Annals of the Royal College of Surgeons of England (1990) vol. 72, 250-252
Comparison of enflurane and halothane in hypotensive eye surgery Anne S Blyth
MB ChB FFARCSI
Senior Registrar
Division of Anaesthesia, Royal Infirmary, Glasgow
Roger L Hughes
MD FFARCS
Consultant Anaesthetist
Colin D Miller
MB ChB
FFARCS*
Registrar
Division of Anaesthesia, Stobhill General Hospital, Glasgow
Key words: Anaesthetics, volatile: enflurane, halothane; Hypotensive
Thirty patients undergoing elective eye surgery had anaesthesia induced with sodium thiopentone, suxamethonium and d-tubocurarine chloride. Patients were ventilated with nitrous oxide, oxygen and either halothane or enflurane. The volatile agents were used to decrease the systolic blood pressure to 80 mmHg. The volatile agent concentration in the blood was measured at 30 min intervals. Both agents were effective in producing hypotension, but enflurane was the more potent hypotensive agent in terms of MAC equivalents. There was no significant differences between the agents with respect to speed of recovery.
During anaesthesia with halothane, the occurrence of hypotension is mainly due to halothane's negative inotrophic action on the myocardium (1). Enflurane is increasingly being used as an alternative to halothane for repeat anaesthesia in order to reduce the incidence of intraoperative cardiac arrythmias and anaesthesia-associated hepatitis (2). Pharmacokinetic data would suggest that recovery from enflurane anaesthesia is faster than for comparable minimum alveolar concentration (MAC) equivalent doses of halothane. While their efficacy as hypotensive agents has been studied in ENT surgery (3), no data is available as to their effect on recovery in hypotensive eye surgery. Present appointment: Consultant Anaesthetist, Division of Anaesthesia, Stobhill General Hospital, Glasgow Present appointment and correspondence to: Dr Anne Blyth, Consultant Anaesthetist, Division of Anaesthesia, Western Infirmary, Glasgow G11 6NT *
eye surgery, recovery
The aim of this study was to compare the hypotensive effects of enflurane and halothane during eye surgery by measuring blood levels of each volatile agent during anaesthesia, and to compare the recovery from anaesthesia using a modification of Aldrete and Kroulik's recovery score (4).
Methods A series of 30 patients aged between 17 and 65 years presenting for elective ophthalmic surgery under general anaesthesia were studied. The trial was approved by the hospital ethical committee. Patients with significant cardiovascular diseases, epilepsy, halothane anaesthesia within the past 3 months, or a history of anaesthesia-related jaundice were excluded from the study. Premedication consisted of 10 mg oral diazepam and 5 mg oral droperidol given 60 min before the induction of anaesthesia. ECG monitoring was continuous from before the induction of anaesthesia until recovery. Blood pressure was measured in the anaesthetic room with a sphygmomanometer, and in theatre and recovery room with a Dinamap® (Criticon®) monitor. Anaesthesia was induced with sodium thiopentone 5 mg/kg intravenously (i.v.) Neuromuscular blockade was initially produced with suxamethonium 1 mg/kg i.v. (for tracheal intubation) and was maintained with d-tubocurarine chloride 0.5 mg/kg i.v. the larynx was sprayed with 4% lignocaine before intubation, after
Comparison of enflurane and halothane Table I. Recovery score
hypotensive
eye surgeiy
251
systolic blood pressure, duration of volatile agent administration, the recovery score at 35 min (Table III), or in the recovery scores at any 5 min interval up to 35 min after discontinuing the volatile agent. The mean maximum inspired volatile agent concentrations during the period of hypotensive anaesthesia were 3.2% and 2% for the enflurane and halothane groups, respectively. The mean inspired volatile agent concentrations per procedure were 2.S57% and 1.48% for the enflurane and halothane groups, respectively. Within each group there was a trend for the younger patients to require higher concentrations of volatile agent than the older patients in order to reach the target blood pressure, but this did not achieve statistical significance. The mean maximum blood concentrations (± one standard deviation) of volatile agent in each group were 12.8 (±5.5) mg/100 ml and 18.6 (±8.5) mg/100 ml in the halothane and enflurane groups, respectively. If these values are substituted in the following equation:
Motor Activity Able to move 4 extremities voluntarily or on command Able to move 2 extremities voluntarily or on command Able to move 0 extremities voluntarily or on command Respiration Breathes adequately Dyspnoea or limited breathing Apnoea Circulation BP±20% preoperative level (mmHg) BP±21-50 preoperative level (mmHg) BP±51% preoperative level (mmHg) Consciousness
Fully awake Arousable Not responding Colour Pink Pale Cyanosed Total
in
2
% volatile
agent =
0
10
which the lungs were ventilated with 10 ml/kg of 33% oxygen in nitrous oxide at a rate of 12 breaths/min. Patients were randomly allocated to receive either halothane (group I, n= 15) or enflurane (group II, n= 15) delivered from a temperature compensated vaporiser (Cyprane®). The volatile agent concentration (halothane 0-5%, enflurane 0-7%) was adjusted to produce a systolic blood pressure of 80 mmHg. Blood samples were taken before the induction of anaesthesia and at 30 min intervals until the end of the study period. The samples were analysed for halothane or enflurane using gas-liquid chromatography (5). The time from the induction of anaesthesia to the end of volatile anaesthesia was recorded. After surgery the rate of recovery from anaesthesia was assessed using a modification of the recovery score described by Aldrete and Kroulik (4) (Table I), in which 'circulation' was assessed by measuring the blood pressure rather than the heart rate. The score was measured at 5 min intervals for 35 min after discontinuing the volatile agent, or until the score reached 10. Data were analysed using Student's t-test and the Mann-Whitney U test. A P value of less than 0.05 was considered to be significant.
Results The operations performed are listed in Table II. There were no statistically significant differences between the groups with respect to age, preoperative
310
x B
0
2 1
1
V
1
x
Molecular
22.4
x
wt
273
where V= volatile agent concentration in the blood and B = blood gas partition coefficient, then vapour concentrations of 0.72% halothane and 1.35% enflurane are obtained. When these vapour concentrations are expressed as a ratio (E:H) of MAC equivalents, a value of 0.84:1 is obtained.
Discussion In this study the ratio of hypotensive effect to anaesthetic potency of the two volatile agents was greater with enflurane than halothane; the hypotensive effect of one MAC equivalent of halothane was the same as 0.84 MAC equivalent of enflurane. This is consistent with the findings of previous authors (6,7), that enflurane produces more marked hypotension in ventilated animals and humans than does halothane, due to enflurane's greater effect on systemic vascular resistance. There were no significant differences in recovery times between the two groups. This may be explained by the
Table II. Surgical procedures performed on each group Ophthalmic procedures performed Group I (halothane) 2 1 8 1 2 1
Bilateral trabeculectomy Dacrocystorhinostomy Intraocular lens implant Right trabeculectomy Bilateral iridectomy Pterygium removal
Group II (enflurane) Bilateral trabeculectomy Dacrocystorhinostomy Intraocular lens implant Right trabeculectomy and left peripheral iridectomy 1 Removal retrolental membrane 1 Right trabeculectomy
1 2 8 2
252
A S Blyth et al.
Table III. Age, systolic blood pressure, duration of volatile agent administration and recovery score at 35 min. Values are given as means ± (standard deviation)
Age (years) Systolic BP (mmHg) Duration of volatile agent administration (min) Recovery scores at 35 min
Group I (halothane)
Group II (enflurane)
48.0 (15.4) 129 (21.3)
53.2 (14.3) 131 (26.7)
70.0 (36.7) 8.93 (1.83)
72.3 (31.0) 9.2 ( 1.7)
long duration of volatile agent administration (mean 71.15 min) and the use of high concentrations of volatile agent (>1.5 MAC). As patient exposure to volatile anaesthetic agents lengthens, the volatile agents are increasingly sequestered in poorly perfused fatty tissues. The drug concentrations in those tissues will be increased by raising the inspired volatile agent concentration, increasing alveolar ventilation, increasing tissue perfusion, and prolonging the duration of drug exposure. As a result, when the administration of volatile agent is stopped, the rate of decrease in drug concentration in well-perfused tissues, particularly the brain, will be delayed and the rate of recovery from different volatile agents will be lengthened. The target cardiovascular parameters were achieved without difficulty in 27 of the patients; however, despite being ventilated with enflurane 7% or halothane 5%, three patients required additional ,-blockade. One patient in the halothane group (aged 36 years) and one patient in the enflurane group (aged 51 years) required 30 mg labetalol i.v. to reach the target blood pressure. One patient in the enflurane group (aged 17 years) required 1 mg propranolol i.v. to control a sinus tachycardia of 110 beats/min. This may reflect the decrease of baroreceptor responses with increasing age (8). Three patients in the halothane group developed nodal arrhythmia when the blood pressure reached 80 mmHg. This may reflect the sino-atrial node's greater sensitivity
to the arrhythmogenic effect of halothane (9). No other arrhythmias were noted. In conclusion, this trial showed that both halothane and enflurane are effective hypotensive agents for eye surgery. Enflurane appears to be the more potent hypotensive agent in terms of MAC equivalents. There were no significant advantages of either agent in terms of speed of recovery. The authors wish to thank the Nursing Staff of Stobhill Theatre Suite, Abbot Laboratories for their sponsorship, Dr R Watson for analysing the blood samples and Mrs C McNeill and Mrs J Scott for their secretarial assistance.
References I Prys-Roberts C, Lloyd JW, Kerr JH, Patterson TJS. Deliberate profound hypotension induced with halothane; studies of haemodynamics and pulmonary gas exchange. BrJr Anaesth 1974;46:105-16. 2 Blogg CE. Halothane and the liver: The problem revisited and made obsolete. Br Med Jr 1986;292:1691. 3 Eltringham Rl, Young PN, Fairbairn MI, Robinson JM. Hypotensive anaesthesia for microsurgery of the middle ear. A comparison between enflurane and halothane. Anaesthesia 1982;37: 1028-32. 4 Aldrete JA, Kroulik D. A post-anesthetic recovery score. Anesth Analg 1970;49:924-34. S Allot PR, Steward A, Mapleson WW. Determination of halothane in gas, blood and tissues by chemical extraction and gas chromatography P. BrJr Anaesth 1971;43:913-17. 6 Hughes RL, Campbell D, Fitch W. Effects of enflurane and halothane on liver blood flow and oxygen consumption in the greyhound. Br J Anaesth 1986;52: 1079-86. 7 Calverley RK, Smith NT, Prys-Roberts C, Eger EI, Jones CW. Cardiovascular effects of enflurane anesthesia during controlled ventilation in man. Anesth Analg 1978;57:612-28. 8 Bristow JD, Gribbin B, Honour AJ, Pickering TG, Sleight P. Diminished baroreflex sensitivity in high blood pressure and aging man. J Physiol 1969;202:45P-46P. 9 Merlos JR, Bosnjak ZJ, Purtock RV, Turner LA, Kampine JP. Halothane and enflurane effects on SA node cells.
Anesthesiology 1980;53:S143. Received 12 December 1989
Comparison of enflurane and halothane in hypotensive eye surgery Anne S Blyth
MB ChB FFARCSI
Senior Registrar
Division of Anaesthesia, Royal Infirmary, Glasgow
Roger L Hughes
MD FFARCS
Consultant Anaesthetist
Colin D Miller
MB ChB
FFARCS*
Registrar
Division of Anaesthesia, Stobhill General Hospital, Glasgow
Key words: Anaesthetics, volatile: enflurane, halothane; Hypotensive
Thirty patients undergoing elective eye surgery had anaesthesia induced with sodium thiopentone, suxamethonium and d-tubocurarine chloride. Patients were ventilated with nitrous oxide, oxygen and either halothane or enflurane. The volatile agents were used to decrease the systolic blood pressure to 80 mmHg. The volatile agent concentration in the blood was measured at 30 min intervals. Both agents were effective in producing hypotension, but enflurane was the more potent hypotensive agent in terms of MAC equivalents. There was no significant differences between the agents with respect to speed of recovery.
During anaesthesia with halothane, the occurrence of hypotension is mainly due to halothane's negative inotrophic action on the myocardium (1). Enflurane is increasingly being used as an alternative to halothane for repeat anaesthesia in order to reduce the incidence of intraoperative cardiac arrythmias and anaesthesia-associated hepatitis (2). Pharmacokinetic data would suggest that recovery from enflurane anaesthesia is faster than for comparable minimum alveolar concentration (MAC) equivalent doses of halothane. While their efficacy as hypotensive agents has been studied in ENT surgery (3), no data is available as to their effect on recovery in hypotensive eye surgery. Present appointment: Consultant Anaesthetist, Division of Anaesthesia, Stobhill General Hospital, Glasgow Present appointment and correspondence to: Dr Anne Blyth, Consultant Anaesthetist, Division of Anaesthesia, Western Infirmary, Glasgow G11 6NT *
eye surgery, recovery
The aim of this study was to compare the hypotensive effects of enflurane and halothane during eye surgery by measuring blood levels of each volatile agent during anaesthesia, and to compare the recovery from anaesthesia using a modification of Aldrete and Kroulik's recovery score (4).
Methods A series of 30 patients aged between 17 and 65 years presenting for elective ophthalmic surgery under general anaesthesia were studied. The trial was approved by the hospital ethical committee. Patients with significant cardiovascular diseases, epilepsy, halothane anaesthesia within the past 3 months, or a history of anaesthesia-related jaundice were excluded from the study. Premedication consisted of 10 mg oral diazepam and 5 mg oral droperidol given 60 min before the induction of anaesthesia. ECG monitoring was continuous from before the induction of anaesthesia until recovery. Blood pressure was measured in the anaesthetic room with a sphygmomanometer, and in theatre and recovery room with a Dinamap® (Criticon®) monitor. Anaesthesia was induced with sodium thiopentone 5 mg/kg intravenously (i.v.) Neuromuscular blockade was initially produced with suxamethonium 1 mg/kg i.v. (for tracheal intubation) and was maintained with d-tubocurarine chloride 0.5 mg/kg i.v. the larynx was sprayed with 4% lignocaine before intubation, after
Comparison of enflurane and halothane Table I. Recovery score
hypotensive
eye surgeiy
251
systolic blood pressure, duration of volatile agent administration, the recovery score at 35 min (Table III), or in the recovery scores at any 5 min interval up to 35 min after discontinuing the volatile agent. The mean maximum inspired volatile agent concentrations during the period of hypotensive anaesthesia were 3.2% and 2% for the enflurane and halothane groups, respectively. The mean inspired volatile agent concentrations per procedure were 2.S57% and 1.48% for the enflurane and halothane groups, respectively. Within each group there was a trend for the younger patients to require higher concentrations of volatile agent than the older patients in order to reach the target blood pressure, but this did not achieve statistical significance. The mean maximum blood concentrations (± one standard deviation) of volatile agent in each group were 12.8 (±5.5) mg/100 ml and 18.6 (±8.5) mg/100 ml in the halothane and enflurane groups, respectively. If these values are substituted in the following equation:
Motor Activity Able to move 4 extremities voluntarily or on command Able to move 2 extremities voluntarily or on command Able to move 0 extremities voluntarily or on command Respiration Breathes adequately Dyspnoea or limited breathing Apnoea Circulation BP±20% preoperative level (mmHg) BP±21-50 preoperative level (mmHg) BP±51% preoperative level (mmHg) Consciousness
Fully awake Arousable Not responding Colour Pink Pale Cyanosed Total
in
2
% volatile
agent =
0
10
which the lungs were ventilated with 10 ml/kg of 33% oxygen in nitrous oxide at a rate of 12 breaths/min. Patients were randomly allocated to receive either halothane (group I, n= 15) or enflurane (group II, n= 15) delivered from a temperature compensated vaporiser (Cyprane®). The volatile agent concentration (halothane 0-5%, enflurane 0-7%) was adjusted to produce a systolic blood pressure of 80 mmHg. Blood samples were taken before the induction of anaesthesia and at 30 min intervals until the end of the study period. The samples were analysed for halothane or enflurane using gas-liquid chromatography (5). The time from the induction of anaesthesia to the end of volatile anaesthesia was recorded. After surgery the rate of recovery from anaesthesia was assessed using a modification of the recovery score described by Aldrete and Kroulik (4) (Table I), in which 'circulation' was assessed by measuring the blood pressure rather than the heart rate. The score was measured at 5 min intervals for 35 min after discontinuing the volatile agent, or until the score reached 10. Data were analysed using Student's t-test and the Mann-Whitney U test. A P value of less than 0.05 was considered to be significant.
Results The operations performed are listed in Table II. There were no statistically significant differences between the groups with respect to age, preoperative
310
x B
0
2 1
1
V
1
x
Molecular
22.4
x
wt
273
where V= volatile agent concentration in the blood and B = blood gas partition coefficient, then vapour concentrations of 0.72% halothane and 1.35% enflurane are obtained. When these vapour concentrations are expressed as a ratio (E:H) of MAC equivalents, a value of 0.84:1 is obtained.
Discussion In this study the ratio of hypotensive effect to anaesthetic potency of the two volatile agents was greater with enflurane than halothane; the hypotensive effect of one MAC equivalent of halothane was the same as 0.84 MAC equivalent of enflurane. This is consistent with the findings of previous authors (6,7), that enflurane produces more marked hypotension in ventilated animals and humans than does halothane, due to enflurane's greater effect on systemic vascular resistance. There were no significant differences in recovery times between the two groups. This may be explained by the
Table II. Surgical procedures performed on each group Ophthalmic procedures performed Group I (halothane) 2 1 8 1 2 1
Bilateral trabeculectomy Dacrocystorhinostomy Intraocular lens implant Right trabeculectomy Bilateral iridectomy Pterygium removal
Group II (enflurane) Bilateral trabeculectomy Dacrocystorhinostomy Intraocular lens implant Right trabeculectomy and left peripheral iridectomy 1 Removal retrolental membrane 1 Right trabeculectomy
1 2 8 2
252
A S Blyth et al.
Table III. Age, systolic blood pressure, duration of volatile agent administration and recovery score at 35 min. Values are given as means ± (standard deviation)
Age (years) Systolic BP (mmHg) Duration of volatile agent administration (min) Recovery scores at 35 min
Group I (halothane)
Group II (enflurane)
48.0 (15.4) 129 (21.3)
53.2 (14.3) 131 (26.7)
70.0 (36.7) 8.93 (1.83)
72.3 (31.0) 9.2 ( 1.7)
long duration of volatile agent administration (mean 71.15 min) and the use of high concentrations of volatile agent (>1.5 MAC). As patient exposure to volatile anaesthetic agents lengthens, the volatile agents are increasingly sequestered in poorly perfused fatty tissues. The drug concentrations in those tissues will be increased by raising the inspired volatile agent concentration, increasing alveolar ventilation, increasing tissue perfusion, and prolonging the duration of drug exposure. As a result, when the administration of volatile agent is stopped, the rate of decrease in drug concentration in well-perfused tissues, particularly the brain, will be delayed and the rate of recovery from different volatile agents will be lengthened. The target cardiovascular parameters were achieved without difficulty in 27 of the patients; however, despite being ventilated with enflurane 7% or halothane 5%, three patients required additional ,-blockade. One patient in the halothane group (aged 36 years) and one patient in the enflurane group (aged 51 years) required 30 mg labetalol i.v. to reach the target blood pressure. One patient in the enflurane group (aged 17 years) required 1 mg propranolol i.v. to control a sinus tachycardia of 110 beats/min. This may reflect the decrease of baroreceptor responses with increasing age (8). Three patients in the halothane group developed nodal arrhythmia when the blood pressure reached 80 mmHg. This may reflect the sino-atrial node's greater sensitivity
to the arrhythmogenic effect of halothane (9). No other arrhythmias were noted. In conclusion, this trial showed that both halothane and enflurane are effective hypotensive agents for eye surgery. Enflurane appears to be the more potent hypotensive agent in terms of MAC equivalents. There were no significant advantages of either agent in terms of speed of recovery. The authors wish to thank the Nursing Staff of Stobhill Theatre Suite, Abbot Laboratories for their sponsorship, Dr R Watson for analysing the blood samples and Mrs C McNeill and Mrs J Scott for their secretarial assistance.
References I Prys-Roberts C, Lloyd JW, Kerr JH, Patterson TJS. Deliberate profound hypotension induced with halothane; studies of haemodynamics and pulmonary gas exchange. BrJr Anaesth 1974;46:105-16. 2 Blogg CE. Halothane and the liver: The problem revisited and made obsolete. Br Med Jr 1986;292:1691. 3 Eltringham Rl, Young PN, Fairbairn MI, Robinson JM. Hypotensive anaesthesia for microsurgery of the middle ear. A comparison between enflurane and halothane. Anaesthesia 1982;37: 1028-32. 4 Aldrete JA, Kroulik D. A post-anesthetic recovery score. Anesth Analg 1970;49:924-34. S Allot PR, Steward A, Mapleson WW. Determination of halothane in gas, blood and tissues by chemical extraction and gas chromatography P. BrJr Anaesth 1971;43:913-17. 6 Hughes RL, Campbell D, Fitch W. Effects of enflurane and halothane on liver blood flow and oxygen consumption in the greyhound. Br J Anaesth 1986;52: 1079-86. 7 Calverley RK, Smith NT, Prys-Roberts C, Eger EI, Jones CW. Cardiovascular effects of enflurane anesthesia during controlled ventilation in man. Anesth Analg 1978;57:612-28. 8 Bristow JD, Gribbin B, Honour AJ, Pickering TG, Sleight P. Diminished baroreflex sensitivity in high blood pressure and aging man. J Physiol 1969;202:45P-46P. 9 Merlos JR, Bosnjak ZJ, Purtock RV, Turner LA, Kampine JP. Halothane and enflurane effects on SA node cells.
Anesthesiology 1980;53:S143. Received 12 December 1989
