 15 to 90 min of anesthesia. Alveolar to arterial O2 tension difference was increased significantly in both groups during anesthesia compared to preanesthetic values. The alveolar to arterial O2 tension difference was significantly higher at all times in the >0.95 FiO2 group compared to the 0.5 FiO2 group. Oxygen delivery did not change from preanesthetic values in either group during anesthesia but was significantly lower than preanesthetic values 10 min after anesthesia in the 0.5 FiO2 group. Shunt fraction increased in both groups during anesthesia attaining statistical significance at varying times. Shunt fraction was significantly increased in both groups 10 min after anesthesia but was not different between groups. Alveolar dead space ventilation increased after 3 hr of anesthesia in both groups. CONCLUSIONS: Reducing FiO2 did not change alveolar dead space ventilation or shunt fraction in dorsally recumbent, mechanically ventilated horses during 3 hr of isoflurane anesthesia. Reducing FiO2 in dorsally recumbent isoflurane anesthetized horses does not improve oxygenation or oxygen delivery.

Closed-Loop Control for Fluid Resuscitation: Recent Advances and Future Challenges.

Fluid therapy is extensively used to treat traumatized patients as well as patients during surgery. The fluid therapy process is complex due to interpatient variability in response to therapy as well as other complicating factors such as comorbidities and general anesthesia. These complexities can result in under- or over-resuscitation. Given the complexity of the fluid management process as well as the increased capabilities in hemodynamic monitoring, closed-loop fluid management can reduce the workload of the overworked clinician while ensuring specific constraints on hemodynamic endpoints are met with higher accuracy. The goal of this paper is to provide an overview of closed-loop control systems for fluid management and highlight several key steps in transitioning such a technology from bench to the bedside.

Effects of perzinfotel on the minimum alveolar concentration of isoflurane in dogs when administered as a preanesthetic via various routes or in combination with butorphanol.

OBJECTIVE: To determine the anesthetic-sparing effects of perzinfotel when administered as a preanesthetic via IV, IM, or SC routes or IM in combination with butorphanol. ANIMALS: 6 healthy sexually intact Beagles (4 males and 2 females; age, 18.5 to 31 months; body weight, 9.8 to 12.4 kg). PROCEDURES: After administration of a placebo, perzinfotel (10 to 30 mg/kg), or a perzinfotel-butorphanol combination, anesthesia was induced in dogs with propofol and maintained with isoflurane in oxygen. The following variables were continuously monitored: bispectral index; heart rate; systolic, diastolic, and mean arterial blood pressures; end-tidal concentration of isoflurane; end-tidal partial pressure of CO(2); oxygen saturation as measured by pulse oximetry; rectal temperature; and inspiration and expiration concentrations of isoflurane. A noxious stimulation protocol was used, and the minimum alveolar concentration (MAC) was determined twice during anesthesia. RESULTS: IV, IM, and SC administration of perzinfotel alone decreased the mean isoflurane MAC values by 32% to 44% and significantly increased bispectral index values. A dose of 30 mg of perzinfotel/kg IM resulted in significant increases in heart rate and diastolic arterial blood pressure. The greatest MAC reduction (59%) was obtained with a combination of 20 mg of perzinfotel/kg IM and 0.2 mg of butorphanol/kg IM, whereas administration of butorphanol alone yielded a 15% reduction in the isoflurane MAC. CONCLUSIONS AND CLINICAL RELEVANCE: SC, IM, or IV administration of perzinfotel prior to induction of isoflurane anesthesia improved anesthetic safety by reducing inhalant anesthetic requirements in healthy dogs.

Effects of perzinfotel, butorphanol tartrate, and a butorphanol-perzinfotel combination on the minimum alveolar concentration of isoflurane in cats.

OBJECTIVE: To determine the effects of perzinfotel, butorphanol, and their combination on the minimal alveolar concentration (MAC) of isoflurane in cats. ANIMALS: 7 healthy sexually intact cats (4 males and 3 females), aged 12 to 17 months and weighing 2.8 to 4.6 kg. PROCEDURES: In a crossover design, saline (0.9% NaCl) solution, perzinfotel (2.5 to 15 mg/kg; IV, IM, and SC), butorphanol tartrate (0.2 mg/kg, IM), or a combination of 5 mg of perzinfotel/kg and 2 mg of butorphanol tartrate/kg (both IM) was administered to 6 cats before 7 separate episodes of anesthesia with isoflurane in oxygen. Heart rate, arterial blood pressure, bispectral index (BIS), and inspiration and expiration concentrations of isoflurane were continuously monitored. The isoflurane MAC was determined twice during anesthesia. RESULTS: IV, IM, and SC administration of perzinfotel at 2.5 to 15 mg/kg resulted in a significant decrease in mean isoflurane MAC by 43.3% to 68.0%. The BIS significantly increased after perzinfotel administration via the same routes at 2.5 to 15 mg/kg and after perzinfotel-butorphanol administration IM. Blood pressure was significantly higher after perzinfotel was administered at 5 mg/kg, IM; 10 mg/kg, IV; and 10 mg/kg, SC than after saline solution administration. CONCLUSIONS AND CLINICAL RELEVANCE: Perzinfotel administration decreased the isoflurane MAC and increased several BIS and blood pressure values in anesthetized cats. Administration of perzinfotel prior to isoflurane anesthesia may improve anesthetic safety by reducing inhalant anesthetic requirements and improving cardiovascular function during anesthesia.

Investigation of escalating and large bolus doses of a novel, nano-droplet, aqueous 1% propofol formulation in cats.

OBJECTIVE: Identify, describe, and quantitate effects of an escalating dose of a nano-droplet formulation of 1% w/v propofol in telemetered cats. STUDY DESIGN: Prospective two-period parallel design with one treatment procedure per period. ANIMALS: Four female intact, purpose-bred domestic short-hair cats. METHODS: Each animal served as its own control in each period. Telemetered cats were anesthetized on two separate occasions. In Phase I, cats received propofol (8 mg kg(-1)) over 90 seconds. Unless a severe adverse event (SAE) had occurred by this time, repeated doses of 4 mg kg(-1) intravenous (IV) propofol were administered every 3 minutes until the onset of an SAE. In Phase 2, the IV dose of propofol required to produce at least one SAE in Phase I was administered unless an SAE occurred before the dose was completed. Propofol infusion ceased after development of the first SAE. Heart rate, heart rhythm, respiratory rate, systolic, diastolic, and mean arterial blood pressure, SpO(2) and body temperature were continuously recorded before, during and after propofol administration. The incidence and time to onset of an SAE and dose of propofol required to produce an SAE were recorded. The response criteria included time to lateral recumbency, times to orotracheal intubation and extubation, time to sternal recumbency during recovery, time to and duration of first adverse event(s), and total dose of propofol administered. RESULTS: The dose of propofol required to produce an SAE in Phase I was 16.6 and 15.2 mg kg(-1) in Phase 2. Hypotension was the first and most frequently observed SAE. CONCLUSIONS: Larger doses of a novel, nano-droplet propofol formulation can produce SAEs similar to those reported for lipid emulsion formulations. CLINICAL RELEVANCE: Systemic arterial blood pressure should be monitored in cats administered IV propofol.

Pain: mechanisms and management in horses.

Pain is a multidimensional sensory phenomenon that has evolved as a protective method for maintaining homeostasis and facilitating tissue repair. Both excitatory and inhibitory physiologic and pathologic mechanisms are involved in its generation and maintenance. Untreated pain and nervous system changes (plasticity) that occur during chronic pain make pain much more difficult or impossible to effectively treat. Therapies directed toward the treatment of pain should be mechanism based and preventative whenever possible. Prospective, randomized clinical trials conducted in horses that suffer from naturally occurring pain will help to determine the current best approaches to effective pain therapy.

NMDA receptor antagonists and pain: ketamine.

N-Methyl-D-aspartate (NMDA) is a synthetic chemical binding molecule (ligand) that selectively binds to the "slow response" glutamate NMDA receptor (NMDAR). NMDARs are important for normal brain function and play a central role in learning, memory, and the development of central nervous system hyperactive states. Diverse chemicals belonging to various drug families have demonstrated NMDAR antagonistic effects. Ketamine has been shown to produce antihyperalgesic effects produced by incision and tissue or nerve damage, and has become popular in equine practice as an anesthetic and more recently as an analgesic for standing surgical procedures and the treatment of laminitis. This review focuses on the development of ketamine as an anesthetic and analgesic in horses.

Myocardial Contractility: Historical and Contemporary Considerations.

The term myocardial contractility is thought to have originated more than 125 years ago and has remained and enigma ever since. Although the term is frequently used in textbooks, editorials and contemporary manuscripts its definition remains illusive often being conflated with cardiac performance or inotropy. The absence of a universally accepted definition has led to confusion, disagreement and misconceptions among physiologists, cardiologists and safety pharmacologists regarding its definition particularly in light of new discoveries regarding the load dependent kinetics of cardiac contraction and their translation to cardiac force-velocity and ventricular pressure-volume measurements. Importantly, the Starling interpretation of force development is length-dependent while contractility is length independent. Most historical definitions employ an operational approach and define cardiac contractility in terms of the hearts mechanical properties independent of loading conditions. Literally defined the term contract infers that something has become smaller, shrunk or shortened. The addition of the suffix "ility" implies the quality of this process. The discovery and clinical investigation of small molecules that bind to sarcomeric proteins independently altering force or velocity requires that a modern definition of the term myocardial contractility be developed if the term is to persist. This review reconsiders the historical and contemporary interpretations of the terms cardiac performance and inotropy and recommends a modern definition of myocardial contractility as the preload, afterload and length-independent intrinsic kinetically controlled, chemo-mechanical processes responsible for the development of force and velocity.

Understanding Volume Kinetics: The Role of Pharmacokinetic Modeling and Analysis in Fluid Therapy.

Fluid therapy is a rapidly evolving yet imprecise clinical practice based upon broad assumptions, species-to-species extrapolations, obsolete experimental evidence, and individual preferences. Although widely recognized as a mainstay therapy in human and veterinary medicine, fluid therapy is not always benign and can cause significant harm through fluid overload, which increases patient morbidity and mortality. As with other pharmaceutical substances, fluids exert physiological effects when introduced into the body and therefore should be considered as "drugs." In human medicine, an innovative adaptation of pharmacokinetic analysis for intravenous fluids known as volume kinetics using serial hemoglobin dilution and urine output has been developed, refined, and investigated extensively for over two decades. Intravenous fluids can now be studied like pharmaceutical drugs, leading to improved understanding of their distribution, elimination, volume effect, efficacy, and half-life (duration of effect) under various physiologic conditions, making evidence-based approaches to fluid therapy possible. This review article introduces the basic concepts of volume kinetics, its current use in human and animal research, as well as its potential and limitations as a research tool for fluid therapy research in veterinary medicine. With limited evidence to support our current fluid administration practices in veterinary medicine, a greater understanding of volume kinetics and body water physiology in veterinary species would ideally provide some evidence-based support for safer and more effective intravenous fluid prescriptions in veterinary patients.

Evaluation of hyperviscous fluid resuscitation in a canine model of hemorrhagic shock: a randomized, controlled study.

BACKGROUND: Enhancing plasma viscosity during fluid resuscitation results in vasodilation and improved microvascular perfusion in rodents subjected to hemorrhagic shock. We hypothesized that resuscitation with hyperviscous lactated Ringer's solution (hyperLRS) would result in improved tissue oxygenation and acid-base values in hemorrhaged dogs. METHODS: Twelve dogs were anesthetized and splenectomized. Vascular catheterization was performed, and tissue oxygen probes were placed in the jejunal serosa and skeletal muscle to assess macro- and microhemodynamic parameters. Baseline (BL) and posthemorrhage data were obtained. After 1 hour of hemorrhagic shock (mean arterial pressure [MAP] 30-40 mm Hg), treatment groups (n = 6) were administered bolus LRS or hyperLRS, and then received sufficient LRS to achieve and maintain an MAP between 60 mm Hg and 70 mm Hg. Data were obtained at 10, 30, 60, 120, and 180 minutes after fluid resuscitation. RESULTS: There were no significant differences between LRS or hyperLRS groups at BL or posthemorrhage. Blood and plasma viscosity were significantly increased by the administration of hyperLRS at all time points postresuscitation compared with LRS. Significantly more fluid was required to maintain MAP, and vascular hindrance was consistently lower in dogs administered hyperLRS versus LRS, suggesting viscosity-induced vasodilation. Central and mesenteric venous oxygen saturations were significantly decreased, whereas lactate and oxygen extraction ratios were significantly increased after hyperLRS administration compared with LRS. The tissue oxygen tension was similar in dogs administered hyperLRS or LRS. CONCLUSIONS: A hyperviscous balanced electrolyte solution did not improve hemodynamic parameters, tissue oxygen tension, or acid-base values despite evidence for viscosity-induced vasodilation.

Evaluation of bispectral index (BIS) as an indicator of central nervous system depression in horses anesthetized with propofol.

The bispectral index (BIS) was evaluated as an indicator of central nervous system (CNS) depression in horses anesthetized with propofol. Five non-premedicated horses were anesthetized with 7 mg/kg, IV propofol and the minimum infusion rate (MIR) of propofol required to maintain anesthesia was determined during intermittent positive pressure ventilation in each horse. The BIS was determined 20 min later and after stabilization at 2.0 MIR, 1.5 MIR, and 1.0 MIR. The BIS was also recorded after the cessation of propofol infusion when the horses regained spontaneous breathing and swallowing reflex. The MIR and plasma concentration (Cp) of propofol were 0.20 +/- 0.03 mg/kg/min and 17.5 +/- 4.0 microg/ml, respectively. The BIS value and Cp were 59 +/- 13 and 26.7 +/- 8.6 microg/ml at 2.0 MIR, 63 +/- 9 and 22.9 +/- 9.7 microg/ml at 1.5 MIR, 64 +/- 13 and 20.1 +/- 5.9 microg/ml at 1.0 MIR, 64 +/- 24 and 13.0 +/- 2.8 microg/ml at return of spontaneous breathing, and 91 +/- 4 and 11.0 +/- 3.4 microg/ml when the swallowing reflex returned, respectively. The BIS value was significantly less in anesthetized horses compared to horses once swallowing returned (p=0.025). The BIS value was significantly correlated with the propofol Cp (r=-0.625, p=0.001). There was not a significant difference in the BIS values during the MIR multiples of propofol. The BIS was a useful indicator of awakening but did not indicate the degree of CNS depression during propofol-anesthesia in horses.

Effects of intravenous administration of perzinfotel, fentanyl, and a combination of both drugs on the minimum alveolar concentration of isoflurane in dogs.

OBJECTIVE-To determine the effects of IV administration of perzinfotel and a perzinfotel-fentanyl combination on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS-6 healthy sexually intact Beagles (3 males and 3 females). PROCEDURES-All dogs were instrumented with a telemetry device for continuous monitoring of heart rate, arterial blood pressure, and core body temperature (at a femoral artery). Dogs were anesthetized with propofol (6 mg/kg, IV) and isoflurane. Isoflurane MAC values were determined in 3 experiments in each dog, separated by at least 7 days, before (baseline) and after the following treatments: no treatment (anesthetic only), perzinfotel (20 mg/kg, IV), fentanyl (5 microg/kg bolus, IV, followed by a continuous IV infusion at 0.15 microg/kg/min), and a fentanyl-perzinfotel combination (20 mg of perzinfotel/kg, IV, plus the fentanyl infusion). Bispectral index and oxygen saturation as measured by pulse oximetry were also monitored throughout anesthesia. RESULTS-Without treatment, the mean +/- SD isoflurane MAC for all 6 dogs was 1.41 +/- 0.10%. Baseline MAC was 1.42 +/- 0.08%. Intravenous administration of perzinfotel, fentanyl, and the perzinfotel-fentanyl combination significantly decreased the MAC by 39%, 35%, and 66%, respectively. Perzinfotel and perzinfotel-fentanyl administration yielded significant increases in the bispectral index. Mean, systolic, and diastolic arterial blood pressures significantly increased from baseline values when perzinfotel was administered. Systolic arterial blood pressure significantly increased from the baseline value when perzinfotel-fentanyl was administered. No adverse effects were detected. CONCLUSIONS AND CLINICAL RELEVANCE-IV administration of perzinfotel, fentanyl, or a perzinfotel-fentanyl combination reduced isoflurane MAC in dogs and increased arterial blood pressure.

Evaluation of a commercial ultrasonographic hemodynamic recording system for the measurement of cardiac output in dogs.

OBJECTIVE: To evaluate the accuracy of a commercial ultrasonographic cardiac output (CO) monitoring system (UCOMS) in anesthetized Beagles as assessed by comparison with thermodilution CO (TDCO). ANIMALS: 8 healthy anesthetized Beagles. PROCEDURES: Simultaneous UCOMS and TDCO measurements of CO were obtained during 4 hemodynamic states: baseline anesthesia (0.5% to 1.5% isoflurane), a higher depth of anesthesia (2% to 3.5% isoflurane) to yield a >or= 15% reduction in systolic arterial blood pressure, IV infusion of colloidal solution to a mean right atrial pressure of >or= 15 mm Hg, and IV infusion of dobutamine at 5 microg/kg/min. Measurements were obtained at 2 probe positions: the subxiphoid region and the right thoracic inlet. Correlation and agreement of results between methods were determined via linear regression analysis and Bland-Altman plots. RESULTS: A significant positive correlation was detected between UCOMS andTDCO measurements obtained at the subxiphoid (R = 0.86) and thoracic inlet (R = 0.83) positions. Bland-Altman plots revealed minimal bias between methods (bias +/- SD, -0.03 +/- 0.73 L/min and -0.20 +/- 0.80 L/min for subxiphoid and thoracic inlet measurements, respectively). However, the percentage error associated with UCOMS measurements made at the 2 positions was > 45%. CONCLUSIONS AND CLINICAL RELEVANCE: When compared with the results of TDCO, CO measured with the UCOMS exceeded commonly accepted limits of error in healthy dogs. The UCOMS was, however, able to track changes in CO across hemodynamic states. Additional research is needed to assess the usefulness of the UCOMS for monitoring CO in critically ill dogs.

Effect of intravenous administration of lactated Ringer's solution or hetastarch for the treatment of isoflurane-induced hypotension in dogs.

OBJECTIVE: To determine the effect of IV administration of crystalloid (lactated Ringer's solution [LRS]) or colloid (hetastarch) fluid on isoflurane-induced hypotension in dogs. ANIMALS: 6 healthy Beagles. PROCEDURES: On 3 occasions, each dog was anesthetized with propofol and isoflurane and instrumented with a thermodilution catheter (pulmonary artery). Following baseline assessments of hemodynamic variables, end-tidal isoflurane concentration was increased to achieve systolic arterial blood pressure (SABP) of 80 mm Hg. At that time (0 minutes), 1 of 3 IV treatments (no fluid, LRS [80 mL/kg/h], or hetastarch [80 mL/kg/h]) was initiated. Fluid administration continued until SABP was within 10% of baseline or to a maximum volume of 80 mL/kg (LRS) or 40 mL/kg (hetastarch). Hemodynamic variables were measured at intervals (0 through 120 minutes and additionally at 150 and 180 minutes in LRS- or hetastarch-treated dogs). Several clinicopathologic variables including total protein concentration, PCV, colloid osmotic pressure, and viscosity of blood were assessed at baseline and intervals thereafter (0 through 120 minutes). RESULTS: Administration of 80 mL of LRS/kg did not increase SABP in any dog, whereas administration of

Effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration of sevoflurane in dogs.

Sparing effects of carprofen and meloxicam with or without butorphanol on the minimum alveolar concentration (MAC) of sevoflurane were determined in 6 dogs. Anesthesia was induced and maintained with sevoflurane in oxygen, and MAC was determined by use of a tail clamp method. The dogs were administered a subcutaneous injection of carprofen (4 mg/kg) or meloxicam (0.2 mg/kg), or no medication (control) one hour prior to induction of anesthesia. Following the initial determination of MAC, butorphanol (0.3 mg/kg) was administered intramuscularly, and MAC was determined again. The sevoflurane MACs for carprofen alone (2.10 +/- 0.26%) and meloxicam alone (2.06 +/- 0.20%) were significantly less than the control (2.39 +/- 0.26%). The sevoflurane MACs for the combination of carprofen with butorphanol (1.78 +/- 0.20%) and meloxicam with butorphanol (1.66 +/- 0.29%) were also significantly less than the control value after the administration of butorphanol (2.12 +/- 0.28%). The sevoflurane sparing effects of the combinations of carprofen with butorphanol and meloxicam with butorphanol were additive.

Anesthetic and cardiopulmonary effects of intramuscular morphine, medetomidine, ketamine injection in dogs.

OBJECTIVE: To determine the quality and duration of anesthesia and the cardiopulmonary effects of a morphine, medetomidine, ketamine (MMK) combination administered intramuscularly (IM) to dogs. STUDY DESIGN: Descriptive injectable anesthetic protocol evaluation. ANIMALS: Eight intact adult Beagle dogs: five males, three females. METHODS: The electrocardiogram, heart rate, direct arterial blood pressure, and core body temperature were monitored in eight chronically instrumented dogs. Each dog received 0.2 mg kg(-1) morphine sulfate, 20 microg kg(-1) medetomidine hydrochloride, and 5 mg kg(-1) ketamine hydrochloride IM. Anesthetic and analgesic effects (clamping the tail and metatarsus) were categorized, and the times to lateral recumbency, orotracheal intubation, extubation, and sternal recumbency were recorded. Respiratory, cardiovascular, temperature, and acid-base variables were recorded 5 minutes before, and 3, 10, 20, 30, 45, 50, and 60 minutes after MMK. Atipamezole, 100 microg kg(-1) IM, was administered 60 minutes after MMK administration and data recorded 10 minutes later. RESULTS: The onset of anesthesia was uneventful and rapid. Time to lateral recumbency was 7.1 +/- 4.1 minutes. The tracheas of four dogs were orally intubated in 5.1 +/- 0.8 minutes. After MMK administration most dogs were unresponsive to noxious stimulation from 20 to 60 minutes and heart rate, cardiac index and venous blood pH were significantly decreased from baseline values. Arterial blood pressure increased initially and then returned to baseline values. Times to extubation (four dogs) and return to sternal recumbency after atipamezole administration were 2.8 +/- 1.8 and 4.3 +/- 4.4 minutes, respectively. CONCLUSION: The IM administration of MMK produced anesthesia and analgesia in Beagle dogs. Hemodynamic data were within accepted normal values. Atipamezole administration produced rapid return to consciousness in all dogs. CLINICAL RELEVANCE: Morphine/medetomidine/ketamine may be used for minor medical and surgical procedures requiring short-term anesthesia and analgesia but it is not recommended for medical procedures that are painful.

Anesthesia-Associated Relative Hypovolemia: Mechanisms, Monitoring, and Treatment Considerations.

Although the utility and benefits of anesthesia and analgesia are irrefutable, their practice is not void of risks. Almost all drugs that produce anesthesia endanger cardiovascular stability by producing dose-dependent impairment of cardiac function, vascular reactivity, and compensatory autoregulatory responses. Whereas anesthesia-related depression of cardiac performance and arterial vasodilation are well recognized adverse effects contributing to anesthetic risk, far less emphasis has been placed on effects impacting venous physiology and venous return. The venous circulation, containing about 65-70% of the total blood volume, is a pivotal contributor to stroke volume and cardiac output. Vasodilation, particularly venodilation, is the primary cause of relative hypovolemia produced by anesthetic drugs and is often associated with increased venous compliance, decreased venous return, and reduced response to vasoactive substances. Depending on factors such as patient status and monitoring, a state of relative hypovolemia may remain clinically undetected, with impending consequences owing to impaired oxygen delivery and tissue perfusion. Concurrent processes related to comorbidities, hypothermia, inflammation, trauma, sepsis, or other causes of hemodynamic or metabolic compromise, may further exacerbate the condition. Despite scientific and technological advances, clinical monitoring and treatment of relative hypovolemia still pose relevant challenges to the anesthesiologist. This short perspective seeks to define relative hypovolemia, describe the venous system's role in supporting normal cardiovascular function, characterize effects of anesthetic drugs on venous physiology, and address current considerations and challenges for monitoring and treatment of relative hypovolemia, with focus on insights for future therapies.