Comparison of isoflurane and sevoflurane for short-term anesthesia in piglets

Transcription

1 Veterinary Anaesthesia and Analgesia, 2007, 34, doi: /j x RESEARCH PAPER Comparison of isoflurane and sevoflurane for short-term anesthesia in piglets David S Hodgson DVM, Diplomate ACVA Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA Correspondence: David S Hodgson, Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA. hodgson@vet.ksu.edu Abstract Objectives To compare isoflurane (ISO) and sevoflurane (SEVO) short-term anesthesia in piglets during castration. Study design Prospective, randomized study. Animals A total of 114 male piglets aged 6 10 days, body weight kg. Methods Piglets were randomly selected from multiple litters and randomly assigned to being anesthetized with ISO or SEVO prior to castration. To calculate appropriate doses for induction and maintenance of anesthesia, a square root of time model was used, with calculations based on metabolic size and attainment of 1.3 minimum alveolar concentration. The equipotent target alveolar concentration of ISO was 1.82% and for SEVO 4.03%. After doses were calculated, a table listing piglet weights and agent requirements was produced. Anesthetics were delivered via liquid anesthetic injection into a previously developed rebreathing inhaler that was filled with oxygen prior to use. Piglets were anesthetized, castrated and allowed to recover prior to return to the sow. Times for induction, recovery and total time to standing were recorded, and end-tidal carbon dioxide (PE CO 2 ) tensions were measured by capnography immediately after mask removal. Each response variable was analyzed in SAS using the Proc Mixed procedure, with piglet weight and days of age as covariates. Castration problems and mortality were assessed relative to unanesthetized littermates. Results There were no statistically significant differences in age, weight or total anesthetic time between the anesthetics. Induction time was shorter, recovery time longer, and PE CO 2 lower with ISO. No morbidity or mortality was associated with either group. Conclusion and clinical relevance Isoflurane and SEVO, delivered in a novel inhaler, provided economical, safe, rapid anesthetic induction and maintenance. Optimal conditions were provided for castration and recoveries were brief and smooth. Statistically significant differences in times would be of minor clinical importance. The cost of anesthesia was much less with ISO than with SEVO. Keywords anesthesia, castration, isoflurane, piglets, sevoflurane, surgery. Introduction The goal has been to explore ways to deliver general anesthesia to piglets for routine shortterm surgical procedures in which rapid induction and recovery from anesthesia are desirable. Previously, a rebreathing inhaler was developed which utilized liquid injection of a volatile anesthetic agent into a vaporization chamber (Hodgson 2006) and demonstrated its successful use during routine piglet castration. 117

2 Isoflurane (ISO), which is well tolerated by many species of mammals and birds, was used for proof of concept of that inhaler and technique. However, because piglets and human infants share many similarities, it is worth noting that with human pediatric patients, the pungent odor and high incidence of laryngospasm make ISO unsuitable for induction (Cravero & Rice 2001). Induction of anesthesia in human pediatric patients are now often accomplished with sevoflurane (SEVO) in oxygen. Sevoflurane also is now used for a variety of veterinary patients and has proved acceptable for mask inductions in many small and exotic pets. Yet, while SEVO has become well accepted as an inhaled agent for smooth mask inductions in humans (Cravero & Rice 2001), it is not customarily used to maintain anesthesia because of a significant incidence of seizure activity during anesthesia and unacceptable agitation during recovery (Holzki & Kretz 1999; Lapin et al. 1999). The goal of the current study was to compare anesthesia with ISO or SEVO for piglet castration. Materials and methods Experimental animals Piglets in this study were 6 10 (7.75 ± 1.04) days of age and weighed kg (6.61 ± 1.59). The 114 males presented for anesthesia during castration were randomly selected from multiple litters in a swine-farrowing unit. Piglets in this facility are routinely castrated at approximately 1 week of age without anesthesia or analgesia. The choice of either ISO or SEVO for anesthesia of a particular piglet was determined randomly. Unselected littermates undergoing routine castration without anesthesia were used to compare surgically related problems and mortality rates. The Kansas State University Institutional Animal Care and Use Committee approved all animal procedures. Inhaler design and use Rebreathing inhalers designed for liquid anesthetic injection (Hodgson 2006) were employed in this study (Fig. 1). The inhalers were fabricated locally utilizing a small lathe and hand tools. The inhaler center body was machined from acetyl plastic. This plastic is inert to the effects of halogenated anesthetics. A stainless steel adaptor was attached to the Microliter syringe Liquid injection port Open - close valve Mask Rebreathing bag Vaporization chamber Figure 1 Components of the anesthetic inhaler for shortterm anesthesia of piglets. proximal end of the center body to accept standard small animal masks. A stainless steel vaporization chamber was attached to the distal end. The vaporization chamber enclosed an internal cotton wick sandwiched between two layers of stainless steel mesh. A nylon stopcock was fitted to the vaporization chamber and functioned as an injection port to deliver liquid anesthetic directly onto the wick and to flush oxygen into the inhaler. The total internal volume of the mask, inhaler, and full rebreathing bag was 250 ml. For increased efficiency, two identical inhalers were used alternately. Before each application, the contents of the inhaler in active use was evacuated into a shrouded charcoal canister. During evacuation, the rebreathing bag was removed from the inhaler. The canister shroud was equipped with a ducted fan below the canister to aspirate residual vapors from the inhaler and rebreathing bag. Prior to anesthetic injection, the rebreathing bag was replaced on the inhaler, the bag was collapsed and the open-close valve moved to the closed position. A calculated dose of either ISO or SEVO was delivered into the inhaler through the liquid injection port with a glass microliter syringe (Model 1750 LT; Hamilton Company, Reno, NV, USA). Following liquid anesthetic injection, oxygen (40 ml second )1 ) was directed through the same port to slowly fill the rebreathing bag and to initiate vaporization. Oxygen was also used to alleviate the possibility of hypoxemia during the anesthetic period. 118 Ó 2007 The Author. Journal compilation Ó 2007 Association of Veterinary Anaesthetists, 34,

3 Calculations of liquid isoflurane and sevoflurane requirements All calculations of ISO and SEVO volumes required for anesthesia utilized the square root of time model (Lowe & Ernst 1981; Hodgson 2006) (Appendix A). To determine the total liquid anesthetic agent required to induce and maintain anesthesia based on the metabolic size (BW kg 0.75 ) of the piglets, we calculated and summed a ventilatory prime dose, an arterial prime dose, and a unit dose. The ventilatory prime dose is the amount of liquid needed to establish the target concentration of anesthetic in the inhaler plus the piglet s pulmonary functional residual capacity (FRC). The arterial prime dose is the amount of liquid needed to establish the desired anesthetic concentration in the circulating blood. The unit dose is the amount of liquid needed to maintain anesthesia for each square root of time increment. The ventilatory prime dose, arterial prime dose, and unit dose were summed to determine the total liquid anesthetic necessary for each piglet weight. The target ISO concentration of 1.82% was based on a minimum alveolar concentration (MAC) value of 1.41% (Hodgson 2006) and a MAC multiple of 1.3; the SEVO concentration of 4.03% was based on a MAC value of 3.3% and a MAC multiple of 1.3. The MAC of 3.3% was based on a study in human neonates 30 days old undergoing a skin incision during a surgical procedure (Lerman et al. 1994). These calculated doses were then converted from metabolic size to scale weight to construct a table (Table 1) that listed a range of piglet weights and the corresponding ISO or SEVO volumes for each weight increment. Experimental protocol Without being informed as to which anesthetic was being used, herd caretakers selected piglets at random from each litter. Litter and pig numbers, noted by reading ear notches, were recorded. Each piglet was weighed on a digital scale and its appropriate anesthetic dose was determined from Table 1. The entire calculated dose was injected into the inhaler as a single injection. Treatment with either ISO or SEVO was randomized. Room temperature for all experiments was C. Barometric pressure averaged 735 mmhg. Each piglet was cradled under the anesthetist s left arm; the mask and inhaler were applied with the right hand. The open-close valve was immediately Table 1 Table for determining isoflurane and sevoflurane dose based on piglet scale weight Weight (lb) (kg) Isoflurane (ml) Sevoflurane (ml) opened to allow the piglet to breathe through the inhaler. During anesthetic induction, were continuously assessed clinical signs of anesthetic depth. These included ventilatory character, heart rate (by palpation), eye signs, and muscle relaxation. After ventilation became regular and the piglet relaxed, the animal was placed on its back in a V-trough and positioned for castration. Times were measured with a digital stopwatch. Induction time was defined as the interval from starting anesthetic induction until the piglet was anesthetized and positioned for surgery. Castration was complete in less than 30 seconds (performed by trained herd caretakers). A surgical plane of anesthesia was maintained until 120 seconds had elapsed since the beginning of anesthetic induction. Immediately after the inhaler was removed, a blunt stainless steel probe attached to a capnograph (model V90040; Surgivet, Waukesha, WI, USA) was inserted into the piglet s nostril to determine end-tidal CO 2 (PE CO 2 ). Inspired or end-tidal anesthetic concentrations were not measured because of lack of equipment at the site. Additionally, the very short anesthetic time would not provide significant equilibration time between the inspired agent and the blood for meaningful interpretation. For recovery and observation, each piglet was placed in a cardboard box ( cm) without being stimulated or handled in any way. When a piglet was standing and able to walk without noticeable ataxia, it was returned to its sow and littermates. Ó 2007 The Author. Journal compilation Ó 2007 Association of Veterinary Anaesthetists, 34,

4 Recovery time was measured from removal of the inhaler from the piglet s nose until it was standing. Total anesthesia time was the same (120 seconds) for all piglets, although castration was often complete seconds before 120 seconds had elapsed. Total anesthetic time was the interval from initiation of anesthesia until the piglet was standing. After each use, the rebreathing bag was removed and room air was aspirated through the inhaler. Waste anesthetic vapors were absorbed into a canister containing activated charcoal. Table 2 Measured parameters (mean ± SD) of piglets anesthetized with isoflurane and sevoflurane for castration Variable Isoflurane Sevoflurane Age (days) 7.8 ± ± 1.0 Weight (kg) 3.1 ± ± 0.7 Induction (seconds)* 44.0 ± ± 8.7 Recovery (seconds)* ± ± 43 Total time (seconds)* ± ± 43 End-tidal CO 2 (mmhg) 39 ± 9 45 ± 9 (kpa) 5.2 ± ± 1.2 Statistical analysis Individual male piglets from each litter and treatment were randomly selected. The remaining male piglets in each litter were castrated by the same herd caretaker after all piglets receiving anesthesia had been processed. These remaining littermates served as a comparison group for the purpose of assessing problems associated with castration or mortality. Each response variable was analyzed in SAS using the Proc Mixed procedure (SAS Version 8; SAS Institute Inc., Cary, NC, USA). The weight of each piglet and days of age were used as covariates in the analysis. Results are reported as mean ± SD. Variables recorded or measured included piglet number, age, weight, induction time, recovery time, total time, and PE CO 2. Results Induction of anesthesia in the piglets was easily accomplished with both SEVO and ISO, and changes in ventilatory excursion were easily observed. Anesthetic depth was monitored and optimal conditions were provided for surgical castration using both anesthetic agents. Piglets placed in a box for recovery typically lay quietly for a short time and then rolled to a sternal position and jumped to their feet. They had good mobility and were able to walk with minimal ataxia as soon as they arose. Results of measured variables are shown in Table 2. There were no significant differences in age, weight, or total anesthetic time between the anesthetic administrations. No surgically related problems or mortality was associated with either treatment or between anesthetized and control piglets. Slight but statistically significant differences were apparent; with ISO, induction times were shorter, recovery times were longer, and PE CO 2 was lower. *Significantly different (p < 0.05); See text for time definitions. Discussion Determining appropriate minimum alveolar concentration values Using the square root of time model (Lowe & Ernst 1981) to determine dose necessitates incorporating a MAC value and a MAC multiple into the calculations, but traditional MAC determination in these piglets was not feasible under field conditions. After preliminary investigations with several values, an ISO MAC of 1.41% was used for the square root of time calculations in our previous study (Hodgson 2006), and a MAC multiple of 1.3 was selected; these values were effective in producing a light surgical plane of anesthesia. To further test this calculated dose, we deleted one unit dose of ISO from this calculated dose. A significant number of piglets were inadequately anesthetized to accomplish castration. We then added one unit dose of ISO to this calculated dose and piglets often became apneic. This bracketed approach has similarity to the up-and-down technique of Dixon (1970), and has been used for other MAC determinations (Lerman et al. 1994). Because we desired to compare the two anesthetic agents at equipotent concentrations, we took a similar approach to evaluate MAC selection for SEVO. After determining a SEVO MAC value that was effective in producing an appropriate surgical plane of anesthesia, we both removed and added one unit dose of SEVO to the calculated dose. Similar results were observed with SEVO as with ISO. When one unit dose was removed, the piglets were inadequately anesthetized to proceed with castration. When one unit dose was added, piglets often became apneic. In determining an appropriate MAC value for calculations in the square root of time model, 120 Ó 2007 The Author. Journal compilation Ó 2007 Association of Veterinary Anaesthetists, 34,

5 surgical incision and castration were the noxious stimuli for piglets anesthetized in our study. Other workers have relied on other stimuli for traditional MAC studies. A tail clamp method has been widely used with various species. However, Satas et al. (1996) reported that halothane MAC and ISO MAC determinations using a hoof clamp were significantly higher than when using a tail clamp in piglets. Using a hoof clamp on piglets 4 10 days old, Lerman et al. (1990) reported a SEVO MAC of 2.12%. Surgical incision has not been compared with these methods in piglets, but after failing to anesthetize the piglets adequately with SEVO for castration using a MAC value both at 2.12% and at several increased concentrations, it was decided that a surgical incision, in piglets, was a more noxious stimulus than a hoof clamp. Because a study with SEVO in 12 human neonates 30 days old determined MAC to be 3.3% when a skin incision was made (Lerman et al. 1994), we anesthetized piglets with SEVO for castration using a MAC value of 3.3% in the square root of time model, and found that it provided adequate anesthesia for castration without adverse responses by the piglets. As a result of the very short anesthetic time, which does not allow time for equilibration between the alveolar gas and the blood, a concern is whether ISO and SEVO are being compared at equipotent doses. Using the above method (addition and removal of one unit dose), we determined that 3.3% SEVO was roughly equivalent to 1.41% ISO. Although the goal was to find a SEVO dose that would be equipotent to the ISO dose in our model and would consistently produce a surgical plane of anesthesia in all piglets, we should note that when using ISO, Schieber et al. (1986) observed marked variability in MAC between piglets, and thus chose to study piglets based on their own individual MAC values rather than an average value for all piglets. We do not know whether similar variability existed in our piglet population when using either ISO or SEVO. However, although we did not determine MAC for either agent during the field study, onlookers and swine herdsmen unaware of which agent was being used were unable to determine a difference in response of the piglets to surgical incision and castration. We believe this provided indirect evidence that the MAC values used in the square root of time model produced equipotent anesthesia in this population of piglets. We know that an effective, clinically appropriate level of anesthesia for castration was repeatedly produced in a wide range of piglet weights using this inhaler and the calculated doses. If the anesthetics are not equipotent, the interpretation of differences in measured variables could be questioned. However, this technique as conducted provided optimal conditions for castration in a commercial facility under field conditions. Induction and recovery times Both agents were associated with rapid, smooth anesthetic induction, which typically was accomplished in less than 1 minute (Table 2). Induction with ISO averaged approximately 3.5 seconds less than that with SEVO, a difference that was statistically significant. The specific reason(s) for the slightly faster induction with ISO is a matter of speculation. It was somewhat unexpected, in that speed of induction and recovery are usually inversely correlated with blood-gas solubility coefficients. At 37 C, the solubility coefficient for ISO is 1.46; for SEVO, it is This difference in solubility would be expected to favor a more rapid induction with the less soluble SEVO (Steffey 1996). In order to accurately compare inhalation anesthetic agents, it is necessary to deliver the agents at equipotent concentrations. The potency of ISO is approximately twice that of SEVO. For piglets to receive equipotent amounts of anesthetic, the volume of SEVO being vaporized from the inhaler wick must be greater than when ISO is used. The vapor pressure of a volatile anesthetic also influences vaporization rate (Steffey 1996). The vapor pressure of ISO at 20 C is 240 mmhg; for SEVO, it is 160 mmhg. This favors a more rapid vaporization of the more potent agent, ISO, and a higher potential concentration at equal time points. However, vaporization rate of these agents in this inhaler has not been measured. Because warm respiratory gases move around the wick on both inspiration and expiration, a piglet s ventilation would also be expected to influence the rate of agent vaporization from the wick. We presumed that the body temperature was similar for both groups. Increases in minute volume would be expected to enhance vaporization. Although we did not observe breath holding with either ISO or SEVO, it is possible that ISO was associated with greater minute ventilation that enhanced vaporization. Recovery times were variable, but piglets in both groups typically revived in a little over 2 minutes (Table 2). While of limited clinical significance, the Ó 2007 The Author. Journal compilation Ó 2007 Association of Veterinary Anaesthetists, 34,

6 mean recovery time for SEVO was statistically shorter than that for ISO, a finding that was expected given that SEVO is less soluble than ISO; provided that all physiologic parameters were similar between the groups, one would expect a more rapid washout. As time from mask application to removal of the inhaler was always for 120 seconds, this factor is constant for both groups and would not contribute to recovery time differences. Total time from initiation of anesthesia to standing In large swine operations, routine husbandry procedures are swiftly accomplished. Routine castration of piglets by trained personnel is often completed in seconds. However, in the absence of anesthesia or sedation, castration is accompanied by much struggling and squealing by the piglets. The stress to the piglets is recognized by sows in adjacent areas, which become agitated and vocal in response to the squealing. In this study, gentle quiet handling of the piglets and use of inhalational anesthesia changed the whole atmosphere in the farrowing unit. Herd workers remarked how quiet it was when the piglets were castrated with anesthesia compared with the procedures normally followed. We did not quantitatively measure stress hormones, effects on outcome, or rate of gain, but all lay persons in attendance deemed the addition of anesthesia to be a more humane way to castrate and process piglets. Swine producers are concerned with changes that have the potential to add significant procedure time. However, supervisors in this facility considered the anesthesia provided during castration to be beneficial and worthwhile, and did not perceive the extra time required to be excessive. There was no mortality or apparent surgically related problems with the treatment groups when compared with piglets castrated without anesthesia, but this is a consideration whenever anesthesia is contemplated. All personnel were made aware that anesthesia use presents some potential risk to the piglets. As with any sedative or anesthetic technique, it is important that it be conducted or supervised by responsible veterinary personnel. Quality of induction and recovery With both anesthetic agents, induction and recovery were smooth and without complication. We did not formally record or quantify the subjective observations by herdsmen and bystanders that ISO inductions seemed smoother. We did not observe breath holding or coughing such as that commonly observed in human neonates in which anesthesia was induced with ISO. Recovery from SEVO anesthesia was very rapid, quiet, and showed no evidence of post-anesthesia restlessness or agitation such as that seen in children maintained with SEVO. Whether we might have seen some of these responses with more prolonged anesthesia is unknown, but post-anesthesia agitation has not been noted in SEVO MAC studies in piglets (Lerman et al. 1990). Herdsmen remarked several times how quiet and stress free the surgical procedures were when the piglets were anesthetized. Prior to our studies, they had never castrated piglets with sedation, analgesics, or anesthesia. End tidal CO 2 partial pressures With both ISO and SEVO, the PE CO 2 values were within a range considered clinically acceptable for ISO- or SEVO-anesthetized animals. More prolonged periods of anesthesia are likely to be associated with a continued rise in carbon dioxide tension, as more rebreathing of expired gases occurred. While differences were slight, SEVO was associated with a statistically greater CO 2 accumulation (Table 2) than ISO. When rebreathing of carbon dioxide is not allowed, PE CO 2 is an indicator of adequacy of ventilation, but in this study, rebreathing of carbon dioxide was allowed for a short time period of time. Slight increases in CO 2 production with SEVO when compared with ISO might provide an alternative explanation. Because inductions were subjectively smoother with ISO, increased struggling associated with SEVO may have increased oxygen consumption and carbon dioxide production during the short induction period. Cost of anesthesia Current anesthetic agent prices favor the use of ISO rather than SEVO. The agent cost for a 2.3 kg piglet is $0.02 for ISO and $0.22 for SEVO. Our results suggest that clinical anesthesia using this rebreathing technique for short-term anesthesia of piglets would not justify the added cost of SEVO. References Cravero JP, Rice LJ (2001) Pediatric anesthesia. In: Clinical Anesthesia (4th edn). Barash PG, Cullen BF, Stoelting 122 Ó 2007 The Author. Journal compilation Ó 2007 Association of Veterinary Anaesthetists, 34,

7 RK (eds). Lippincott-Williams & Wilkins, Philadelphia. pp Dixon WJ (1970) Quantal-response variable experimentation: the up-and-down method. In: Statistics in Endocrinology. McArthur JW, Colton T (eds). MIT, Cambridge, MA. pp Hodgson DS (2006) An inhaler device using liquid injection of isoflurane for short term anesthesia in piglets. Vet Anaesth Analg 33, Holzki J, Kretz FJ (1999) Changing aspects of sevoflurane in paediatric anaesthesia: Paediatr Anaesth 9, Lapin SL, Auden SM, Goldsmith LJ et al. (1999) Effects of sevoflurane anaesthesia on recovery in children: a comparison with halothane. Paediatr Anaesth 9, Lerman J, Oyston JP, Gallagher TM et al. (1990) The minimum alveolar concentration (MAC) and hemodynamic effects of halothane, isoflurane, and sevoflurane in newborn swine. Anesthesiology 73, Lerman J, Sikich RN, Kleinman S et al. (1994) The pharmacology of sevoflurane in infants and children. Anesthesiology 80, Lowe HJ, Ernst EA (1981) The Quantitative Practice of Anesthesia Use of the Closed Circuit. Williams & Wilkins, Baltimore. pp , 70 71, Satas S, Haaland K, Thorsen M et al. (1996) MAC for halothane and isoflurane during normothermia and hypothermia in the newborn piglet. Acta Anaesthesiol Scand 40, Schieber RA, Namnoum A, Sugden A et al. (1986) Hemodynamic effects of isoflurane in the newborn piglet: comparison with halothane. Anesth Analg 65, Steffey EP (1996) Inhalation anesthetics. In: Veterinary Anesthesia (3rd edn). Thurmon JC, Tranquilli WJ, Benson GJ (eds). Williams & Wilkins, Baltimore. pp , 316. Received 5 July 2005; accepted 15 May Appendix A Calculations of isoflurane or sevoflurane liquid required to construct Table 1 Ventilatory prime dose ¼ (volume of inhaler + piglet FRC) (fmac) Arterial prime dose ¼ Ca_Q Unit dose ¼ 2Ca _ Q Volume of inhaler device with bag, small mask, and adaptor ¼ 250 ml. FRC ¼ kg ml MAC ISO ¼ 1.41% MAC SEVO ¼ 3.3% Desired MAC multiple ¼ 1.3 fmac ISO ¼ desired MAC multiple MAC ISO ¼ 1.82% ¼ fmac SEVO ¼ desired MAC multiple MAC SEVO ¼ 4.29% ¼ kb/g ISO ¼ solubility of ISO in tissues ¼ 1.5 kb/g SEVO ¼ solubility of SEVO in tissues ¼ 0.69 Ca ¼ fmac kb/g Ca ISO ¼ fmac kb/ G ¼ 1.82% 1.5 ¼ ¼ Ca SEVO ¼ fmac kb/g ¼ 4.29% 0.69 ¼ ¼ _Q ¼ Cardiac output ¼ 2 kg 0.75 ml minute )1 ISO 1 ml liquid ¼ 206 ml vapor at 37 C (ml ISO vapor)/206 ¼ ml ISO liquid SEVO 1 ml liquid ¼ 183 ml vapor at 37 C (ml SEVO vapor)/183 ¼ ml SEVO liquid Example calculations for a 3 lb (1.36 kg) piglet using ISO liquid kg 0.75 ¼ ¼ 1.26 Volume of inhaler device with bag, small mask, and adaptor ¼ 250 ml. FRC ¼ kg ml ¼ ¼ 95 ml fmac ¼ desired MAC multiple MAC ISO ¼ % ¼ 1.82% ¼ Ventilatory prime dose: The amount of ISO or SEVO liquid required to establish the desired anesthetic concentration in the inhaler and the piglet s FRC. Arterial prime dose: The amount of ISO or SEVO liquid required to establish the desired anesthetic concentration in the piglet s blood. Unit dose: The amount of ISO or SEVO liquid required to maintain anesthesia for each square root of time increment. Ca ¼ fmac kb/g ¼ ¼ _Q ¼ Cardiac output ¼ 2 kg 0.75 ¼ ¼ 2.52 dl ¼ 252 ml minute )1 Ventilatory prime dose ¼ (volume of inhaler + piglet FRC) (fmac) ¼ ( ml) ¼ 345 ml ¼6.28 ml ISO vapor ¼ 6.28/206 ¼ ml ISO liquid Arterial prime dose ¼ Ca _Q ¼ ¼ 6.9 ml ISO vapor ¼ 6.9/206 ¼ ml ISO liquid Ó 2007 The Author. Journal compilation Ó 2007 Association of Veterinary Anaesthetists, 34,

8 Unit dose ¼ 2Ca _ Q ¼ ¼ 13.8 ml ISO vapor ¼ 13.8/206 ¼ ml ISO liquid Required ISO liquid for a 3 lb (1.36) kg piglet Ventilatory prime dose ¼ Arterial prime dose ¼ one unit dose ¼ ml Total dose ¼ ml 124 Ó 2007 The Author. Journal compilation Ó 2007 Association of Veterinary Anaesthetists, 34,