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Biomedical subjects

Ann E Wagner

Publications and source records attributed to Ann E Wagner.

15 recordsLinked to original sources

Pharmacokinetics and pharmacodynamics of morphine in llamas.

OBJECTIVE: To assess the pharmacokinetics and pharmacodynamics of morphine in llamas. ANIMALS: 6 healthy adult llamas. PROCEDURES: Llamas received morphine sulfate in a randomized crossover design. In phase 1, they received IV or IM administration of morphine at 0.05 or 0.5 mg/kg, respectively; in phase 2, they received IV administration of morphine at 0.05, 0.25, or 0.5 mg/kg. Plasma morphine and morphine-6-glucuronide concentrations were determined by validated methods. Body temperature, heart rate, respiratory rate, sedation, and analgesia were assessed and compared with plasma concentrations by regression analysis. RESULTS: Total body clearance was similar between IV administration of morphine sulfate at 0.25 and 0.5 mg/kg (mean +/- SD, 25.3 +/- 6.9 mL/min/kg and 27.3 +/- 5.9 mL/min/kg, respectively), and linearity was demonstrated between these doses. Bioavailability of morphine following IM administration at 0.5 mg/kg was 120 +/- 30%. Body temperature and sedation increased as the dose of morphine administered increased. Heart rate was unaffected by varying doses. Respiratory rate decreased as dose increased. Analgesia was difficult to assess as a result of high individual variability. Intravenous administration of morphine at 0.25 mg/kg provided the most consistent increase in tolerance to electric stimulation. Pharmacodynamic modeling revealed a sigmoidal relationship between plasma concentration and sedation score. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine was characterized by a large apparent volume of distribution and high systemic clearance in llamas. A prolonged half-life was observed with IM injection. Intravenous administration of morphine sulfate at 0.25 mg/kg every 4 hours is suggested for further study.

Analgesia↗

Influence of gastrointestinal tract disease on pharmacokinetics of lidocaine after intravenous infusion in anesthetized horses.

OBJECTIVE: To determine the disposition of lidocaine after IV infusion in anesthetized horses undergoing exploratory laparotomy because of gastrointestinal tract disease. ANIMALS: 11 horses (mean +/- SD, 10.3 +/- 7.4 years; 526 +/- 40 kg). PROCEDURE: Lidocaine hydrochloride (loading infusion, 1.3 mg/kg during a 15-minute period [87.5 microg/kg/min]; maintenance infusion, 50 microg/kg/min for 60 to 90 minutes) was administered IV to dorsally recumbent anesthetized horses. Blood samples were collected before and at fixed time points during and after lidocaine infusion for analysis of serum drug concentrations by use of liquid chromatography-mass spectrometry. Serum lidocaine concentrations were evaluated by use of standard noncompartmental analysis. Selected cardiopulmonary variables, including heart rate (HR), mean arterial pressure (MAP), arterial pH, PaCO2, and PaO2, were recorded. Recovery quality was assessed and recorded. RESULTS: Serum lidocaine concentrations paralleled administration, increasing rapidly with the initiation of the loading infusion and decreasing rapidly following discontinuation of the maintenance infusion. Mean +/- SD volume of distribution at steady state, total body clearance, and terminal half-life were 0.70 +/- 0.39 L/kg, 25 +/- 3 mL/kg/min, and 65 +/- 33 minutes, respectively. Cardiopulmonary variables were within reference ranges for horses anesthetized with inhalation anesthetics. Mean HR ranged from 36 +/- 1 beats/min to 43 +/- 9 beats/min, and mean MAP ranged from 74 +/- 18 mm Hg to 89 +/- 10 mm Hg. Recovery quality ranged from poor to excellent. CONCLUSIONS AND CLINICAL RELEVANCE: Availability of pharmacokinetic data for horses with gastrointestinal tract disease will facilitate appropriate clinical dosing of lidocaine.

Anesthesia↗

Evaluation of hemodynamic measurements, including lithium dilution cardiac output, in anesthetized dogs undergoing ovariohysterectomy.

OBJECTIVE: To measure cardiac output in healthy female anesthetized dogs by use of lithium dilution cardiac output and determine whether changes in mean arterial pressure were caused by changes in cardiac output or systemic vascular resistance. DESIGN: Prospective clinical study. ANIMALS: 20 healthy female dogs. PROCEDURE: Dogs were anesthetized for ovariohysterectomy. Ten dogs breathed spontaneously throughout anesthesia, and 10 dogs received intermittent positive-pressure ventilation. Cardiovascular and respiratory measurements, including lithium dilution cardiac output, were performed during anesthesia and surgery. RESULTS: Mean arterial pressure and systemic vascular resistance index were low after induction of anesthesia and just prior to surgery and increased significantly after surgery began. Cardiac index (cardiac output indexed to body surface area) did not change significantly throughout anesthesia and surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Results provide baseline data for cardiac output and cardiac index measurements during clinical anesthesia and surgery in dogs. Changes in mean arterial pressure do not necessarily reflect corresponding changes in cardiac index.

Anesthesia, General↗

Disorganization: the forgotten executive dysfunction in high-functioning autism (HFA) spectrum disorders.

Executive function (EF) abilities were investigated in 72 children with high-functioning autism (HFA) spectrum disorders through the collection of parent ratings and performance on laboratory measures of EF. In addition, discrepancy analysis was used to isolate executive functioning on tasks that carry multiple demands. Comparison of HFA and Asperger Disorder (AD) groups did not reveal consistent differences in EF. Results did indicate global EF deficits in the combined group of children with HFA and AD. Within the EF domain, specific deficits in flexibility and organization were most prominent.

Adolescent↗

Evaluation of xylazine and ketamine for total intravenous anesthesia in horses.

OBJECTIVE: To evaluate the use of xylazine and ketamine for total i.v. anesthesia in horses. ANIMALS: 8 horses. PROCEDURE: Anesthetic induction was performed on 4 occasions in each horse with xylazine (0.75 mg/kg, i.v.), guaifenesin (75 mg/kg, i.v.), and ketamine (2 mg/kg, i.v.). Intravenous infusions of xylazine and ketamine were then started by use of 1 of 6 treatments as follows for which 35, 90, 120, and 150 represent infusion dosages (microg/kg/min) and X and K represent xylazine and ketamine, respectively: X35 + K90 with 100% inspired oxygen (O2), X35 + K120-(O2), X35 + K150-(O2), X70 + K90-(O2), K150-(O2), and X35 + K120 with a 21% fraction of inspired oxygen (ie, air). Cardiopulmonary measurements were performed. Response to a noxious electrical stimulus was observed at 20, 40, and 60 minutes after induction. Times to achieve sternal recumbency and standing were recorded. Quality of sedation, induction, and recovery to sternal recumbency and standing were subjectively evaluated. RESULTS: Heart rate and cardiac index were higher and total peripheral resistance lower in K150-(O2) and X35 + K120-air groups. The mean arterial pressure was highest in the X35 + K120-air group and lowest in the K150-(O2) group (125 +/- 6 vs 85 +/- 8 at 20 minutes, respectively). Mean Pa(O2) was lowest in the X35 + K120-air group. Times to sternal recumbency and standing were shortest for horses receiving K150-(O2) (23 +/- 6 minutes and 33 +/- 8 minutes, respectively) and longest for those receiving X70 + K90-(O2) (58 +/- 28 minutes and 69 +/- 27 minutes, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Infusions of xylazine and ketamine may be used with oxygen supplementation to maintain 60 minutes of anesthesia in healthy adult horses.

Anesthesia, Intravenous↗

Influence of general anesthesia on pharmacokinetics of intravenous lidocaine infusion in horses.

OBJECTIVE: To compare the disposition of lidocaine administered IV in awake and anesthetized horses. ANIMALS: 16 horses. PROCEDURE: After instrumentation and collection of baseline data, lidocaine (loading infusion, 1.3 mg/kg administered during 15 minutes (87 microg/kg/min); constant rate infusion, 50 microg/kg/min) was administered IV to awake or anesthetized horses for a total of 105 minutes. Blood samples were collected at fixed times during the loading and maintenance infusion periods and after the infusion period for analysis of serum lidocaine concentrations by use of liquid chromatography with mass spectral detection. Selected cardiopulmonary parameters including heart rate (HR), mean arterial pressure (MAP), arterial pH, PaCO2, and PaO2 were also recorded at fixed time points during lidocaine administration. Serum lidocaine concentrations were evaluated by use of standard noncompartmental analysis. RESULTS: Serum lidocaine concentrations were higher in anesthetized than awake horses at all time points during lidocaine administration. Serum lidocaine concentrations reached peak values during the loading infusion in both groups (1,849 +/- 385 ng/mL and 3,348 +/- 602 ng/mL in awake and anesthetized horses, respectively). Most lidocaine pharmacokinetic variables also differed between groups. Differences in cardiopulmonary variables were predictable; for example, HR and MAP were lower and PaO2 was higher in anesthetized than awake horses but within reference ranges reported for horses under similar conditions. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthesia has an influence on the disposition of lidocaine in horses, and a change in dosing during anesthesia should be considered.

Anesthesia, General↗

Cardiopulmonary changes induced during one-lung ventilation in anesthetized dogs with a closed thoracic cavity.

OBJECTIVE: To evaluate the effects of one-lung ventilation (OLV) on oxygen delivery (DO2) in anesthetized dogs with a closed thoracic cavity. ANIMALS: 7 clinically normal adult Walker Hound dogs. PROCEDURE: Dogs were anesthetized. Catheters were inserted in a dorsal pedal artery and the pulmonary artery. Dogs were positioned in right lateral recumbency. Data were collected at baseline (Paco2 of 35 to 45 mm Hg), during two-lung ventilation, and 15 minutes after creating OLV. Hemodynamic and respiratory variables were analyzed and calculations performed to obtain DO2, and values were compared among the various time points by use of an ANOVA for repeated measures. RESULTS: OLV induced a significant augmentation of shunt fraction that resulted in a significant reduction in Pao2, arterial oxygen saturation, and arterial oxygen content. Cardiac index was not significantly changed. The net result was that DO2 was not significantly affected by OLV. CONCLUSIONS AND CLINICAL RELEVANCE: Use of OLV in healthy dogs does not induce significant changes in DO2, which is the ultimate variable to use when evaluating tissue oxygenation. One-lung ventilation can be initiated safely in dogs before entering the thoracic cavity during surgery. Additional studies are necessary to evaluate OLV in clinically affected patients and variations in age, body position, and type of anesthetic protocol.

Analysis of Variance↗

Cardiopulmonary effects of positive end-expiratory pressure during one-lung ventilation in anesthetized dogs with a closed thoracic cavity.

OBJECTIVE: To evaluate the effects on oxygen delivery (DO2) of 2.5 and 5 cm H2O of positive end-expiratory pressure (PEEP) applied to the dependent lung during one-lung ventilation (OLV) in anesthetized dogs with a closed thoracic cavity. ANIMALS: 7 clinically normal adult Walker Hound dogs. PROCEDURE: Dogs were anesthetized, and catheters were inserted in a dorsal pedal artery and the pulmonary artery. Dogs were positioned in right lateral recumbency, and data were collected during OLV (baseline), after application of 2.5 cm H2O of PEEP for 15 minutes during OLV, and after application of 5 cm H2O of PEEP for 15 minutes during OLV. Hemodynamic and respiratory variables were analyzed and calculations performed to obtain DO2, and values were compared among the various time points by use of an ANOVA for repeated measures. RESULTS: PEEP induced a significant decrease in shunt fraction that resulted in a significant increase in arterial oxygen saturation. However, it failed to significantly affect arterial oxygen content (CaO2) or cardiac output. Thus, DO2 was not affected in healthy normoxemic dogs as a net result of the application of PEEP. CONCLUSIONS AND CLINICAL RELEVANCE: The use of PEEP during OLV in anesthetized dogs with a closed thoracic cavity did not affect DO2. Use of PEEP during OLV in dogs with a closed thoracic cavity is recommended because it does not affect cardiac output and any gain in CaO2 will be beneficial for DO2 in critically ill patients.

Analysis of Variance↗

Comparison of opioid and alpha-2 adrenergic receptor binding in horse and dog brain using radioligand autoradiography.

OBJECTIVE: To test the hypothesis that the distribution, density, and subtype of opioid and alpha (alpha)-2 adrenergic receptors within the central nervous system (CNS) are significantly different between horse and dog. STUDY DESIGN: Prospective experimental study. ANIMALS: Three dogs (3 years of age) and three horses (2-5 years of age). Animals were opioid- and alpha-2 agonist-free at the time of euthanasia. METHODS: Brain tissue was obtained at 126 days post-surgery from dogs and 72 days post-surgery from horses. The brains were removed, sectioned coronally into 1-cm slabs, frozen in methylbutane, which was cooled by liquid nitrogen, and stored at -70 degrees C. Receptor autoradiography was performed using established techniques. [3H]DAMGO, [3H]U-69593, and [3H]RX821002 were used for mu ( micro )-opioid, kappa (kappa)-opioid, and alpha-2 adrenergic-binding assays, respectively. Species differences were analyzed separately for each major brain region by repeated measures anova for subregions followed by Fisher's protected Latin square design (LSD). p < 0.05 was considered significant. RESULTS: There was higher binding of micro -opioid receptors in the frontal cortex, left somatosensory cortex, colliculus (mid-brain), and granule cell layer of the cerebellum of horses than that of dogs. There was higher binding to kappa-opioid receptors in the frontal cortex of dogs compared to horses, whereas binding to kappa-opioid receptors in the cerebellum was higher in horses. Binding to alpha-2 adrenergic receptors in the mid-brain was significantly higher in dogs than in horses. There was higher binding of alpha-2 adrenergic receptors in the dorsomedial and dorsolateral periaqueductal grey of dogs as compared to that of horses. CONCLUSION: The results of this study show that the distribution of these receptors is different between horses and dogs. Further work is needed to understand the relevance of these differences to clinical responses to opioids and alpha-2 adrenergic agonists in these species.

Animals↗

The sedative and behavioral effects of nalbuphine in dogs.

We compared the degree of sedation and frequency and intensity of adverse behaviors in dogs associated with nalbuphine when combined with acepromazine or xylazine compared with those of acepromazine or xylazine alone. Twenty-four dogs (13 female, 11 male) undergoing routine ovariohysterectomy or castration were randomly assigned to one of four groups. Group NX received 0.5 mg/kg nalbuphine and 0.5 mg/kg xylazine subcutaneously (s.c.). Group X received 0.5 mg/kg xylazine s.c. Group NA received 0.5 mg/kg nalbuphine and 0.05 mg/kg acepromazine s.c. Group A received 0.05 mg/kg acepromazine s.c. All dogs received 0.01 mg/kg glycopyrrolate s.c. All doses were administered preoperatively. Preoperative resting measurements of heart rate, respiratory rate, rectal temperature, and body weight were obtained. Sedation was scored both inside and outside a kennel prior to drug administration and at 10, 20, and 30 min after drug administration. Dogs were assessed for behavioral responses (leg withdrawal, shivering, rigidity, orienting, panting, struggling, vocalization, wide-eyed facial expression, breath holding, salivating, hiding, biting, or requiring a muzzle) during three time periods: placing the dog on the table, clipping and prepping of forelimb, and intravenous catheterization. Postoperative recovery behaviors were scored. Expired halothane concentrations were recorded at 15, 30, and 45 min postinduction. Significant differences occurred in the level of sedation at 30 min between dogs receiving nalbuphine and xylazine or xylazine only compared with dogs receiving acepromazine. There was a significant difference in behavioral scores with respect to leg withdrawal and orienting during clipping/prepping between dogs receiving nalbuphine and xylazine compared with dogs receiving xylazine. The combination of nalbuphine and xylazine is a useful premedicant which provided greater sedation than acepromazine and reduced some anxiety behaviors more than did xylazine alone. Nalbuphine is an inexpensive opioid and currently is not a controlled substance in the U.S.

Acepromazine↗

Use of low doses of ketamine administered by constant rate infusion as an adjunct for postoperative analgesia in dogs.

OBJECTIVE: To compare indicators of postoperative pain and behavior in dogs with and without a low-dose ketamine infusion added to usual perioperative management. DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: 27 dogs undergoing forelimb amputation. PROCEDURE: Dogs were anesthetized with glycopyrrolate, morphine, propofol, and isoflurane. Thirteen dogs were treated with ketamine IV, as follows: 0.5 mg/kg (0.23 mg/lb) as a bolus before surgery, 10 microg/kg/min (4.5 microg/lb/min) during surgery, and 2 microg/kg/min (0.9 microg/lb/min) for 18 hours after surgery. Fourteen dogs received the same volume of saline (0.9% NaCl) solution. All dogs received an infusion of fentanyl (1 to 5 microg/kg/h [0.45 to 2.27 pg/lb/h]) for the first 18 hours after surgery. Dogs were evaluated for signs of pain before surgery, at the time of extubation, and 1, 2, 3, 4, 12, and 18 hours after extubation. Owners evaluated their dogs' appetite, activity, and wound soreness on postoperative days 2, 3, and 4. RESULTS: Dogs that received ketamine infusions had significantly lower pain scores 12 and 18 hours after surgery and were significantly more active on postoperative day 3 than dogs that received saline solution infusions. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that perioperative administration of low doses of ketamine to dogs may augment analgesia and comfort in the postoperative surgical period.

Amputation, Surgical↗

Use of biphasic electrical cardioversion for treatment of idiopathic atrial fibrillation in two horses.

Rectilinear biphasic cardioversion was used in 2 horses with idiopathic sustained atrial fibrillation; 1 horse converted to sustained sinus rhythm. Variables that potentially affected outcome of the electrical cardioversion procedures in these horses included duration of arrhythmia, placement of cardioverter pads and paddles, serum electrolyte concentrations, and treatment with quinidine. Serum cardiac troponin I concentration, measured to determine whether the myocardium was damaged from the electrical shocks, was within the reference range in both horses after the procedure. Biphasic electrical cardioversion may provide an alternative to pharmacologic cardioversion with quinidine in horses. The rectilinear biphasic defibrillator-cardioverter uses a unique biphasic waveform to deliver constant current to the myocardium during cardioversion, regardless of transthoracic impedance. Biphasic cardioversion is safer and more effective than traditional monophasic cardioversion in humans and animals.

Animals↗

Adaptive skills and executive function in autism spectrum disorders.

There is active debate regarding the nature of executive dysfunction in autism. Additionally, investigations have yet to show a relationship between deficits in executive function and the everyday behavioral difficulties that may originate from them. The present study examined the relationship between executive abilities and adaptive behavior in 35 children with Autism Spectrum Disorders, using two parent reports of everyday functioning, the Vineland Adaptive Behavior Scales (VABS) and the Behavior Rating Inventory of Executive Function (BRIEF). Results found several relationships: The Initiate and Working Memory domains were negatively correlated with most domains of adaptive behavior. Also, the Communication and Socialization domains of the VABS were negatively correlated with several areas of executive functioning, suggesting that impairments in executive abilities are strongly associated with the deficits in communication, play and social relationships found in children with autism.

Adaptation, Psychological↗

Observations of private veterinary practices in Colorado, with an emphasis on anesthesia.

RATIONALE FOR THE STUDY: To give academic faculty in anesthesia a better understanding of the anesthetic techniques used by veterinarians in private practice, in order to enhance their teaching of anesthesiology to veterinary students. METHODOLOGY: Two anesthesia faculty members visited 20 different small-animal veterinary practices, interviewing veterinarians and technical staff about their use of anesthesia and their anesthesia-related problems. RESULTS: Compared to most university veterinary teaching hospitals, private practitioners tended to use fewer anesthetic drugs, provide fewer analgesics, do more out-patient procedures, and rarely monitor blood pressure in anesthetized animals. CONCLUSION: Techniques of anesthesia and monitoring used in private veterinary practice are often quite different from those used in large university teaching hospitals.

Anesthesia↗