Pharmacokinetics of inhaled anesthetics in green iguanas (Iguana iguana)

OBJECTIVE: To test the hypothesis that differences in anesthetic uptake and elimination in iguanas would counter the pharmacokinetic effects of blood:gas solubility and thus serve to minimize kinetic differences among inhaled agents. ANIMALS: 6 green iguanas (Iguana iguana). PROCEDURES: Iguanas were anesthetized with isoflurane, sevoflurane, or desflurane in a Latin-square design. Intervals from initial administration of an anesthetic agent to specific induction events and from cessation of administration of an anesthetic agent to specific recovery events were recorded. End-expired gas concentrations were measured during anesthetic washout. RESULTS: Significant differences were not detected for any induction or recovery events for any inhalation agent in iguanas. Washout curves best fit a 2-compartment model, but slopes for both compartments did not differ significantly among the 3 anesthetics. CONCLUSIONS AND CLINICAL RELEVANCE: Differences in blood:gas solubility for isoflurane, sevoflurane, and desflurane did not significantly influence differences in pharmacokinetics for the inhalation agents in iguanas.     

Kinetics and potency of halothane,isoflurane, and desflurane in the Northern Leopard frog <Emphasis Type="Italic">Rana pipiens</Emphasis>

Equilibration between delivered and effect site anesthetic partial pressure is slow in frogs. The use of less soluble agents or overpressure delivery may speed equilibration. Ten Northern leopard frogs were exposed to 3-4 constant concentrations of halothane, isoflurane or desflurane and their motor response to noxious electrical stimulation of the forelimb evaluated every 30 minutes until a stable proportion of frogs were immobile. Each frog received each anesthetic and concentration in random order and allowed at least 14 hours to recover between anesthetic exposures. An overpressure technique based upon the kinetics in the first study was then tested with 4 concentrations of desflurane. For halothane, isoflurane and desflurane respectively; the proportion of frogs immobile in response to stimulus became stable after 510, 480 and 180 minutes, and ED50 values were 1.36, 1.67 and 6.78 % atm. Desflurane ED50 delivered by overpressure was not significantly different at 6.85 % atm. Halothane, isoflurane and desflurane are effective general anesthetics in frogs with potencies similar to those reported in mammals. The time required for anesthetic equilibration is fastest with desflurane and can be hastened further by initial delivery of higher partial pressures.     

Recent advances in inhalation anesthesia.

Both desflurane and sevoflurane offer theoretical and practical advantages over other inhalation anesthetics for horses. The lower solubility of both agents provides improved control of delivery and helps to counteract the confounding influence of the voluminous patient breathing circuit commonly used for anesthetizing horses. The lower solubility should account for faster rates of recovery compared with the older agents; whether or not the quality of recovery differs remains to be objectively evaluated in a broad range of circumstances. The pharmacodynamic effects are, in large part, similar to those of isoflurane (e.g., low arrhythmogenicity) but with some differences. For example, desflurane may be overall more sparing to cardiovascular function (especially during controlled ventilation) compared with isoflurane and sevoflurane, which are roughly similar. Respiratory depression with both new agents is equal to or more depressing than isoflurane, suggesting the use of mechanical ventilation, especially in circumstances of prolonged management (i.e., hours of anesthesia). Both new anesthetics, not surprisingly, are expensive. From this point there are some agent-unique considerations. The anesthetic potency of both agents is less than that of isoflurane, which influences the cost of anesthesia, but also places an upper limit on inspired oxygen concentration (of particular concern with desflurane). Both agents require new vaporizers, but because of the high boiling point and steep vapor-pressure curve of desflurane, new technology was required. This translates into more costly equipment, adding to the cost of desflurane use. In addition, electricity is necessary for the new desflurane vaporizer to function, which limits its portability and adds additional practical considerations in its clinical use. On the other hand, desflurane strongly resists degradation both in vitro and in vivo, but in vitro degradation of sevoflurane by CO2 absorbents may produce renal injury. This may be true especially in association with low fresh-gas inflow rates (used to reduce the cost of using the new agent), and university based practices, where prolonged anesthesia is common.     

Tissue solubility of four volatile anesthetics in fresh and frozen tissue specimens from swine

OBJECTIVE: To determine tissue solubilities of desflurane, sevoflurane, enflurane, and halothane in swine and to evaluate the effects of freezing specimens on tissue solubility, SAMPLE POPULATION: Arterial blood samples and specimens of brain, heart, liver, kidney, muscle, and subcutaneous fat from 5 healthy female adult Chinese Meishan pigs. PROCEDURE: Each tissue specimen was divided into 2 parts. One part was used to measure tissue-gas partition coefficients immediately after collection. The other part was frozen at -20 C for 6 days prior to determination of tissue-gas partition coefficients. Tissue-gas and blood-gas partition coefficients were measured by use of gas chromatography, and tissue-blood partition coefficients were calculated. Regression analysis was performed to determine whether fat-gas partition coefficients were correlated with lean tissue-gas partition coefficients. RESULTS: Tissue-gas and blood-gas partition coefficients of halothane were greater than those of enflurane followed by coefficients of sevoflurane and desflurane. However, the order of anesthetic agents with the greatest to smallest tissue-blood partition coefficients was sevoflurane, halothane, enflurane, and desflurane. Muscle-gas partition coefficients of sevoflurane and enflurane, liver-gas partition coefficients of desflurane and halothane, and the kidney-gas partition coefficient of enflurane were significantly greater in frozen specimens, compared with fresh specimens. Lean tissue-gas partition coefficients of all 4 volatile anesthetics correlated directly with fat-gas partition coefficients. CONCLUSIONS AND CLINICAL RELEVANCE: The fat content of lean tissue is an important factor in determining the tissue solubility of volatile anesthetics. Freezing specimens before determination of tissue-gas partition coefficients may result in a false increase in tissue solubility.     

Median effective dose of isoflurane, sevoflurane, and desflurane in green iguanas

OBJECTIVE: To determine the median effective dose (ED(50); equivalent to the minimum alveolar concentration [MAC]) of isoflurane, sevoflurane, and desflurane for anesthesia in iguanas. ANIMALS: 6 healthy adult green iguanas. PROCEDURE: In unmedicated iguanas, anesthesia was induced and maintained with each of the 3 volatile drugs administered on separate days according to a Latin square design. Iguanas were endotracheally intubated, mechanically ventilated, and instrumented for cardiovascular and respiratory measurements. During each period of anesthesia, MAC was determined in triplicate. The mean value of 2 consecutive expired anesthetic concentrations, 1 that just permitted and 1 that just prevented gross purposeful movement in response to supramaximal electrical stimulus, and that were not different by more than 15%, was deemed the MAC. RESULTS: Mean +/- SD values for the third MAC determination for isoflurane, sevoflurane, and desflurane were 1.8 +/- 0.3%, 3.1 +/- 1.0%, and 8.9 +/- 2.1% of atmospheric pressure, respectively. The MAC for all inhaled agents was, on average, 22% greater for the first measurement than for the third measurement. CONCLUSIONS AND CLINICAL RELEVANCE: Over time, MACs decreased for all 3 agents. Final MAC measurements were similar to values reported for other species. The decrease in MACs over time may be at least partly explained by limitations of anesthetic uptake and distribution imposed by the reptilian cardiorespiratory system. Hence, for a constant end-tidal anesthetic concentration in an iguana, the plane of anesthesia may deepen over time, which could contribute to increased morbidity during prolonged procedures.     

A technique to depress desflurane vapor pressure

OBJECTIVE: To determine whether the vapor pressure of desflurane could be decreased by using a solvent to reduce the anesthetic molar fraction in a solution (Raoult's Law). We hypothesized that such an anesthetic mixture could produce anesthesia using a nonprecision vaporizer instead of an agent-specific, electronically controlled, temperature and pressure compensated vaporizer currently required for desflurane administration. ANIMAL: One healthy adult female dog. PROCEDURE AND RESULTS: Propylene glycol was used as a solvent for desflurane, and the physical characteristics of this mixture were evaluated at various molar concentrations and temperatures. Using a circle system with a breathing bag attached at the patient end and a mechanical ventilator to simulate respiration, an in-circuit, nonprecision vaporizer containing 40% desflurane and 60% propylene glycol achieved an 11.5% +/- 1.0% circuit desflurane concentration with a 5.2 +/- 0.4 (0 = off, 10 = maximum) vaporizer setting. This experiment was repeated with a dog attached to the breathing circuit under spontaneous ventilation with a fresh gas flow of 0.5 L minute(-1). Anesthesia was maintained for over 2 hours at a mean vaporizer setting of 6.2 +/- 0.4, yielding mean inspired and end-tidal desflurane concentrations of 8.7% +/- 0.5% and 7.9% +/- 0.7%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Rather than alter physical properties of vaporizers to suit a particular anesthetic agent, this study demonstrates that it is also possible to alter physical properties of anesthetic agents to suit a particular vaporizer. However, propylene glycol may not prove an ideal solvent for desflurane because of its instability in solution and substantial-positive deviation from Raoult's Law.     

Inhalant anesthetic requirement in cats is animal-dependent

Minimum alveolar concentration (MAC) of an inhalant is an indicator of its anesthetic potency. Individuals vary in their sensitivity to anesthetic agents as demonstrated by different individual MAC values. We hypothesized that individual animal sensitivity would be maintained with different inhalant anesthetics. As part of separate studies, six female DSH cats, aged 24 ± 2.5 (mean ± SD) months and weighing 3.5 ± 0.3 kg, were studied similarly on three separate occasions over a 12‐month period to determine the MAC of isoflurane (ISO), sevoflurane (SEVO), and desflurane (DES), respectively. In each study, chamber induction was followed by orotracheal intubation, and anesthesia was maintained via a nonrebreathing circuit. ECG, pulse oximetry, Doppler systolic blood pressure, end‐tidal gases, and esophageal temperature were monitored. End‐tidal gases were hand‐sampled from a catheter whose tip lay level with the distal end of the ET tube. Gases were analyzed by Raman spectrometry and, for each agent, the analyzer was calibrated with at least three gas standards. MAC was determined in triplicate using standard tail‐clamp technique. Data were analyzed by two‐way anova followed by Tukey's test and significant differences were found. Average MACs (%) for ISO, SEVO, and DES were 1.90 ± 0.18, 3.41 ± 0.65, and 10.27 ± 1.06, respectively. Body temperatures, Doppler systolic blood pressure, and SpO₂ were recorded at the time of MAC determinations for ISO, SEVO, and DES were 38.3 ± 0.3, 38.6 ± 0.1, 38.3 ± 0.35 °C; 71 ± 8, 75 ± 16, 88 ± 12 mm Hg; 99 ± 1, 99 ± 1, 99 ± 1%, respectively. Both the anesthetic agent and the individual cat had significant effects on MAC (p = 0.0001 and 0.0185, respectively). MAC varied between individuals and cats were consistent in their order of sensitivity to inhalant anesthetics across the three agents. Within this group of cats, the relationship of individual MAC to the group MAC for each of the three inhalant agents was maintained. This suggests that any individual may be consistently more or less sensitive to a variety of inhalant agents.     

Desflurane vapor pressure depression

Due to its high vapor pressure and low boiling point, desflurane requires a specially designed, electronically controlled, temperature and pressure compensated vaporizer to regulate agent delivery to the anesthetic circuit. However, if the vapor pressure and boiling point were decreased, desflurane could be used in any conventional variable bypass vaporizer. Raoult's Law states that the vapor pressure of a liquid is proportional to its molar fraction in a solution. Accordingly, propylene glycol was used as a solvent for desflurane, and the physical characteristics of this mixture were evaluated at various molar concentrations and temperatures. Desflurane boiling point increased and vapor pressure decreased as a nonlinear function of dilution, but these changes were less than predicted by Raoult's Law. Using a circle system with a breathing bag attached at the patient end and a mechanical ventilator to simulate respiration, an in‐circuit, nonprecision vaporizer containing 40% desflurane and 60% propylene glycol achieved a 11.5 ± 1.0% (mean ± SD) circuit desflurane concentration with a 5.2 ± 0.4 (0 = off, 10 = maximum) vaporizer setting. This experiment was repeated with a dog attached to the breathing circuit under spontaneous ventilation with a fresh gas flow of 0.5 L min^–1. Anesthesia was maintained for over two hours at a mean vaporizer setting of 6.2 ± 0.4, yielding mean inspired and end‐tidal desflurane concentrations of 8.7 ± 0.5% and 7.9 ± 0.7%, respectively. Within 5 minutes after cessation of anesthesia, the dog was awake, extubated and standing. In clinical practice, propylene glycol may not prove an ideal solvent for desflurane due to its instability in solution and substantial positive deviation from Raoult's Law. However, rather than alter the vaporizer to suit physical properties of anesthetic agents, this study demonstrates that it may also be possible to alter anesthetic agents to suit physical properties of the vaporizer.     

Advantages and guidelines for using nitrous oxide.

Nitrous oxide is useful as an adjunct to methoxyflurane anesthesia and prolonged halothane anesthesia. Nitrous oxide is also useful in the debilitated patient in which the potent volatile anesthetics induce excessive cardiovascular depression. Finally nitrous oxide is useful for smoothing an inadequate anesthetic plane induced by the potent volatile anesthetics.     

Cardiopulmonary and acid-base effects of desflurane and sevoflurane in spontaneously breathing cats

The cardiopulmonary effects of desflurane and sevoflurane anesthesia were compared in cats breathing spontaneously. Heart (HR) and respiratory (RR) rates; systolic (SAP), diastolic (DAP) and mean arterial (MAP) pressures; partial pressure of end tidal carbon dioxide (PETCO2), arterial blood pH (pH), arterial partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2); base deficit (BD), arterial oxygen saturation (SaO2) and bicarbonate ion concentration (HCO3) were measured. Anesthesia was induced with propofol (8+/-2.3mg/kg IV) and maintained with desflurane (GD) or sevoflurane (GS), both at 1.3 MAC. Data were analyzed by analysis of variance (ANOVA), followed by the Tukey test (P<0.05). Both anesthetics showed similar effects. HR and RR decreased when compared to the basal values, but remained constant during inhalant anesthesia and PETCO2 increased with time. Both anesthetics caused acidemia and hypercapnia, but BD stayed within normal limits. Therefore, despite reducing HR and SAP (GD) when compared to the basal values, desflurane and sevoflurane provide good stability of the cardiovascular parameters during a short period of inhalant anesthesia (T20-T60). However, both volatile anesthetics cause acute respiratory acidosis in cats breathing spontaneously.     

Effects of desflurane and mode of ventilation on cardiovascular and respiratory functions and clinicopathologic variables in horses

OBJECTIVE: To quantitate the effects of desflurane and mode of ventilation on cardiovascular and respiratory functions and identify changes in selected clinicopathologic variables and serum fluoride values associated with desflurane anesthesia in horses. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized on 2 occasions: first, to determine the minimum alveolar concentration (MAC) of desflurane in O2 and second, to characterize cardiopulmonary and clinicopathologic responses to 1X, 1.5X, and 1.75X desflurane MAC during both controlled and spontaneous ventilation. RESULTS: Mean +/- SEM MAC of desflurane in horses was 8.06 +/- 0.41 %; inhalation of desflurane did not appear to cause airway irritation. During spontaneous ventilation, mean PaCO2 was 69 mm Hg. Arterial blood pressure, stroke volume, and cardiac output decreased as the dose of desflurane increased. Conditions of intermittent positive pressure ventilation and eucapnia resulted in further cardiovascular depression. Horses recovered quickly from anesthesia with little transient or no clinicopathologic evidence of adverse effects. Serum fluoride concentration before and after administration of desflurane was below the limit of detection of 0.05 ppm (2.63microM/L). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that desflurane, like other inhalation anesthetics, causes profound hypoventilation in horses. The magnitude of cardiovascular depression is related to dose and mode of ventilation; cardiovascular depression is less severe at doses of 1X to 1.5X MAC, compared with known effects of other inhalation anesthetics under similar conditions. Desflurane is not metabolized to an important degree and does not appear to prominently influence renal function or hepatic cellular integrity or function.     

The immune response to anesthesia: Part 1

ObjectiveTo review the immune response to anesthesia including mechanical ventilation, inhaled anesthetic gases, and injectable anesthetics and sedatives.Study designReview.Methods and databasesMultiple literature searches were performed using PubMed and Google Scholar from spring 2012 through fall 2013. Relevant anesthetic and immune terms were used to search databases without year published or species constraints. The online database for Veterinary Anaesthesia and Analgesia and the Journal of Veterinary Emergency and Critical Care were searched by issue starting in 2000 for relevant articles.ConclusionRecent research data indicate that commonly used volatile anesthetic agents, such as isoflurane and sevoflurane, may have a protective effect on vital organs. With the lung as the target organ, protection using an appropriate anesthetic protocol may be possible during direct pulmonary insults, including mechanical ventilation, and during systemic disease processes, such as endotoxemia, generalized sepsis, and ischemia-reperfusion injury.     

Anesthesia in ophthalmic surgery

Ophthalmic surgical patients can be routinely anesthetized without complications if the surgeon has a thorough understanding of the effects of anesthetic agents on ocular physiology. The regulation of intraocular pressure is important for successful ophthalmic surgery and can be greatly affected by the anesthetic procedure. Agents utilized to intentionally decrease intraocular pressure are often employed for intraocular procedures. These agents have profound systemic effects that must be anticipated. Adverse drug interactions between sympathomimetic mydriatics and halogenated inhalation anesthetics also must be considered.     

Regional anesthesia

Organ toxicity from local anesthetic agents is rare. This makes these agents an attractive option in the high-risk patient. Complications associated with local anesthetics are related to overdosage. Overdosage with local anesthetic agents administered epidurally may cause motor paralysis and hind-limb weakness. Systemic signs of local anesthetic overdosage include changes in central nervous system activity (excitement or depression), muscle tremors, and hypotension. Because the dose required to produce these effects in the horse is high (12 mg/kg), this complication is uncommon. Few side effects and low cost justify the use of local anesthetic techniques in equine practice.     

Anesthesia of the sighthound

The sighthounds are an ancient group of dog breeds that have been selectively bred for high-speed pursuit of prey by sight. Probably as a consequence of this selection process, these dogs have a number of idiosyncrasies that can potentially adversely affect their anesthetic management. These include (1) nervous demeanor which can lead to stress-induced clinical complications, such as hyperthermia; (2) lean body conformation with high surface-area-to-volume ratio, which predisposes these dogs to hypothermia during anesthesia; (3) hematological differences such as a higher packed cell volume and lower serum protein compared with other dog breeds which may complicate interpretation of preanesthetic blood work; (4) Impaired biotransformation of drugs by the liver resulting in prolonged recovery from certain intravenous anesthetics, especially thiopental; and increased risks of drug interactions. Safe anesthetic management of sighthounds should include sedative premedication and appropriate use of analgesic drugs to minimize perioperative stress. Thiopental, or any other thiobarbiturate, should not be used in these dogs. Propofol, ketamine/diazepam combination, and methohexital are recommended alternative intravenous anesthetics. Avoid coadministration of agents that inhibit drug biotransformation, such as chloramphenicol. Inhalation anesthesia using isoflurane is the preferred anesthetic maintenance technique. Core body temperature should be monitored closely and techniques to minimize hypothermia should be employed both during anesthesia and into the recovery period.     

Sedation and anesthesia of pet rabbits

Pet rabbits frequently become stressed when handled and may require sedation or chemical immobilization for procedures such as blood collection, IV catheter placement, radiography, deep ear cleaning, and dentistry. Common surgical procedures requiring general anesthesia include spay, castration, gastrotomy, cystotomy, and orthopedic procedures. Rabbits may be difficult to safely sedate or anesthetize. Individual rabbits may have varying sensitivity to the depressant effects of anesthetics. The apparent sensitivity of the rabbit's respiratory center to anesthetic drugs and the narrow range between anesthetic and toxic doses in this species add to the unpredictable character of rabbit anesthesia. Furthermore, mortality following anesthesia and surgery in sick rabbits is common. Strategically, safe anesthesia of rabbits must include the planning of procedures so that anesthetic time is minimized. Clinicians must be on guard for individual variation in response to drugs. Minimizing the use of cardiovascular depressant agents, use of agents with a high therapeutic index, and careful titration of doses to effect, along with thorough cardiorespiratory monitoring, will permit attainment of appropriate anesthetic depth with the widest margin of safety. This article presents several injectable and inhalant anesthetic protocols that may assist in effective management of many types of rabbit patient.     

Anesthesia for geriatric patients.

Choosing the best anesthetic agents for each geriatric animal does not in itself ensure a successful outcome. Aggressive, careful, vigilant monitoring during the anesthetic and recovery periods is required to detect and correct alterations in homeostasis that may develop during the perianesthetic period. With appropriate preoperative screening, informed choice and judicious dosing of anesthetics, and careful monitoring and supportive care, the risk of anesthesia in geriatric animals can be greatly reduced.     

The case for maintenance of general anesthesia with an inhalational agent.

Control of anesthetic depth is the primary advantage of general anesthesia with inhalational anesthetics as opposed to injectable agents. In addition, inhalational anesthetics provide good intraoperative stress reduction, adequate muscle relaxation, and an elimination pathway (lungs) independent of liver and kidney function. There is little postoperative respiratory depression and no rebound effect, which is sometimes seen with injectable anesthetics. The incidence of anesthetic-related toxicity is rare and is not considered a problem.     

Anesthesia and surgery of laboratory animals

This article reviews anesthetics and anesthetic techniques applicable to small laboratory animals. Anesthetic and analgesic dosage tables are presented for each species to guide the practitioner. The actions of the various agents are reviewed in the text, and key references are presented. Surgical considerations are also reviewed.     

Advantages and guidelines for using isoflurane.

Isoflurane offers many advantages over other inhalational anesthetics. Its faster induction and recovery, relative sparing effect on cardiovascular function and cerebral blood flow autoregulation, and negligible metabolism make this drug particularly useful in the anesthetic management of the debilitated, aged, or unusual veterinary patient.