Biomedical subjects

E P Steffey

Publications and source records attributed to E P Steffey.

At least 19 recordsLinked to original sources

PubMed2007

Influence of general anaesthesia on the pharmacokinetics of intravenous fentanyl and its primary metabolite in horses.

REASONS FOR PERFORMING STUDY: In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined. OBJECTIVES: To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2. METHODS: A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were anaesthetised with isoflurane and maintained at 1.2 x minimum alveolar anaesthetic concentration. After a 30 min equilibration period, a single dose of fentanyl (4 microg/kg bwt, i.v.) was administered to each horse. Plasma fentanyl and PMA concentrations were measured at various time points using liquid chromatography-mass spectrometry. RESULTS: Anaesthesia with isoflurane significantly decreased mean fentanyl clearance (P < 0.05). The fentanyl elimination half-life, in awake and anaesthetised horses, was 1 h and volume of distribution at steady state was 0.37 and 0.26 l/kg bwt, respectively. Anaesthesia with isoflurane also significantly decreased PMA apparent clearance and volume of distribution. The elimination half-life of PMA was 2 and 1.5 h in awake and anaesthetised horses, respectively. CONCLUSIONS AND POTENTIAL RELEVANCE: Pharmacokinetics of fentanyl and PMA in horses were substantially altered in horses anaesthetised with isoflurane. These pharmacokinetic parameters provide information necessary for determination of suitable fentanyl loading and infusion doses in awake and isoflurane-anaesthetised horses.

Anesthesia, General↗

PubMed2006

The effects of i.v. fentanyl administration on the minimum alveolar concentration of isoflurane in horses.

BACKGROUND: Fentanyl decreases the minimum alveolar concentration (MAC) of inhaled anaesthetics and has been used clinically to reduce the requirements of other anaesthetic drugs in humans and small animals. We hypothesized that i.v. fentanyl would decrease the MAC of isoflurane in horses in a dose-dependent manner. METHODS: Following determination of baseline MAC of isoflurane, fentanyl was administered i.v. to target plasma concentrations of 1, 8 and 16 ng ml(-1). Each horse was randomly assigned two of three target concentrations administered in ascending order. Loading and infusion doses for each horse were determined from previously derived individual pharmacokinetic values. Isoflurane MAC determination began 45 min after fentanyl administration at each target fentanyl concentration. Venous blood was collected at fixed intervals during the infusion for measurement of plasma fentanyl concentrations. RESULTS: Mean actual fentanyl plasma concentrations were 0 (baseline), and 0.72 (SD 0.26), 8.43 (3.22), and 13.31 (6.66) ng ml(-1) for the target concentrations of 1, 8 and 16 ng ml(-1), respectively. The corresponding isoflurane MAC values were a baseline of 1.57 (0.23), and 1.51 (0.24), 1.41 (0.23) and 1.37 (0.09)%, respectively. The fentanyl concentrations of 0.72 and 8.43 ng ml(-1) did not significantly alter the MAC of isoflurane, but an 18 (7)% ISO-MAC reduction was observed at the 13.31 ng ml(-1) concentration. CONCLUSIONS: These results cautiously encourage further study of fentanyl as an opioid anaesthetic adjunct to inhalant anaesthesia in horses.

Adjuvants, Anesthesia↗

PubMed2005

A new airway device for small laboratory animals.

There is a need for a device for improved management of the airway of small laboratory animals during general anaesthesia. This report introduces such a device, referred to here as the airway device (AD). The AD has some similarity to the laryngeal mask airway (LMA) developed for human patients, but the mask portion of the device is specifically designed for small laboratory animals. In addition, the device has an oesophageal extension and unlike the LMA does not have a cuff associated with the mask. This report also shares experience of tests of one prototype AD with six New Zealand white rabbits. The AD was used for administering isoflurane and its effectiveness was evaluated during conditions of spontaneous and controlled intermittent positive pressure ventilation. The results provide encouragement for further development of the AD for airway management of small laboratory animals.

Anesthesia, General↗

PubMed2004

Animal dependence of inhaled anaesthetic requirements in cats.

BACKGROUND: The minimum alveolar concentration (MAC) of an inhaled anaesthetic describes its potency as a general anaesthetic. Individuals vary in their sensitivity to anaesthetics and we sought to determine whether an individual animal's sensitivity to inhaled anaesthetics would be maintained across different agents. METHODS: Six female mongrel cats, age 2 yr (range 1.8-2.3) and mean weight 3.5 (SD 0.3) kg, were studied on three separate occasions over a 12-month period to determine the MAC of isoflurane, sevoflurane and desflurane. Induction of anaesthesia in a chamber was followed by orotracheal intubation and maintenance of anaesthesia with the inhaled agent in oxygen delivered via a non-rebreathing circuit. MAC was determined in triplicate using standard tail-clamp technique. RESULTS: Mean MAC values for isoflurane, sevoflurane and desflurane were 1.90 (SD 0.18), 3.41 (0.65) and 10.27 (1.06)%, respectively. Body temperature, systolic pressure and Sp(O(2)) recorded at the time of MAC determinations for isoflurane, sevoflurane and desflurane were 38.3 (0.3), 38.6 (0.1) and 38.3 (0.3) degrees C; 71.2 (8.3), 74.6 (15.9) and 88.0 (12.0) mmHg; 99.2 (1.1), 99.1 (1.3) and 99.4 (0.8)%, respectively. Both the anaesthetic agent and the individual cat had significant effects on MAC. Correlation coefficients for comparisons between desflurane and isoflurane, desflurane and sevoflurane, and sevoflurane and isoflurane were 0.90, 0.89 and 0.97, respectively. CONCLUSIONS: These findings show that an individual has a consistent degree of sensitivity to a variety of inhaled anaesthetics, suggesting a genetic basis for sensitivity to inhaled anaesthetic effects.

Anesthetics, Inhalation↗

PubMed2002

The effect of intravenous administration of variable-dose flumazenil after fixed-dose ketamine and midazolam in healthy cats.

The effects of intravenous administration of variable-dose flumazenil (0, 0.001, 0.005, 0.01, and 0.1 mg/kg) after ketamine (3 mg/kg) and midazolam (0.0 and 0.5 mg/kg) were studied in 18 healthy unmedicated cats from time of administration until full recovery. End-points were chosen to determine whether flumazenil shortened the recovery period and/or modified behaviors previously identified and attributed to midazolam. Overall, flumazenil administration had little effect on recovery or behaviors. One minute after flumazenil administration, all cats were recumbent but a greater proportion of cats which received the highest dose assumed sternal recumbency with head up than any other group. Although not significant, those cats that received the highest flumazenil dose also had shorter mean times for each of the initial recovery stages (lateral recumbency with head up, sternal recumbency with head up and walking with ataxia) than any of the other treatment groups that received midazolam. For complete recovery, flumazenil did decrease the proportion of the cats that was sedated, but did not shorten the time to walking without ataxia. Based on this study, the administration of flumazenil in veterinary practice, at the doses studied, to shorten and/or improve the recovery from ketamine and midazolam in healthy cats cannot be recommended.

Anesthetics, Intravenous↗

PubMed2002

Serum fluoride concentrations, biochemical and histopathological changes associated with prolonged sevoflurane anaesthesia in horses.

The volatile anaesthetic sevoflurane is degraded to fluoride (F-) and a vinyl ether (Compound A), which have the potential to harm kidney and liver. Whether renal and hepatic injuries can occur in horses is unknown. Cardiopulmonary, biochemical and histopathological changes were studied in six healthy thoroughbred horses undergoing 18 h of low-flow sevoflurane anaesthesia. Serum F- concentrations were measured and clinical laboratory tests performed to assess hepatic and renal function before and during anaesthesia. Necropsy specimens of kidney and liver were harvested for microscopic examination and compared to pre-experimental needle biopsies. Cardiopulmonary parameters were maintained at clinically acceptable levels throughout anaesthesia. Immediately after initiation of sevoflurane inhalation, serum F- levels began to rise, reaching an ongoing 38-45 micromol 1(-1) plateau at 8 h of anaesthesia. Serum biochemical analysis revealed only mild increases in glucose and creatinine kinase and a decrease in total calcium. Beyond 10 h of anaesthesia mild, time-related changes in urine included increased volume, glucosuria and enzymuria. Histological examination revealed mild microscopic changes in the kidney involving mainly the distal tubule, but no remarkable alterations in liver tissue. These results indicate that horses can be maintained in a systemically healthy state during unusually prolonged sevoflurane anaesthesia with minimal risk of hepatocellular damage from this anaesthetic. Furthermore, changes in renal function and morphology observed after sevoflurane inhalation are judged minimal and appear to be clinically irrelevant; they may be the result of anaesthetic duration, physiological stressors, sevoflurane (or its degradation products) or other unkown factors associated with these animals and study conditions.

Anesthetics, Inhalation↗

PubMed2000

Use of orally administered carfentanil prior to isoflurane-induced anesthesia in a Kodiak brown bear.

A captive 590-kg (1,298-lb) 22-year-old castrated male Kodiak brown bear was evaluated because of a soft tissue mass in the right carpal and antebrachial regions. General anesthesia was deemed necessary on 3 occasions for various procedures including radiographic evaluation and biopsy, excision, and radiation treatment. The bear was given carfentanil orally to induce sedation, followed by i.m. administration of tiletamine-zolazepam (on 1 occasion) and atropine. Anesthesia was maintained by administration of isoflurane in oxygen. After each procedure, effects of carfentanil were reversed by administration of naltrexone. Although there was some variability, blood pressure, nasal temperature, heart rate, respiratory rate, oxygen saturation, PO2, and PCO2 remained within a clinically acceptable ranges.

Acid-Base Equilibrium↗

PubMed2000

Facilitation of Asian elephant (Elephas maximus) standing immobilization and anesthesia with a sling.

An Asian elephant (Elephas maximus) required general anesthesia for orthopedic foot surgery. The elephant was unable to lie down, so it was placed in a custom-made sling, administered i.m. etorphine hydrochloride in the standing position, and lowered to lateral recumbency. General anesthesia was maintained with isoflurane administered through an endotracheal tube. After surgery, the isoflurane anesthesia was terminated, with immobilization maintained with additional i.v. etorphine. The elephant was lifted to the vertical position, and the immobilizing effects of etorphine were reversed with naltrexone. The suspension system and hoist for the sling were designed specifically for the elephant house.

Anesthesia, General↗

PubMed2000

Effects of xylazine hydrochloride during isoflurane-induced anesthesia in horses.

OBJECTIVE: To quantitate dose- and time-related anesthetic-sparing effects of xylazine hydrochloride (XYL) during isoflurane-induced anesthesia in horses and to characterize selected physiologic responses of anesthetized horses to administration of XYL. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized 2 times to determine the minimum alveolar concentration (MAC) of isoflurane in O2 and to characterize the anesthetic-sparing effect (MAC reduction) after IV administration of XYL (0.5 and 1 mg/kg of body weight, random order). Selected measures of cardiopulmonary function, blood glucose concentrations, and urinary output also were measured during the anesthetic studies. RESULTS: Isoflurane MAC (mean +/- SEM) was reduced by 24.8 +/- 0.5 and 34.2 +/- 1.9% at 42 +/- 7 and 67 +/- 10 minutes, respectively, after administration of XYL at 0.5 and 1 mg/kg. Amount of MAC reduction by XYL was dose- and time-dependent. Overall, cardiovascular and respiratory values varied little among treatments. Administration of XYL increased blood glucose concentration; the magnitude of change was dose- and time-dependent. Urine volume increased but not significantly. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of XYL reduced the anesthetic requirement for isoflurane in horses. The magnitude of the decrease is dose- and time-dependent. Administration of XYL increases blood glucose concentration in anesthetized horses in a dose-related manner.

Anesthetics, Inhalation↗

PubMed2000

Use of sevoflurane for anesthetic management of horses during thoracotomy.

OBJECTIVE: To evaluate sevoflurane as an inhalation anesthetic for thoracotomy in horses. ANIMALS: 18 horses between 2 and 15 years old. PROCEDURE: 4 horses were used to develop surgical techniques and were euthanatized at the end of the procedure. The remaining 14 horses were selected, because they had an episode of bleeding from their lungs during strenuous exercise. General anesthesia was induced with xylazine (1.0 mg/kg of body weight, IV) followed by ketamine (2.0 mg/kg, IV). Anesthesia was maintained with sevoflurane in oxygen delivered via a circle anesthetic breathing circuit. Ventilation was controlled to maintain PaCO2 at approximately 45 mm Hg. Neuromuscular blocking drugs (succinylcholine or atracurium) were administered to eliminate spontaneous breathing efforts and to facilitate surgery. Cardiovascular performance was monitored and supported as indicated. RESULTS: 2 of the 14 horses not euthanatized died as a result of ventricular fibrillation. Mean (+/- SD) duration of anesthesia was 304.9 +/- 64.1 minutes for horses that survived and 216.7 +/- 85.5 minutes for horses that were euthanatized or died. Our subjective opinion was that sevoflurane afforded good control of anesthetic depth during induction, maintenance, and recovery. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of sevoflurane together with neuromuscular blocking drugs provides stable and easily controllable anesthetic management of horses for elective thoracotomy and cardiac manipulation.

Anesthesia, General↗

PubMed2000

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

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

Analgesics, Opioid↗

PubMed1999

Deep sedation and mechanical ventilation without paralysis for 3 weeks in normal beagles: exaggerated resistance to metocurine in gastrocnemius muscle.

BACKGROUND: Patients in the intensive care unit may have muscle weakness in the recovery phase, and disuse atrophy may play a role in this weakness. To assess this problem, the authors measured changes in the potency of the nondepolarizing neuromuscular blocking agent metocurine in a canine model that involved 3 weeks of intensive care, nonparalyzing anesthesia with pentobarbital, and positive-pressure ventilation. METHODS: Six dogs were anesthetized with pentobarbital to a sufficient depth that spontaneous and reflex muscle movements were absent. Their tracheas were intubated, their lungs were mechanically ventilated, and they received round-the-clock intensive medical and nursing care for 3 weeks. Transduced gastrocnemius muscle responses to metocurine were determined weekly. A 4- to 15-min infusion of 148-4,300 microg/min (longer durations and greater concentrations on progressive weeks) yielded more than 80% paralysis. Serial metocurine plasma concentrations during the onset of the block and recovery provided data to determine pharmacokinetics using NONMEM. Metocurine plasma concentrations and the degree of paralysis were used to model the effect compartment equilibration constant, and the Hill equation was used to yield the slope factor and potency within the effect compartment. RESULTS: The metocurine effect compartment concentration associated with a 50% diminution of twitch height after 3 weeks was 1,716+/-1,208 ng/ml (mean +/- SD), which was significantly different from 257+/-34 ng/ml, the value on day 0. There were no pharmacokinetic differences. CONCLUSION: The absence of muscle tone and reflex responsiveness for 3 weeks was associated with exaggerated resistance to the neuromuscular blocker metocurine.

Animals↗

PubMed1999

Cardiac output measurements using sonomicrometer crystals on the left ventricle at rest and exercise.

Eight horses were fitted surgically with 8 ultrasonic sonomicrometer crystals each attached to their left ventricular pericardia and a left atrial catheter. Three horses returned to treadmill performance with a maximum rate of oxygen consumption similar to their presurgical values. These horses were evaluated to determine how well sonomicrometer estimates of cardiac output agreed with those obtained by a steady-state method, the Fick principle. Variance between the 2 was similar to the coefficient of variation (approximately 12.5%) of the Fick estimates. We conclude that left ventricular sonomicrometer measurements in horses appear to give a reasonable estimate of ventricular dimensions and can, therefore, be used potentially to evaluate such variables as diastolic flow.

Animals↗

PubMed1999

Assessment of isoflurane-induced anesthesia in ferrets and rats.

OBJECTIVE: To characterize isoflurane (ISO)-induced anesthesia in ferrets and rats. ANIMALS: 8 ferrets (Mustela putorius furo) and 8 Sprague-Dawley rats. PROCEDURE: Ferrets and rats were anesthetized in a similar manner, using ISO in oxygen. Minimum alveolar concentration (MAC) was determined, using the tail-clamp method. Immediately thereafter, assessments were recorded for 0.8, 1.0, 1.5, and 2.0 MAC (order randomized) of ISO. RESULTS: MAC of ISO was (mean +/- SEM) 1.74 +/- 0.03 and 1.58 +/- 0.05% for ferrets and rats, respectively. Mean arterial blood pressure (MAP) was 75.0 +/- 4.3 and 107.9 +/- 2.7 mm Hg at 0.8 MAC for ferrets and rats, respectively, and decreased in a parallel dose-dependent manner. Respiratory frequency decreased in rats as ISO dose increased; however, respiratory frequency increased in ferrets as ISO dose increased from 0.8 to 1.5 MAC but then decreased at 2.0 MAC. At 0.8 MAC, hypoventilation was much greater in ferrets (PaCO2 = 71.4 +/- 3.5 mm Hg), compared with rats (PaCO2 = 57.7 +/- 1.9 mm Hg). In both species, PaCO2 progressively increased as anesthetic dose increased. Eyelid aperture of ferrets increased in a dose-dependent manner. Pupil diameter in ferrets and rats increased as ISO dose increased. CONCLUSIONS AND CLINICAL RELEVANCE: The MAP and PaCO2 in ferrets and rats and eyelid aperture in ferrets consistently and predictably changed in response to changes in anesthetic dose of ISO. Magnitude of respiratory depression was greater in ferrets than rats. Changes in MAP and PaCO2 in ferrets and rats and eyelid aperture in ferrets are consistent guides to changes in depth of ISO-induced anesthesia.

Anesthetics, Inhalation↗

PubMed1999

Comparison of clinical signs and hemodynamic variables used to monitor rabbits during halothane- and isoflurane-induced anesthesia.

OBJECTIVE: To characterize variables used to monitor rabbits during inhalation anesthesia. ANIMALS: 8 male New Zealand White rabbits. PROCEDURE: Rabbits were similarly anesthetized with halothane (HAL) or isoflurane (ISO) in a crossover study; half received HAL followed by ISO, and the protocol was reversed for the remaining rabbits. After induction, minimum alveolar concentration (MAC) was determined for each agent, using the tail-clamp method, and variables were recorded at 0.8, 1.0, 1.5, and 2.0 MAC (order randomized). RESULTS: Mean +/- SEM MAC was 1.42 +/- 0.05 and 2.07 +/- 0.09% for HAL and ISO, respectively. Directly measured auricular mean arterial blood pressure was 52.8 +/- 5.6 and 54.8 +/- 6.1 mm Hg at 0.8 MAC for HAL and ISO, respectively, and decreased from these values in a parallel dose-dependent manner. Respiratory frequency remained constant (range, 69 to 78 breaths/min) over the range of HAL doses but incrementally decreased from a mean of 53 (at 0.8 MAC) to 32 breaths/min (at 2.0 MAC) for ISO. The PaCO2 was similar at 0.8 MAC for HAL and ISO and progressively increased with increasing doses of both agents; PaCO2 at 2.0 MAC for ISO was significantly greater than that at 2.0 MAC for HAL (79.8 +/- 13.7 vs 54.9 +/- 4.0 mm Hg, respectively). Eyelid aperture consistently increased in a dose-dependent manner for both anesthetics. CONCLUSIONS: Arterial blood pressure, PaCO2, and eyelid aperture consistently and predictably changed in rabbits in response to changes in anesthetic doses. The magnitude of respiratory depression was greater for ISO than for HAL.

Anesthesia, Inhalation↗

PubMed1998

The optimal intravenous dose of midazolam after intravenous ketamine in healthy awake cats.

The effects of intravenous administration of variable-dose midazolam (0, 0.05, 0.075, 0.1, 0.3 and 0.5 mg/kg) and ketamine (3 mg/kg) were studied in twenty-four healthy unmedicated cats from time of administration until full recovery. End-points were chosen to determine the optimal dose to allow a short period of restraint without noxious stimuli, a short period of restraint with noxious stimuli and endotracheal intubation. Recovery characteristics, as well as undesirable behaviours observed during recovery, were also recorded. The dose of midazolam to achieve lateral recumbency with head down was found to be 0.016 mg/kg in 50% of the population (ED50) and 0.054 mg/kg in 95% (ED95) of the population. A midazolam dose of 0.286 mg/kg was required to prevent conscious perception of a stimulus to the ulnar nerve in 50% of the population and 0.652 mg/kg in 95% of the population. The ED50 and ED95 of midazolam required to prevent swallowing in response to a laryngoscope placed on the back of the tongue were found to be 0.265 mg/kg and 0.583 mg/kg, respectively. The ED50 doses of 0.265 mg/kg for intubation and 0.286 mg/kg for restraint with noxious stimulation were close to the tested dose of 0.3 mg/kg. At that dose, the lack of responses lasted 3.67 +/- 2.27 min for laryngoscope and 2.50 +/- 2.20 min for ulnar nerve stimulation, with recovery to walking with ataxia taking 41.50 +/- 15.18 min and complete recovery taking 3.6 +/- 1.3 h. The predominant behavioural pattern during recovery was found to be normal, but some cats also exhibited abnormal behavioural patterns. Nine of the twelve cats exhibited an abnormal arousal state, with 4 being restless and 5 being sedated. Seven of the twelve cats exhibited an abnormal behaviour when approached, with three of the cats being more difficult to approach and four of the cats being easier to approach. Eight of the twelve cats exhibited an abnormal behavioural pattern when restrained, with the cats equally divided between more difficult and easier to restrain. Five of the twelve cats vocalized more during the recovery. The ED50 of 0.042 mg/kg to induce chemical restraint without a noxious stimulus is close to the tested dose of 0.05 mg/kg. At that dose, cats remained lateral with head down for 5.49 +/- 4.02 min, took 25.96 +/- 5.77 min to walk with ataxia and 1.7 +/- 0.4 h for complete recovery. The predominant behavioural patterns during recovery were normal, with several cats exhibiting some abnormal patterns. Two cats were sedated, one cat was more difficult to approach, one cat was easier to restrain and three cats were more vocal.

Anesthetics, Dissociative↗

PubMed1998

Ventilatory effects of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (2N) in swine.

UNLABELLED: Nonimmobilizers (inhaled compounds that do not suppress movement in response to a noxious stimulus) resemble anesthetics in their capacity to suppress memory, but unlike anesthetics, they can cause convulsions. Higher concentrations of nonimmobilizers may cause death, even with apparent suppression of convulsions by the concurrent administration of conventional inhaled anesthetics. We hypothesized that nonimmobilizers can depress ventilation and can cause death by adding to the depression of ventilation produced by conventional anesthetics. To test these hypotheses, we administered 1,2-dichlorohexafluorocyclobutane (2N) to four pigs anesthetized with desflurane. The addition of 2N decreased PaCO2 and tended to increase the slope of the ventilatory response to imposed increases in PETCO2. Limited results from study of two other nonimmobilizers (2,3-dichlorooctafluorobutane and perfluoropentane), in two pigs each, were consistent with the findings for 2N. However, experimental limitations (e.g., toxicity of 2,3-dichlorooctafluorobutane, and hypoxia from perfluoropentane) confound interpretation of these latter results. Our findings do not support our hypotheses--2N (and presumably all nonimmobilizers) seems to be a respiratory stimulant, not a depressant. IMPLICATIONS: A new class of inhaled compounds, nonimmobilizers, allow tests of how inhaled anesthetics act. Nonimmobilizers may act like anesthetics (e.g., impair learning) or may not (e.g., do not prevent movement in response to a noxious stimulus). The present work shows that, unlike anesthetics,nonimmobilizers do not depress breathing.

Anesthetics↗

PubMed1998

Plasma electrolyte and metabolite concentrations associated with pentobarbital or pentobarbital-propofol anesthesia during three weeks' mechanical ventilation and intensive care in dogs.

Propofol and pentobarbital were used for deep sedation during prolonged mechanical ventilation (3 weeks) and nutritional supplementation in 17 clinically normal dogs in an intensive care setting. Tolerance developed to both drugs. Propofol, in combination with pentobarbital, at an infusion rate of 75 micrograms/kg of body weight per minute was preferred. Pentobarbital infusion alone, begun at the rate of 5 to 6 mg.kg-1.h-1, was satisfactory. The combination of both drugs provided smooth, stable anesthesia and required minimal interventions by intensive care unit personnel. Blood gas tensions and electrolyte, parathyroid hormone (PTH), and metabolite concentrations were generally stable throughout, unless condition of the dog deteriorated (e.g., infection, pneumothorax). Hematocrit and red blood cell count decreased with time, likely attributable principally to multiple blood sample collections. White blood cell count, alkaline phosphatase, phosphate, fibrinogen, cholesterol, and triglyceride values increased with time, in association with pentobarbital and the combination of pentobarbital and propofol. Some of these changes appear to have been related to generic responses to stress and inflammation, some to altered metabolism, and some to the lipid solvent of propofol. The increase in triglyceride concentration was greater when propofol was used. Mortality was 47%, with death occurring between days 2 and 18.

Anesthesia, Intravenous↗