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Biomedical subjects

A E Wagner

Publications and source records attributed to A E Wagner.

At least 19 recordsLinked to original sources

Effects of diazepam and flumazenil on minimum alveolar concentrations for dogs anesthetized with isoflurane or a combination of isoflurane and fentanyl.

OBJECTIVE: To determine the effect of a constant-rate infusion of fentanyl on minimum alveolar concentration (MAC) of isoflurane and to determine the interaction between fentanyl and a benzodiazepine agonist (diazepam) and antagonist (flumazenil) in isoflurane-anesthetized dogs. ANIMALS: 8 mixed-breed adult dogs. PROCEDURE: Dogs were anesthetized with isoflurane 3 times during a 6-week period. After a 30-minute equilibration period, each MAC determination was performed in triplicate, using standard techniques. Fentanyl was administered as a bolus (10 microg/kg of body weight, IV) that was followed by a constant infusion (0.3 microg/kg per min, IV) throughout the remainder of the experiment. After determining isoflurane-fentanyl MAC in triplicate, each dog received saline (0.9% NaCl) solution, diazepam, or flumazenil. After 30 minutes, MAC was determined again. RESULTS: Fentanyl significantly decreased isoflurane MAC (corrected to a barometric pressure of 760 mm Hg) from 1.80+/-0.21 to 0.85+/-0.14%, a reduction of 53%. Isoflurane-fentanyl-diazepam MAC (0.48+/-0.29%) was significantly less than isoflurane-fentanyl-saline MAC (0.79+/-0.21%). Percentage reduction in isoflurane MAC was significantly greater for fentanyl-diazepam (74%), compared with fentanyl-saline (54%) or fentanyl-flumazenil (61%). Mean fentanyl concentrations for the entire experiment were increased over time and were higher in the diazepam group than the saline or flumazenil groups. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl markedly decreased isoflurane MAC in dogs. Diazepam, but not flumazenil, further decreased isoflurane-fentanyl MAC. Our results indicate that diazepam enhances, whereas flumazenil does not affect, opioid-induced CNS depression and, possibly, analgesia in dogs.

Adjuvants, Anesthesia↗

Changes in anesthetic sensitivity and glutamate receptors in the aging canine brain.

This study investigated whether the aging process in dogs is associated with an increased sensitivity to inhalation anesthesia and whether age-related changes in glutamate receptors are related to the increased sensitivity. The mean minimum alveolar concentration (MAC) of isoflurane was 1.82 +/- .08% for 2-3 year olds and 1.45 +/- .06% for 11 years olds, indicating that there was an increased potency of isoflurane in the older dogs as compared to the young. These older animals also showed a significant decrease in binding of [3H]glutamate and [3H]dizocilpine ([3H]MK801) to N-methyl-D-aspartate (NMDA) receptors in multiple cortical and hippocampal regions. The density of binding to NMDA receptors in the cortex, using a single concentration of ligand, correlated significantly with individual MAC values. These results demonstrate that dogs experience an increase in anesthetic potency with increased age, similar to humans, and that age-related changes in the NMDA receptor may represent one mechanism underlying this increased sensitivity to anesthesia.

Aging↗

Neurodevelopmental outcome in ECMO vs near-miss ECMO patients at 5 years of age.

The objective of this study was to compare the outcome of children at 5 years of age who were treated with extracorporeal membrane oxygenation (ECMO) and those who were critically ill but did not meet ECMO criteria, identified as near-miss ECMO. In one of the longest studies of its kind, we compared the neurodevelopmental outcome of 76 5-year-old ECMO-treated children with 20 5-year-old near-miss ECMO patients with similar primary diagnoses. The two groups were compared for demographic data, level of ventilatory support, and degree of hyperventilation. The comprehensive assessment protocol included an assessment of intelligence (IQ), attainment of preacademic and early academic skills, and parents' report of adaptive behavior. Both groups had similar demographic data and primary diagnosis. The near-miss ECMO patients required increased ventilatory support but not significantly more than the ECMO patients. The cognitive outcome was similar in both groups with mean estimated Full-Scale IQ in the normal range for near-miss and ECMO groups (89 and 97, respectively). Rates of severe mental handicap (FSIQ < 70) (near-miss = 11%, ECMO = 12%) and risk for school failure (near-miss = 38%, ECMO = 37%) were also similar. More parents of near-miss ECMO patients reported immature adaptive skills than did parents of ECMO patients, although the numbers were small in each group. Rates of parent-reported child behavior problems were similar in both groups. ECMO and near-miss ECMO patients have similar cognitive and adaptive outcomes at 5 years of age. A significant number in each group are at risk of school failure and should be closely followed up.

Central Nervous System Diseases↗

Cardiopulmonary measurements in dogs undergoing gastropexy without gastrectomy for correction of gastric dilatation-volvulus.

OBJECTIVE: To measure cardiopulmonary variables, including cardiac index, in dogs with naturally acquired gastric dilatation-volvulus (GDV). DESIGN: Prospective clinical study. ANIMALS: 6 dogs with GDV. PROCEDURE: In addition to typical medical and surgical management of GDV, the dorsal metatarsal and pulmonary arteries and right atrium of the dogs were catheterized to obtain cardiopulmonary measurements before and during anesthesia and surgery. RESULTS: All dogs underwent gastropexy but none required gastrectomy. Mean cardiac index and mean arterial blood pressure for this small population of dogs with GDV were not significantly different from those reported for clinically normal awake or anesthetized dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with naturally acquired GDV without gastric necrosis may not have the classic characteristics, including decreased cardiac index and hypotension, of hypovolemic circulatory shock.

Animals↗

Attitudes of veterinary medical students, house officers, clinical faculty, and staff toward pain management in animals.

OBJECTIVE: To determine whether animal factors and level of professional veterinary medical training were associated with attitudes toward pain management in animals. DESIGN: Exploratory, descriptive survey. SAMPLE POPULATION: Students in the College of Veterinary Medicine and Biomedical Sciences professional veterinary medical curriculum (approx 540) and clinical faculty (approx 50), house officers (approx 25), and support staff (approx 100) in the Colorado State University Veterinary Teaching Hospital. PROCEDURE: A descriptive survey including demographic, descriptive, and case-based questions was distributed to participants. Participation was voluntary and survey results were anonymous. RESULTS: 357 of 720 surveys were completed and returned (31 by faculty, 29 by staff, 18 by house officers, and 279 by students). There was a high degree of concordance among survey participants regarding the overall importance of treating pain in animals. The extent to which pain should be alleviated and animal factors, such as breed, behavior, and clinical circumstances, accounted for much of the discordance among survey groups. Fourth-year veterinary students indicated that they were occasionally less likely to treat animals for pain than were second- or third-year veterinary students. CLINICAL IMPLICATIONS: The diversity of opinions regarding the necessity or desirability of treating pain in animals, the apparent decrease in the likelihood of senior veterinary students to treat animals for pain under certain circumstances, and evidence of knowledge deficits regarding analgesic treatments among all groups contribute to the likelihood that pain in animals will neither be consistently recognized nor appropriately treated.

Analgesia↗

Monitoring adequacy of ventilation by capnometry during thoracotomy in dogs.

OBJECTIVE: To determine whether end-tidal partial pressure of carbon dioxide (PETCO2) was a reliable estimate of PaCO2 in dogs undergoing thoracotomy. DESIGN: Case series. ANIMALS: 18 dogs that underwent thoracotomy. PROCEDURE: PaCO2 and PETCO2 were measured shortly after induction of anesthesia, while dogs were breathing spontaneously; 5 minutes prior to initial skin incision, while dogs were receiving intermittent positive-pressure ventilation (IPPV); 5, 30, and 60 minutes after the thoracic cavity was opened, while dogs were receiving IPPV; and after the thoracic cavity was closed and evacuated, when dogs were again breathing spontaneously. For each period, arterial-end-tidal difference in partial pressure of carbon dioxide (PaCO2-PETCO2) was compared with PaCO2-PETCO2 for the preceding period. RESULTS: Significant changes in PaCO2-PETCO2 from one period to the next were not detected except when values obtained 5 minutes after the thoracic cavity was opened were compared with values obtained 5 minutes before incision. The PaCO2-PETCO2 was not constant for individual dogs. CLINICAL IMPLICATIONS: PETCO2 was not a reliable indicator of adequacy of ventilation during thoracotomy in these dogs, because it differed greatly from PaCO2, and PaCO2-PETCO2 was not consistent.

Animals↗

Pattern of neuropsychological deficit at age five years following neonatal unilateral brain injury.

The pattern of language deficit following left-hemisphere brain injury and visual/spatial deficit following right-hemisphere injury in an adult or older child is well recognized, but has been inconsistently reported following presumed neonatal brain injury. Our prospective study of 24 children at age 5 with documented neonatal unilateral brain injury lends support to the theory of hemisphere specialization at the time of birth. Twelve children who had unilateral left-hemisphere lesion were compared to 12 children with unilateral right-hemisphere lesion of similar timing and severity. Relative visual/spatial deficit following right-hemisphere lesion and receptive language deficit following left-hemisphere lesion were identified. Lateralized measures of grip strength, fine motor speed, and fine motor dexterity were not significantly different between the groups for either hand in this nonhemiparetic study sample. Only one child with a left-hemisphere lesion was left-handed, and only one child (right-lesion) had a hemiparesis.

Brain Injuries↗

The effects of hyperoxia on the biosynthesis of cyclooxygenase products and haemodynamic response to nitric oxide synthase inhibition with L-NAME in endotoxaemic pigs.

The interaction between constitutive nitric oxide and oxygen may depend on the degree of tissue oxygenation and may play a critical role in the pathophysiological response to endotoxaemia. We investigated if hyperoxia (100% O2) attenuated the systemic and pulmonary vasoconstriction and increased biosynthesis of thromboxane B2 (TXB2) and 6-keto-prostaglandin (PG) F1alpha induced by inhibition of nitric oxide synthase with NG-nitro-L-arginine-methyl-ester (L-NAME) in a porcine model of endotoxaemia. Twenty-two domestic, random source pigs, weighing 15.4 +/- 2.7 kg (mean +/- standard deviation) were the subjects of this study. Pigs were anaesthetized with isoflurane in 100% O2, orotracheally intubated and ventilated to maintain normocapnia, and then instrumented for haemodynamic monitoring. Following instrumentation, pigs were maintained at an end-tidal isoflurane concentration of 2%. Pigs were randomly assigned to treatment groups: saline + 30% O2 (Control, n = 6); Escherichia coli lipopolysaccharide (5 microg/kg/h from 1 to 2 h followed by 2 microg/kg/h from 2 to 5 h) + 30% O2 (LPS, n = 4); L-NAME (0.5 mg/kg/h, from 0 to 5 h) + LPS + 100% O2 (n = 6); and L-NAME + LPS + 30% O2 (n = 6). L-NAME and endotoxin significantly (P < 0.05) increased mean arterial pressure, mean pulmonary arterial pressure, and systemic and pulmonary vascular resistance index beginning at 90 min. When results were pooled across all time periods, mean arterial pressure and mean pulmonary arterial pressure were significantly higher in the L-NAME + LPS + 30% O2 group than all other groups, reflecting pulmonary and systemic vasoconstriction. Hyperoxia attenuated the L-NAME + LPS-induced increases in TXB2 and 6-keto-PGF1alpha concentrations at 90 and 120 min and 120 min, respectively, although the differences were not statistically significant. These results support the observation that nitric oxide synthase inhibition with L-NAME has deleterious haemodynamic effects in this model of endotoxaemia. The temporal attenuation of L-NAME-induced pulmonary and systemic vasoconstriction by hyperoxia suggested that the haemodynamic effects of acute endotoxaemia were in part influenced by the relative amounts of nitric oxide and oxygen present.

6-Ketoprostaglandin F1 alpha↗

Severity of brain injury following neonatal extracorporeal membrane oxygenation and outcome at age 5 years.

Neurodevelopmental evaluation in childhood provides an opportunity to study complex neurological compensation following documented neonatal brain injury, and furnishes important clinical information which may have an impact on patient care. We studied 152 term children treated with extracorporeal membrane oxygenation (ECMO) as neonates and who received routine neonatal neuroimaging and comprehensive neurodevelopmental evaluation at age 5 years. The cohort was divided into four groups based on an independent neuroimaging score: No lesion, N=88; Mild lesion, N=38; Moderate lesion, N=12; and Severe lesion, N=14. Standardized testing at age 5 included complete neuropsychological assessment, neurological evaluation, and assessment of motor function. All testing was conducted without knowledge of the neuroimaging score. The occurrence of disability by severity of neuroimaging was: No lesion=10%; Mild=13%; Moderate=33%; Severe=57%. The relative risk within the ECMO population for disability at age 5 after moderate or severe neonatal lesion was 4.3 (CI=1.0 to 17.5) and 11.7 (CI=3.3 to 41.3), respectively. The remaining non-disabled children who had moderate to severe lesions functioned within normal limits. Severity of neonatal neuroimaging was inversely associated with IQ scores, pre-academic skills, and neuromotor function. The effect size was small but the rank order was predictable. Our data identify in 5-year-old children an impact of brain lesion severity demonstrated on routine neonatal neuroimaging. The results indicate potential compensation following moderate and severe lesions, and suggest a subtle but consistent influence of even mild neonatal brain injury.

Central Nervous System Diseases↗

Evaluation of five common induction protocols by comparison of hemodynamic responses to surgical manipulation in halothane-anesthetized horses.

OBJECTIVE: To determine whether hemodynamic responses of halothane-anesthetized horses undergoing surgical procedures depended on anesthetic induction protocols used, and to determine whether hemodynamic responses to surgical manipulation could be detected. DESIGN: Prospective experimental study without controls. ANIMALS: 36 clinically normal horses. PROCEDURE: Horses were allotted to 5 groups according to anesthetic induction protocol: acepromazine/guaifenesin/thiamylal, acepromazine/guaifenesin/ketamine, xylazine/guaifenesin/thiamylal, xylazine/guaifenesin/ketamine, and xylazine/diazepam/ketamine. Anesthesia was maintained with halothane. Hemodynamic measurements and blood gas values were obtained prior to the start of surgery, during surgery, and after surgery. RESULTS: Few differences in hemodynamic measurements existed between horses in which anesthesia was induced by 5 anesthetic induction protocols, whether prior to the start of surgery or for pooled values for all 3 measurement periods. Hemodynamic responses to surgical manipulation were marked and included increased mean arterial pressure and systemic vascular resistance, and decreased cardiac index and oxygen delivery. CLINICAL IMPLICATIONS: Choice of anesthetic induction protocol has little impact on hemodynamic function during surgery in halothane-anesthetized horses. Surgical stimulation may increase blood pressure, but does not improve cardiac index or oxygen delivery.

Acepromazine↗

Neurodevelopmental status at age five years of neonates treated with extracorporeal membrane oxygenation.

OBJECTIVE: To determine the neurodevelopmental status at age 5 years among children who received extracorporeal membrane oxygenation (ECMO) in the newborn period as a treatment for severe cardiorespiratory failure. METHODS: We conducted a prospective cohort study of 103 five-year-old ECMO-treated children born between June 1984 and July 1988, and treated at our institution. Thirty-seven healthy control children were recruited locally. The assessment protocol included a complete neuropsychologic assessment, psychosocial assessment with parent questionnaires, a standard neurologic evaluation, assessment of gross motor and fine motor function, a medical history, and physical examination. RESULTS: Major disability was present in 17 of the ECMO cohort. Eleven ECMO-treated children (11%) were mentally retarded, one of whom was profoundly impaired. Two additional children had severe learning disabilities. Cerebral palsy was diagnosed in 5 (5%) ECMO-treated children, but all cases were mild in nature and the patients were walking unaided. One child has paraplegia. The mean Full Scale, Verbal, and Performance IQs of the EMCO-treated children were within the normal range, but as a group were significantly lower than in control children (96 vs 115, p < 0.001). Children treated with ECMO had increased risk relative to the control children for academic difficulties at school age (49% VS 22%, P < 0.01) and a higher rate of behavioral problems reported by parents (42% vs 16%, p = 0.01). CONCLUSIONS: The rate of major disability was comparable to that in other high-risk populations. The high rate of behavioral problems and increased risk of subsequent school failure among nonretarded ECMO-treated children supports the need for close follow-up of these children after hospital discharge.

Child Development↗

Congenital diaphragmatic hernia: long-term outcome in neonates treated with extracorporeal membrane oxygenation.

As more infants with congenital diaphragmatic hernia (CDH) survive with extracorporeal membrane oxygenation (ECMO), it seems prudent to detail the longterm outcome in these medically complex infants. Eighteen children with CDH-treated with postoperative ECMO were recruited for participation in this study. The mean duration of ECMO was 193 hours (range 82 to 493 hours), mean time to extubation after ECMO was 142 hours (range 34 to 312 hours), and median duration of hospitalization was 46 days (range 30 to 181 days). Of the 18 infants, 4 (22%) were discharged home requiring oxygen therapy. At follow-up the notable findings were a high incidence of gastroesophageal reflux and failure to thrive. At both 1 and 2 years of age, 50% of infants were at less than the 5th percentile for weight. At 1 and 2 years of age, 39% and 21%, respectively, were at less than the 5th percentile for weight/length ratio. A total of 16 children (89%) had clinical evidence of reflux, and 8 (44%) were discharged home on a regimen of nasogastric feedings. Reherniation occurred in 4 children (22%) and was more frequent when a patch was used. An electrocardiogram showed right ventricular hypertrophy in 6 (43%); oxygen saturation by pulse oximetry was > 95% in all children, and pulmonary artery pressure was estimated by Doppler echocardiography to be normal in 12 of 14 children examined. The neurodevelopmental outcome (Bayley Scales or Stanford-Binet scale) at 1 to 4 years of age was not dissimilar from that of other ECMO-treated children. Given the severity of illness in the neonatal period, the general health and development of children with CDH surviving after ECMO are good. Surprisingly few children have long-term respiratory complications related to pulmonary hypoplasia. Follow-up in the first few years should be aimed at aggressive nutritional intervention to prevent the growth failure that appears to be prevalent in these children.

Brain Diseases↗

Effects of ephedrine on cardiovascular function and oxygen delivery in isoflurane-anesthetized dogs.

The hemodynamic effects of 2 dosages of ephedrine were studied in 6 dogs anesthetized with isoflurane only (end-tidal concentration equivalent to 1.5 times minimum alveolar concentration). Following instrumentation, baseline (time 0) measurements included heart rate (HR), respiratory rate, mean arterial blood pressure (MAP), cardiac output, and blood gas tensions. Cardiac index (CI), stroke volume (SV), systemic vascular resistance (SVR), arterial oxygen content (CaO2), and oxygen delivery and consumption (DO2 and VO2, respectively) were calculated. Three dogs were given ephedrine IV at a dosage of 0.1 mg/kg of body weight, and 3 dogs were given ephedrine IV at a dosage of 0.25 mg/kg. Measurements were recorded at 5, 10, 15, 30, and 60 minutes. Each dog then received the alternate dosage of ephedrine, and measurements were again recorded at the same intervals. Effects of ephedrine varied with dosage. Neither dosage was associated with significant changes in pH, PaO2, PaCO2, VO2, or respiratory rate. Ephedrine at a dosage of 0.1 mg/kg caused transient significant increases in MAP, CI, SV, CaO2, and DO2, significant decreases in HR and SVR, and a late, slight decrease in CaO2. Ephedrine at a dosage of 0.25 mg/kg caused a greater and more prolonged increase in MAP, as well as increases in CI, SV, and SVR, and a decrease in HR. The higher dosage of ephedrine also caused a pronounced increase in hemoglobin concentration and CaO2, resulting in a 20 to 35% increase in DO2 throughout the 60-minute experiment.

Anesthesia↗