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A comparison of the duration and quality of recovery from isoflurane, sevoflurane and desflurane anaesthesia in dogs undergoing magnetic resonance imaging
Veterinary Anaesthesia and Analgesia, 2009, 36, 220–229
doi:10.1111/j.1467-2995.2009.00451.x
RESEARCH PAPER
A comparison of the duration and quality of recovery from isoflurane, sevoflurane and desflurane anaesthesia in dogs undergoing magnetic resonance imaging Angeles Jimenez Lozano LV, CertVA, MRCVS, David C Brodbelt MA, VetMB, PhD, DVA, Diplomate ECVAA, MRCVS, Kate E Borer BVSc, Diplomate ECVAA, DVA, MRCVS, Elizabeth Armitage-Chan MA, VetMB, Diplomate ACVA, MRCVS, KW Clarke MA, VetMB, Diplomate VetMed, DVA, Diplomate ECVA, FRCVS & Hatim IK Alibhai BVSc, MVM, PhD & Diplomate ECVAA Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, UK
Correspondence: Angeles Jimenez Lozano, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, UK. E-mail: [email protected]
Abstract Objective To compare the recovery after anaesthesia with isoflurane, sevoflurane and desflurane in dogs undergoing magnetic resonance imaging (MRI) of the brain. Study design Prospective, randomized clinical trial. Animals Thirty-eight dogs weighing 23.7 ± 12.6 kg. Methods Following pre-medication with meperidine, 3 mg kg)1 administered intramuscularly, anaesthesia was induced intravenously with propofol (mean dose 4.26 ± 1.3 mg kg)1), the trachea was intubated, and an inhalational anaesthetic agent was administered in oxygen. The dogs were randomly allocated to one of three groups: group I (n = 13) received isoflurane, group S (n = 12) received sevoflurane and group D (n = 13) received desflurane. Parameters recorded included cardiopulmonary data, body temperature, end-tidal anaesthetic concentration, duration of anaesthesia, and recovery times and quality. Qualitative data were compared using chi-squared and Fisher’s exact tests and quantitative data with ANOVA and Kruskal–Wallis test. Post-hoc comparisons for quantitative data were undertaken with the Mann–Whitney U-test. Results The duration of anaesthesia [mean and standard deviation (SD)] in group I was: 105.3 220
(27.48) minutes, group S: 120.67 (19.4) minutes, and group D: 113.69 (26.68) minutes (p = 0.32). Times to extubation [group I: 8 minutes, (interquartile range 6–9.5), group S: 7 minutes (IQR 5–7), group D: 5 minutes (IQR 3.5–7), p = 0.017] and to sternal recumbency [group I: 11 minutes (IQR 9.5–13.5), group S: 9.5 minutes (IQR 7.25– 11.75), group D: 7 minutes (range 3.5–11.5), p = 0.048] were significantly different, as were times to standing. One dog, following sevoflurane, had an unacceptable quality of recovery, but most other recoveries were calm, with no significant difference between groups. Conclusions and clinical relevance All three agents appeared suitable for use. Dogs’ tracheas were extubated and the dogs recovered to sternal recumbency most rapidly after desflurane. This may be advantageous for animals with some neurological diseases and for day case procedures. Keywords desflurane, dog, inhalational, isoflurane, recovery, sevoflurane.
Introduction Isoflurane is now the most widely used inhalational anaesthetic agent in veterinary anaesthesia. In medical anaesthesia, the increasing demand for a complete and rapid recovery from anaesthesia, especially for the ambulatory patient
Inhalational anaesthesia for MRI in dogs AJ Lozano et al.
has led to the introduction of two newer agents, sevoflurane and desflurane. A major advantage of these newer agents is superior pharmacokinetic properties, including low solubility in blood and tissues (Eger & Shafer 2005a), resulting in faster induction and recovery characteristics. An additional advantage of rapid kinetics is improved control of the depth of anaesthesia (Young & Apfelbaum 1995). Dogs undergoing magnetic resonance imaging (MRI) of the brain require anaesthesia for the procedure. A rapid recovery is desirable but avoidance of excitation is equally important. Excitatory emergence phenomena may precipitate an epileptic crisis in susceptible animals and excessive excitement or agitation during recovery can increase intra-cranial pressure (ICP). Although neither isoflurane, desflurane nor sevoflurane has been reported to cause brain epileptiform activity (Scheller et al. 1990, Clarke 1999) there are few reports evaluating their recovery qualities in small animals. Studies in cats (Hikasa et al. 1996), dogs (Johnson et al. 1998), piglets (Hodgson 2007) and rats (Eger & Johnson 1987b) have demonstrated quicker recoveries from sevoflurane compared with isoflurane, and desflurane compared with isoflurane, but these publications gave few details concerning quality of recovery. The clinical medical literature reports conflicting results. Some papers described smoother and faster recoveries following desflurane (Chen et al. 2001, Heavner et al. 2003, Iannuzzi et al. 2005, Mayer et al. 2006,) and sevoflurane (Sloan et al. 1996) compared with isoflurane. In contrast, others described a higher incidence of agitation and emergence phenomena in children being anaesthetized with sevoflurane compared to halothane (Cravero et al. 2000) and desflurane (Mayer et al. 2006). The aim of the current study was to evaluate the recovery characteristics of isoflurane, sevoflurane and desflurane as part of the routine anaesthetic protocol for dogs undergoing MRI of the brain. These animals were to be discharged from the hospital as soon as possible following their MRI scans, thus when taken together with their existing neurological conditions, the animals should have benefited from a rapid and smooth recovery from anaesthesia. The hypothesis of the study was that desflurane would provide the shortest duration of recovery, followed by sevoflurane and then isoflurane, and that quality of recovery would be acceptable in all cases.
Materials and methods Animals This study received ethical approval from the University Ethics Committee. Thirty-eight clientowned dogs, body weight 23.7 ± 12.6 kg, were admitted as ‘day cases’ to the Queen Mother Hospital for MRI scan of the brain to assist diagnosis of their neurological condition. Following MRI examination, some animals also underwent other diagnostic procedures, including cerebrospinal fluid tap and/or radiography. The dogs all underwent a full physical examination and, based on this and on medical history, were all classed as ASA (American Society of Anesthesiologists) II–III. Exclusion criteria from the study were dogs classified as ASA IV–V and those with a body weight less than 7 kg (necessary to enable the use of a circle breathing system). The dogs were randomly allocated to one of three groups. In group I (n = 13), anaesthesia was maintained with isoflurane; in group S with sevoflurane (n = 11) and in group D with desflurane (n = 13). Study protocol All animals were anaesthetized in an induction room and once anaesthesia was stable, were transported to the MRI room where the procedure was performed. Once MRI was completed, the dogs were returned to the induction room for further diagnostic procedures and for recovery. It was necessary to disconnect the dogs from the anaesthetic machine whilst moving from one room to the other. The following strategy was used to avoid reduction of depth of anaesthesia: the 2L reservoir bag from the circle breathing system (semi-disposable circle rebreathing system; Burtons, Marden, Kent, UK) was filled with oxygen and anaesthetic agent, the adjustable pressure limiting valve closed and the breathing system was detached from the anaesthetic machine and sealed. Thus the animals were breathing the vapour from the reservoir bag maintaining a continuous uptake of anaesthetic agent until the breathing system was re-connected to the anaesthetic machine. At that point, the delivery of fresh oxygen and anaesthetic from the vaporizer was continued. Anaesthetic protocol Food but not water was withheld for a minimum period of 8 hours before the start of the procedure.
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Prior to pre-medication, a video-film was made of each dog’s behaviour for subsequent assessment of its demeanour. Dogs were pre-medicated with meperidine (Pethidine injection; Martindale Pharmaceuticals, Romford, Essex, UK), 3 mg kg)1 intramuscularly (IM) at least 30 minutes before induction of anaesthesia. Level of sedation was assessed on a simple descriptive scale of 1–4 (Table 1). The cephalic vein was catheterized, and then the animal was brought to the induction room and was pre-oxygenated with 5 L minute)1 of oxygen administered by mask for at least 5 minutes. Anaesthesia was induced with an intravenous [IV] injection of propofol (Rapinovet; Schering-Plough Animal Health, Cork, Ireland) administered slowly to effect to allow endotracheal intubation. The endotracheal tube was then connected to the circle breathing system containing the carbon dioxide absorbent (Loflosorb; Intersurgical, Wokingham, UK). Anaesthesia was maintained using one of the three inhalational anaesthetic agents under study in oxygen as determined by the random selection. Vaporizer settings were adjusted to achieve an adequate plane of anaesthesia. Isoflurane (Isoflo; Abbott Animal Health, Maidenhead, UK) was administered from a Tec 3 isoflurane vaporizer (TEC 3; Medical supplies & services Int. Ltd., Leek, UK), sevoflurane (Sevoflo; Abbott Animal Health, UK) from a Penlon Sigma Elite sevoflurane vaporizer Table 1 Description of sedation score categories
Category
Description
1
Not very/not sedated: Able to stand up and walk. Fully responsive, wagging the tail. No signs of depression, drowsiness, ataxia or altered character with respect to how it was without any medication. Resistance to catheterization, to restraint or being placed on the table Slightly sedated: Able to stand up and walk. Fully responsive but slower to react. Not wagging tail. Mild signs of depression, drowsiness, ataxia or mild changes in character. Mild resistance to catheterization, restraint or position on the table Sedated: Able to stand up but reluctant to walk and/or ataxic. Slow reaction to stimuli. Signs of depression, drowsiness, ataxia and changed character. No resistance to catheterization, restraint or positioning on the table Deeply/very sedated: Unable to stand up and walk. Unresponsive to stimuli. Depressed, drowsy and sleepy. Easy catheterization, no restraint needed, no response
2
3
4
222
(Penlon, Abingdon, Oxford, UK) and desflurane (Suprane, desflurane USP; Baxter, Northampton, UK) from a Tec 6 desflurane vaporizer (TEC 6, Datex Ohmeda, Hatfield, UK). In the early stages of anaesthesia, the fresh gas oxygen flows were 4 L minute)1. Once anaesthesia was stable, fresh gas flow was reduced to 2 L minute)1. Patients breathed spontaneously unless end-tidal carbon dioxide (PE¢CO2) reached more than 45 mmHg (6 kPa); if that occurred, manual or mechanical intermittent positive pressure ventilation (Pneumac; VentiPac, Luton, UK) was used to maintain PE¢CO2 between 40 and 45 mmHg (5.3– 6 kPa). Measures were taken to prevent hypothermia, and included covering the main body surface with blankets and wrapping the distal part of the limbs with insulating plastic material. If at any time anaesthetic depth lightened to the extent that the patient moved, propofol was administered at doses of 1–2 mg kg)1 intravenously (IV). Monitoring Basic physiological parameters were monitored and recorded at 5-minute intervals whilst the animal was not in the MRI scanner. This monitoring consisted of PE¢CO2, expired concentration of the volatile agent (ET agent) and respiratory rate (fR) from the capnograph (Capnomac Ultima, Datex Ohmeda, UK) and pulse rate (PR) and arterial haemoglobin oxygen saturation (SpO2) from a pulse oximeter (Kontron multiparametric monitor; Kontron UK, Watford, UK). Electrical monitoring in the MRI unit was restricted to PE¢CO2 and fR (Normocap 200; Datex Ohmeda, UK), although the animals were observed continually and there was rapid access available to the dogs at any time. Rectal temperature was measured at the beginning and at the end of the anaesthetic. Other parameters recorded were the time from pre-medication to induction of anaesthesia, dose of propofol at induction and any increments required, times of administration of the inhalational agent, total anaesthetic time and recovery as described below. Recovery At the end of all procedures, the animals were allowed to recover. The vaporizer was turned off, the fresh gas oxygen flow increased to 8 L minute)1 and the reservoir bag emptied once every minute.
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After 5 minutes, the endotracheal tube was disconnected from the breathing system and the dogs were allowed to breathe room air. Tracheal extubation was performed when the animals regained the gag or cough reflex. The recovery from this point was recorded by video camera, as well as being assessed by the anaesthetist. Once the dog was in a sternal position, it was moved to the wards and placed in its kennel to recover and was under continuous close observation. Dogs were not stimulated or aided to attain standing position. The time when the vaporizer was switched off was taken as the reference start point for recording recovery times to extubation, to sternal position and to standing. The end points were when the dogs achieved these positions by their own effort, with no external help or encouragement. Fifteen animals did not stand by 45 minutes after the termination of anaesthesia, when direct observation by the anaesthetist was discontinued and monitoring was continued by other staff members. To facilitate statistical analysis, standing times were categorized as <20, 20–45 or >45 minutes. Quality of recovery assessment The assessment of quality of recovery started immediately after extubation and continued until at least 45 minutes after anaesthesia. Assessments were made directly by the anaesthetist, then at a later time from the videos by two other anaesthetists who were unaware which anaesthetic agent had been used. Each recovery was scored by all observers using two different systems. A visual analogue scale (VAS) defined one extreme at 0 mm as a perfect recovery whilst the other end, 100 mm, was defined as the worst recovery imaginable. The second method used was a simple descriptive scale (SDS) of 1–5 as described in Table 2. If the quality of recovery was considered unacceptable (SDS score 5, VAS > 70 mm), rescue medication was administered and included diazepam and medetomidine. Apparent dysphoric or distressful episodes at emergence were treated with medetomidine 2 lg kg)1 IV. Seizures were treated with diazepam 0.2– 0.5 mg kg)1 IV and repeated to effect. Statistical analysis Statistical analysis was undertaken with standard computer software (SPSS for Windows v.15.0; SPSS Inc., Chicago, IL, USA). Physiological data were
Table 2 Description of Simple Descriptive Scale (SDS) categories for quality of recovery
Categories
Description
1
Very smooth, no excitement, vocalization, trembling or vomiting. No convulsions Quite smooth, a little excitement. No paddling, vocalization, trembling or vomiting. No convulsions Moderately smooth with excitement. Some paddling, vocalization, trembling or vomiting observed. No convulsions Not smooth and with excitement. Paddling, vocalization, trembling or vomiting observed. No convulsions Extreme excitement observed with aggression, vocalization, violent movements or convulsions observed. Rescue sedation or anticonvulsant therapy needed
2
3
4
5
selected for analysis at three time points; 10 minutes following first administration of the inhalation agent (T1), in the scanner 60 minutes after induction (T2) and following MRI after 90 minutes (T3). End-tidal concentration of inhalation agent also was measured just prior to the end of the anaesthetic (T4). Minimum alveolar concentration (MAC) multiples of ET agent were calculated on the basis that isoflurane MAC was 1.34 vol% (Steffey & Howland 1977; Kazama & Ikeda 1988), sevoflurane MAC 2.23 vol% (Kazama & Ikeda 1988; Scheller et al. 1990) and desflurane MAC 8.76 vol% (Doorley et al. 1988; Hammond et al. 1994). Qualitative data (e.g. sex, ASA grade, standing times) were compared with chi-squared and Fisher’s exact tests and quantitative data (e.g. PR, age, extubation times) with ANOVA or Kruskal–Wallis test as appropriate. Post hoc comparisons for quantitative data were undertaken with the Mann–Whitney U-test. For quality of recovery, the level of agreement between observers was assessed using Bland– Altman plots for comparison of VAS scores and weighted kappa for SDS scores. Statistical significance was set at the 5% level. Results There were no significant differences between groups for age, body weight, sex or ASA physical status (Table 3). There was no significant difference between groups in the number of dogs which were receiving long term phenobarbital medication to
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significantly different between groups (Table 4). However, two dogs in group D required additional doses of propofol before or after the MRI procedure. These dogs became very lightly anaesthetized during pre- or post-MRI transport, and the further propofol was necessary to maintain anaesthesia in transit. There were no significant differences between groups in rectal temperatures or in
control their seizures. The degree of sedation after meperidine pre-medication was not significantly different between groups (p = 0.87). Thirteen dogs showed no apparent sedation (category 1), 17 moderate sedation (category 2) and eight good sedation (category 3). The total propofol dose (including increments) used during the anaesthetic procedure was not
Age, years (median, IQR) Body weight, kg [mean (SD) ] Sex M:F ASA II:ASA III Extra procedures (CSF, radiographs, ultrasound), n Seizures, n (phenobarbital medication) Vestibular signs Clinical signs, n Neck pain Behaviour changes Nerve paralysis/muscle atrophy
Group I
Group S
Group D
p-value
3.25 (2.62–6.75) 24.78 (13.85)
2.83 (0.84–7.12) 26.98 (13.68)
4.75 (2.91–8.8) 20.43 (10.01)
0.355
9:4 10:3 8
8:3 8:3 11
9:4 9:4 7
8 (3)
9 (3)
7 (4)
3
1
3
1 1 0
0 1 1
2 1 0
Table 3 Patient characteristics, main clinical sign on presentation and procedures performed in addition to MRI
0.423 0.152 0.332
MRI, magnetic resonance imaging; IQR, interquartile range; CSF, cerebrospinal fluid.
Table 4 Anaesthetic doses, duration, physiological and cardiopulmonary measurements, expressed as mean and SD or median and IQR as appropriate
Total propofol mg kg)1 [mean (SD)] Total anaesthetic time minutes, [mean (SD)] Body temperature induction, C, [mean (SD)] Body temperature recovery, C, [mean (SD)] PE¢CO2 [median (IQR)] (during anaesthesia T1, T2, T3) mmHg kPa End-tidal inhalant concentration vol%, [mean (SD)] (during anaesthesia, T1, T3) MAC multiple* [median (IQR)] End-tidal inhalant concentration vol% [mean (SD)] (end of anaesthesia, T4) MAC multiple* [median (IQR)] Respiratory rate, breaths minute)1 [mean (SD)] (during anaesthesia T1, T2, T3) Heart rate, beats minute)1 [median (IQR)] (during anaesthesia T1, T2, T3)
Group I
Group S
Group D
4.28 (1.04) 105.3 (27.48) 37.98 (0.59) 35.85 (0.89) 45 (40.5–48.5)
3.8 (1.34) 120.67 (19.4) 37.81 (0.54) 36.19 (1.18) 40.5 (35–47)
4.68 (1.44) 113.69 (26.68) 38.14 (0.61) 35.93 (1.19) 48 (43.5–51)
p-value
0.24 0.32 0.38 0.81 0.11
5.9 (5.4–6.4) 0.96 (0.317)
5.4 (4.6–6.2) 2.08 (0.502)
6.4 (5.8–6.8) 5.52 (1.64)
0.68 (0.59–0.81) 1.18 (0.15)
0.95 (0.78–1.04) 2.5 (0.49)
0.67 (0.43–0.79) 8.04 (1.39)
0.89 (0.78–0.97) 11.14 (3.36)
1.14 (0.95–1.21) 15.75 (9.5)
0.93 (0.81–1.07) 13.39 (6.43)
0.21
91 (80–109)
96 (91–103.7)
98 (85–123.5)
0.52
<0.01
<0.01
SD, standard deviation; IQR, interquartile range; MAC, minimum alveolar concentration. *MAC values (%), mean taken from: Isoflurane 1.34% (Kazama & Ikeda 1988; Steffey & Howland 1977), sevoflurane 2.23% (Kazama & Ikeda 1988; Scheller et al. 1990) and desflurane 8.76% (Doorley et al. 1988; Hammond et al. 1994).
224
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duration of anaesthesia (Table 4); nor were there significant differences between groups in PR, fR or PE¢CO2. The number of animals which were ventilated were seven dogs in group I, nine dogs in group S and nine patients in group D; there was no difference between groups (p = 0.48). There was a significant difference in MAC multiples of the inhalational anaesthetic agent both over the anaesthetic course (T1, T3) and prior to disconnection (T4), between groups I and S (p < 0.02) and between groups S and D (p < 0.01) (Table 4). A higher MAC multiple was seen for patients in group S, but groups I and D did not differ. End-tidal concentrations of anaesthetic agents immediately before the end of the procedure (time between 90 and 140 minutes depending on length of anaesthetic) were [mean (SD)]: group I 1.18% (0.15), group S 2.5% (0.49), group D 8.04% (1.39). Recovery times were significantly faster for the dogs in group D than in group I for both extubation (p = 0.005) and sternal recumbency (p = 0.024); but differences between groups D and S and between groups I and S were not statistically significant (Table 5). Categorized standing times
were significantly different between groups (p = 0.049): dogs in group D being more likely to stand earlier compared with group I (p = 0.047) (Table 5). One dog in group D started to retch after extubation, and was placed in sternal recumbency for safety. Most recoveries were classified using the SDS as being between score 1 and 3 (very to moderately smooth; Table 6). However, in three dogs in group I and one dog in group S, recoveries were classified as 4 (not smooth and had some excitement) by one or more observers. Additionally, one dog in group S had an unacceptable recovery with extreme excitement, paddling and vocalization. It responded to anticonvulsant therapy with diazepam and sedation with medetomidine. Three observers (A, B and C) assigned scores to each patient using the VAS and SDS scales, for the evaluation of quality of recovery. There were no significant differences between groups for VAS quality of recovery for any of the observers (Table 6). The level of agreement of VAS assessment between observers was moderate; limits of agreement between A and B were )20.9 to 30.4 mm,
Table 5 Times to extubation, sternal recumbency and standing expressed as median and IQR
Group I
Extubation times, minutes Sternal times, minutes Standing times (minutes), n <20 20–45 >45
Group S
8 (6–9.5)*
7 (5–7)
11 (9.5–13.5)**
1 5 7
9.5 (7.25–11.75)
5 4 2
Group D
p-value
5 (3.5–7)*
0.017
7 (3.5–11.5)**
0.048
6 1 6
0.049
IQR, interquartile range. Significant differences between group I and D for extubation time: *p = 0.005 and for sternal time: **p = 0.024. One dog that received sedation because of excitement in recovery was excluded here.
Table 6 Quality of recovery as assessed with the VAS and SDS by observers A, B and C expressed as median and IQR
VAS, mm Observer Observer Observer SDS Observer Observer Observer
A B C A B C
Group I
Group S
Group D
p-value
15 (7.5–37.5) 9 (5–14.5) 17 (9–33)
10.8 (5.3–14.5) 5.5 (4.3–17) 17.5 (6.3–48.7)
11 (5–13.3) 9 (6–14.5) 9 (5–25)
0.37 0.93 0.39
1 (1–2.5) 1 (1–2) 1 (1–2)
0.79 0.64 0.81
2 (1–3) 1 (1–2) 1 (1–3)
1 (1–2.5) 1 (1–2.5) 2 (1–3.5)
VAS, visual analogue scale; SDS, simple descriptive scale; IQR, interquartile range.
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mean difference 4.7 mm, limits of agreement between A and C were )45.6 to 34.6 mm, mean difference )5.5 mm and limits of agreement between B and C )41.1 to 20.5 mm, mean difference )10.2 mm. Similarly, there was no difference between groups in the SDS as assessed by three observers (p = 0.705 for A, p = 1.00 for B, p = 0.767 for C). Level of agreement between observers was moderate with weighted kappa values of 0.43 for observers A and B, 0.28 for A and C, and 0.4 for B and C. Discussion The aim of this study was to evaluate and assess the clinical use of three different inhalational agents for the anaesthesia of outpatients undergoing MRI of the brain, with particular reference to speed and quality of recovery. All three agents provided adequate anaesthesia for the procedures undertaken, patients generally recovered calmly and times to extubation and sternal recumbency occurred most rapidly with desflurane, suggesting when an early recovery is considered advantageous this agent may be preferred. Although conditions for anaesthesia were adequate in all animals, two dogs which received desflurane had an episode of arousal following the move between the MRI scanner and the procedures room, and required an increment of propofol before adequate anaesthesia could be re-established. Transport did pose problems because the dog remained connected to a closed circle breathing system, but no fresh inhalation agent could be added. Thus, the arousal might have been due to low desflurane concentrations resulting from the anaesthetist’s lack of experience of this agent, or to a decrease in anaesthetic concentration during disconnection/reconnection to the anaesthetic machine. The rapid kinetics of desflurane meant that a decrease in anaesthetic concentration was more likely to occur than when isoflurane or sevoflurane were used under the same circumstances (Hargasser et al. 1995; Young & Apfelbaum 1995; Heavner et al. 2003; Eger & Shafer 2005b). It was anticipated, on the basis of published work (Hikasa et al. 1996; Mutoh et al. 1997; Johnson et al. 1998; Galloway et al. 2004) that PR with sevoflurane would be lower than with isoflurane or desflurane, and that desflurane would cause the least respiratory depression. However, in the current clinical study such differences were not 226
observed and the cardiopulmonary parameters monitored, including heart and fR, PE¢CO2 and numbers of dogs requiring ventilation to maintain PE¢CO2, did not differ between the three agents. In the current study, dogs recovered to extubation and achieved sternal recumbency in the shortest time following desflurane anaesthesia, the next fastest was sevoflurane and patients recovered most slowly following isoflurane. The differences in recovery times were as expected from the kinetics of the agents, and as noted in previous studies in the human literature (Nathanson et al. 1995; Campbell et al. 1996; Welborn et al. 1996; Chen et al. 2001; Heavner et al. 2003; Iannuzzi et al. 2005). Veterinary studies have compared isoflurane and sevoflurane in a number of species, with varying results. In some studies, recovery from sevoflurane was significantly faster than from isoflurane (Eger & Johnson 1987b; Hikasa et al. 1996; Matthews et al. 1998) whereas in others differences were not significant (Johnson et al. 1998; Hodgson 2007; Love et al. 2007). In horses, recovery to standing was faster with desflurane than with isoflurane (Bradbrook et al. 2006) but in sheep there was no significant difference between times of recovery from isoflurane, sevoflurane or desflurane (Mohamadnia et al. 2007). Nonetheless, that desflurane anaesthesia resulted in more rapid recovery was as anticipated from the kinetics of the agents (Clarke 1999; Eger & Shafer 2005a). The prolonged time to standing reported in the current study resulted in substantial missing data, necessitating categorization of final recovery into three time groups for statistical analysis. Although differences reached statistical significance, this study did not demonstrate clear biological superiority of any agent for recovery to standing unaided. Positioning the dog in the enclosed space of the kennel additionally discouraged standing and the ability to assess time to standing. Although all dogs were able to stand on admission, the multiple neurological signs in some (circling, ataxia, nystagmus and loss of balance) also influenced the ability to stand after the procedures and assessment of this endpoint. However, all groups were homogeneous for clinical signalment and main neurological signs on presentation and groups should have been affected equally. Factors which influence the speed of recovery from inhalational anaesthesia include the condition of the dog prior to and after anaesthesia, the additional sedative, analgesic and anaesthetic induction agents administered, the kinetics of the inhalation agents,
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the duration of anaesthesia, the depth of anaesthesia at the time of commencement of the recovery process, and the body temperature of the animal at the time of recovery. Phenobarbital medication received prior to admission could contribute to increased sedation, and delayed recovery, but receipt of such medication was similar in all groups. The pre-medication and induction agents were chosen to minimize postanaesthetic effect of the injectable agents and are used commonly by small animal practising veterinary surgeons in the UK. Meperidine has a marketing licence for dogs and is an opioid with a relatively short duration of action of 90–120 minutes (Waterman & Kalthum 1989). Experience with meperidine premedication at the Royal Veterinary College has been that in ASA I–II dogs the degree of sedation is minimal to mild only, and publications from others sources support this finding (Wilson et al. 2007). In this study, however, some dogs were categorized as ‘good sedation’, and this was considered an exaggerated response, probably due to a more severe neurological condition. However, there were no significant differences between groups in the degree of sedation recorded, and any impact of pre-medication on recovery was likely to be similar across groups. Propofol, when used as an anaesthetic induction agent in the dog, has a short duration of action as it is rapidly distributed, rapidly eliminated and shows minimal accumulation (Watkins et al. 1987; Musk et al. 2005). The dose of propofol used, inclusive of the increments, did not differ between groups. Thus,
after the minimum time of 2 hours of the procedure, the influence of the noninhalational drugs should be very minor, and would have been equal in all groups. Body temperature was measured rectally and although this does not equate to body core temperature, it gives an accurate reflection (Sessler 1993). In our study, although measures were taken to avoid hypothermia, there was a significant reduction of body temperature over time in the dogs. Hypothermia decreases MAC (Vitez et al. 1974; Eger & Johnson 1987a) and impairs drug metabolism, potentially prolonging recovery from anaesthesia (Insler & Sessler 2006). However, in the current study the degree of hypothermia was similar across groups and hence the effect of decrease in body temperature on recovery was likely to be similar in the three groups. An important factor influencing speed of recovery is the depth of anaesthesia at the time of switching off the vaporizer at the end of the procedure. In this study, end-tidal agent concentrations were converted to MAC multiples for comparative purposes. Published MAC values vary and here the average of the two published values for the dog was taken as the reference value for the MAC multiple calculations. Differences between values published in different studies for isoflurane (Steffey & Howland 1977; Kazama & Ikeda 1988) and sevoflurane (Kazama & Ikeda 1988; Scheller et al. 1990) were small, but the two published MAC values for
25 Observer A Observer B
Number of dogs
20
Observer C
15
10
5
ISO SEVO DES
ISO SEVO DES
ISO SEVO DES
ISO SEVO DES
ISO SEVO DES
CAT 1
CAT 2
CAT 3
CAT 4
CAT 5
Figure 1 Summary of quality of recovery as assessed with the simple descriptive scale (SDS) recovery score by three observers, A, B and C. The X axis represents the SDS recovery score categories (CAT 1–5) subdivided by the treatment groups (groups I, S and D). The Y axis indicates the number of dogs in each treatment group, classified in each SDS recovery score category by the three observers. SDS recovery score categories are defined in Table 2, group I (n = 13) received isoflurane, group S (n = 11) received sevoflurane and group D (n = 13) received desflurane. A category 5 was awarded by all observers when poor quality of recovery prevented a video being obtained (one dog in group S). 2009 The Authors. Journal compilation 2009 Association of Veterinary Anaesthetists, 36, 220–229
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desflurane in dogs of 7.2 vol% (Doorley et al. 1988) and 10.3 vol% (Hammond et al. 1994) differ by more than 40%. Using these MAC values, the MAC multiple of sevoflurane was significantly higher than that of the other two agents both during and at the end of the procedure. This might have slowed recovery times, but if the lower MAC value of 7.2 vol% for desflurane had been used for the MAC multiple calculations, the differences would not have been significant. However, the MAC multiples reported for isoflurane and desflurane were very similar and a difference in relative depth during or at termination of anaesthesia was unlikely to explain the main finding that recoveries were fastest after desflurane anaesthesia compared to isoflurane. The quality of recovery from anaesthesia is at least as important as the speed of recovery in cases with neurological compromise. Emergence from anaesthesia and extubation periods are often associated with sympathetic stimulation (Bruder & Ravussin 1999) which may increase arterial blood pressure, ICP and oxygen consumption. In this current study, most recoveries were smooth and differences were not statistically significant between groups. There were no poor quality recoveries (category 4 or 5 as judged by the SDS method) following desflurane anaesthesia (Fig. 1) which was in agreement with clinical studies in horses (Bradbrook et al. 2006). Only one dog had an unacceptable recovery. This dog had been anaesthetized with sevoflurane, recovered violently, vocalized and appeared to seizure. It did not improve with diazepam administration but calmed following medetomidine administration. The apparent seizure activity could have resulted from its neurological condition and/or could have been potentiated by the inhalational agent. Sevoflurane has been shown to increase epileptiform activity to a greater degree than the other two agents (Iijima et al. 2000) in human patients already suffering from epilepsy. However, emergence delirium from sevoflurane anaesthesia is well recognized in human anaesthesia (Cravero et al. 2000; Mayer et al. 2006) and violent recoveries from sevoflurane anaesthesia have been documented on occasions in the veterinary literature (Clarke et al. 1996; Steffey et al. 2005; Mohamadnia et al. 2007). Assessment of quality of recovery is subjective. In this study, two different assessment methods were used, and three assessors (two assessing from video recordings and blinded to the agent used). Both methods of assessment indicated that there were no significant differences in recovery quality across 228
groups. There was only a moderate level of agreement between the three observers in actual scores awarded and lack of agreement in individual animals was likely to reflect the subjective nature of recovery assessment, but all observers consistently classified treatment groups as of similar quality (Fig. 1). In conclusion, this study demonstrated that all three inhalational agents were suitable for outpatient anaesthesia in dogs with neurological conditions and provided in general a good and smooth recovery. Dogs recovered to sternal recumbency most rapidly after desflurane; thus desflurane might be advantageous when a rapid emergence from anaesthesia is required. References Bradbrook C, Sigurdsson S, Borer K et al. (2006) A comparison in clinical cases of recovery from anaesthesia following maintenance with desflurane or isoflurane in horses: preliminary results. Proceedings of the WCVA congress, Santos, Brazil (abstract). Bruder N, Ravussin P (1999) Recovery from anesthesia and postoperative extubation of neurosurgical patients: a review. J Neurosurg Anesthesiol 11, 282–293. Campbell C, Andreen M, Battito MF et al. (1996) A phase III, multicenter, open-label, randomized, comparative study evaluating the effect of sevoflurane versus isoflurane on the maintenance of anesthesia in adult ASA class I, II, and III inpatients. J Clin Anesth 8, 557– 563. Chen X, Zhao M, White PF et al. (2001) The recovery of cognitive function after general anesthesia in elderly patients: a comparison of desflurane and sevoflurane. Anesth Analg 93, 1489–1494. Clarke KW (1999) Desflurane and sevoflurane. New volatile anesthetic agents. Vet Clin North Am Small Anim Pract 29, 793–810. Clarke KW, Lee HY, Brown LA (1996) Sevoflurane anaesthesia in the horse. J Vet Anesth 23, 85. Cravero J, Surgenor S, Whalen K (2000) Emergence agitation in paediatric patients after sevoflurane anaesthesia and no surgery: a comparison with halothane. Paediatr Anaesth 10, 419–424. Doorley BM, Waters SJ, Terrell RC et al. (1988) MAC of I-653 in beagle dogs and New Zealand white rabbits. Anesthesiology 69, 89–91. Eger EI II, Johnson BH (1987a) MAC of I-653 in rats, including a test of the effect of body temperature and anesthetic duration. Anesth Analg 66, 974–976. Eger EI II, Johnson BH (1987b) Rates of awakening from anesthesia with I-653, halothane, isoflurane, and sevoflurane: a test of the effect of anesthetic concentration and duration in rats. Anesth Analg 66, 977–982.
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Eger EI II, Shafer SL (2005a) The complexity of recovery from anesthesia. J Clin Anesth 17, 411–412. Eger EI II, Shafer SL (2005b) Tutorial: context-sensitive decrement times for inhaled anesthetics. Anesth Analg 101, 688–696. Galloway DS, Ko JC, Reaugh HF et al. (2004) Anesthetic indices of sevoflurane and isoflurane in unpremedicated dogs. J Am Vet Med Assoc 225, 700–704. Hammond RA, Alibhai HIK, Walsh KP et al. (1994) Desflurane in the dog: minimum alveolar concentration (MAC) alone and in combination with nitrous oxide. J Vet Anaesth 21, 21–23. Hargasser S, Hipp R, Breinbauer B et al. (1995) A lower solubility recommends the use of desflurane more than isoflurane, halothane, and enflurane under low-flow conditions. J Clin Anesth 7, 49–53. Heavner JE, Kaye AD, Lin BK et al. (2003) Recovery of elderly patients from two or more hours of desflurane or sevoflurane anaesthesia. Br J Anaesth 91, 502–506. Hikasa Y, Kawanabe H, Takase K et al. (1996) Comparisons of sevoflurane, isoflurane, and halothane anesthesia in spontaneously breathing cats. Vet Surg 25, 234–243. Hodgson DS (2007) Comparison of isoflurane and sevoflurane for short-term anesthesia in piglets. Vet Anaesth Analg 34, 117–124. Iannuzzi E, Iannuzzi M, Viola G et al. (2005) Desflurane and sevoflurane in elderly patients during general anesthesia: a double blind comparison. Minerva Anestesiol 71, 147–155. Iijima T, Nakamura Z, Iowa Y et al. (2000) The epileptogenic properties of the volatile anaesthetics sevoflurane and isoflurane in patients with epilepsy. Anesth Analg 91, 989–995. Insler SR, Sessler DI (2006) Perioperative thermoregulation and temperature monitoring. Anesthesiol Clin 24, 823–837. Johnson RA, Striler E, Sawyer DC et al. (1998) Comparison of isoflurane with sevoflurane for anesthesia induction and recovery in adult dogs. Am J Vet Res 59, 478–481. Kazama T, Ikeda K (1988) Comparison of MAC and the rate of rise of alveolar concentration of sevoflurane with halothane and isoflurane in the dog. Anesthesiology 68, 435–437. Love EJ, Holt PE, Murison PJ (2007) Recovery characteristics following maintenance of anaesthesia with sevoflurane or isoflurane in dogs premedicated with acepromazine. Vet Rec 161, 217–221. Matthews NS, Hartsfield SM, Mercer D et al. (1998) Recovery from sevoflurane anesthesia in horses: comparison to isoflurane and effect of postmedication with xylazine. Vet Surg 27, 480–485. Mayer J, Boldt J, Rohm KD et al. (2006) Desflurane anesthesia after sevoflurane inhaled induction reduces severity of emergence agitation in children undergoing
minor ear-nose-throat surgery compared with sevoflurane induction and maintenance. Anesth Analg 102, 400–404. Mohamadnia AR, Hughes G, Clarke KW (2008) Maintenance of anaesthesia in sheep with isoflurane, desflurane or sevoflurane. Vet Rec 163, 210–215. Musk GC, Pang DS, Beths T et al. (2005) Target-controlled infusion of propofol in dogs – evaluation of four targets for induction of anaesthesia. Vet Rec 157, 766–770. Mutoh T, Nishimura R, Kim HY et al. (1997) Cardiopulmonary effects of sevoflurane, compared with halothane, enflurane, and isoflurane, in dogs. Am J Vet Res 58, 885–890. Nathanson MH, Fredman B, Smith I et al. (1995) Sevoflurane versus desflurane for outpatient anesthesia: a comparison of maintenance and recovery profiles. Anesth Analg 81, 1186–1190. Scheller MS, Nakakimura K, Fleischer JE et al. (1990) Cerebral effects of sevoflurane in the dog: comparison with isoflurane and enflurane. Br J Anaesth 65, 388– 392. Sessler DI (1993) Perianesthetic thermoregulation and heat balance in humans. FASEB J 7, 638–644. Sloan MH, Conard PF, Karsunky PK et al. (1996) Sevoflurane versus isoflurane: induction and recovery characteristics with single-breath inhaled inductions of anesthesia. Anesth Analg 82, 528–532. Steffey EP, Howland D Jr (1977) Isoflurane potency in the dog and cat. Am J Vet Res 38, 1833–1836. Steffey EP, Mama KR, Galey FD et al. (2005) Effects of sevoflurane dose and mode of ventilation on cardiopulmonary function and blood biochemical variables. Am J Vet Res 66, 606–614. Vitez TS, White PF, Eger EI II (1974) Effects of hypothermia on halothane MAC and isoflurane MAC in the rat. Anesthesiology 41, 80–81. Waterman AE, Kalthum W (1989) Pharmacokinetics of intramuscularly administered pethidine in dogs and the influence of anaesthesia and surgery. Vet Rec 124, 293– 296. Watkins SB, Hall LW, Clarke KW (1987) Propofol as an intravenous anaesthetic agent in dogs. Vet Rec 120, 326–329. Welborn LG, Hannallah RS, Norden JM et al. (1996) Comparison of emergence and recovery characteristics of sevoflurane, desflurane, and halothane in pediatric ambulatory patients. Anesth Analg 83, 917–920. Wilson DV, Evans AT, Mauer WA (2007) Pre-anesthetic meperidine: associated vomiting and gastroesophageal reflux during the subsequent anesthetic in dogs. Vet Anaesth Analg 34, 15–22. Young CJ, Apfelbaum JL (1995) Inhalational anesthetics: desflurane and sevoflurane. J Clin Anesth 7, 564–577. Received 28 January 2008; accepted 1 July 2008.
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doi:10.1111/j.1467-2995.2009.00451.x
RESEARCH PAPER
A comparison of the duration and quality of recovery from isoflurane, sevoflurane and desflurane anaesthesia in dogs undergoing magnetic resonance imaging Angeles Jimenez Lozano LV, CertVA, MRCVS, David C Brodbelt MA, VetMB, PhD, DVA, Diplomate ECVAA, MRCVS, Kate E Borer BVSc, Diplomate ECVAA, DVA, MRCVS, Elizabeth Armitage-Chan MA, VetMB, Diplomate ACVA, MRCVS, KW Clarke MA, VetMB, Diplomate VetMed, DVA, Diplomate ECVA, FRCVS & Hatim IK Alibhai BVSc, MVM, PhD & Diplomate ECVAA Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, UK
Correspondence: Angeles Jimenez Lozano, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, UK. E-mail: [email protected]
Abstract Objective To compare the recovery after anaesthesia with isoflurane, sevoflurane and desflurane in dogs undergoing magnetic resonance imaging (MRI) of the brain. Study design Prospective, randomized clinical trial. Animals Thirty-eight dogs weighing 23.7 ± 12.6 kg. Methods Following pre-medication with meperidine, 3 mg kg)1 administered intramuscularly, anaesthesia was induced intravenously with propofol (mean dose 4.26 ± 1.3 mg kg)1), the trachea was intubated, and an inhalational anaesthetic agent was administered in oxygen. The dogs were randomly allocated to one of three groups: group I (n = 13) received isoflurane, group S (n = 12) received sevoflurane and group D (n = 13) received desflurane. Parameters recorded included cardiopulmonary data, body temperature, end-tidal anaesthetic concentration, duration of anaesthesia, and recovery times and quality. Qualitative data were compared using chi-squared and Fisher’s exact tests and quantitative data with ANOVA and Kruskal–Wallis test. Post-hoc comparisons for quantitative data were undertaken with the Mann–Whitney U-test. Results The duration of anaesthesia [mean and standard deviation (SD)] in group I was: 105.3 220
(27.48) minutes, group S: 120.67 (19.4) minutes, and group D: 113.69 (26.68) minutes (p = 0.32). Times to extubation [group I: 8 minutes, (interquartile range 6–9.5), group S: 7 minutes (IQR 5–7), group D: 5 minutes (IQR 3.5–7), p = 0.017] and to sternal recumbency [group I: 11 minutes (IQR 9.5–13.5), group S: 9.5 minutes (IQR 7.25– 11.75), group D: 7 minutes (range 3.5–11.5), p = 0.048] were significantly different, as were times to standing. One dog, following sevoflurane, had an unacceptable quality of recovery, but most other recoveries were calm, with no significant difference between groups. Conclusions and clinical relevance All three agents appeared suitable for use. Dogs’ tracheas were extubated and the dogs recovered to sternal recumbency most rapidly after desflurane. This may be advantageous for animals with some neurological diseases and for day case procedures. Keywords desflurane, dog, inhalational, isoflurane, recovery, sevoflurane.
Introduction Isoflurane is now the most widely used inhalational anaesthetic agent in veterinary anaesthesia. In medical anaesthesia, the increasing demand for a complete and rapid recovery from anaesthesia, especially for the ambulatory patient
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has led to the introduction of two newer agents, sevoflurane and desflurane. A major advantage of these newer agents is superior pharmacokinetic properties, including low solubility in blood and tissues (Eger & Shafer 2005a), resulting in faster induction and recovery characteristics. An additional advantage of rapid kinetics is improved control of the depth of anaesthesia (Young & Apfelbaum 1995). Dogs undergoing magnetic resonance imaging (MRI) of the brain require anaesthesia for the procedure. A rapid recovery is desirable but avoidance of excitation is equally important. Excitatory emergence phenomena may precipitate an epileptic crisis in susceptible animals and excessive excitement or agitation during recovery can increase intra-cranial pressure (ICP). Although neither isoflurane, desflurane nor sevoflurane has been reported to cause brain epileptiform activity (Scheller et al. 1990, Clarke 1999) there are few reports evaluating their recovery qualities in small animals. Studies in cats (Hikasa et al. 1996), dogs (Johnson et al. 1998), piglets (Hodgson 2007) and rats (Eger & Johnson 1987b) have demonstrated quicker recoveries from sevoflurane compared with isoflurane, and desflurane compared with isoflurane, but these publications gave few details concerning quality of recovery. The clinical medical literature reports conflicting results. Some papers described smoother and faster recoveries following desflurane (Chen et al. 2001, Heavner et al. 2003, Iannuzzi et al. 2005, Mayer et al. 2006,) and sevoflurane (Sloan et al. 1996) compared with isoflurane. In contrast, others described a higher incidence of agitation and emergence phenomena in children being anaesthetized with sevoflurane compared to halothane (Cravero et al. 2000) and desflurane (Mayer et al. 2006). The aim of the current study was to evaluate the recovery characteristics of isoflurane, sevoflurane and desflurane as part of the routine anaesthetic protocol for dogs undergoing MRI of the brain. These animals were to be discharged from the hospital as soon as possible following their MRI scans, thus when taken together with their existing neurological conditions, the animals should have benefited from a rapid and smooth recovery from anaesthesia. The hypothesis of the study was that desflurane would provide the shortest duration of recovery, followed by sevoflurane and then isoflurane, and that quality of recovery would be acceptable in all cases.
Materials and methods Animals This study received ethical approval from the University Ethics Committee. Thirty-eight clientowned dogs, body weight 23.7 ± 12.6 kg, were admitted as ‘day cases’ to the Queen Mother Hospital for MRI scan of the brain to assist diagnosis of their neurological condition. Following MRI examination, some animals also underwent other diagnostic procedures, including cerebrospinal fluid tap and/or radiography. The dogs all underwent a full physical examination and, based on this and on medical history, were all classed as ASA (American Society of Anesthesiologists) II–III. Exclusion criteria from the study were dogs classified as ASA IV–V and those with a body weight less than 7 kg (necessary to enable the use of a circle breathing system). The dogs were randomly allocated to one of three groups. In group I (n = 13), anaesthesia was maintained with isoflurane; in group S with sevoflurane (n = 11) and in group D with desflurane (n = 13). Study protocol All animals were anaesthetized in an induction room and once anaesthesia was stable, were transported to the MRI room where the procedure was performed. Once MRI was completed, the dogs were returned to the induction room for further diagnostic procedures and for recovery. It was necessary to disconnect the dogs from the anaesthetic machine whilst moving from one room to the other. The following strategy was used to avoid reduction of depth of anaesthesia: the 2L reservoir bag from the circle breathing system (semi-disposable circle rebreathing system; Burtons, Marden, Kent, UK) was filled with oxygen and anaesthetic agent, the adjustable pressure limiting valve closed and the breathing system was detached from the anaesthetic machine and sealed. Thus the animals were breathing the vapour from the reservoir bag maintaining a continuous uptake of anaesthetic agent until the breathing system was re-connected to the anaesthetic machine. At that point, the delivery of fresh oxygen and anaesthetic from the vaporizer was continued. Anaesthetic protocol Food but not water was withheld for a minimum period of 8 hours before the start of the procedure.
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Prior to pre-medication, a video-film was made of each dog’s behaviour for subsequent assessment of its demeanour. Dogs were pre-medicated with meperidine (Pethidine injection; Martindale Pharmaceuticals, Romford, Essex, UK), 3 mg kg)1 intramuscularly (IM) at least 30 minutes before induction of anaesthesia. Level of sedation was assessed on a simple descriptive scale of 1–4 (Table 1). The cephalic vein was catheterized, and then the animal was brought to the induction room and was pre-oxygenated with 5 L minute)1 of oxygen administered by mask for at least 5 minutes. Anaesthesia was induced with an intravenous [IV] injection of propofol (Rapinovet; Schering-Plough Animal Health, Cork, Ireland) administered slowly to effect to allow endotracheal intubation. The endotracheal tube was then connected to the circle breathing system containing the carbon dioxide absorbent (Loflosorb; Intersurgical, Wokingham, UK). Anaesthesia was maintained using one of the three inhalational anaesthetic agents under study in oxygen as determined by the random selection. Vaporizer settings were adjusted to achieve an adequate plane of anaesthesia. Isoflurane (Isoflo; Abbott Animal Health, Maidenhead, UK) was administered from a Tec 3 isoflurane vaporizer (TEC 3; Medical supplies & services Int. Ltd., Leek, UK), sevoflurane (Sevoflo; Abbott Animal Health, UK) from a Penlon Sigma Elite sevoflurane vaporizer Table 1 Description of sedation score categories
Category
Description
1
Not very/not sedated: Able to stand up and walk. Fully responsive, wagging the tail. No signs of depression, drowsiness, ataxia or altered character with respect to how it was without any medication. Resistance to catheterization, to restraint or being placed on the table Slightly sedated: Able to stand up and walk. Fully responsive but slower to react. Not wagging tail. Mild signs of depression, drowsiness, ataxia or mild changes in character. Mild resistance to catheterization, restraint or position on the table Sedated: Able to stand up but reluctant to walk and/or ataxic. Slow reaction to stimuli. Signs of depression, drowsiness, ataxia and changed character. No resistance to catheterization, restraint or positioning on the table Deeply/very sedated: Unable to stand up and walk. Unresponsive to stimuli. Depressed, drowsy and sleepy. Easy catheterization, no restraint needed, no response
2
3
4
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(Penlon, Abingdon, Oxford, UK) and desflurane (Suprane, desflurane USP; Baxter, Northampton, UK) from a Tec 6 desflurane vaporizer (TEC 6, Datex Ohmeda, Hatfield, UK). In the early stages of anaesthesia, the fresh gas oxygen flows were 4 L minute)1. Once anaesthesia was stable, fresh gas flow was reduced to 2 L minute)1. Patients breathed spontaneously unless end-tidal carbon dioxide (PE¢CO2) reached more than 45 mmHg (6 kPa); if that occurred, manual or mechanical intermittent positive pressure ventilation (Pneumac; VentiPac, Luton, UK) was used to maintain PE¢CO2 between 40 and 45 mmHg (5.3– 6 kPa). Measures were taken to prevent hypothermia, and included covering the main body surface with blankets and wrapping the distal part of the limbs with insulating plastic material. If at any time anaesthetic depth lightened to the extent that the patient moved, propofol was administered at doses of 1–2 mg kg)1 intravenously (IV). Monitoring Basic physiological parameters were monitored and recorded at 5-minute intervals whilst the animal was not in the MRI scanner. This monitoring consisted of PE¢CO2, expired concentration of the volatile agent (ET agent) and respiratory rate (fR) from the capnograph (Capnomac Ultima, Datex Ohmeda, UK) and pulse rate (PR) and arterial haemoglobin oxygen saturation (SpO2) from a pulse oximeter (Kontron multiparametric monitor; Kontron UK, Watford, UK). Electrical monitoring in the MRI unit was restricted to PE¢CO2 and fR (Normocap 200; Datex Ohmeda, UK), although the animals were observed continually and there was rapid access available to the dogs at any time. Rectal temperature was measured at the beginning and at the end of the anaesthetic. Other parameters recorded were the time from pre-medication to induction of anaesthesia, dose of propofol at induction and any increments required, times of administration of the inhalational agent, total anaesthetic time and recovery as described below. Recovery At the end of all procedures, the animals were allowed to recover. The vaporizer was turned off, the fresh gas oxygen flow increased to 8 L minute)1 and the reservoir bag emptied once every minute.
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After 5 minutes, the endotracheal tube was disconnected from the breathing system and the dogs were allowed to breathe room air. Tracheal extubation was performed when the animals regained the gag or cough reflex. The recovery from this point was recorded by video camera, as well as being assessed by the anaesthetist. Once the dog was in a sternal position, it was moved to the wards and placed in its kennel to recover and was under continuous close observation. Dogs were not stimulated or aided to attain standing position. The time when the vaporizer was switched off was taken as the reference start point for recording recovery times to extubation, to sternal position and to standing. The end points were when the dogs achieved these positions by their own effort, with no external help or encouragement. Fifteen animals did not stand by 45 minutes after the termination of anaesthesia, when direct observation by the anaesthetist was discontinued and monitoring was continued by other staff members. To facilitate statistical analysis, standing times were categorized as <20, 20–45 or >45 minutes. Quality of recovery assessment The assessment of quality of recovery started immediately after extubation and continued until at least 45 minutes after anaesthesia. Assessments were made directly by the anaesthetist, then at a later time from the videos by two other anaesthetists who were unaware which anaesthetic agent had been used. Each recovery was scored by all observers using two different systems. A visual analogue scale (VAS) defined one extreme at 0 mm as a perfect recovery whilst the other end, 100 mm, was defined as the worst recovery imaginable. The second method used was a simple descriptive scale (SDS) of 1–5 as described in Table 2. If the quality of recovery was considered unacceptable (SDS score 5, VAS > 70 mm), rescue medication was administered and included diazepam and medetomidine. Apparent dysphoric or distressful episodes at emergence were treated with medetomidine 2 lg kg)1 IV. Seizures were treated with diazepam 0.2– 0.5 mg kg)1 IV and repeated to effect. Statistical analysis Statistical analysis was undertaken with standard computer software (SPSS for Windows v.15.0; SPSS Inc., Chicago, IL, USA). Physiological data were
Table 2 Description of Simple Descriptive Scale (SDS) categories for quality of recovery
Categories
Description
1
Very smooth, no excitement, vocalization, trembling or vomiting. No convulsions Quite smooth, a little excitement. No paddling, vocalization, trembling or vomiting. No convulsions Moderately smooth with excitement. Some paddling, vocalization, trembling or vomiting observed. No convulsions Not smooth and with excitement. Paddling, vocalization, trembling or vomiting observed. No convulsions Extreme excitement observed with aggression, vocalization, violent movements or convulsions observed. Rescue sedation or anticonvulsant therapy needed
2
3
4
5
selected for analysis at three time points; 10 minutes following first administration of the inhalation agent (T1), in the scanner 60 minutes after induction (T2) and following MRI after 90 minutes (T3). End-tidal concentration of inhalation agent also was measured just prior to the end of the anaesthetic (T4). Minimum alveolar concentration (MAC) multiples of ET agent were calculated on the basis that isoflurane MAC was 1.34 vol% (Steffey & Howland 1977; Kazama & Ikeda 1988), sevoflurane MAC 2.23 vol% (Kazama & Ikeda 1988; Scheller et al. 1990) and desflurane MAC 8.76 vol% (Doorley et al. 1988; Hammond et al. 1994). Qualitative data (e.g. sex, ASA grade, standing times) were compared with chi-squared and Fisher’s exact tests and quantitative data (e.g. PR, age, extubation times) with ANOVA or Kruskal–Wallis test as appropriate. Post hoc comparisons for quantitative data were undertaken with the Mann–Whitney U-test. For quality of recovery, the level of agreement between observers was assessed using Bland– Altman plots for comparison of VAS scores and weighted kappa for SDS scores. Statistical significance was set at the 5% level. Results There were no significant differences between groups for age, body weight, sex or ASA physical status (Table 3). There was no significant difference between groups in the number of dogs which were receiving long term phenobarbital medication to
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significantly different between groups (Table 4). However, two dogs in group D required additional doses of propofol before or after the MRI procedure. These dogs became very lightly anaesthetized during pre- or post-MRI transport, and the further propofol was necessary to maintain anaesthesia in transit. There were no significant differences between groups in rectal temperatures or in
control their seizures. The degree of sedation after meperidine pre-medication was not significantly different between groups (p = 0.87). Thirteen dogs showed no apparent sedation (category 1), 17 moderate sedation (category 2) and eight good sedation (category 3). The total propofol dose (including increments) used during the anaesthetic procedure was not
Age, years (median, IQR) Body weight, kg [mean (SD) ] Sex M:F ASA II:ASA III Extra procedures (CSF, radiographs, ultrasound), n Seizures, n (phenobarbital medication) Vestibular signs Clinical signs, n Neck pain Behaviour changes Nerve paralysis/muscle atrophy
Group I
Group S
Group D
p-value
3.25 (2.62–6.75) 24.78 (13.85)
2.83 (0.84–7.12) 26.98 (13.68)
4.75 (2.91–8.8) 20.43 (10.01)
0.355
9:4 10:3 8
8:3 8:3 11
9:4 9:4 7
8 (3)
9 (3)
7 (4)
3
1
3
1 1 0
0 1 1
2 1 0
Table 3 Patient characteristics, main clinical sign on presentation and procedures performed in addition to MRI
0.423 0.152 0.332
MRI, magnetic resonance imaging; IQR, interquartile range; CSF, cerebrospinal fluid.
Table 4 Anaesthetic doses, duration, physiological and cardiopulmonary measurements, expressed as mean and SD or median and IQR as appropriate
Total propofol mg kg)1 [mean (SD)] Total anaesthetic time minutes, [mean (SD)] Body temperature induction, C, [mean (SD)] Body temperature recovery, C, [mean (SD)] PE¢CO2 [median (IQR)] (during anaesthesia T1, T2, T3) mmHg kPa End-tidal inhalant concentration vol%, [mean (SD)] (during anaesthesia, T1, T3) MAC multiple* [median (IQR)] End-tidal inhalant concentration vol% [mean (SD)] (end of anaesthesia, T4) MAC multiple* [median (IQR)] Respiratory rate, breaths minute)1 [mean (SD)] (during anaesthesia T1, T2, T3) Heart rate, beats minute)1 [median (IQR)] (during anaesthesia T1, T2, T3)
Group I
Group S
Group D
4.28 (1.04) 105.3 (27.48) 37.98 (0.59) 35.85 (0.89) 45 (40.5–48.5)
3.8 (1.34) 120.67 (19.4) 37.81 (0.54) 36.19 (1.18) 40.5 (35–47)
4.68 (1.44) 113.69 (26.68) 38.14 (0.61) 35.93 (1.19) 48 (43.5–51)
p-value
0.24 0.32 0.38 0.81 0.11
5.9 (5.4–6.4) 0.96 (0.317)
5.4 (4.6–6.2) 2.08 (0.502)
6.4 (5.8–6.8) 5.52 (1.64)
0.68 (0.59–0.81) 1.18 (0.15)
0.95 (0.78–1.04) 2.5 (0.49)
0.67 (0.43–0.79) 8.04 (1.39)
0.89 (0.78–0.97) 11.14 (3.36)
1.14 (0.95–1.21) 15.75 (9.5)
0.93 (0.81–1.07) 13.39 (6.43)
0.21
91 (80–109)
96 (91–103.7)
98 (85–123.5)
0.52
<0.01
<0.01
SD, standard deviation; IQR, interquartile range; MAC, minimum alveolar concentration. *MAC values (%), mean taken from: Isoflurane 1.34% (Kazama & Ikeda 1988; Steffey & Howland 1977), sevoflurane 2.23% (Kazama & Ikeda 1988; Scheller et al. 1990) and desflurane 8.76% (Doorley et al. 1988; Hammond et al. 1994).
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duration of anaesthesia (Table 4); nor were there significant differences between groups in PR, fR or PE¢CO2. The number of animals which were ventilated were seven dogs in group I, nine dogs in group S and nine patients in group D; there was no difference between groups (p = 0.48). There was a significant difference in MAC multiples of the inhalational anaesthetic agent both over the anaesthetic course (T1, T3) and prior to disconnection (T4), between groups I and S (p < 0.02) and between groups S and D (p < 0.01) (Table 4). A higher MAC multiple was seen for patients in group S, but groups I and D did not differ. End-tidal concentrations of anaesthetic agents immediately before the end of the procedure (time between 90 and 140 minutes depending on length of anaesthetic) were [mean (SD)]: group I 1.18% (0.15), group S 2.5% (0.49), group D 8.04% (1.39). Recovery times were significantly faster for the dogs in group D than in group I for both extubation (p = 0.005) and sternal recumbency (p = 0.024); but differences between groups D and S and between groups I and S were not statistically significant (Table 5). Categorized standing times
were significantly different between groups (p = 0.049): dogs in group D being more likely to stand earlier compared with group I (p = 0.047) (Table 5). One dog in group D started to retch after extubation, and was placed in sternal recumbency for safety. Most recoveries were classified using the SDS as being between score 1 and 3 (very to moderately smooth; Table 6). However, in three dogs in group I and one dog in group S, recoveries were classified as 4 (not smooth and had some excitement) by one or more observers. Additionally, one dog in group S had an unacceptable recovery with extreme excitement, paddling and vocalization. It responded to anticonvulsant therapy with diazepam and sedation with medetomidine. Three observers (A, B and C) assigned scores to each patient using the VAS and SDS scales, for the evaluation of quality of recovery. There were no significant differences between groups for VAS quality of recovery for any of the observers (Table 6). The level of agreement of VAS assessment between observers was moderate; limits of agreement between A and B were )20.9 to 30.4 mm,
Table 5 Times to extubation, sternal recumbency and standing expressed as median and IQR
Group I
Extubation times, minutes Sternal times, minutes Standing times (minutes), n <20 20–45 >45
Group S
8 (6–9.5)*
7 (5–7)
11 (9.5–13.5)**
1 5 7
9.5 (7.25–11.75)
5 4 2
Group D
p-value
5 (3.5–7)*
0.017
7 (3.5–11.5)**
0.048
6 1 6
0.049
IQR, interquartile range. Significant differences between group I and D for extubation time: *p = 0.005 and for sternal time: **p = 0.024. One dog that received sedation because of excitement in recovery was excluded here.
Table 6 Quality of recovery as assessed with the VAS and SDS by observers A, B and C expressed as median and IQR
VAS, mm Observer Observer Observer SDS Observer Observer Observer
A B C A B C
Group I
Group S
Group D
p-value
15 (7.5–37.5) 9 (5–14.5) 17 (9–33)
10.8 (5.3–14.5) 5.5 (4.3–17) 17.5 (6.3–48.7)
11 (5–13.3) 9 (6–14.5) 9 (5–25)
0.37 0.93 0.39
1 (1–2.5) 1 (1–2) 1 (1–2)
0.79 0.64 0.81
2 (1–3) 1 (1–2) 1 (1–3)
1 (1–2.5) 1 (1–2.5) 2 (1–3.5)
VAS, visual analogue scale; SDS, simple descriptive scale; IQR, interquartile range.
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mean difference 4.7 mm, limits of agreement between A and C were )45.6 to 34.6 mm, mean difference )5.5 mm and limits of agreement between B and C )41.1 to 20.5 mm, mean difference )10.2 mm. Similarly, there was no difference between groups in the SDS as assessed by three observers (p = 0.705 for A, p = 1.00 for B, p = 0.767 for C). Level of agreement between observers was moderate with weighted kappa values of 0.43 for observers A and B, 0.28 for A and C, and 0.4 for B and C. Discussion The aim of this study was to evaluate and assess the clinical use of three different inhalational agents for the anaesthesia of outpatients undergoing MRI of the brain, with particular reference to speed and quality of recovery. All three agents provided adequate anaesthesia for the procedures undertaken, patients generally recovered calmly and times to extubation and sternal recumbency occurred most rapidly with desflurane, suggesting when an early recovery is considered advantageous this agent may be preferred. Although conditions for anaesthesia were adequate in all animals, two dogs which received desflurane had an episode of arousal following the move between the MRI scanner and the procedures room, and required an increment of propofol before adequate anaesthesia could be re-established. Transport did pose problems because the dog remained connected to a closed circle breathing system, but no fresh inhalation agent could be added. Thus, the arousal might have been due to low desflurane concentrations resulting from the anaesthetist’s lack of experience of this agent, or to a decrease in anaesthetic concentration during disconnection/reconnection to the anaesthetic machine. The rapid kinetics of desflurane meant that a decrease in anaesthetic concentration was more likely to occur than when isoflurane or sevoflurane were used under the same circumstances (Hargasser et al. 1995; Young & Apfelbaum 1995; Heavner et al. 2003; Eger & Shafer 2005b). It was anticipated, on the basis of published work (Hikasa et al. 1996; Mutoh et al. 1997; Johnson et al. 1998; Galloway et al. 2004) that PR with sevoflurane would be lower than with isoflurane or desflurane, and that desflurane would cause the least respiratory depression. However, in the current clinical study such differences were not 226
observed and the cardiopulmonary parameters monitored, including heart and fR, PE¢CO2 and numbers of dogs requiring ventilation to maintain PE¢CO2, did not differ between the three agents. In the current study, dogs recovered to extubation and achieved sternal recumbency in the shortest time following desflurane anaesthesia, the next fastest was sevoflurane and patients recovered most slowly following isoflurane. The differences in recovery times were as expected from the kinetics of the agents, and as noted in previous studies in the human literature (Nathanson et al. 1995; Campbell et al. 1996; Welborn et al. 1996; Chen et al. 2001; Heavner et al. 2003; Iannuzzi et al. 2005). Veterinary studies have compared isoflurane and sevoflurane in a number of species, with varying results. In some studies, recovery from sevoflurane was significantly faster than from isoflurane (Eger & Johnson 1987b; Hikasa et al. 1996; Matthews et al. 1998) whereas in others differences were not significant (Johnson et al. 1998; Hodgson 2007; Love et al. 2007). In horses, recovery to standing was faster with desflurane than with isoflurane (Bradbrook et al. 2006) but in sheep there was no significant difference between times of recovery from isoflurane, sevoflurane or desflurane (Mohamadnia et al. 2007). Nonetheless, that desflurane anaesthesia resulted in more rapid recovery was as anticipated from the kinetics of the agents (Clarke 1999; Eger & Shafer 2005a). The prolonged time to standing reported in the current study resulted in substantial missing data, necessitating categorization of final recovery into three time groups for statistical analysis. Although differences reached statistical significance, this study did not demonstrate clear biological superiority of any agent for recovery to standing unaided. Positioning the dog in the enclosed space of the kennel additionally discouraged standing and the ability to assess time to standing. Although all dogs were able to stand on admission, the multiple neurological signs in some (circling, ataxia, nystagmus and loss of balance) also influenced the ability to stand after the procedures and assessment of this endpoint. However, all groups were homogeneous for clinical signalment and main neurological signs on presentation and groups should have been affected equally. Factors which influence the speed of recovery from inhalational anaesthesia include the condition of the dog prior to and after anaesthesia, the additional sedative, analgesic and anaesthetic induction agents administered, the kinetics of the inhalation agents,
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the duration of anaesthesia, the depth of anaesthesia at the time of commencement of the recovery process, and the body temperature of the animal at the time of recovery. Phenobarbital medication received prior to admission could contribute to increased sedation, and delayed recovery, but receipt of such medication was similar in all groups. The pre-medication and induction agents were chosen to minimize postanaesthetic effect of the injectable agents and are used commonly by small animal practising veterinary surgeons in the UK. Meperidine has a marketing licence for dogs and is an opioid with a relatively short duration of action of 90–120 minutes (Waterman & Kalthum 1989). Experience with meperidine premedication at the Royal Veterinary College has been that in ASA I–II dogs the degree of sedation is minimal to mild only, and publications from others sources support this finding (Wilson et al. 2007). In this study, however, some dogs were categorized as ‘good sedation’, and this was considered an exaggerated response, probably due to a more severe neurological condition. However, there were no significant differences between groups in the degree of sedation recorded, and any impact of pre-medication on recovery was likely to be similar across groups. Propofol, when used as an anaesthetic induction agent in the dog, has a short duration of action as it is rapidly distributed, rapidly eliminated and shows minimal accumulation (Watkins et al. 1987; Musk et al. 2005). The dose of propofol used, inclusive of the increments, did not differ between groups. Thus,
after the minimum time of 2 hours of the procedure, the influence of the noninhalational drugs should be very minor, and would have been equal in all groups. Body temperature was measured rectally and although this does not equate to body core temperature, it gives an accurate reflection (Sessler 1993). In our study, although measures were taken to avoid hypothermia, there was a significant reduction of body temperature over time in the dogs. Hypothermia decreases MAC (Vitez et al. 1974; Eger & Johnson 1987a) and impairs drug metabolism, potentially prolonging recovery from anaesthesia (Insler & Sessler 2006). However, in the current study the degree of hypothermia was similar across groups and hence the effect of decrease in body temperature on recovery was likely to be similar in the three groups. An important factor influencing speed of recovery is the depth of anaesthesia at the time of switching off the vaporizer at the end of the procedure. In this study, end-tidal agent concentrations were converted to MAC multiples for comparative purposes. Published MAC values vary and here the average of the two published values for the dog was taken as the reference value for the MAC multiple calculations. Differences between values published in different studies for isoflurane (Steffey & Howland 1977; Kazama & Ikeda 1988) and sevoflurane (Kazama & Ikeda 1988; Scheller et al. 1990) were small, but the two published MAC values for
25 Observer A Observer B
Number of dogs
20
Observer C
15
10
5
ISO SEVO DES
ISO SEVO DES
ISO SEVO DES
ISO SEVO DES
ISO SEVO DES
CAT 1
CAT 2
CAT 3
CAT 4
CAT 5
Figure 1 Summary of quality of recovery as assessed with the simple descriptive scale (SDS) recovery score by three observers, A, B and C. The X axis represents the SDS recovery score categories (CAT 1–5) subdivided by the treatment groups (groups I, S and D). The Y axis indicates the number of dogs in each treatment group, classified in each SDS recovery score category by the three observers. SDS recovery score categories are defined in Table 2, group I (n = 13) received isoflurane, group S (n = 11) received sevoflurane and group D (n = 13) received desflurane. A category 5 was awarded by all observers when poor quality of recovery prevented a video being obtained (one dog in group S). 2009 The Authors. Journal compilation 2009 Association of Veterinary Anaesthetists, 36, 220–229
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desflurane in dogs of 7.2 vol% (Doorley et al. 1988) and 10.3 vol% (Hammond et al. 1994) differ by more than 40%. Using these MAC values, the MAC multiple of sevoflurane was significantly higher than that of the other two agents both during and at the end of the procedure. This might have slowed recovery times, but if the lower MAC value of 7.2 vol% for desflurane had been used for the MAC multiple calculations, the differences would not have been significant. However, the MAC multiples reported for isoflurane and desflurane were very similar and a difference in relative depth during or at termination of anaesthesia was unlikely to explain the main finding that recoveries were fastest after desflurane anaesthesia compared to isoflurane. The quality of recovery from anaesthesia is at least as important as the speed of recovery in cases with neurological compromise. Emergence from anaesthesia and extubation periods are often associated with sympathetic stimulation (Bruder & Ravussin 1999) which may increase arterial blood pressure, ICP and oxygen consumption. In this current study, most recoveries were smooth and differences were not statistically significant between groups. There were no poor quality recoveries (category 4 or 5 as judged by the SDS method) following desflurane anaesthesia (Fig. 1) which was in agreement with clinical studies in horses (Bradbrook et al. 2006). Only one dog had an unacceptable recovery. This dog had been anaesthetized with sevoflurane, recovered violently, vocalized and appeared to seizure. It did not improve with diazepam administration but calmed following medetomidine administration. The apparent seizure activity could have resulted from its neurological condition and/or could have been potentiated by the inhalational agent. Sevoflurane has been shown to increase epileptiform activity to a greater degree than the other two agents (Iijima et al. 2000) in human patients already suffering from epilepsy. However, emergence delirium from sevoflurane anaesthesia is well recognized in human anaesthesia (Cravero et al. 2000; Mayer et al. 2006) and violent recoveries from sevoflurane anaesthesia have been documented on occasions in the veterinary literature (Clarke et al. 1996; Steffey et al. 2005; Mohamadnia et al. 2007). Assessment of quality of recovery is subjective. In this study, two different assessment methods were used, and three assessors (two assessing from video recordings and blinded to the agent used). Both methods of assessment indicated that there were no significant differences in recovery quality across 228
groups. There was only a moderate level of agreement between the three observers in actual scores awarded and lack of agreement in individual animals was likely to reflect the subjective nature of recovery assessment, but all observers consistently classified treatment groups as of similar quality (Fig. 1). In conclusion, this study demonstrated that all three inhalational agents were suitable for outpatient anaesthesia in dogs with neurological conditions and provided in general a good and smooth recovery. Dogs recovered to sternal recumbency most rapidly after desflurane; thus desflurane might be advantageous when a rapid emergence from anaesthesia is required. References Bradbrook C, Sigurdsson S, Borer K et al. (2006) A comparison in clinical cases of recovery from anaesthesia following maintenance with desflurane or isoflurane in horses: preliminary results. Proceedings of the WCVA congress, Santos, Brazil (abstract). Bruder N, Ravussin P (1999) Recovery from anesthesia and postoperative extubation of neurosurgical patients: a review. J Neurosurg Anesthesiol 11, 282–293. Campbell C, Andreen M, Battito MF et al. (1996) A phase III, multicenter, open-label, randomized, comparative study evaluating the effect of sevoflurane versus isoflurane on the maintenance of anesthesia in adult ASA class I, II, and III inpatients. J Clin Anesth 8, 557– 563. Chen X, Zhao M, White PF et al. (2001) The recovery of cognitive function after general anesthesia in elderly patients: a comparison of desflurane and sevoflurane. Anesth Analg 93, 1489–1494. Clarke KW (1999) Desflurane and sevoflurane. New volatile anesthetic agents. Vet Clin North Am Small Anim Pract 29, 793–810. Clarke KW, Lee HY, Brown LA (1996) Sevoflurane anaesthesia in the horse. J Vet Anesth 23, 85. Cravero J, Surgenor S, Whalen K (2000) Emergence agitation in paediatric patients after sevoflurane anaesthesia and no surgery: a comparison with halothane. Paediatr Anaesth 10, 419–424. Doorley BM, Waters SJ, Terrell RC et al. (1988) MAC of I-653 in beagle dogs and New Zealand white rabbits. Anesthesiology 69, 89–91. Eger EI II, Johnson BH (1987a) MAC of I-653 in rats, including a test of the effect of body temperature and anesthetic duration. Anesth Analg 66, 974–976. Eger EI II, Johnson BH (1987b) Rates of awakening from anesthesia with I-653, halothane, isoflurane, and sevoflurane: a test of the effect of anesthetic concentration and duration in rats. Anesth Analg 66, 977–982.
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