The effect of nitrous oxide on halothane, isoflurane and sevoflurane requirements in ventilated dogs undergoing ovariohysterectomy

Veterinary Anaesthesia and Analgesia, 2006, 33, 343–350

doi:10.1111/j.1467-2995.2005.00274.x

RESEARCH PAPER

The effect of nitrous oxide on halothane, isoflurane and sevoflurane requirements in ventilated dogs undergoing ovariohysterectomy T Duke

BVetMed, DVA, DACVA, DECVA,

NA Caulkett

DVM, MVetSc, DACVA

& JM Tataryn

DVM

Department Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada Correspondence: T Duke, Department Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK, Canada, S7N 5B4. E-mail: [email protected]

Abstract Objective To examine the effect of 64% nitrous oxide (N2O) on halothane (HAL), isoflurane (ISO) or sevoflurane (SEV) requirements in dogs undergoing ovariohysterectomy. Study design Prospective, randomized, clinical trial. Animals Ninety, healthy dogs of (mean ± SD) body weight 21.2 ± 10.0 kg and age 17.8 ± 22.8 months. Materials and methods After premedication with acepromazine, hydromorphone and glycopyrrolate, anesthesia was induced with thiopental administered to effect. Dogs received one of six inhalant protocols (n ¼ 15 group): HAL; HAL/N2O; ISO; ISO/N2O; SEV; or SEV/N2O. End-tidal CO2 was maintained at 40 ± 2 mmHg with intermittent positive pressure ventilation (IPPV). Body temperature, heart rate, indirect systemic arterial blood pressures, inspired and endtidal CO2, volatile agent, N2O and O2 were recorded every 5 minutes. The vaporizer setting was decreased in 0.25–0.5% decrements to elicit a palpebral reflex, and this level maintained. Statistical analysis included two-way ANOVA for repeated measures with Bonferroni’s correction factor and statistical significance assumed when p < 0.05. Percentage reduction in end-tidal volatile agent was calculated at 60 minutes after starting study. Results End-tidal HAL, ISO and SEV decreased when N2O was administered. Percentage reduction: HAL

(12.4%); ISO (37.1%) and SEV (21.4%). Diastolic, mean and systolic blood pressures increased in ISO/ N2O compared with ISO. Heart rate increased in ISO/N2O and SEV/N2O compared with ISO and SEV, respectively. Systolic, mean and diastolic blood pressures increased in SEV compared with HAL and ISO. Systolic, mean, diastolic blood pressures and heart rate increased in SEV/N2O and ISO/N2O compared with HAL/N2O. Conclusions N2O reduces HAL, ISO and SEV requirements in dogs undergoing ovariohysterectomy. Cardiovascular stimulation occurred when N2O was used with ISO, less so with SEV and not with HAL. Keywords dog, halothane, isoflurane, nitrous oxide, sevoflurane.

Introduction Nitrous oxide (N2O) has been used in humans since 1844, and became popular in veterinary anesthesia with the introduction of methoxyflurane and halothane (HAL) (Carmichael 1971). Nitrous oxide is principally used for its analgesic rather than anesthetic properties as the minimum alveolar concentration (MAC) for general anesthesia in dogs is high and cannot be achieved in clinical practice (Carmichael 1971; Steffey et al. 1974a). In some countries only 13% of veterinary practices routinely use N2O (Nicholson & Watson 2001). Nitrous oxide is, however, still recommended as an analgesic 343

Effect of N2O on HAL, ISO, SEV requirements in dogs T Duke et al.

adjuvant for ‘balanced anesthesia’ techniques and to reduce volatile anesthetic agent requirements (Ilkiw 1999). The anesthetic-sparing effects of N2O on HAL requirements have been studied in the rat, dog, cat, and horse (Steffey & Howland 1978; DeYoung & Sawyer 1980; Cole et al. 1990; Hikasa et al. 1996). The ability to reduce administered volatile anesthetic concentrations may improve the hemodynamic status of the patient. The addition of N2O in spontaneously breathing dogs receiving varying concentrations of HAL has been found to stimulate cardiovascular function, but N2O did not provide the same stimulation in mechanically ventilated dogs (Steffey et al. 1974b, 1975). Studies investigating the effects of N2O with isoflurane (ISO) and sevoflurane (SEV) have been reported in humans (Katoh & Ikeda 1987; Murray et al. 1991; Fragen & Dunn 1996; Nakahara et al. 1997; Swan et al. 1999) however, studies investigating effects of N2O with ISO or SEV in animals are limited. The cardiopulmonary and anesthetic-sparing effects of N2O with HAL, ISO and SEV have been investigated in spontaneously breathing cats under laboratory conditions (Hikasa et al. 1996; Pypendop et al. 2003), but no laboratory or clinical studies have been reported in dogs. This study was performed to examine the anesthetic-sparing ability and cardiovascular effects of N2O in ventilated dogs receiving either HAL, ISO or SEV while undergoing routine ovariohysterectomy. Materials and methods Dogs undergoing routine ovariohysterectomy at the Veterinary Teaching Hospital of the Western College of Veterinary Medicine over a 3-year-period (January, 2001 to December, 2003) were used for this study. Standard physical and hematologic examinations (hematocrit, total protein, glucose and urea nitrogen) were performed and only healthy dogs were admitted for surgery. Dogs were fasted overnight and water was removed on the morning of surgery. Ninety dogs of mean body weight (±SD) 21.2 (±10.0) kg (range: 2.2–50.0 kg), and mean age (±SD) 17.8 (±22.8) months (range: 5–124 months) were entered into the study. The dogs were assigned randomly to six treatment groups (n ¼ 15); each treatment group received a different inhalational anesthetic technique. The six inhalant techniques were: HAL (MTC Pharmaceuticals, Cambridge, ON, Canada); HAL/N2O; ISO (IsoFlo; Abbott Laborator344

ies Ltd, Saint-Laurent, Quebec, Canada); ISO/N2O; SEV (Sevrane; Abbott Laboratories Ltd) or, SEV/ N2O. All dogs were premedicated with 0.05 mg kg)1 body weight acepromazine maleate (Ayerst Veterinary Laboratories, Guelph, ON, Canada), 0.1 mg kg)1 body weight hydromorphone (Sabex; Boucherville, QC, Canada) and 0.01 mg kg)1 body weight glycopyrrolate (Sabex) simultaneously administered by intramuscular injection 20 minutes before induction. Anesthesia was induced with thiopental to effect (Pentothal; Abbott Laboratories Ltd) administered intravenously through an over-the-needle catheter aseptically placed in a cephalic vein. A balanced electrolyte solution (lactated Ringer’s) was administered at a rate of 10 mL kg)1 hour)1 throughout the procedure until sternal recumbency was obtained in the recovery period. The trachea was intubated with a cuffed endotracheal tube and the tube connected to a circle or Bain anestheticbreathing system. Bain systems were used on dogs weighing <10 kg body weight. Volatile anesthetic agents were delivered to the breathing system using O2, with or without N2O, and out-of-circuit precision vaporizers. Monitoring included: pulse oximetry (data not statistically analyzed); indirect oscillotonometric arterial blood pressure using cuff widths 40–50% of limb circumference (Heska Vet/BP Plus 6500; Waukesha, WI, USA); esophageal body temperature (PB240 Operating Room Monitor; Puritan Bennet Corporation, Wilmington, MA, USA); inspired and expired CO2, N2O, O2 and volatile agent using a calibrated sidestream gas analyzer (POET IQ Anesthesia Gas Monitor; Criticare Systems Inc., Waukesha, WI, USA). To avoid contamination of end-tidal gases with fresh gas, a 5-cm catheter was inserted into the gas analyzer’s sampling port and directed distally into the endotracheal tube. Gases removed from the circuit for analysis were scavenged and not returned to the circuit. In groups HAL/N2O, ISO/N2O and SEV/N2O the O2 and N2O flowmeters were adjusted, using the sidestream gas analyzer, to maintain inspired concentration of 30% O2. An O2 flow rate of 30 mL kg)1 minute)1 with or without N2O at a flow rate of 60 mL kg)1 minute)1 was used with the circle system, but flows were adjusted slightly to maintain 30% inspired O2 with the remainder consisting of N2O and the volatile agent. An O2 flow of 100 mL kg)1 minute)1 with or without N2O at a flow rate of 200 mL kg)1 minute)1 was used with Bain circuits, with similar minor adjustments Ó 2006 Association of Veterinary Anaesthetists, 33, 343–350

Effect of N2O on HAL, ISO, SEV requirements in dogs T Duke et al.

Ó 2006 Association of Veterinary Anaesthetists, 33, 343–350

the p value for the ANOVA was significant, individual comparisons were made between treatment groups using a Bonferroni’s correction factor. At 60 minutes after start of data collection the percentage reduction in end-tidal anesthetic agent was calculated and compared using a nonpaired two sample t-test. Body weight and induction dose of thiopental were compared between groups using one-way ANOVA, and age compared between groups using Kruskall–Wallis ANOVA. All data are presented as mean ± SD and statistical significance was assumed if p < 0.05. Results There was no difference detected with the use of different breathing systems within a group so all data were combined for further analyses. End-tidal volatile agent concentrations with or without N2O are presented in Figs 1–3. The end-tidal volatile agent concentrations, inspired N2O concentrations and percentage reductions at 60 minutes are presented in Table 1. Heart rates and mean systemic arterial blood pressures are presented in Table 2. At 60 minutes after start of the study, HAL, ISO and SEV requirements were reduced by 12.4%, 37.1% and 21.4% respectively, through the use of N2O. Statistically significant treatment effects were identified in the following: a decrease in the endtidal concentrations of HAL, ISO and SEV required to maintain anesthesia when N2O is used; an increase in diastolic, mean and systolic blood pressure in the ISO/N2O group compared with the ISO group, and an increase in heart rate in the ISO/N2O and SEV/N2O groups compared with ISO

0.9

End-tidal halothane (%)

to maintain 30% inspired O2. The lungs were ventilated using a volume cycled ventilator (Ohio Medical Products, Madison, WI, USA) at a tidal volume of 10 mL kg)1. The respiration rate was altered in order to maintain end-tidal CO2 in the range 40 ± 2 mmHg. Measurements of temperature, indirect systolic, mean and diastolic arterial blood pressure, inspired and expired gases were recorded every 5 minutes. Administration of N2O and all recordings for the study commenced approximately 30 minutes after induction. In order to ascertain the minimum requirement of volatile agent that could be administered, the vaporizer dial was turned down in 0.25–0.5% decrements to a point at which it was just possible to elicit a palpebral reflex. If necessary, the vaporizer setting was increased if there was deemed to be a response to surgical stimulation (movement, increased arterial blood pressure or heart rate change of > 10%). Once anesthesia was stable, the vaporizer dial setting was again decreased. These manipulations were performed by the assigned final year student with close supervision of an experienced anesthesia technician or clinician. Body temperature was maintained using warm water circulating blankets and a forced warm air heating device (BairHugger Model 505; Arizant Healthcare Inc., Eden Prairie, MN, USA). Once the procedure was complete the dog was allowed to recover from anesthesia, and 0.1 mg kg)1 IM hydromorphone and 0.2 mg kg)1 SC meloxicam (Metacam; Boehringer Ingelheim Ltd, Burlington, ON, Canada) were adminstered. All statistical analyses were performed using computer software (GraphPad Prism version 3.02 for Windows, GraphPad Software, San Diego, CA, USA; Statistix7 for Windows, Analytical Software, Tallahassee, FL, USA). Only dogs providing at least 70 minutes of data were entered into the study. Data were analyzed for normal distribution using probability plots before further statistical analyses. Data were examined to see if choice of breathing circuit affected results and data combined if no effect was detected. Data from groups receiving one volatile agent were compared with data from the group receiving the same volatile agent with N2O. The volatile agents were also compared with each other with or without N2O administration. Blood pressures, heart rate, end-tidal volatile agent, and body temperature measurements were analyzed using 2-way ANOVA for repeated measures. When

0.8 0.7 0.6 0.5

Halothane 0.4

Halo/N2O

0.3 0

10

20

30

40

50

60

70

80

Time (minutes)

Figure 1 End-tidal halothane concentration (mean ± SD) in dogs receiving halothane (n ¼ 15) or halothane plus nitrous oxide (n ¼ 15) during ovariohysterectomy. 345

End-tidal isoflurane (%)

Effect of N2O on HAL, ISO, SEV requirements in dogs T Duke et al.

SEV/N2O group compared with the HAL/N2O group, and increases in systolic, mean and diastolic blood pressures in the ISO/N2O group compared with the HAL/N2O group. When N2O was not administered there was a statistical increase in systolic, mean and diastolic blood pressures in the SEV group compared with the HAL group. Mean and diastolic blood pressures were greater in the SEV group, compared with the ISO group. No statistically significant differences were found in body weight, age, induction dose of thiopental (mean of all doses ± SD; 7.6 ± 2.0 mg kg)1), inspired N2O and O2, end-tidal CO2 and body temperature between groups. No hemoglobin saturation below 95% was recorded.

Isoflurane Iso/N2O

1.25

* 1.00

0.75

0.50

0.25 0

10

20

30

40

50

60

70

80

Time (minutes) Figure 2 End-tidal isoflurane concentration (mean ± SD) in dogs receiving isoflurane (n ¼ 15) or isoflurane plus nitrous oxide (n ¼ 15) during ovariohysterectomy.

End-tidal sevoflurane (%)

Discussion Sevoflurane Sevo/N2O

2.0

The results of this study indicate that N2O reduced the requirement of all three volatile anesthetic agents. Percentage HAL requirements were reduced by the least amount in our study, and greater reductions have been found in laboratory studies. Inspired concentrations of 66% nitrous oxide have been found to reduce HAL requirements in unpremedicated dogs by approximately 22% (DeYoung & Sawyer 1980). Other studies have reported HAL requirements decrease by 33% in dogs with 75% N2O (Steffey et al. 1974a), by 39% with 66% N2O in ketamine-premedicated cats (Hikasa et al. 1996), and by 25% with 50% N2O in unpremedicated horses (Steffey & Howland 1978). It is unclear why our study did not demonstrate a greater decrease in HAL requirements in dogs undergoing routine surgery, and as far as the authors are aware, there are no clinical studies reported with which to compare our findings. The disparity may be related to differ-

1.5

1.0 0

10

20

30

40

50

60

70

80

Time (minutes) Figure 3 End-tidal sevoflurane concentration (mean ± SD) in dogs receiving sevoflurane (n ¼ 15) or sevoflurane plus nitrous oxide (n ¼ 15) during ovariohysterectomy.

and SEV groups, respectively. When N2O was administered there were increases in systolic, mean and diastolic blood pressures and heart rate in the

Group

Bain versus Circle

End-tidal volatile agent (%)

Inspired N2O (%)

Percentage reduction if N2O used (%)

HAL only HAL/N2O ISO only ISO/N2O SEV only SEV/N2O

1:14 3:12 3:12 3:12 3:12 0:15

0.67 0.59 0.91 0.57 1.59 1.25

NA 64.1 ± 2.5 (58–69) NA 64.2 ± 2.2 (55–69) NA 64.6 ± 1.9 (60–69)

NA 12.4* NA 37.1* NA 21.4*

± ± ± ± ± ±

0.28 0.17 0.49 0.24 0.50 0.34

(0.3–1.2) (0.3–0.9) (0.3–2.0) (0.2–1.0) (1.0–2.8) (0.5–1.9)

Table 1 Results of end-tidal volatile agent concentration (mean ± SD and range) in dogs receiving halothane (HAL), isoflurane (ISO) or sevoflurane (SEV), with or without nitrous oxide (N2O) at 60 minutes after start of study, with numbers of dogs using Bain or Circle breathing system

NA ¼ Not applicable *Statistically different p < 0.05.

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Ó 2006 Association of Veterinary Anaesthetists, 33, 343–350 10

15

20

25

30

35

40

45

50

55

60

65

70

94 ± 18.0 96* ± 21.5

92 ± 20.2

61 ± 8.6

68 ± 10.1 74 ± 14.0 86 ± 18.4 91 ± 17.0 90 ± 15.4 89 ± 18.0 86 ± 14.7 89 ± 14.6 92 ± 13.6 91 ± 14.9

86 ± 13.9

88 ± 14.1

87 ± 13.8

107 ± 18.6 110 ± 22.0 110 ± 19.5 111 ± 20.6 112 ± 17.2 114 ± 16.5 115 ± 19.3 117 ± 27.5 120 ± 16.6 122 ± 17.6 122 ± 18.8 122* ± 16.3 124* ± 19.2 124* ± 17.0

108 ± 16.9 105 ± 16.7 107 ± 15.4 101 ± 15.8 101 ± 16.2 103 ± 24.3 97 ± 15.4 102 ± 11.6 101 ± 13.0 104 ± 12.5 103 ± 14.8 102 ± 17.6 101 ± 17.8 105 ± 15.4 61 ± 8.6 68 ± 10.1 74 ± 14.0 86 ± 18.4 91 ± 17.0 90 ± 15.4 89 ± 18.0 86 ± 14.7 89 ± 14.6 92 ± 13.6 91 ± 14.9 86 ± 13.9 88 ± 14.1 87 ± 13.8

66 ± 12.0 67 ± 11.0 78 ± 18.0 86 ± 17.6 85 ± 11.1 92 ± 22.4 88 ± 15.8 95 ± 16.0 96 ± 20.2 89 ± 18.3 91 ± 18.5

104 ± 14.4 103 ± 18.5 108 ± 18.4 111 ± 21.0 106 ± 19.6 115 ± 16.8 117 ± 21.1 118 ± 20.3 117 ± 22.4 115 ± 24.0 120 ± 27.0 120 ± 27.4 122 ± 25.4 124 ± 25.2

104 ± 15.6 98 ± 19.5 102 ± 20.6 98 ± 17.4 106 ± 17.9 103 ± 19.4 105 ± 18.0 100 ± 22.8 108 ± 20.4 107 ± 21.1 105 ± 22.9 114 ± 21.4 115 ± 21.4 115 ± 19.0 65 ± 12.6 70 ± 15.9 72 ± 16.2 82 ± 17.0 82 ± 12.7 85 ± 14.4 83 ± 13.3 84 ± 13.0 84 ± 11.5 82 ± 11.6 83 ± 12.1 84 ± 15.1 79 ± 14.6 81 ± 11.9

96 ± 20.5 97 ± 22.5 101 ± 16.5 99 ± 14.5 102 ± 18.7 109 ± 19.1 109 ± 15.1 108 ± 16.1 106 ± 14.8 110 ± 16.1 106 ± 14.1 110 ± 14.6 110 ± 13.6 113 ± 13.7 64 ± 8.4 63 ± 13.2 72 ± 20.5 79 ± 21.0 82 ± 19.0 80 ± 16.9 86 ± 20.8 87 ± 21.7 82 ± 16.9 83 ± 14.9 84 ± 14.2 84 ± 14.4 84 ± 16.3 84 ± 15.6

97 ± 20.7 96 ± 15.9 100 ± 19.5 101 ± 21.4 102 ± 21.4 99 ± 14.0 103 ± 15.6 103 ± 20.0 107 ± 21.1 106 ± 21.1 107 ± 20.3 111 ± 19.0 113 ± 15.7 115 ± 18.4 63 ± 7.2 63 ± 9.5 69 ± 13.3 81 ± 16.5 83 ± 18.1 83 ± 13.4 83 ± 18.1 84 ± 14.5 81 ± 14.2 81 ± 12.6 84 ± 15.2 81 ± 16.4 82 ± 17.1 81 ± 17.6

5

MAP, mean arterial blood pressure. a, c, e denotes statistical difference from b, d, f respectively (p < 0.05). *denotes statistical difference from equivalent time-point in same volatile agent group without N2O.

HAL: Heart rate (beats minute)1) MAPe (mmHg) HAL/N2O: Heart ratec (beats minute)1) MAPc (mmHg) ISO: Heart ratea (beats minute)1) MAPa,e (mmHg) ISO/N2O: Heart rateb,d (beats minute)1) MAPb,d (mmHg) SEV: Heart ratea (beats minute)1) MAPf (mmHg) SEV/N2O: Heart rateb,d (beats minute)1) MAPd (mmHg)

Group

Time from start (minutes)

Table 2 Cardiovascular data (mean ± SD) from dogs anesthetized with halothane (HAL), isoflurane (ISO) or sevoflurane (SEV) with or without nitrous oxide (N2O)

Effect of N2O on HAL, ISO, SEV requirements in dogs T Duke et al.

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Effect of N2O on HAL, ISO, SEV requirements in dogs T Duke et al.

ences in the methodology used to measure anesthetic requirements and the use of additional drugs in the clinical situation. The greatest reduction in volatile agent requirements occurred in dogs receiving ISO and N2O, but other studies have not been published to compare these results. Isoflurane requirements were decreased by 26% in cats with concurrent use of N2O (Hikasa et al. 1996), and by 40% with 75% N2O in swine (Tranquilli et al. 1985). Sevoflurane requirements were decreased by 23% in cats, similar to the results of our study (Hikasa et al. 1996). In children, SEV requirements were found to be decreased by 40%, and in adults by 50–61.4% (Katoh & Ikeda 1987; Fragen & Dunn 1996; Swan et al. 1999). The greater anesthetic sparing ability of N2O may be related to the higher anesthetic potency of N2O in humans, and this makes it difficult to compare studies between humans and animals (Tranquilli et al. 1985). Sixty minutes was chosen as the time-point for calculating percent volatile agent reduction as it provided enough time to allow vaporizer settings and stabilization. Error may have occurred from selection of this time-point, and another time may have produced a different result. To test this theory, three other times (55, 65 and 70 minutes) were retrospectively analyzed and the results were similar to those at 60 minutes. In order to reduce the error from using clinical cases for this type of study, all dogs received the same premedicants and induction agent, and measurements commenced at least 30 minutes post-induction. Error from use of multiple observers was reduced as much as possible by supervising anesthesia technicians ensuring the defined end-points were met. The same procedure was chosen to limit the error that may arise from using dogs undergoing different types of surgical stimulation. As high levels of CO2 can interfere with studies of anesthetic depth and cardiovascular measurements we chose to ventilate all dogs and maintain endtidal CO2 at 40 ± 2 mmHg. Previous studies investigating the effects of N2O on the cardiovascular system have found use of a ventilator can limit cardiovascular stimulatory effects of N2O (Steffey et al. 1974b). Any differences in the effects of N2O on the cardiovascular system between ventilated or nonventilated dogs breathing ISO or SEV have not been published. Nitrous oxide administered alone or with volatile anesthetics causes minimal changes in cardiovas348

cular function, or can lead to myocardial depression and increased blood pressure through increased systemic vascular resistance (Eisele et al. 1969; Loh et al. 1973; Pypendop et al. 2003). There are minimal differences in cardiovascular parameters between HAL-anesthetized dogs or those receiving 75% inspired N2O and HAL, and our study confirms these findings (Smith & Corbascio 1966; Steffey et al. 1974b). It is thought that HAL may suppress preganglionic and postganglionic sympathetic activity and reduce the sympathomimetic actions of N2O (Miller et al. 1969). In comparing the two more recently introduced volatile agents with or without N2O on systemic blood pressure, it is interesting to note that the increase in arterial blood pressure in the ISO/N2O group compared with the ISO group, yet no difference was found between the SEV/N2O group and the SEV group. This may have been related to the greater percent reduction in ISO compared with SEV requirements with N2O. No differences in cardiovascular parameters were found in spontaneously breathing cats breathing ISO or SEV, with or without N2O (Hikasa et al. 1996). Another study in ISO-anesthetized cats, however, found that blood pressure increased when 70% N2O was administered (Pypendop et al. 2003). Methodology differences exist between these studies; in that, in the former study volatile agent concentrations were decreased whereas end-tidal ISO concentration remained constant in the latter study. A study reported in humans confirmed the observations that arterial blood pressure is higher with ISO and N2O, compared with SEV and N2O (Campbell et al. 1995). Another report also indicated that arterial blood pressure in humans breathing SEV or SEV/ N2O did not differ, which was similar to the results of our study (Barr et al. 2002). When N2O was not administered, we found the systemic blood pressures of dogs receiving SEV was higher compared with dogs receiving ISO or HAL, and this has also been shown in cats (Hikasa et al. 1996). All groups demonstrated an increase in blood pressure over time and this can be attributed to surgical manipulations. Heart rate was not significantly increased in HAL/N2O-anesthetized dogs in our study compared with HAL-anesthetized dogs, and this is similar to published reports (Steffey et al. 1974b). Heart rate was increased in ISO/N2O-anesthetized dogs compared with the dogs breathing only isoflurane, and this is similar to ISO-anesthetized cats receiving Ó 2006 Association of Veterinary Anaesthetists, 33, 343–350

Effect of N2O on HAL, ISO, SEV requirements in dogs T Duke et al.

70% N2O during noxious stimulation (Pypendop et al. 2003). We found that heart rate was greatly increased in SEV/N2O-anesthetized dogs, compared with the constant heart rate of dogs receiving only SEV, but this was not demonstrated in cats or humans breathing SEV and N2O (Campbell et al. 1995; Hikasa et al. 1996). The heart rate in the SEV-only group may have remained stable as a response to higher mean and diastolic blood pressures in this group, compared with those in the ISO-only and HAL-only groups. When N2O was not administered there were no differences in heart rate between the volatile agents. Atrioventricular conduction times did not change in ISO- or SEV-anesthetized dogs but are longer if HAL is used in pentobarbital anesthetised dogs (Nakaigawa et al. 1995). Most studies have shown that ISO and SEV increase heart rate more than HAL (Mutoh et al. 1997). The reason for disparity in heart rate change between this and other studies is not clear. In conclusion, the co-administration of N2O with HAL, ISO and SEV allowed for lower concentrations of the volatile agent to be administered, but appeared to have most anesthetic sparing effect and cardiostimulatory actions with ISO in ventilated dogs. Acknowledgements The authors would like to thank the staff of the Veterinary Teaching Hospital, especially anesthesia technicians: D. Bachiu, B. Beierle, J. Caulkett, S. Martin, C. McCracken, N. Schueller, and J. Walchuk; students of the Classes of 2002, 2003 and 2004, and Drs M. Corrigan, P. Crawford, M. Read and S. Singh for their assistance with this study. References Barr G, Anderson R, Jakobsson J (2002) The effects of nitrous oxide on the auditory evoked potential index during sevoflurane anaesthesia. Anaesthesia 57, 736– 739. Campbell C, Nahrwold ML, Miller DD (1995) Clinical comparison of sevoflurane and isoflurane when administered with nitrous oxide for surgical procedures of intermediate duration. Can J Anaesth 42, 884–890. Carmichael JA (1971) Nitrous oxide in small animal anesthesia. J Am Vet Med Ass 159, 857–862. Cole DJ, Kalichman MW, Shapiro HM et al. (1990) The nonlinear potency of sub-MAC concentrations of nitrous oxide in decreasing the anesthetic requirement of Ó 2006 Association of Veterinary Anaesthetists, 33, 343–350

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Steffey EP, Gillespie JR, Berry JD et al. (1974b) Circulatory effects of halothane and halothane-nitrous oxide anesthesia in the dog: Controlled ventilation. Am J Vet Res 35, 1289–1293. Steffey EP, Gillespie JR, Berry JD et al. (1975) Circulatory effects of halothane and halothane-nitrous oxide anesthesia in the dog: Spontaneous ventilation. Am J Vet Res 36, 197–200. Swan HD, Crawford MW, Pua HL et al. (1999) Additive contribution of nitrous oxide to sevoflurane minimum

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