- Email: [email protected]
Cardiopulmonary effects of butorphanol in sevoflurane-anesthetized guineafowl (Numida meleagris)
Veterinary Anaesthesia and Analgesia, 2014, 41, 284–289
doi:10.1111/vaa.12108
SHORT COMMUNICATION
Cardiopulmonary effects of butorphanol in sevofluraneanesthetized guineafowl (Numida meleagris) Andre Escobar*, Carlos AA Valad~ ao*, Robert J Brosnan†, Fabıola N Fl^ ores*, Maristela CS Lopes* & F abio N Gava* *Department of Veterinary Clinics and Surgery, College of Agricultural and Veterinary Sciences, S~ ao Paulo State University, Jaboticabal, SP, Brazil †Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA
Correspondence: Andre Escobar, Department of Veterinary Clinics and Surgery, College of Agricultural and Veterinary Sciences, S~ao Paulo State University, Via de Acesso Prof. Paulo Donato Castellane s/n, Jaboticabal, SP 14884-900, Brazil. E-mail: [email protected]
Abstract Objective To evaluate the cardiopulmonary changes induced by intravenous butorphanol administration in guineafowl anesthetized with sevoflurane. Study design Prospective experimental trial. Animals Eight adult guineafowl (Numida meleagris) weighing 1.61 0.49 kg were used for the study. Methods Birds were anesthetized with sevoflurane and allowed to breathe spontaneously. After endotracheal intubation, end-tidal sevoflurane was adjusted to 1.0 individual sevoflurane MAC that was previously determined in triplicate using a standard bracketing technique. The brachial artery was catheterized for direct pressure measurement and blood sampling. Heart rate and rhythm were monitored by electrocardiography and respiratory rate was recorded. Baseline data were recorded 30 minutes after induction. Then, end-tidal sevoflurane was adjusted to 0.8 individual MAC and after 15 minutes physiologic variables were measured again. Subsequently, butorphanol (4 mg kg 1) was administered intravenously over 10 seconds and physiologic responses were recorded at 1, 5, 10, 15, 20, 30 and 45 minutes after administration.
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Results Butorphanol administration was associated with arrhythmias in all birds, including seconddegree atrioventricular block, sinus arrest, ventricular and supraventricular tachycardia and ventricular premature complexes. Heart rate and arterial blood pressures decreased significantly 1 minute after butorphanol administration. Two birds developed severe hypotension, apnea and ventricular fibrillation 5 minutes after administration, and one died. Conclusions and clinical relevance The butorphanol dose (4 mg kg 1) that produces clinically relevant sevoflurane MAC reduction in guineafowl caused severe adverse cardiopulmonary effects in two birds and was considered unsafe under the conditions used in this study. Keywords anesthesia, birds, butorphanol, cardiac arrhythmias, monitoring, sevoflurane. Introduction In the past, most birds were anesthetized by use of only an inhalation anesthetic agent, while the use of opioids was rare (Concannon et al. 1995). Currently, balanced anesthesia techniques are commonly used in birds to decrease the prevalence of cardiovascular depression associated with inhalation anesthesia and for post-operative pain relief (Klaphake et al. 2006).
Sevoflurane and butorphanol anesthesia in guineafowl A Escobar et al. Butorphanol is a j-opioid receptor agonist and a l-opioid receptor antagonist, and is considered by some veterinarians to be the opioid of choice for use in birds for its analgesic and anesthetic-sparing effects (Curro et al. 1994; Paul-Murphy et al. 2009). Preoperative butorphanol administration (2 mg kg 1) by intramuscular (IM) injection has been reported to be safe and effective in Hispaniolan Amazon parrots anesthetized with sevoflurane, however, a decrease in heart rate (HR) was noted when butorphanol was injected during anesthesia (Klaphake et al. 2006). It has been previously reported that butorphanol significantly decreased the MAC for sevoflurane in guineafowl, but that this effect was small and of short duration (Escobar et al. 2012). In that study, butorphanol at a dosage of 4 mg kg 1 reduced the MAC for sevoflurane by 20% by 15 minutes after intravenous (IV) administration, but no clinically significant anesthetic-sparing effect was detected at 30 minutes after administration. To the author’s knowledge there are no published studies evaluating the cardiopulmonary effects of butorphanol (4 mg kg 1) IV in anesthetized birds or comparing equipotent doses of an inhalation anesthetic agent alone and the agent with butorphanol. The aim of this study was to compare the cardiopulmonary effects of equipotent doses of sevoflurane with and without butorphanol in guineafowl. Material and methods Animals Eight guineafowl (one male and seven females) aged 4–7 months old and weighing 1.61 0.49 kg were used in the study. The birds were housed in a stall (3 9 4 9 3 m), and water and food were provided ad libitum. Results of physical examination and hematologic tests were unremarkable. Food and water were not withheld from the birds before anesthesia. Study procedures were approved by the local Animal Care and Use Committee. Experimental procedures Anesthesia was induced in each bird with sevoflurane (Sevocris; Crist alia Produtos Quımicos e Farmac^euticos Ltda, Brazil) in oxygen via face mask connected to a Bain circuit with an oxygen flow rate of 3 L minute 1 and an initial sevoflurane vaporizer setting of 8% (Vaporizador HB 4.4 for Sevoflurane;
HB Hospitalar, Brazil). Each bird was intubated with an uncuffed endotracheal tube (2.5 or 3.0 mm internal diameter) and positioned in dorsal recumbency. Oxygen flow rate was reduced to 1 L minute 1 and the birds were allowed to breathe spontaneously. End-tidal sevoflurane concentration (E′Sevo) was adjusted to 1.0 individual MAC that had been determined for each bird as part of a previous study (Escobar et al. 2012). End-expiration gas samples were collected by hand using a glass syringe over 7–10 breaths from a 3.5 Fr catheter (Tom Cat 3.5 Fr; Ortovet, Brazil) located within the lumen of the endotracheal tube with the tip close to the distal end. End-tidal carbon dioxide partial pressure (PE′CO2) and E′Sevo were measured using an infrared gas analyzer (Infra red gas analyzer DXAjaga-1 (AGA); Dixtal, Brazil) that was calibrated before and during the study for each bird with room air and three known sevoflurane concentrations (1%, 2.5%, and 5%) (Sevoflurane in N2 and O2; White Martins Gases Industriais SA, Brazil). Inspired carbon dioxide partial pressure was monitored continuously to ensure that there was no rebreathing in the Bain circuit. A 22-gauge catheter (BD Angiocath; BD, Brazil) was placed in an ulnar vein for administration of drugs and saline solution (0.9% NaCl). Saline was infused at 5 mL kg 1 hour 1 by syringe pump (Medfusion 2010i; Medex Inc., GA, USA). Clip electrodes were attached to the skin at the base of the right and left wings and each medial thigh region for recording a Lead II electrocardiogram (ECG) (ECGPC; TEB, Brazil). The cloacal temperature was monitored using a mercury thermometer (Veterinary Thermometer; Incoterm, Brazil) and was maintained between 40.5 ° and 41.5 °C by application of a circulating warm water blanket (T/ Pump; Gaymar, NY, USA), warm water containers, and a heat lamp. A 24-gauge catheter was inserted into the brachial artery after it had been exposed through a skin incision. A pressure transducer (Dixtal 2010; Dixtal) was connected to the catheter for continuous measurement of systolic (SAP), diastolic (DAP), and mean (MAP) arterial pressures. The accuracy of the transducers was verified using a mercury column. The zero reference point was set at the level of sternal extremity of the coracoid bone. Arterial blood (0.5 mL) was drawn through the arterial catheter into a heparinized syringe after first withdrawing and discarding 0.2 mL of blood. The blood samples were submitted for measurement of pH, partial pressures of carbon dioxide (PaCO2) and
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 41, 284–289
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Sevoflurane and butorphanol anesthesia in guineafowl A Escobar et al.
oxygen (PaO2), and electrolytes (Omni C; Roche Diagnostics, Brazil), and values were corrected for body temperature using standard mammalian correction factors. Cardiopulmonary evaluation Baseline variables were measured 30 minutes after induction of anesthesia (T-30). Subsequently, E′Sevo was set to 0.8 individual MAC and after an interval of 15 minutes cardiopulmonary variables were recorded again (T0). Butorphanol tartrate (4 mg kg 1; Torbugesic; Fort Dodge Animal Health, Brazil) was administered IV over 10 seconds and physiologic responses were measured at 1 (T1), 5 (T5), 10 (T10), 15 (T15), 20 (T20), 30 (T30) and 45 minutes (T45) after administration. At the end of the study, instruments and catheters were removed and the skin was sutured. Oxygen was administered until animals were extubated, when they received meloxicam, 0.5 mg kg 1, by subcutaneous injection. Statistical analysis A Shapiro–Wilk test was used to test whether data deviated from normality. For physiologic data that were normally distributed, repeated-measures ANOVA, followed by the Tukey’s test was used to compare the means of physiologic variables at baseline (T-30 and T0) and after butorphanol administration. The median and range were reported for data that were not normally distributed and the Friedman test, followed by the Tukey’s test was used to compare the variables. For all tests, values of p ≤ 0.05 were considered significant. Results The median time for instrumentation was 20 minutes (16–26 minutes). One minute after butorphanol administration, HR and blood pressures significantly decreased (Table 1). Arterial pH was decreased at T5 and T15 compared to T-30 and T0, and PaCO2 was significantly increased at T30 compared to T0 (Table 1). There was a significant decrease in the arterial Na and an increase in the K values, compared to values at T-30 (154 3 and 3.14 0.46 mmol L 1), at T30 (151 2 and 3.81 0.36 mmol L 1) and T45 (151 2 and 3.73 0.35 mmol L 1), respectively. There were no significant changes in fR, PE′CO2, temperature, 286
PaO2, or base excess (BE) (Table 1). Ionized calcium and chloride concentrations were 0.83 0.11 mmol L 1 and 117 2 mmol L 1 at T-30, respectively, and were not significantly changed during anesthesia. No cardiac arrhythmias were recorded at T-30 and T0. Cardiac arrhythmias were recorded in all birds after administration of butorphanol, including second-degree atrioventricular block (25% and 14% of birds at T1 and T30, respectively), ventricular premature complexes (13%, 25%, 14%, 43%, 29%, 29% and 14% of birds at T1, T5, T10, T15, T20, T30 and T45, respectively), sinus arrest of a few seconds duration (38% of birds at T1), ventricular tachycardia (25% of birds at T5), and supraventricular tachycardia (63% and 13% of birds at T1 and T5, respectively). Apnea and ventricular fibrillation were recorded in two birds five minutes after butorphanol injection. Cardiopulmonary resuscitation was performed, and consisted of artificial ventilation and precordial thumping achieved by using two fingers to moderately depress the bird’s sternum every 10 seconds for 1 minute or until normal sinus rhythm returned. Sinus rhythm and spontaneous ventilation was restored in one bird but the other bird died. For this reason, cardiopulmonary measurements were included from only seven birds, although ECG data was reported for eight birds until T5. Discussion Butorphanol supposedly has fewer adverse effects on cardiopulmonary function than many l-opioid agonists (Lamont & Mathews 2007). In the present study, the butorphanol dose associated with a clinically significant reduction in sevoflurane MAC in guineafowl, caused cardiac arrhythmias in all birds and cardiopulmonary arrest in two. In a previous study, no cardiopulmonary adverse effects were detected when the same dose of butorphanol was administered to sevoflurane anesthetized, mechanically ventilated guineafowl (Escobar et al. 2012). In that study the ECG was not monitored, and it is possible those birds did have cardiac arrhythmias. In addition, 5 minutes after administering butorphanol, when the most number of cardiac arrhythmias were recorded, plasma concentrations were probably higher than at the first time point in the previous study (15 minutes after administration) when physiological variables were measured and no adverse effects were detected (Escobar et al. 2012). The effects of butorphanol
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 41, 284–289
195 (179–241)
HR (beats minute 1)
1.9 2.7
1.7 1.3
BE (mmol/L)
–
–
–
–
–
–
41.1 0.6
6.1 0.9
46 7
86 51†
74 49†
94 52†
2.6 1.8
6.1 1.7
46 13
52.4 5.6
393 42
7.32 0.06 *,†
41 0.5
6.5 1.7
49 13
129 18
122 27
138 28
21 (14–55)
162 (149–196)
145 *,† (92–165) 21 (0–51)
T5 (n = 7)
T1 (n = 7)
–
–
–
–
–
–
41.1 0.5
6.4 1.9
48 14
113 29
99 20
116 18
19 (13–48)
184 (159–246)
T10 (n = 7)
2.3 2.2
6.1 1.5
46 11
53.2 5.3
399 40
7.33 0.07 *,†
41.1 0.5
6.7 1.9
50 14
102 32
97 29
114 31
19 (12–52)
177 (159–253)
T15 (n = 7)
n = number of guineafowl. *Significantly different from values at T-30 (p ≤ 0.05). †Significantly different from values at T0 (p ≤ 0.05).
41 10 5.5 1.3
42 9
5.6 1.2
52.5 4.7
50.5 8.8
PaO2 (kPa)
PaCO2 (mmHg)
394 35
377 66
PaO2 (mmHg)
PaCO2 (kPa)
40.7 0.6 7.37 0.05
40.7 0.6
7.37 0.06
T (°C)
pH
46 14 6.1 1.9
46 10
6.1 1.3
106 25
117 22
DAP (mmHg)
MAP (mmHg)
PE′CO2 (kPa)
116 19 125 18
125 22
SAP (mmHg)
PE′CO2 (mmHg)
133 22
17 (12–35)
17 (8–48)
183 (173–209)
T0 (n = 7)
fR (breaths minute )
1
T-30 (n = 7)
Variable
Time points
–
–
–
–
–
–
41.1 0.3
6.4 1.5
48 11
113 29
101 29
119 32
18 (12–27)
177 (173–248)
T20 (n = 7)
1.2 1.4
6.3 1.5†
47 11†
53.6 12
402 90
7.34 0.07
41.3 0.4
7.1 1.3
53 10
102 32
90 32
109 31
19 (12–160)
177 (134–391)
T30 (n = 7)
1.3 1.7
5.7 1.1
43 8
53.5 14
401 103
7.36 0.07
41.4 0.5
6.9 1.5
52 11
104 27
91 26
112 26
21 (16–193)
164 (128–400)
T45 (n = 7)
Table 1 Time-related changes in heart rate (HR), respiratory rate (fR), arterial blood pressures (SAP, DAP and MAP), end-tidal carbon dioxide (PE′CO2), temperature (T), arterial blood gas and acid-base balance during sevoflurane anesthesia in guineafowl at 1.0 MAC (T-30) and at 0.8 MAC before (T0) and after butorphanol (4 mg kg 1) administration (T1 to T45) during spontaneous ventilation. For data considered normally distributed mean SD were reported, and for data not considered normally distributed median (range) were reported
Sevoflurane and butorphanol anesthesia in guineafowl A Escobar et al.
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 41, 284–289
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Sevoflurane and butorphanol anesthesia in guineafowl A Escobar et al.
on sevoflurane MAC is short lived in guineafowl (Escobar et al. 2012), and pharmacokinetic studies in other birds confirm its short half-life (Riggs et al. 2008). However, cardiac arrhythmias were detected for up to 45 minutes after butorphanol was administered, even after 30 minutes when there was no clinically significant anesthetic-sparing effect. A probable explanation for the cardiac arrhythmias, bradycardia and hypotension recorded in this study could be an increase in vagal tone and a decrease in the ventricular blood flow associated with butorphanol administration (Santos et al. 2011). The high dose and the relatively rapid IV administration may have contributed to these adverse effects. In dogs anesthetized with desflurane, butorphanol decreased HR, fR and MAP (Santos et al. 2011). In Hispaniolan Amazon parrots, a decrease in HR was recorded when butorphanol (2 mg kg 1) was administered IM after induction of sevoflurane anesthesia, although an increase in HR was noted when butorphanol was administered before induction (Klaphake et al. 2006). Sevoflurane anesthesia causes dose-dependent respiratory depression in birds (Escobar et al. 2009). Balanced anesthetic techniques are used in birds to decrease MAC, thus potentially decreasing the prevalence of cardiopulmonary changes associated with inhalant anesthetics while also providing analgesia (Klaphake et al. 2006). In contrast to the previous study in which ventilation was controlled (Escobar et al. 2012), the birds of this study breathed spontaneously so that the respiratory effects of butorphanol in the sevoflurane-anesthetized birds could be assessed. The guineafowl developed moderate to severe respiratory acidosis after the administration of butorphanol. Cardiac arrhythmias were detected after administration of butorphanol and lasted until the end of the anesthetic period. Thus it is possible that hypercapnia was a cause of the arrhythmias. Studies have reported that hypercapnia can cause arrhythmias in birds anesthetized with inhalation anesthetics (Pare et al. 2013). A control group of birds receiving only sevoflurane may have provided further insight into the origin of the arrhythmias. Controlled ventilation may be advisable in anesthetized birds to prevent hypercapnia. The aim of this study was to compare equipotent doses of sevoflurane alone with sevoflurane combined with butorphanol. In a previous study in anesthetized guineafowl, sevoflurane MAC was reduced by 20% 15 minutes after IV injection of 288
butorphanol (4 mg kg 1) (Escobar et al. 2012). This MAC-sparing effect diminished with time and was clinically insignificant by 30 minutes after butorphanol administration. The MAC-sparing effect in the first 15 minutes after injection of butorphanol was not determined. It is possible that the birds in this study were at a deeper plane of anesthesia (i.e., >1 MAC) at T1 and T5, which could explain cardiac arrest in two of the birds. Equipotency probably existed at baseline (T-30) and at 15 minutes after butorphanol administration (T15). By 30 minutes after butorphanol administration (T30), butorphanol does not have clinically significant anestheticsparing effect in the guineafowl, thus data at T30 and T45 may be comparable to data at T0, corresponding to 0.8 MAC of sevoflurane. In spontaneously breathing sevoflurane-anesthetized guineafowl, the butorphanol dose that produces clinically relevant MAC reduction also causes adverse cardiopulmonary effects in some birds when injected IV. In light of these effects, butorphanol should be considered unsafe when administered under conditions used in this study. Our findings also strongly support the routine use of ECG monitoring in anesthetized birds, especially when butorphanol is administered during general anesthesia. Acknowledgements We thank the Conselho Nacional de Desenvolvimento Cientıfico e Tecnol ogico – CNPq for funding the study and author’s scholarship. References Concannon KT, Dodam JR, Hellyer PW (1995) Influence of a mu- and kappa-opioid agonist on isoflurane minimal anesthetic concentration in chickens. Am J Vet Res 56, 806–811. Curro TG, Brunson DB, Paul-Murphy J (1994) Determination of the ED50 of isoflurane and evaluation of the isoflurane-sparing effect of butorphanol in cockatoos (Cacatua spp.). Vet Surg 23, 429–433. Escobar A, Thiesen R, Vitaliano SN et al. (2009) Some cardiopulmonary effects of sevoflurane in crested caracara (Caracara plancus). Vet Anaesth Analg 36, 436–441. Escobar A, Valad~ ao CA, Brosnan RJ et al. (2012) Effects of butorphanol on the minimum anesthetic concentration for sevoflurane in guineafowl (Numida meleagris). Am J Vet Res 73, 183–188. Klaphake E, Schumacher J, Greenacre C et al. (2006) Comparative anesthetic and cardiopulmonary effects of
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 41, 284–289
Sevoflurane and butorphanol anesthesia in guineafowl A Escobar et al. pre- versus postoperative butorphanol administration in Hispaniolan Amazon parrots (Amazona ventralis) anesthetized with sevoflurane. J Avian Med Surg 20, 2–7. Lamont A, Mathews KA (2007) Opioids, nonsteroidal antiinflammatories, and analgesic adjuvants. In: Lumb and Jones’ Veterinary Anesthesia and Analgesia (4th edn). Tranquilli WJ, Thurmon JC, Grimm KA (eds). Blackwell Publishing, Ames, USA. pp. 241–271. Pare M, Ludders JW, Erb HN (2013) Association of partial pressure of carbon dioxide in expired gas and arterial blood at three different ventilation states in apneic chickens (Gallus domesticus) during air sac insufflation anesthesia. Vet Anaesth Analg 40, 245–256.
Paul-Murphy JR, Sladky KK, Krugner-Higby LA et al. (2009) Analgesic effects of carprofen and liposomeencapsulated butorphanol tartrate in Hispaniolan parrots (Amazona ventralis) with experimentally induced arthritis. Am J Vet Res 70, 1201–1210. Riggs SM, Hawkins MG, Craigmill AL et al. (2008) Pharmacokinetics of butorphanol tartrate in red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus). Am J Vet Res 69, 596–603. Santos PS, Nunes N, Souza AP et al. (2011) Hemodynamic effects of butorphanol in desflurane-anesthetized dogs. Vet Anaesth Analg 38, 467–474. Received 25 June 2012; accepted 13 August 2013.
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 41, 284–289
289
doi:10.1111/vaa.12108
SHORT COMMUNICATION
Cardiopulmonary effects of butorphanol in sevofluraneanesthetized guineafowl (Numida meleagris) Andre Escobar*, Carlos AA Valad~ ao*, Robert J Brosnan†, Fabıola N Fl^ ores*, Maristela CS Lopes* & F abio N Gava* *Department of Veterinary Clinics and Surgery, College of Agricultural and Veterinary Sciences, S~ ao Paulo State University, Jaboticabal, SP, Brazil †Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA
Correspondence: Andre Escobar, Department of Veterinary Clinics and Surgery, College of Agricultural and Veterinary Sciences, S~ao Paulo State University, Via de Acesso Prof. Paulo Donato Castellane s/n, Jaboticabal, SP 14884-900, Brazil. E-mail: [email protected]
Abstract Objective To evaluate the cardiopulmonary changes induced by intravenous butorphanol administration in guineafowl anesthetized with sevoflurane. Study design Prospective experimental trial. Animals Eight adult guineafowl (Numida meleagris) weighing 1.61 0.49 kg were used for the study. Methods Birds were anesthetized with sevoflurane and allowed to breathe spontaneously. After endotracheal intubation, end-tidal sevoflurane was adjusted to 1.0 individual sevoflurane MAC that was previously determined in triplicate using a standard bracketing technique. The brachial artery was catheterized for direct pressure measurement and blood sampling. Heart rate and rhythm were monitored by electrocardiography and respiratory rate was recorded. Baseline data were recorded 30 minutes after induction. Then, end-tidal sevoflurane was adjusted to 0.8 individual MAC and after 15 minutes physiologic variables were measured again. Subsequently, butorphanol (4 mg kg 1) was administered intravenously over 10 seconds and physiologic responses were recorded at 1, 5, 10, 15, 20, 30 and 45 minutes after administration.
284
Results Butorphanol administration was associated with arrhythmias in all birds, including seconddegree atrioventricular block, sinus arrest, ventricular and supraventricular tachycardia and ventricular premature complexes. Heart rate and arterial blood pressures decreased significantly 1 minute after butorphanol administration. Two birds developed severe hypotension, apnea and ventricular fibrillation 5 minutes after administration, and one died. Conclusions and clinical relevance The butorphanol dose (4 mg kg 1) that produces clinically relevant sevoflurane MAC reduction in guineafowl caused severe adverse cardiopulmonary effects in two birds and was considered unsafe under the conditions used in this study. Keywords anesthesia, birds, butorphanol, cardiac arrhythmias, monitoring, sevoflurane. Introduction In the past, most birds were anesthetized by use of only an inhalation anesthetic agent, while the use of opioids was rare (Concannon et al. 1995). Currently, balanced anesthesia techniques are commonly used in birds to decrease the prevalence of cardiovascular depression associated with inhalation anesthesia and for post-operative pain relief (Klaphake et al. 2006).
Sevoflurane and butorphanol anesthesia in guineafowl A Escobar et al. Butorphanol is a j-opioid receptor agonist and a l-opioid receptor antagonist, and is considered by some veterinarians to be the opioid of choice for use in birds for its analgesic and anesthetic-sparing effects (Curro et al. 1994; Paul-Murphy et al. 2009). Preoperative butorphanol administration (2 mg kg 1) by intramuscular (IM) injection has been reported to be safe and effective in Hispaniolan Amazon parrots anesthetized with sevoflurane, however, a decrease in heart rate (HR) was noted when butorphanol was injected during anesthesia (Klaphake et al. 2006). It has been previously reported that butorphanol significantly decreased the MAC for sevoflurane in guineafowl, but that this effect was small and of short duration (Escobar et al. 2012). In that study, butorphanol at a dosage of 4 mg kg 1 reduced the MAC for sevoflurane by 20% by 15 minutes after intravenous (IV) administration, but no clinically significant anesthetic-sparing effect was detected at 30 minutes after administration. To the author’s knowledge there are no published studies evaluating the cardiopulmonary effects of butorphanol (4 mg kg 1) IV in anesthetized birds or comparing equipotent doses of an inhalation anesthetic agent alone and the agent with butorphanol. The aim of this study was to compare the cardiopulmonary effects of equipotent doses of sevoflurane with and without butorphanol in guineafowl. Material and methods Animals Eight guineafowl (one male and seven females) aged 4–7 months old and weighing 1.61 0.49 kg were used in the study. The birds were housed in a stall (3 9 4 9 3 m), and water and food were provided ad libitum. Results of physical examination and hematologic tests were unremarkable. Food and water were not withheld from the birds before anesthesia. Study procedures were approved by the local Animal Care and Use Committee. Experimental procedures Anesthesia was induced in each bird with sevoflurane (Sevocris; Crist alia Produtos Quımicos e Farmac^euticos Ltda, Brazil) in oxygen via face mask connected to a Bain circuit with an oxygen flow rate of 3 L minute 1 and an initial sevoflurane vaporizer setting of 8% (Vaporizador HB 4.4 for Sevoflurane;
HB Hospitalar, Brazil). Each bird was intubated with an uncuffed endotracheal tube (2.5 or 3.0 mm internal diameter) and positioned in dorsal recumbency. Oxygen flow rate was reduced to 1 L minute 1 and the birds were allowed to breathe spontaneously. End-tidal sevoflurane concentration (E′Sevo) was adjusted to 1.0 individual MAC that had been determined for each bird as part of a previous study (Escobar et al. 2012). End-expiration gas samples were collected by hand using a glass syringe over 7–10 breaths from a 3.5 Fr catheter (Tom Cat 3.5 Fr; Ortovet, Brazil) located within the lumen of the endotracheal tube with the tip close to the distal end. End-tidal carbon dioxide partial pressure (PE′CO2) and E′Sevo were measured using an infrared gas analyzer (Infra red gas analyzer DXAjaga-1 (AGA); Dixtal, Brazil) that was calibrated before and during the study for each bird with room air and three known sevoflurane concentrations (1%, 2.5%, and 5%) (Sevoflurane in N2 and O2; White Martins Gases Industriais SA, Brazil). Inspired carbon dioxide partial pressure was monitored continuously to ensure that there was no rebreathing in the Bain circuit. A 22-gauge catheter (BD Angiocath; BD, Brazil) was placed in an ulnar vein for administration of drugs and saline solution (0.9% NaCl). Saline was infused at 5 mL kg 1 hour 1 by syringe pump (Medfusion 2010i; Medex Inc., GA, USA). Clip electrodes were attached to the skin at the base of the right and left wings and each medial thigh region for recording a Lead II electrocardiogram (ECG) (ECGPC; TEB, Brazil). The cloacal temperature was monitored using a mercury thermometer (Veterinary Thermometer; Incoterm, Brazil) and was maintained between 40.5 ° and 41.5 °C by application of a circulating warm water blanket (T/ Pump; Gaymar, NY, USA), warm water containers, and a heat lamp. A 24-gauge catheter was inserted into the brachial artery after it had been exposed through a skin incision. A pressure transducer (Dixtal 2010; Dixtal) was connected to the catheter for continuous measurement of systolic (SAP), diastolic (DAP), and mean (MAP) arterial pressures. The accuracy of the transducers was verified using a mercury column. The zero reference point was set at the level of sternal extremity of the coracoid bone. Arterial blood (0.5 mL) was drawn through the arterial catheter into a heparinized syringe after first withdrawing and discarding 0.2 mL of blood. The blood samples were submitted for measurement of pH, partial pressures of carbon dioxide (PaCO2) and
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 41, 284–289
285
Sevoflurane and butorphanol anesthesia in guineafowl A Escobar et al.
oxygen (PaO2), and electrolytes (Omni C; Roche Diagnostics, Brazil), and values were corrected for body temperature using standard mammalian correction factors. Cardiopulmonary evaluation Baseline variables were measured 30 minutes after induction of anesthesia (T-30). Subsequently, E′Sevo was set to 0.8 individual MAC and after an interval of 15 minutes cardiopulmonary variables were recorded again (T0). Butorphanol tartrate (4 mg kg 1; Torbugesic; Fort Dodge Animal Health, Brazil) was administered IV over 10 seconds and physiologic responses were measured at 1 (T1), 5 (T5), 10 (T10), 15 (T15), 20 (T20), 30 (T30) and 45 minutes (T45) after administration. At the end of the study, instruments and catheters were removed and the skin was sutured. Oxygen was administered until animals were extubated, when they received meloxicam, 0.5 mg kg 1, by subcutaneous injection. Statistical analysis A Shapiro–Wilk test was used to test whether data deviated from normality. For physiologic data that were normally distributed, repeated-measures ANOVA, followed by the Tukey’s test was used to compare the means of physiologic variables at baseline (T-30 and T0) and after butorphanol administration. The median and range were reported for data that were not normally distributed and the Friedman test, followed by the Tukey’s test was used to compare the variables. For all tests, values of p ≤ 0.05 were considered significant. Results The median time for instrumentation was 20 minutes (16–26 minutes). One minute after butorphanol administration, HR and blood pressures significantly decreased (Table 1). Arterial pH was decreased at T5 and T15 compared to T-30 and T0, and PaCO2 was significantly increased at T30 compared to T0 (Table 1). There was a significant decrease in the arterial Na and an increase in the K values, compared to values at T-30 (154 3 and 3.14 0.46 mmol L 1), at T30 (151 2 and 3.81 0.36 mmol L 1) and T45 (151 2 and 3.73 0.35 mmol L 1), respectively. There were no significant changes in fR, PE′CO2, temperature, 286
PaO2, or base excess (BE) (Table 1). Ionized calcium and chloride concentrations were 0.83 0.11 mmol L 1 and 117 2 mmol L 1 at T-30, respectively, and were not significantly changed during anesthesia. No cardiac arrhythmias were recorded at T-30 and T0. Cardiac arrhythmias were recorded in all birds after administration of butorphanol, including second-degree atrioventricular block (25% and 14% of birds at T1 and T30, respectively), ventricular premature complexes (13%, 25%, 14%, 43%, 29%, 29% and 14% of birds at T1, T5, T10, T15, T20, T30 and T45, respectively), sinus arrest of a few seconds duration (38% of birds at T1), ventricular tachycardia (25% of birds at T5), and supraventricular tachycardia (63% and 13% of birds at T1 and T5, respectively). Apnea and ventricular fibrillation were recorded in two birds five minutes after butorphanol injection. Cardiopulmonary resuscitation was performed, and consisted of artificial ventilation and precordial thumping achieved by using two fingers to moderately depress the bird’s sternum every 10 seconds for 1 minute or until normal sinus rhythm returned. Sinus rhythm and spontaneous ventilation was restored in one bird but the other bird died. For this reason, cardiopulmonary measurements were included from only seven birds, although ECG data was reported for eight birds until T5. Discussion Butorphanol supposedly has fewer adverse effects on cardiopulmonary function than many l-opioid agonists (Lamont & Mathews 2007). In the present study, the butorphanol dose associated with a clinically significant reduction in sevoflurane MAC in guineafowl, caused cardiac arrhythmias in all birds and cardiopulmonary arrest in two. In a previous study, no cardiopulmonary adverse effects were detected when the same dose of butorphanol was administered to sevoflurane anesthetized, mechanically ventilated guineafowl (Escobar et al. 2012). In that study the ECG was not monitored, and it is possible those birds did have cardiac arrhythmias. In addition, 5 minutes after administering butorphanol, when the most number of cardiac arrhythmias were recorded, plasma concentrations were probably higher than at the first time point in the previous study (15 minutes after administration) when physiological variables were measured and no adverse effects were detected (Escobar et al. 2012). The effects of butorphanol
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 41, 284–289
195 (179–241)
HR (beats minute 1)
1.9 2.7
1.7 1.3
BE (mmol/L)
–
–
–
–
–
–
41.1 0.6
6.1 0.9
46 7
86 51†
74 49†
94 52†
2.6 1.8
6.1 1.7
46 13
52.4 5.6
393 42
7.32 0.06 *,†
41 0.5
6.5 1.7
49 13
129 18
122 27
138 28
21 (14–55)
162 (149–196)
145 *,† (92–165) 21 (0–51)
T5 (n = 7)
T1 (n = 7)
–
–
–
–
–
–
41.1 0.5
6.4 1.9
48 14
113 29
99 20
116 18
19 (13–48)
184 (159–246)
T10 (n = 7)
2.3 2.2
6.1 1.5
46 11
53.2 5.3
399 40
7.33 0.07 *,†
41.1 0.5
6.7 1.9
50 14
102 32
97 29
114 31
19 (12–52)
177 (159–253)
T15 (n = 7)
n = number of guineafowl. *Significantly different from values at T-30 (p ≤ 0.05). †Significantly different from values at T0 (p ≤ 0.05).
41 10 5.5 1.3
42 9
5.6 1.2
52.5 4.7
50.5 8.8
PaO2 (kPa)
PaCO2 (mmHg)
394 35
377 66
PaO2 (mmHg)
PaCO2 (kPa)
40.7 0.6 7.37 0.05
40.7 0.6
7.37 0.06
T (°C)
pH
46 14 6.1 1.9
46 10
6.1 1.3
106 25
117 22
DAP (mmHg)
MAP (mmHg)
PE′CO2 (kPa)
116 19 125 18
125 22
SAP (mmHg)
PE′CO2 (mmHg)
133 22
17 (12–35)
17 (8–48)
183 (173–209)
T0 (n = 7)
fR (breaths minute )
1
T-30 (n = 7)
Variable
Time points
–
–
–
–
–
–
41.1 0.3
6.4 1.5
48 11
113 29
101 29
119 32
18 (12–27)
177 (173–248)
T20 (n = 7)
1.2 1.4
6.3 1.5†
47 11†
53.6 12
402 90
7.34 0.07
41.3 0.4
7.1 1.3
53 10
102 32
90 32
109 31
19 (12–160)
177 (134–391)
T30 (n = 7)
1.3 1.7
5.7 1.1
43 8
53.5 14
401 103
7.36 0.07
41.4 0.5
6.9 1.5
52 11
104 27
91 26
112 26
21 (16–193)
164 (128–400)
T45 (n = 7)
Table 1 Time-related changes in heart rate (HR), respiratory rate (fR), arterial blood pressures (SAP, DAP and MAP), end-tidal carbon dioxide (PE′CO2), temperature (T), arterial blood gas and acid-base balance during sevoflurane anesthesia in guineafowl at 1.0 MAC (T-30) and at 0.8 MAC before (T0) and after butorphanol (4 mg kg 1) administration (T1 to T45) during spontaneous ventilation. For data considered normally distributed mean SD were reported, and for data not considered normally distributed median (range) were reported
Sevoflurane and butorphanol anesthesia in guineafowl A Escobar et al.
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 41, 284–289
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Sevoflurane and butorphanol anesthesia in guineafowl A Escobar et al.
on sevoflurane MAC is short lived in guineafowl (Escobar et al. 2012), and pharmacokinetic studies in other birds confirm its short half-life (Riggs et al. 2008). However, cardiac arrhythmias were detected for up to 45 minutes after butorphanol was administered, even after 30 minutes when there was no clinically significant anesthetic-sparing effect. A probable explanation for the cardiac arrhythmias, bradycardia and hypotension recorded in this study could be an increase in vagal tone and a decrease in the ventricular blood flow associated with butorphanol administration (Santos et al. 2011). The high dose and the relatively rapid IV administration may have contributed to these adverse effects. In dogs anesthetized with desflurane, butorphanol decreased HR, fR and MAP (Santos et al. 2011). In Hispaniolan Amazon parrots, a decrease in HR was recorded when butorphanol (2 mg kg 1) was administered IM after induction of sevoflurane anesthesia, although an increase in HR was noted when butorphanol was administered before induction (Klaphake et al. 2006). Sevoflurane anesthesia causes dose-dependent respiratory depression in birds (Escobar et al. 2009). Balanced anesthetic techniques are used in birds to decrease MAC, thus potentially decreasing the prevalence of cardiopulmonary changes associated with inhalant anesthetics while also providing analgesia (Klaphake et al. 2006). In contrast to the previous study in which ventilation was controlled (Escobar et al. 2012), the birds of this study breathed spontaneously so that the respiratory effects of butorphanol in the sevoflurane-anesthetized birds could be assessed. The guineafowl developed moderate to severe respiratory acidosis after the administration of butorphanol. Cardiac arrhythmias were detected after administration of butorphanol and lasted until the end of the anesthetic period. Thus it is possible that hypercapnia was a cause of the arrhythmias. Studies have reported that hypercapnia can cause arrhythmias in birds anesthetized with inhalation anesthetics (Pare et al. 2013). A control group of birds receiving only sevoflurane may have provided further insight into the origin of the arrhythmias. Controlled ventilation may be advisable in anesthetized birds to prevent hypercapnia. The aim of this study was to compare equipotent doses of sevoflurane alone with sevoflurane combined with butorphanol. In a previous study in anesthetized guineafowl, sevoflurane MAC was reduced by 20% 15 minutes after IV injection of 288
butorphanol (4 mg kg 1) (Escobar et al. 2012). This MAC-sparing effect diminished with time and was clinically insignificant by 30 minutes after butorphanol administration. The MAC-sparing effect in the first 15 minutes after injection of butorphanol was not determined. It is possible that the birds in this study were at a deeper plane of anesthesia (i.e., >1 MAC) at T1 and T5, which could explain cardiac arrest in two of the birds. Equipotency probably existed at baseline (T-30) and at 15 minutes after butorphanol administration (T15). By 30 minutes after butorphanol administration (T30), butorphanol does not have clinically significant anestheticsparing effect in the guineafowl, thus data at T30 and T45 may be comparable to data at T0, corresponding to 0.8 MAC of sevoflurane. In spontaneously breathing sevoflurane-anesthetized guineafowl, the butorphanol dose that produces clinically relevant MAC reduction also causes adverse cardiopulmonary effects in some birds when injected IV. In light of these effects, butorphanol should be considered unsafe when administered under conditions used in this study. Our findings also strongly support the routine use of ECG monitoring in anesthetized birds, especially when butorphanol is administered during general anesthesia. Acknowledgements We thank the Conselho Nacional de Desenvolvimento Cientıfico e Tecnol ogico – CNPq for funding the study and author’s scholarship. References Concannon KT, Dodam JR, Hellyer PW (1995) Influence of a mu- and kappa-opioid agonist on isoflurane minimal anesthetic concentration in chickens. Am J Vet Res 56, 806–811. Curro TG, Brunson DB, Paul-Murphy J (1994) Determination of the ED50 of isoflurane and evaluation of the isoflurane-sparing effect of butorphanol in cockatoos (Cacatua spp.). Vet Surg 23, 429–433. Escobar A, Thiesen R, Vitaliano SN et al. (2009) Some cardiopulmonary effects of sevoflurane in crested caracara (Caracara plancus). Vet Anaesth Analg 36, 436–441. Escobar A, Valad~ ao CA, Brosnan RJ et al. (2012) Effects of butorphanol on the minimum anesthetic concentration for sevoflurane in guineafowl (Numida meleagris). Am J Vet Res 73, 183–188. Klaphake E, Schumacher J, Greenacre C et al. (2006) Comparative anesthetic and cardiopulmonary effects of
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Sevoflurane and butorphanol anesthesia in guineafowl A Escobar et al. pre- versus postoperative butorphanol administration in Hispaniolan Amazon parrots (Amazona ventralis) anesthetized with sevoflurane. J Avian Med Surg 20, 2–7. Lamont A, Mathews KA (2007) Opioids, nonsteroidal antiinflammatories, and analgesic adjuvants. In: Lumb and Jones’ Veterinary Anesthesia and Analgesia (4th edn). Tranquilli WJ, Thurmon JC, Grimm KA (eds). Blackwell Publishing, Ames, USA. pp. 241–271. Pare M, Ludders JW, Erb HN (2013) Association of partial pressure of carbon dioxide in expired gas and arterial blood at three different ventilation states in apneic chickens (Gallus domesticus) during air sac insufflation anesthesia. Vet Anaesth Analg 40, 245–256.
Paul-Murphy JR, Sladky KK, Krugner-Higby LA et al. (2009) Analgesic effects of carprofen and liposomeencapsulated butorphanol tartrate in Hispaniolan parrots (Amazona ventralis) with experimentally induced arthritis. Am J Vet Res 70, 1201–1210. Riggs SM, Hawkins MG, Craigmill AL et al. (2008) Pharmacokinetics of butorphanol tartrate in red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus). Am J Vet Res 69, 596–603. Santos PS, Nunes N, Souza AP et al. (2011) Hemodynamic effects of butorphanol in desflurane-anesthetized dogs. Vet Anaesth Analg 38, 467–474. Received 25 June 2012; accepted 13 August 2013.
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