Comparative Hemodynamic Effects of Halothane and Halothane-Acepromazine at Equipotent Doses in Dogs Christie J. Boyd, Wayne N. McDonell and Anne Valliant
ABSTRACT The purpose of this study was to compare the cardiovascular effects of halothane when used alone at increasing doses (1.2, 1.45 and 1.7 minimum alveolar concentration, MAC) to those produced with equipotent doses of halothane after potentiation of the anesthetic effect with acepromazine (ACP) sedation (45% reduction of halothane MAC). Six healthy mature dogs were used on three occasions. The treatments were halothane and intramuscular (IM) saline (1.0 mL), halothane and ACP (0.04 mg/kg IM), or halothane and ACP (0.2 mg/kg IM). Anesthesia was induced and maintained with halothane in oxygen and the dogs were prepared for the collection of arterial and mixed venous blood and for the determination of heart rate, systolic, diastolic and mean arterial pressure, mean pulmonary artial pressure (PAP), central venous pressure and cardiac output. Following animal preparation the saline or ACP was administered and positive pressure ventilation instituted. Twentyfive minutes later the dogs were exposed to the first of three anesthetic levels, with random assignment of the sequence of administration. At each anesthetic level, measurements were obtained at 20 and 35 min. Calculated values included cardiac index, stroke index, left ventricular work, systemic vascular resistance, arterial oxygen content, mixed venous oxygen content, oxygen delivery and oxygen consumption. Heart rate was significantly higher with halothane alone than with both halothane-ACP combinations and was significantly higher with high
dose ACP compared to low dose ACP. Systolic and mean blood pressures were lowest with halothane alone and highest with 0.2 mg/kg ACP, the differences being significant for each treatment. Oxygen uptake and PAP were significantly lower in dogs treated with ACP. It was concluded that ACP does not potentiate the cardiovascular depression that accompanies halothane anesthesia when the resultant lower dose requirements of halothane are taken into consideration.
RESUME Le but de cette etude etait de comles effets cardio-vasculaires de l'halothane utilise seul a doses croissantes (1.2, 1.45 et 1.7 concentration alveolaire minimum, CAM) a ceux de doses equieffectives d'halothane apres potentialisation de l'effet anesthesique (45 /o de riduction du CAM de l'halothane) par une sedation a l'acepromazine (ACP). Six chiens matures et en bonne condition physique ont ete utilises a trois occasions. Les traitements consistaient en: halothane et saline (1 mL) intramusculaire (IM), halothane et ACP (0.04 mg/kg, IM) et halothane et ACP (0.2 mg/kg, IM). L'anesthesie a ete induite et maintenue par un melange d'halothane et d'oxygene et les chiens ont ete prepares pour la prise de sang arteriel et veineux ainsi que pour la determination de la frequence cardiaque, des pressions arterielles moyenne, systolique et diastolique, de la pression pulmonaire arterielle moyenne (PAP), de la pression veineuse centrale et du debit cardiaque. Une fois l'animal prepare, de parer
la saline ou de l'ACP etaient administrees et la ventilation A pression positive instituee. Apres vingt-cinq minutes les chiens etaient exposes au premier des trois niveaux d'anesthesie, suivant une sequence d'administration aleatoire. Des mesures furent prises a 20 et 35 minutes pour chacun des niveaux d'anesthesie. Les valeurs calculees etaient l'indice cardiaque, l'indice de travail systolique, le travail ventriculaire gauche, la resistance vasculaire systemique, la concentration en oxygene du sang arteriel et veineux, le relachement d'oxygene et la consommation d'oxygene. La frequence cardiaque etait significativement plus elev6e lorsque l'halothane etait utilise seul plutot qu'en combinaison avec l'ACP, et elle etait significativement plus dievee lorsque 1'ACP 6tait utilise A fortes doses plutot qu'A faibles doses. Les pressions sanguines moyenne et systolique etaient significativement plus faibles lorsque l'halothane etait utilise seul que lorsque combine avec 0.2 mg/kg d'ACP. La prise d'oxygene et la PAP etaient significativement inf6rieures chez les chiens traites avec I'ACP. II a ete conclu que l'ACP ne potentialise pas la dipression cardiovasculaire qui accompagne l'anesthesie A I'halothane lorsque l'on considere les doses minimales d'halothane requises. (Traduit par D' Helone H6on) INTRODUCTION Halothane and the other inhalation anesthetic agents commonly used in veterinary medicine all produce significant dose related cardiovascular
Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario NIG 2W1. Reprint requests to Dr. W.N. McDonell. This study was supported through funds from Pet Trust. Submitted June 12, 1990.
Can J Vet Res 1991; 55: 107-112
107
depression in the dog (1-3). Mechanisms whereby this cardiovascular depression may be minimized are of considerable clinical importance. Premedicant agents are often administered to dogs prior to general anesthesia to minimize stress and facilitate handling, to reduce induction and maintenance anesthetic agent requirements and to provide for smoother postanesthesia recovery. The phenothiazine tranquillizer acepromazine (ACP) has been widely used for many years to provide preanesthetic sedation in dogs (4). A major side effect of ACP is its dose dependent alpha1-adrenoreceptor antagonist activity which results in hypotension (4-8). It has been suggested that this effect is clinically insignificant until the intravenous dosage of ACP exceeds 0.4 mg/kg in halothane-anesthetized dogs (9). A reduction in the halothane minimum alveolar concentration (MAC) requirement occurs with intramuscular injection of clinical doses of ACP (10,11). However, the cardiorespiratory effects of the resultant halothane reduction have not been evaluated. A recent investigation into the use of a 5-hydroxytryptamine antagonist demonstrated that the agent actually potentiated the cardiovascular depressant effects of halothane, despite reducing the halothane requirement by 40% (12). The objective of this study was to compare the cardiovascular effects of halothane when used alone at increasing doses to those produced with equipotent doses of halothane after potentiation of the anesthetic effect with ACP sedation.
MATERIALS AND METHODS
Six mature mixed breed dogs (4 males, 2 females) weighing 19 to 23 kg were used. The animals were judged to be healthy based on history, physical examination, thoracic radiographs, and arterial blood gas, hematocrit and total protein determination. Individual animals were studied on three occasions in a random fashion with a minimum of seven days between exposures. The animals were maintained and the experiments were con108
ducted in accordance with the guidelines of the Canadian Council on Animal Care. On each study day anesthesia was induced by mask with halothane (Fluothane, Ayerst Laboratories, Montreal, Quebec) in oxygen (02). The trachea was intubated and anesthesia was maintained with halothane (1.2-1.5%) using a coaxial circuit system (Bain, Inter-City Medigas, Kitchener, Ontario) and a fresh gas flow of 200 mL 02/kg/min. The cephalic vein was catheterized for fluid administration (Plasmalyte 148, Travenol Canada Inc., Mississauga, Ontario) at a rate of 3 mL/kg/h. A 7F Swan-Ganz thermodilution catheter (American Edwards Laboratories, Irvine, California) was passed through the right heart into the pulmonary artery via the right jugular vein using a percutaneous sheath introducer set (Arrow International Inc., Reading, Pennsylvania). Correct catheter placement was verified with fluoroscopy and injection of a small amount of radio-opaque dye (Omnipaque® 300, Winthrop Laboratories, Aurora, Ontario). A catheter was inserted percutaneously into the dorsal pedal artery for blood pressure measurements and arterial blood sampling. Following animal preparation on each study day (mean anesthesia time 43 min, range 35 to 58 min), one of three treatments was administered by injection deep into the quadriceps muscle using a randomized Latin square design. The treatments were 1.0 mL 0.9% NaCl, 0.04 mg/kg ACP and 0.20 mg/kg ACP (Atravet®, Ayerst Laboratories, Montreal, Quebec). Positive pressure ventilation was instituted to maintain eucapnia. End tidal halothane and carbon dioxide (CO2) concentrations were monitored using an infrared gas analyzer (Datex Instrumentation Corp., Helsinki). The analyzer was calibrated before each experiment with a standardized calibration gas mixture (Puritan Bennet, Wilmington, Massachusetts) and the calibration was verified using a known halothane concentration (2.97% halothane in nitrogen) (Matheson Gas Products, Whitby, Ontario). Twenty-five minutes were allowed before the animals were stabilized at the first of three halothane MAC levels.
Cardiovascular measurements were recorded at 1.2, 1.45 and 1.7 MAC halothane, with a random sequence of exposure. The MAC of halothane was considered to be 1.04% (10,13) and the reduction in halothane requirements with both ACP doses was 45% as previously determined by Heard et al (10). The control dogs thus received 1.2, 1.5 and 1.8%, and the ACP treated dogs 0.7, 0.8 and 1.0% end tidal halothane concentration. Measurements were made following a 20 min stabilization period at each MAC level and repeat measurements were obtained 15 min later. This sequence was repeated for the second and third halothane MAC levels. Systolic (SBP), diastolic (DBP) and mean (MBP) arterial blood pressures, central venous pressure (CVP) and mean pulmonary arterial pressure (PAP) were recorded with ventilation momentarily suspended (Tektronix 414 Recorder, Tektronix Inc., Beaverton, Oregon). The zero reference for all pressure measurements was the sternal manubrium. Heart rate and rhythm were determined from continuous lead two electrocardiographic monitoring. Cardiac output (CO) determinations were made using the thermodilution technique (COM-2 Cardiac Output Computer, Edwards Laboratories, Santa Ana, California). An injectate volume of 5 mL of 51o dextrose in water, cooled on ice to 1-2°C was used. Injections were made during a period of apnoea produced by switching the ventilator off. At least three consecutive determinations were made at each time interval and the mean value of the three CO determinations was used as the value for that sampling period. Arterial and mixed venous blood samples were collected anaerobically in heparinized glass syringes and stored on ice until analyzed. Samples were analyzed at the end of each study by an automated digital blood gas machine (ABL3 MK2 Blood Microsystems, Radiometer, London, Ontario). Values were corrected to body temperature. Packed cell volume (microhematocrit) and total protein (refractometry) were determined for each sample. Cardiac index (CI), stroke index (SI), systemic vascular resistance (SVR), left ventricular work (LVW), oxygen content of arterial blood (CaO2) and oxygen delivery
DBP, MBP, CI, SI, LVW and Do2 decreased with increasing significantly 1. Cardiac index (CI) halothane (Tables II and IV). levels of = CO CI (mL/kg/min) Heart rate, CVP and PAP tended to BWt = cardiac output in mL/min Where CO increase with increasing levels of = body weight in kg BWt halothane, however, these changes were not statistically significant. 2. Stroke index (SI) Heart rate was significantly higher = CI SI (mL/kg/beat) with halothane alone than with either HR = heart rate in beats/min Where HR halothane-ACP combinations and was significantly higher with high dose 3. Left ventricular work (LVW) compared to low dose ACP ACP LVW (kg-m/min) = CO x MBP x 0.0135 (Table II). Systolic blood pressure = cardiac output in L/min Where CO MBP = mean arterial blood pressure in mmHg (Table III), MBP and SVO2 (Table IV) 0.0135 = conversion factor for L-mmHg to kg-m were lowest with halothane alone and highest with 0.2 mg/kg ACP, dif4. Systematic vascular resistance (SVR) ferences being significant for each = MBP-CVP x 79.9 SVR (dynes/sec/cm -5) treatment. Stroke index (Table II), CO = mean arterial blood pressure in mmHg Where MBP venous base excess and venous 'pH CVP = central venous pressure in mmHg (Table III) were significantly higher for CO = cardiac output in L/min both halothane-ACP combinations 79.9 = conversion factor for mmHg-min/L to dynes/sec/cm-5 than for halothane alone. End tidal 5. Oxygen content of arterial blood (CaO2) CO2, arterial PCO2 (Table III), PAP CaO2 (mL/L) = [(1.39 x Hb x SaO2) + (0.0031 X PaO2J X 10 (Table II), and VO2 were significantly = mLO2/1 .0 g fully saturated Hb Where 1.39 higher for those dogs exposed to = hemoglobin in g/dL Hb halothane alone than the ACP treated = arterial oxyhemoglobin saturation SaO2 dogs. Mixed venous PG2 levels were 0.0031 = solubility of 02 in whole blood as vol%/mmHg = partial pressure Of 02 in arterial blood in mmHg significantly higher in dogs receiving PaO2 0.2 mg/kg ACP than in those treated 6. Oxygen content of mixed venous blood (CVO2) with 0.04 mg/kg ACP or receiving = [(1.39 x Hb x SV02) + (0.0031 x PVO2)] x 10 CV02 (mL/L) halothane alone (Table III). None of = mixed venous oxyhemoglobin saturation Where Sv02 the other blood gas and acid-base = partial pressure Of 02 in mixed venous blood Pv02 parameters changed significantly. 7. Oxygen delivery (Do2) Cardiac index and Do (Table IV) CO X CaO2 Do2 (mL/min) tended to be lower wiih halothane Where CO cardiac output in mL/min alone than in both halothane-ACP 8. Oxygen uptake (Vo2) groups, particularly at the higher MAC CO (CaO2 Cv02) V02 (mL/min) levels, but these differences were not cardiac output in mL/min Where CO statistically significant. No differences or trends were noted in DBP, CVP, SVR, LVW, TP, or PCV values. (Do2) were calculated (Table I). Mixed A p value c0.05 was considered venous hemoglobin saturation (Sv02) significant. DISCUSSION was determined using a nomogram (Radiometer A/S, Copenhagan, The effect of halothane alone on RESULTS Denmark). Oxygen content of mixed cardiovascular parameters was similar venous blood and oxygen uptake No significant differences in the to previously reported studies in dogs (VO2) were derived from the measured measured or calculated cardiovascular (1,2). A temporal improvement in carand calculated data (Table I). The paired Student's t-test was used parameters were found between the diovascular function with duration of to statistically analyze for differences two sampling periods at each halo- halothane anesthesia has been reported between the two sampling periods at thane or halothane-ACP MAC level. in dogs (1). The dogs in this study were each MAC level and to evaluate the The results for these two sampling exposed to the three halothane MAC difference in the cardiovascular periods were thus combined for further levels in a random fashion in order to response to halothane alone at the analysis (n = 12). Body temperature reduce the influence of these temporal three MAC levels (15). The effects of and total protein decreased signifi- changes on our experimental results. treatment and MAC level were cantly between the 20 to 35 min sam- Reported effects of halothane on HR are variable. Heart rate is little examined statistically using a two-way pling period. Analysis of our results for the dogs influenced by anesthetic depth in analysis of variance (15). Differences between treatments were examined by exposed to halothane alone at increas- horses (15) and humans (16). In dogs Duncan's multiple range test (15). ing concentrations showed that SBP, HR has been said to remain constant TABLE I. Formulae used for calculations
=
=
=
=
-
C)
Co
Co a)
'a 0
2
a)
.0 '5
E2U
C;~ &.0
Co 0 V
.0 a)
0,
ABSTRACT The purpose of this study was to compare the cardiovascular effects of halothane when used alone at increasing doses (1.2, 1.45 and 1.7 minimum alveolar concentration, MAC) to those produced with equipotent doses of halothane after potentiation of the anesthetic effect with acepromazine (ACP) sedation (45% reduction of halothane MAC). Six healthy mature dogs were used on three occasions. The treatments were halothane and intramuscular (IM) saline (1.0 mL), halothane and ACP (0.04 mg/kg IM), or halothane and ACP (0.2 mg/kg IM). Anesthesia was induced and maintained with halothane in oxygen and the dogs were prepared for the collection of arterial and mixed venous blood and for the determination of heart rate, systolic, diastolic and mean arterial pressure, mean pulmonary artial pressure (PAP), central venous pressure and cardiac output. Following animal preparation the saline or ACP was administered and positive pressure ventilation instituted. Twentyfive minutes later the dogs were exposed to the first of three anesthetic levels, with random assignment of the sequence of administration. At each anesthetic level, measurements were obtained at 20 and 35 min. Calculated values included cardiac index, stroke index, left ventricular work, systemic vascular resistance, arterial oxygen content, mixed venous oxygen content, oxygen delivery and oxygen consumption. Heart rate was significantly higher with halothane alone than with both halothane-ACP combinations and was significantly higher with high
dose ACP compared to low dose ACP. Systolic and mean blood pressures were lowest with halothane alone and highest with 0.2 mg/kg ACP, the differences being significant for each treatment. Oxygen uptake and PAP were significantly lower in dogs treated with ACP. It was concluded that ACP does not potentiate the cardiovascular depression that accompanies halothane anesthesia when the resultant lower dose requirements of halothane are taken into consideration.
RESUME Le but de cette etude etait de comles effets cardio-vasculaires de l'halothane utilise seul a doses croissantes (1.2, 1.45 et 1.7 concentration alveolaire minimum, CAM) a ceux de doses equieffectives d'halothane apres potentialisation de l'effet anesthesique (45 /o de riduction du CAM de l'halothane) par une sedation a l'acepromazine (ACP). Six chiens matures et en bonne condition physique ont ete utilises a trois occasions. Les traitements consistaient en: halothane et saline (1 mL) intramusculaire (IM), halothane et ACP (0.04 mg/kg, IM) et halothane et ACP (0.2 mg/kg, IM). L'anesthesie a ete induite et maintenue par un melange d'halothane et d'oxygene et les chiens ont ete prepares pour la prise de sang arteriel et veineux ainsi que pour la determination de la frequence cardiaque, des pressions arterielles moyenne, systolique et diastolique, de la pression pulmonaire arterielle moyenne (PAP), de la pression veineuse centrale et du debit cardiaque. Une fois l'animal prepare, de parer
la saline ou de l'ACP etaient administrees et la ventilation A pression positive instituee. Apres vingt-cinq minutes les chiens etaient exposes au premier des trois niveaux d'anesthesie, suivant une sequence d'administration aleatoire. Des mesures furent prises a 20 et 35 minutes pour chacun des niveaux d'anesthesie. Les valeurs calculees etaient l'indice cardiaque, l'indice de travail systolique, le travail ventriculaire gauche, la resistance vasculaire systemique, la concentration en oxygene du sang arteriel et veineux, le relachement d'oxygene et la consommation d'oxygene. La frequence cardiaque etait significativement plus elev6e lorsque l'halothane etait utilise seul plutot qu'en combinaison avec l'ACP, et elle etait significativement plus dievee lorsque 1'ACP 6tait utilise A fortes doses plutot qu'A faibles doses. Les pressions sanguines moyenne et systolique etaient significativement plus faibles lorsque l'halothane etait utilise seul que lorsque combine avec 0.2 mg/kg d'ACP. La prise d'oxygene et la PAP etaient significativement inf6rieures chez les chiens traites avec I'ACP. II a ete conclu que l'ACP ne potentialise pas la dipression cardiovasculaire qui accompagne l'anesthesie A I'halothane lorsque l'on considere les doses minimales d'halothane requises. (Traduit par D' Helone H6on) INTRODUCTION Halothane and the other inhalation anesthetic agents commonly used in veterinary medicine all produce significant dose related cardiovascular
Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario NIG 2W1. Reprint requests to Dr. W.N. McDonell. This study was supported through funds from Pet Trust. Submitted June 12, 1990.
Can J Vet Res 1991; 55: 107-112
107
depression in the dog (1-3). Mechanisms whereby this cardiovascular depression may be minimized are of considerable clinical importance. Premedicant agents are often administered to dogs prior to general anesthesia to minimize stress and facilitate handling, to reduce induction and maintenance anesthetic agent requirements and to provide for smoother postanesthesia recovery. The phenothiazine tranquillizer acepromazine (ACP) has been widely used for many years to provide preanesthetic sedation in dogs (4). A major side effect of ACP is its dose dependent alpha1-adrenoreceptor antagonist activity which results in hypotension (4-8). It has been suggested that this effect is clinically insignificant until the intravenous dosage of ACP exceeds 0.4 mg/kg in halothane-anesthetized dogs (9). A reduction in the halothane minimum alveolar concentration (MAC) requirement occurs with intramuscular injection of clinical doses of ACP (10,11). However, the cardiorespiratory effects of the resultant halothane reduction have not been evaluated. A recent investigation into the use of a 5-hydroxytryptamine antagonist demonstrated that the agent actually potentiated the cardiovascular depressant effects of halothane, despite reducing the halothane requirement by 40% (12). The objective of this study was to compare the cardiovascular effects of halothane when used alone at increasing doses to those produced with equipotent doses of halothane after potentiation of the anesthetic effect with ACP sedation.
MATERIALS AND METHODS
Six mature mixed breed dogs (4 males, 2 females) weighing 19 to 23 kg were used. The animals were judged to be healthy based on history, physical examination, thoracic radiographs, and arterial blood gas, hematocrit and total protein determination. Individual animals were studied on three occasions in a random fashion with a minimum of seven days between exposures. The animals were maintained and the experiments were con108
ducted in accordance with the guidelines of the Canadian Council on Animal Care. On each study day anesthesia was induced by mask with halothane (Fluothane, Ayerst Laboratories, Montreal, Quebec) in oxygen (02). The trachea was intubated and anesthesia was maintained with halothane (1.2-1.5%) using a coaxial circuit system (Bain, Inter-City Medigas, Kitchener, Ontario) and a fresh gas flow of 200 mL 02/kg/min. The cephalic vein was catheterized for fluid administration (Plasmalyte 148, Travenol Canada Inc., Mississauga, Ontario) at a rate of 3 mL/kg/h. A 7F Swan-Ganz thermodilution catheter (American Edwards Laboratories, Irvine, California) was passed through the right heart into the pulmonary artery via the right jugular vein using a percutaneous sheath introducer set (Arrow International Inc., Reading, Pennsylvania). Correct catheter placement was verified with fluoroscopy and injection of a small amount of radio-opaque dye (Omnipaque® 300, Winthrop Laboratories, Aurora, Ontario). A catheter was inserted percutaneously into the dorsal pedal artery for blood pressure measurements and arterial blood sampling. Following animal preparation on each study day (mean anesthesia time 43 min, range 35 to 58 min), one of three treatments was administered by injection deep into the quadriceps muscle using a randomized Latin square design. The treatments were 1.0 mL 0.9% NaCl, 0.04 mg/kg ACP and 0.20 mg/kg ACP (Atravet®, Ayerst Laboratories, Montreal, Quebec). Positive pressure ventilation was instituted to maintain eucapnia. End tidal halothane and carbon dioxide (CO2) concentrations were monitored using an infrared gas analyzer (Datex Instrumentation Corp., Helsinki). The analyzer was calibrated before each experiment with a standardized calibration gas mixture (Puritan Bennet, Wilmington, Massachusetts) and the calibration was verified using a known halothane concentration (2.97% halothane in nitrogen) (Matheson Gas Products, Whitby, Ontario). Twenty-five minutes were allowed before the animals were stabilized at the first of three halothane MAC levels.
Cardiovascular measurements were recorded at 1.2, 1.45 and 1.7 MAC halothane, with a random sequence of exposure. The MAC of halothane was considered to be 1.04% (10,13) and the reduction in halothane requirements with both ACP doses was 45% as previously determined by Heard et al (10). The control dogs thus received 1.2, 1.5 and 1.8%, and the ACP treated dogs 0.7, 0.8 and 1.0% end tidal halothane concentration. Measurements were made following a 20 min stabilization period at each MAC level and repeat measurements were obtained 15 min later. This sequence was repeated for the second and third halothane MAC levels. Systolic (SBP), diastolic (DBP) and mean (MBP) arterial blood pressures, central venous pressure (CVP) and mean pulmonary arterial pressure (PAP) were recorded with ventilation momentarily suspended (Tektronix 414 Recorder, Tektronix Inc., Beaverton, Oregon). The zero reference for all pressure measurements was the sternal manubrium. Heart rate and rhythm were determined from continuous lead two electrocardiographic monitoring. Cardiac output (CO) determinations were made using the thermodilution technique (COM-2 Cardiac Output Computer, Edwards Laboratories, Santa Ana, California). An injectate volume of 5 mL of 51o dextrose in water, cooled on ice to 1-2°C was used. Injections were made during a period of apnoea produced by switching the ventilator off. At least three consecutive determinations were made at each time interval and the mean value of the three CO determinations was used as the value for that sampling period. Arterial and mixed venous blood samples were collected anaerobically in heparinized glass syringes and stored on ice until analyzed. Samples were analyzed at the end of each study by an automated digital blood gas machine (ABL3 MK2 Blood Microsystems, Radiometer, London, Ontario). Values were corrected to body temperature. Packed cell volume (microhematocrit) and total protein (refractometry) were determined for each sample. Cardiac index (CI), stroke index (SI), systemic vascular resistance (SVR), left ventricular work (LVW), oxygen content of arterial blood (CaO2) and oxygen delivery
DBP, MBP, CI, SI, LVW and Do2 decreased with increasing significantly 1. Cardiac index (CI) halothane (Tables II and IV). levels of = CO CI (mL/kg/min) Heart rate, CVP and PAP tended to BWt = cardiac output in mL/min Where CO increase with increasing levels of = body weight in kg BWt halothane, however, these changes were not statistically significant. 2. Stroke index (SI) Heart rate was significantly higher = CI SI (mL/kg/beat) with halothane alone than with either HR = heart rate in beats/min Where HR halothane-ACP combinations and was significantly higher with high dose 3. Left ventricular work (LVW) compared to low dose ACP ACP LVW (kg-m/min) = CO x MBP x 0.0135 (Table II). Systolic blood pressure = cardiac output in L/min Where CO MBP = mean arterial blood pressure in mmHg (Table III), MBP and SVO2 (Table IV) 0.0135 = conversion factor for L-mmHg to kg-m were lowest with halothane alone and highest with 0.2 mg/kg ACP, dif4. Systematic vascular resistance (SVR) ferences being significant for each = MBP-CVP x 79.9 SVR (dynes/sec/cm -5) treatment. Stroke index (Table II), CO = mean arterial blood pressure in mmHg Where MBP venous base excess and venous 'pH CVP = central venous pressure in mmHg (Table III) were significantly higher for CO = cardiac output in L/min both halothane-ACP combinations 79.9 = conversion factor for mmHg-min/L to dynes/sec/cm-5 than for halothane alone. End tidal 5. Oxygen content of arterial blood (CaO2) CO2, arterial PCO2 (Table III), PAP CaO2 (mL/L) = [(1.39 x Hb x SaO2) + (0.0031 X PaO2J X 10 (Table II), and VO2 were significantly = mLO2/1 .0 g fully saturated Hb Where 1.39 higher for those dogs exposed to = hemoglobin in g/dL Hb halothane alone than the ACP treated = arterial oxyhemoglobin saturation SaO2 dogs. Mixed venous PG2 levels were 0.0031 = solubility of 02 in whole blood as vol%/mmHg = partial pressure Of 02 in arterial blood in mmHg significantly higher in dogs receiving PaO2 0.2 mg/kg ACP than in those treated 6. Oxygen content of mixed venous blood (CVO2) with 0.04 mg/kg ACP or receiving = [(1.39 x Hb x SV02) + (0.0031 x PVO2)] x 10 CV02 (mL/L) halothane alone (Table III). None of = mixed venous oxyhemoglobin saturation Where Sv02 the other blood gas and acid-base = partial pressure Of 02 in mixed venous blood Pv02 parameters changed significantly. 7. Oxygen delivery (Do2) Cardiac index and Do (Table IV) CO X CaO2 Do2 (mL/min) tended to be lower wiih halothane Where CO cardiac output in mL/min alone than in both halothane-ACP 8. Oxygen uptake (Vo2) groups, particularly at the higher MAC CO (CaO2 Cv02) V02 (mL/min) levels, but these differences were not cardiac output in mL/min Where CO statistically significant. No differences or trends were noted in DBP, CVP, SVR, LVW, TP, or PCV values. (Do2) were calculated (Table I). Mixed A p value c0.05 was considered venous hemoglobin saturation (Sv02) significant. DISCUSSION was determined using a nomogram (Radiometer A/S, Copenhagan, The effect of halothane alone on RESULTS Denmark). Oxygen content of mixed cardiovascular parameters was similar venous blood and oxygen uptake No significant differences in the to previously reported studies in dogs (VO2) were derived from the measured measured or calculated cardiovascular (1,2). A temporal improvement in carand calculated data (Table I). The paired Student's t-test was used parameters were found between the diovascular function with duration of to statistically analyze for differences two sampling periods at each halo- halothane anesthesia has been reported between the two sampling periods at thane or halothane-ACP MAC level. in dogs (1). The dogs in this study were each MAC level and to evaluate the The results for these two sampling exposed to the three halothane MAC difference in the cardiovascular periods were thus combined for further levels in a random fashion in order to response to halothane alone at the analysis (n = 12). Body temperature reduce the influence of these temporal three MAC levels (15). The effects of and total protein decreased signifi- changes on our experimental results. treatment and MAC level were cantly between the 20 to 35 min sam- Reported effects of halothane on HR are variable. Heart rate is little examined statistically using a two-way pling period. Analysis of our results for the dogs influenced by anesthetic depth in analysis of variance (15). Differences between treatments were examined by exposed to halothane alone at increas- horses (15) and humans (16). In dogs Duncan's multiple range test (15). ing concentrations showed that SBP, HR has been said to remain constant TABLE I. Formulae used for calculations
=
=
=
=
-
C)
Co
Co a)
'a 0
2
a)
.0 '5
E2U
C;~ &.0
Co 0 V
.0 a)
0,
