Search Results

You are looking at 1 - 10 of 99 items for :

  • "respiratory" x
  • Pharmacology x
  • Refine by Access: All Content x
Clear All

SUMMARY

Objective

To determine the maximal IV administered dose of propofol that would not induce a serious adverse event in nonsedated dogs.

Animals

6 clinically normal dogs (3 males and 3 females) between 8 and 12 months old and weighing between 8.8 and 11.3 kg.

Procedure

Propofol was administered IV at an initial dosage of 6.5 mg/kg of body weight at a rate of 20 mg/10 s. Subsequent doses were incrementally increased by 2.5 mg/kg (eg, second dose: 9 mg/kg) and separated by a minimum of 3 days. This procedure was repeated until a dose that induced a serious respiratory, cardiovascular, or neurologic adverse effect was determined.

Results

Apnea was determined to be the serious adverse effect for all dogs. Duration of apnea varied between dogs, but increased in a dose-dependent manner at dosages > 14 mg/kg.

Conclusions

Respiratory depression and apnea are the most likely adverse effects induced by IV administration of propofol to dogs. Propofol administered IV at a rate of 20 mg/kg/10 s induces minimal cardiovascular depression at dosages in excess of the apneic dosage.

Clinical Relevance

Respiratory depression and apnea should be expected as potential adverse effects after IV administration of propofol to dogs, particularly when administered at rapid rates of infusion. (Am J Vet Res 1998:59:157–161)

Free access
in American Journal of Veterinary Research

Summary

Pharmacokinetic determinants of spiramycin and its distribution into the respiratory tract were studied in 2 groups of calves, 4 to 10 weeks old. Group-A calves (n = 4) were used to determine pharmacokinetic variables of spiramycin after iv (15 and 30 mg/kg of body weight) and oral administrations of the drug (30 mg/kg) and to measure distribution of spiramycin into nasal and bronchial secretions. Group-B calves (n = 4) were used to determine distribution of spiramycin into lung tissue and bronchial mucosa. Spiramycin disposition was best described by use of an open 3-compartment model. Mean (± SD) elimination half-life was 28.7 ± 12.3 hours, and steadystate volume of distribution was 23.5 ± 6.0 L/kg. Bioavailability after oral administration was 4 ± 3%. High and persistent concentrations of spiramycin were achieved in the respiratory tract tissues and fluids. Tissue-to-plasma concentration ratio was 58 for lung tissue and 18 for bronchial mucosa at 3 hours after spiramycin administration and 137 and 49, respectively at 24 hours. Secretion-to-plasma concentration ratio was 4 for nasal secretions and 7 for bronchial secretions, and remained almost constant with time. Thus, spiramycin penetrates well into the respiratory tract, although the value in bronchial secretions is lower than that in lung tissues and bronchial mucosa. Calculations indicate that a loading dose of 45 mg/kg, administered iv, followed by a maintenance dose of 20 mg/kg, iv, once daily is required to maintain active concentrations of spiramycin against bovine pathogens in bronchial secretions.

Free access
in American Journal of Veterinary Research

Summary

To assess the effects on heart and lung function, a tiletamine-zolazepam (tz) anesthetic combination was evaluated in 10 Dorset-type ewes. Ewes were randomly allotted to 2 equal groups. Ewes of groups 1 and 2 were given a single bolus of tz (12 and 24 mg/kg of body weight, iv, respectively) at time zero. Hemodynamic, pulmonary, and ventilation variables were measured at 15-minute intervals to 120 minutes. Blood gas variables were evaluated at 5-minute intervals for the first 30 minutes, then at 15-minute intervals to 120 minutes. In all sheep, tz administration induced rapid, smooth induction, with gradual and unremarkable recovery. Anesthesia duration was not significantly different between groups (mean ± sd, 39 ± 5 and 40 ± 14 minutes for groups 1 and 2, respectively). Immediate drug effects included apnea, decreased mean arterial blood pressure, and arterial hypoxemia. Cardiac output was significantly decreased in both groups at all times after drug administration. Significant changes in group-1 ewes included increased pulmonary and systemic vascular resistances and decreased inspired minute ventilation, tidal volume, and respiratory airflow. Significant changes in group-2 ewes included increased systemic vascular resistance and decreased pulmonary arterial pressure, inspired minute ventilation, and respiratory airflow. Both drug dosages induced apneustic breathing patterns and caused significant changes in arterial and venous blood hemoglobin concentrations and pcv. Tiletamine-zolazepam is useful for intermediate-duration anesthesia in sheep. However, because of alterations in cardiopulmonary function, its use at the dosages evaluated by us is not recommended in studies, in which minimal effects on heart and lung function are required, or in sheep with compromised heart or lung function.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To evaluate the effects of detomidine and butorphanol in combination on respiratory function in horses and to determine whether these effects are more severe in horses with pre-existing respiratory dysfunction.

Design

Pulmonary function testing and arterial blood gas analyses were performed before and after administration of a combination of detomidine (10 μg/kg of body weight, IV) and butorphanol (20 μg/kg, IV).

Animals

5 horses with chronic obstructive pulmonary disease and 5 horses free of respiratory disease (controls).

Procedures

Flow rates were obtained from a pneumotachograph attached to a face mask, and esophageal pressure was measured with a catheter placed in the distal third of the esophagus. Respiratory rate, tidal volume (VT), minute ventilation (VE), maximal change in transpulmonary pressure, pulmonary resistance, and dynamic compliance were calculated by use of a pulmonary function computer. Arterial blood was collected from the transverse facial artery, and blood gas partial pressures were measured with an automated blood gas analyzer.

Results

The combination of detomidine and butorphanol caused significant changes with time in respiratory rate, VT, VE, Paco2, and Paco2 . Changes with time in VT, VE, and maximal change in transpulmonary pressure were significantly different between groups.

Conclusion

The combination of detomidine and butorphanol affects respiratory function in horses, and the observed changes are affected by the presence of preexisting respiratory dysfunction.

Clinical Relevance

Changes in respiratory function after administration of a combination of detomidine and butorphanol are not necessarily more severe in horses with pre-existing respiratory dysfunction. (Am J Vet Res 1996; 57:705–709)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To examine effects of 0.25 mg of xylazine/kg of body weight diluted to a total volume of 6 ml/450 kg with sterile 0.9% NaCl, administered into the epidural space of the sacrococcygeal joint on perineal analgesia, sedation, ataxia, and respiratory and cardiovascular function in standing mares:

Design

Randomized, blinded study, using xylazine (treatment) and 0.9% NaCl (controls). At least 2 weeks elapsed between the treatments.

Animals

Eight healthy mares.

Procedure

Blood samples were drawn. Systemic hemodynamics were determined, including cardiac output and pulmonary arterial, systemic arterial, and right atrial pressures. Two-way ANOVA with repeated measures was used to detect significant (P < 0.05) differences between mean scores of analgesia, sedation, ataxia, and cardiorespiratory variables before and during a 3-hour testing period. Analgesia was determined by lack of sensory perception to electrical stimulation at the perineal dermatome and no response to needle prick stimulation extending from coccyx to S3 dermatomes. Sedation was determined by head ptosis.

Results

Epidurally administered xylazine induced variable bilateral caudal analgesia extending from coccyx to S3, with minimal sedation, ataxia, and cardiovascular and respiratory depression in standing mares. Analgesia was attained at 15 ± 6 minutes and lasted for 165 to over 180 minutes. Heart and respiratory rates, systolic, diastolic, and mean arterial blood pressure, PCV, hemoglobin concentration, arterial oxygen content, and oxygen transport were decreased after xylazine, but not 0.9% NaCl, treatment. Cardiac output, stroke volume, mean right atrial pressure, mean pulmonary artery pressure, systemic vascular resistance, pulmonary vascular resistance, arterial and mixed venous pH and gas tensions (Po2 and Pco2 ), oxygen consumption, blood temperature, and rectal temperature did not change significantly (P < 0.05) after epidural administration of xylazine or 0.9% NaCl.

Conclusions

Caudal epidurally administered xylazine (0.25 mg/kg in 6 ml of 0.9% NaCl) can be given safely to induce prolonged (> 2 hours) caudal analgesia with minimal sedation, ataxia, and circulatory and respiratory disturbances in conscious, standing mares.

Free access
in American Journal of Veterinary Research
Author:

Summary

Pharmacokinetic determinants of danofloxacin (1.25 mg/kg of body weight, iv) and its penetration into the respiratory tract tissues were studied in sixteen 4- to 6-week-old calves. The disposition curve was best described by an open 3-compartment model. Mean elimination half-life was 7.4 hours and the steady-state volume of distribution was 4.3 L/kg. The large volume of distribution was confirmed by a rapid and high penetration of the drug into respiratory tract tissues and secretions. In all structures (lung tissue, bronchial mucosa, bronchial secretions, and nasal secretions), danofloxacin concentration peaked 1 hour after drug administration. The area under the curve ratio for concentrations in tissue or secretions to concentrations in plasma was approximately 5 for lung tissue, 3 for bronchial mucosa, 0.85 for bronchial secretions, and 0.42 for nasal secretions. Protein binding of danofloxacin was 49% in plasma, 31% in bronchial secretions, and 14% in nasal secretions, resulting in consistently higher free danoflaxacin concentrations in bronchial secretions than in plasma. Accumulation of danofloxacin within bronchial mucosa and the high concentration of free drug in bronchial secretions suggested that an active process may be involved in the transport of danofloxacin across the airway epithelium. The dose of danofloxacin administered provided drug concentrations above the minimal inhibitory concentration of common respiratory pathogens for up to 12 hours in bronchial mucosa, up to 8 hours in bronchial secretions, and up to 4 hours in nasal secretions.

Free access
in American Journal of Veterinary Research

Summary

Cardiovascular and respiratory changes that accompany markedly long periods (12 hours) of halothane anesthesia were characterized. Eight spontaneously breathing horses were studied while they were positioned in left lateral recumbency and anesthetized only with halothane in oxygen maintained at a constant end-tidal concentration of 1.06% (equivalent to 1.2 times the minimal alveolar concentration for horses). Results of circulatory and respiratory measurements during the first 5 hours of constant conditions were similar to those previously reported from this laboratory (ie, a time-related significant increase in systemic arterial blood pressure, cardiac output, stroke volume, left ventricular work, pcv, plasma total solids concentration, and little change in respiratory system function). Beyond 5 hours of anesthesia, arterial blood pressure did not further increase, but remained above baseline. Cardiac output continued to increase, because heart rate significantly (P < 0.05) increased. Peak inspiratory gas flow increased significantly (P < 0.05) in later stages of anesthesia. There was a significant decrease in inspiratory time beginning at 4 hours. Although PaO2 and PaCO2 did not significantly change during the 12 hours of study, P v ̄ O 2 increased significantly (P < 0.05) and progressively with time, beginning 6 hours after the beginning of constant conditions. Metabolic acidosis increased with time (significantly [P < 0.05] starting at 9 hours), despite supplemental iv administered NaHCO3, Plasma concentrations of eicosanoids: 6-ketoprostaglandin F (pgf a stable metabolite of pgi 1), pgf , pge, and thromboxane (TxB2, a stable metabolite of TxA2) were measured in 5 of the 8 horses before and during anesthesia. Significant changes from preanesthetic values were not detected. Dynamic thoracic wall and lung compliances decreased with time.

Free access
in American Journal of Veterinary Research

SUMMARY

The cardiovascular and respiratory effects of 3 rapidly acting barbiturates, thiopental sodium, thiamylal sodium, and methohexital sodium, were studied in dogs from completion of injection until 12.5 minutes after injection. The doses administered were 19.4 mg of thiopental/kg of body weight, 18.4 mg of thiamylal/kg, and 9.7 mg of methohexital/kg, which were chosen as equipotent doses necessary to inhibit the laryngoscopic reflex in 50% of the population. To determine the cardiovascular and respiratory effects for each drug, the values at each measurement time following injection were compared with baseline values (T0). At the 15- and 30-second measurement times following thiopental administration, stroke volume (sv) decreased; heart rate (hr), left atrial pressure, and mean pulmonary arterial pressure increased; and cardiac index (ci), myocardial contractility, and systemic and pulmonary vascular resistances were not different from baseline values. Mean arterial pressure (map) was not different from the baseline value at 15 seconds, but was increased from 30 seconds to 2 minutes. All values except hr had returned to baseline values by 7.5 minutes. At all measurement times, arterial oxygen tension and arterial pH were decreased, and arterial carbon dioxide tension increased from baseline values.

Although the cardiovascular and respiratory changes following administration of thiamylal and methohexital were similar to those described for thiopental, some differences were found. Following thiamylal administration, systemic vascular resistance increased at 1 minute, pulmonary vascular resistance increased at 1 and 2 minutes, and myocardial contractility increased at 1 and 2 minutes. Following methohexital administration, map decreased at 15 seconds, and sv decreased at all measurement times. Cardiac index increased at 30 seconds, 1 minute, and 2 minutes; myocardial contractility increased at 1, 2, and 2.5 minutes; and blood-gas and pH had returned to baseline by 12.5 minutes. To determine differences between drugs, the cardiovascular and respiratory values for each drug were compared at each measurement time. Changes in hr and sv induced by the 3 drugs were similar at all measurement times. Mean arterial pressure at 15 and 30 seconds was lower following methohexital administration than after thiopental or thiamylal administration. Cardiac index was higher at 1 minute following methohexital administration, compared with that after thiamylal administration, whereas systemic vascular resistance was higher at 1 minute following thiamylal administration, compared with that after methohexital administration. The increase in left atrial pressure was greater following thiamylal administration than after thiopental administration at 30 seconds to 5 minutes or after methohexital administration at 1 to 5 minutes. Mean pulmonary arterial pressure was significantly higher at 2 to 4 minutes following thiamylal administration than after methohexital administration. Pulmonary vascular resistance was higher at 1 minute following thiamylal administration, compared with that after thiopental and methohexital administration. At 1 and 2 minutes, myocardial contractility was significantly higher following methohexital administration, compared with that after thiobarbiturate administration. Arterial oxygen tension was lower at 12.5 minutes following administration of the thiobarbiturates, compared with that after methohexital administration. When compared with methohexital administration, arterial carbon dioxide tension was higher at 7.5 and 12.5 minutes following thiamylal administration. The decrease in pH following thiamylal administration was greater at all measurement times, compared with that after thiopental and methohexital administration.

Free access
in American Journal of Veterinary Research

SUMMARY

We studied the temporal changes in respiratory mechanics associated with xylazine administration (1.1 mg/kg of body weight, iv) in standing horses (experiment 1), and determined the effects of head and neck position (experiment 2) and atropine administration (experiment 3) on the observed changes.

Thoroughbred geldings, 3 to 5 years old (5 in experiment 1, 4 in experiments 2 and 3) were used. Flow rates were obtained from a pneumotachograph and a differential transducer attached to a tight-fitting mask. Electronic integration of the flow signal gave tidal volume. Total pulmonary pressure (PL) was defined as the difference between esophageal pressure, measured with a balloon sealed to the end of a polyethylene catheter, and mask pressure. In experiment 3, a blunt cannula positioned in the dorsal third of the eighth or tenth intercostal space was used to estimate transpulmonary pressure. Lateral tracheal pressure was measured, using a polypropylene catheter inserted percutaneously in the mid-extrathoracic tracheal lumen. Upper and lower airway pressures were defined as the difference between mask pressure or transpulmonary pressure and lateral tracheal pressure, respectively.

Five observations were made: (1) There was a significant (P < 0.05) increase in PL from 10 to 40 minutes after administration of xylazine. (2) Although an overall agreement between head and neck position and PL was detected, the maximal PL value was not always obtained with lowest head and neck position. (3) Lower and upper airway resistance increased with low head carriage, with a greater increase in upper airway resistance resulting in a decrease in lower to total airway resistance ratio. (4) Increased airway resistance was reversed by elevating the head and neck. (5) Atropine did not prevent the increase in airway resistance during sedation with xylazine and had no effect on resistance with changes in head position.

Free access
in American Journal of Veterinary Research

Summary

Dexmedetomidine (dex), an α2-receptor agonist, is the pharmacologically active d-isomer of medetomidine, a compound used as a sedative in veterinary medicine. Isoflurane anesthetic requirement (minimum alveolar concentration; mac), rectal temperature, and cardiorespiratory variables were studied in chronically instrumented Yucatan miniature swine during dex (20 μg/kg of body weight)-induced changes in body temperature. All studies were performed at room temperature of 22 C. The dex was given as a 2-minute infusion into the left atrium. Each pig was studied twice. For protocol 1, the core temperature of the pigs was maintained at (mean ± SD) 38.2 ± 0.5 C by use of a thermostatically controlled water blanket and a heating lamp. For protocol 2, the core temperature was not externally manipulated and it decreased from 38.2 ± 0.4 C to 32.2 ± 1.2 C during the more than 3 hours of the protocol. Control isoflurane mac was 1.66 ± 0.2% and was 1.74 ± 0.3% for protocols 1 and 2, respectively; dex decreased mac by 34 and 44%, respectively. For protocol 1, reduction in mac after dex administration returned by 50 and 80% at 84 and 138 minutes, respectively. If rectal temperature was not maintained (eg, allowed to decrease), mac was reduced by 57% at the same time as the return to 80% in the swine with maintained body temperature. Respiratory rate and minute ventilation were significantly higher in swine with maintained temperature. The PaCO2 , was lower and, accordingly, pH was higher in these swine. Blood pressure and heart rate were not affected by temperature changes.

Free access
in American Journal of Veterinary Research