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Effect of alfentanil on hypnotic and antinociceptive components of thiopental sodium anesthesia
JO qldap tsuogxxalu!
s8mp
.eIsaylsaue tsawmuq_nzq ‘:sp!o!dO
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Alfentanil-thiopental anesthetic interactions: Mehta et al.
Introduction A small dose of an opioid usually is used in combination with thiopental sodium for induction of anesthesia to suppress the intubation response.‘,” Dundee et cd3 have reported that a small dose of fentanyl(lO0 pg per patient) or alfentanil (300 Fg) reduced the titrated dose of thiopental required to abolish the eyelash reflex. This result suggests that the addition of an opioid can contribute not only to suppression of the nociceptive reflexes, but also to the hypnotic effect of thiopental. Thiopental-fentanyl and thiopentalmorphine hypnotic synergism also have been demonstrated in animal experiments.4 The aim of the present study was to compare the effects of alfentanil on hypnotic and antinociceptive components of thiopental anesthesia. The authors suggest that the addition of alfentanil to thiopental would result in different
outcomes
for
these
2 components.
Materials and Methods Eighty unpremeditated, ASA physical status I or II adult female patients scheduled for various surgeries participated in the study that was approved by the Institutional Review Board for Human Use of the University of Alabama at Birmingham. Patients’ ages ranged from 18 to 60 years, with a weight range of 50 to 90 kg. Those who had received opioids or sedatives within 1 month of the investigation were excluded from the study. The following 3 endpoints of anesthesia were determined: Eye opening in the response to voice command (EOVC) was determined 1 minute after injection of thiopental sodium. Absence of the response to 2 consecutive voice commands was regarded as a positive response to the agent(s). If the EOVC was blocked, the next endpoint was tested. Eye opening in the response to noxious stimulation (EONS). Pressure on the trapezius muscle was used as the stimulation.5.” With the use of a Pressure Threshold Meter (Pain Diagnostics and Thermography Co., Great Neck, NY), the pressure of 10 kg/cm2 was held against the muscle for 30 seconds (this pressure was well above the pain threshold for this area, 4.2 -+ 1.2 kg/cm’). If the eyes were opened, the application of pressure was stopped. Purposeful movement in the response to noxious stimulation (PMNS). Any purposeful movement with closed eyes during the pressure on the trapezius muscle was considered a positive response to the stimulation.
Patients were assigned to 1 of 2 groups: salinethiopental and alfentanil-thiopental. The patients of each group were divided into 8 subgroups of 5 patients with predetermined doses of drug(s) in each subgroup. The thiopental dose range was from 2 mg/ kg to 6 mg/kg in the saline-thiopental group, and from 1 mg/kg to 5 mg/kg in the alfentanil-thiopental group, with an alfentanil fixed dose of 0.01 mg/kg. Dose selection was made randomly with blocked allocation of patients. The person who determined the responses was blinded to the patient group or subgroup. Drugs were injected intravenously in a volume of 10 ml into a rapidly flowing intravenous (IV) infusion via the port nearest the IV catheter over 15 seconds. In the saline-thiopental group, saline (10 ml) was injected first, followed 1 minute later by thiopental. The response to the verbal command was determined 1 minute after the injection, followed by the determination of the responses to the pressure. In the alfentanil-thiopental group, alfentanil was injected first, followed 1 minute later by thiopental. The responses were determined at the same time intervals as in the first group. After the endpoints were determined, all patients received additional doses of thiopental, if needed, to assure that anesthesia was adequate before injection of succinylcholine chloride for intubation. For each of the 3 endpoints, the percentages of patients unable to respond was converted into probit values and plotted against logarithmic values for the respective doses. Dose-response curves and EDs0 values were determined with the use of probit analysis.7 Differences between the ED5o values were compared by using pairwise t-test on the log ED5o values.
Results The study groups were comparable with respect to age and weight (Table 1). Figure 1 represents the thiopental dose-response curves for the 3 endpoints with and without the addition of 0.01 mg/kg alfentanil. The thiopental ED,, values obtained from these curves are presented in Table 2. For EOVC, the ED,, value
Table
1.
Characteristics
Variable
of Patients
Saline-Thiopental Group
AlfentanilThiopental Group
40 31 k 7*
n (all females) Age (years) Weight (kg) Race (Black/White)
65 ? 11* 26114
40 32 k 5 69 k 12
22118
*Mean k SD.
J. Clin.
Anesth.,
vol. 3, July/August
1991
281
I
I
I
I
I
I
1
1.5
2
3
4
6
THIOPENTAL (mg - kg-l) 1. Thiopental dose-response curves for different endpoints of anesthesia with and without the addition of alfentanil. Shown along the vertical axis are the percentage of patients (on a probit scale) that reached the specified endpoints; along the horizontal axis, the dose of thiopental (on a log scale). EOVC (circles) represents eye opening response to verbal command; EONS (squares) represents eye opening response to noxious stimulation (pressure on the trapezius muscle); and PMNS (triangles) represents purposeful movement response to noxious stimulation. Each symbol (circle, square, or triangle) represents the effect in a subgroup of 5 patients at the indicated dosage. Arrows superimposed on symbols indicate that their actual locations are higher or lqwer (restriction due to probit scale of the figure). Broken lines represent dose-response curves with the addition of alfentanil 0.01 mg/kg. Figure
was 2.6 mglkg (95% confidence limits, 2.2 and 2.8 mgl kg); for EONS, the ED,,, was 3.2 (2.8, 3.5) mg/kg; and for PMNS, the ED-,,, was 4.2 (3.8, 4.7) mg/kg. The addition of alfentanil shifted the thiopental dose-response curves for all 3 endpoints to the left along the dose axis. As a result, the ED,, values were decreased to 1.9 mg/kg (p < 0.02) for EOVC, 1.9 mg/kg (p < 0.0005) for EONS, and 2.4 mg/kg (p < 0.0001) for PMNS. The increase in the thiopental potency for PMNS was significantly greater than that for EOVC (75% 7~s 36%; p = 0.02, Figure 21, which indicates that alfen282
.J. Clin. Anesth.. vol. 3, .July/August 1991
tanil potentiates the suppression of the nociceptive reflexes by thiopental to a greater extent than does the hypnotic effect of thiopental.
Discussion Thiopental ED,,, values obtained in this study are comparable to those reported in the literature. The thiopental ED,,, value for the loss of consciousness, 2.6 mg/kg, is close to the ED,,, values for the same endpoint reported by Stella et aLx and Tverskoy et al.,”
Alfentanil-thiopental anesthetic interactions: Mehta et al. Table 2.
Effect
of Alfentanil
(0.01
EOVC
EONS
PMNS
ED,,,
2.0 (1.5, 2.4)
ED,,, ED,,,
2.6 (2.2, 3.1 (2.8,
2.8) 4.1)
1.6 (1.1, 1.9 (1.6, 2.4 (2.1,
1.8) 2.2) 3.2)
ED,,, ED,,, ED,,
2.5 (1.9, 3.2 (2.8, 4.0 (3.6,
2.8) 3.5) 5.2)
1.5 (1.1, 1.9 (1.6, 2.4 (2.1,
1.8) 2.2) 3.2)
ED,,
3.2 (2.4, 4.2 (3.8, 5.6 (5.0,
3.6) 4.7) 7.4)
1.8 (1.3, 2.4 (2.1, 3.2 (2.8,
2.1) 2.8) 4.2)
EOVC
= blockade of eye opening response to verbal command. = blockade of eye opening response to noxious
PMNS
= blockade of purposeful indicate
95% confidence
& f 80 t? 1 58 40 E l.: 20 P 2 PMNS
$ p = 0.02 from EOVC t p = 0.06 from EOVC
2. Comparison
of the alfentanil-induced
changes
in thiopental potency regarding different endpoints of anesthesia. EOVC, eye opening response to verbal command; and
EONS, PMNS,
eye opening purposeful
response
to noxious
movement
response
stimulation; to
noxious
stimulation.
2.2 mg/kg and 2.9 mg/kg, respectively.
stimulation.
movement response to noxious stimulation.
~80
EONS
Potency
Alfentanil
EONS
EOVC
Anesthetic
Saline
ED,,, ED,,,
Numbers in parentheses
Figure
on Thiopental
Thiopental (mg/kg)
Level of Response
Endpoint
*0
mg/kg)
The thiopental EDSo value of 4.2 mg/kg for prevention of movement response to the painful pressure on the trapezius muscle correlates well with the thiopental ED,o value of 3.7 mg/kg for loss of movement response to trapezius muscle squeeze reported by Brett and Fisher.” The present thiopental ED,, value of 3.2 mg/kg for loss of the eye opening response to the painful pressure of
limits.
the trapezius muscle was less than that for the movement of extremities in response to the pressure (4.2 mg/kg), indicating that the eye opening reflex to noxious stimulation is more sensitive to thiopental. Alfentanil strengthened both the hypnotic and antinociceptive components of thiopental anesthesia, although to a different degree: it strengthened the antinociceptive component more so than the hypnotic. With the addition of alfentanil, the thiopental potency for blockade of the eye opening response to verbal command (hypnosis) was increased by 36% at a time when thiopental potency value for blockade of purposeful movement response to noxious stimulation was increased to a greater degree, 75% (p = 0.02 for the difference). Alfentanil strengthened the effects of thiopental in a dose of 0.01 mg/kg. This dose constitutes only l/13 of the alfentanil ED,,, value for the loss of consciousness, 130 pg/kg.lO At the same time, 0.01 mg/kg of alfentanil is already a borderline analgesic dose. In a previous study,” alfentanil was found to increase the pain threshold to pressure on the trapezius muscle starting with a dose of 0.01 mg/ kg. Therefore, the more distinct contribution of alfentanilO.0 1 mg/kg to the antinociceptive component of anesthesia compared with the hypnotic component seems logical. At the same time, it should be taken into consideration that the antianalgesic effect of thiopentallz,ls might decrease, at least to some degree, the antinociceptive contribution of alfentanil. Alfentanil has been found to profoundly potentiate the hypnotic effect of midazolam.” In comparison to this effect, alfentanil-induced potentiation of the hypnotic action of thiopental is rather mild. Compare a J. Clin. Anesth., vol. 3, July/August 1991
283
Table 3. Thiopental
No ALF
ALF
hI;wtitl DE, Rosenberg H. I\ukbtlrg SJ. et al: l.o\~(Io\t. lent;~t~vl bluiitb c-irculaton resporises to tidw~l i~iti~txttion. .-\twd~ .\rulg 3982;61:680-4. 3. Dundee JW’. Hallida\ F,!, MCMUI-ray ‘I:], Harper Kit’: l‘he effect on thiopelltal Pi-etreatriient with opioitis. intluc tion ;uitl on the onset oi action of niida/ol;iirl. ‘) _.
Potentiatiorl of’ the Hypnotic Ef’frc 15 of and Midazolam by Alfenranil
Increase in Potency (%)
, \~u~.\/ku\icrI CC-if;41: 1,!I!)-ti 1. MidaLolam t E&, (mg/kg) Thiopental$ ED-,,, (mg/kg)
0.270
0.125”
116
2.6
1.9**
36
ALF = Alfentanil. * = ti mcgikg alferltanil. ** = 10 mcg/kg alfentanil.
tlkr.
II.
$This study.
116% alfentanil-induced increase in the midazolam hypnotic potency with a 36% increase in the thiopental hypnotic potency (Table ?). Enhancement of the hypnotic effect of thiopental by opioids was reported in several studies.“,” In one of the studies,” alfentanil in a small dose of 300 kg (per patient) reduced the titrated dose of thiopental required to abolish the eyelash reflex by 18%, which is comparable to the decrease of the thiopental ED,,, for the hypnotic effect reported here. The effect of alfentanil on the antinociceptive component of thiopental anesthesia is more significant and, therefore, has an important clinical implication: the decrease in the dose of thiopental necessary for blockade of movement response to noxious stimulation (from ED,, of 5.6 mgikg to 3.2 mg/ kg) suggests the possibility of a faster and more complete recovery from anesthesia. In conclusion, alfentanil enhances both the antinociceptive and hypnotic components of thiopental anesthesia but to a different degree, its contribution to antinociception was more pronounced.
References 1. Dahlgren
N, Messeter K: Treatment of stress response to laryngoscopy and intubation with fentanyl. Anaesthesis 1981;36: 1022-6.
284
J. Clin. Anesth.,
vol. 3, July/August
1991
-I. Kissin 1, Masor~.JO, Hradlev EL Jr.: Morphine and tenrar~yl hypnotic interactions with thiopental. .4~rc/kr\& o’q I9H7:67:331-5. 5. Becker KE: Plasma levels of thiopental necessar) tor anesthesia. ,4n~cthesiolo~q 1978349: 192-6. 6. Brett CM, Fisher DM: Thiopental dose-response relations in nnpremedicated infants, children, and adults. .-\,~#i At$g 1987;66: 1024-27. 7. bhiey (Iambridge DJ: !‘r(Jhil L~r~ct/y.ri.c, 3rd rd. London: CJni\ersity Press, 197 1.. 8. St& I,, Torri (;. Castiglioni CL: ‘I‘he relative potencies of’thiopentone. ketamine, propanidid, alphaxalone and diazepani. HI- / Artcr~tfh 1979;5 1: 119-22. 9. l‘verskoy M, ‘Fleyshman G, Bradley EL. Jr, Kissin I: ~lida~ol;lm-thiopental anesthetic interac&ns in IXtients. ,4t~& .4~ulg 1988;67:342-5. 0. \‘inik HR, Hradlev EL .Jr, Kissin I: Midazolam-alfentanil synergism for anesthetic induction in patients.
Armth Aru1g 3989;69:213-17. 1. Kissin I, Vinik HK, Castillo R, Bradley EL Jr: Alfentarlil potentiates midazolam-induced unconsciousness in subanalgesic- doses. Amsth Arzalg 1990:71:65-Y. 2. (:lutton-Kroc-k.J: Some pain threshold studies with particular reference to thiopentone. Ananthiu 1960; 15:7 l2. 13. Dundee JW: Alterations in response to sonlatic pail1 associated with anaesthesia. II: The effect of thiopenI-&. tone and pentobarbitone. HrJ Anarsth 1960;32:40714. Horrigan RW, Moyers JR, Johnson BH, Eger EI, II, Margolis A, (Coldsmith s: Etomidate vs. thiopental with and without fentanyl-a comparative study of awakening in III~. Anccthukdo,g 1980;52:362-4.
s8mp
.eIsaylsaue tsawmuq_nzq ‘:sp!o!dO
fe!sayisaue :sp.tomda~
Alfentanil-thiopental anesthetic interactions: Mehta et al.
Introduction A small dose of an opioid usually is used in combination with thiopental sodium for induction of anesthesia to suppress the intubation response.‘,” Dundee et cd3 have reported that a small dose of fentanyl(lO0 pg per patient) or alfentanil (300 Fg) reduced the titrated dose of thiopental required to abolish the eyelash reflex. This result suggests that the addition of an opioid can contribute not only to suppression of the nociceptive reflexes, but also to the hypnotic effect of thiopental. Thiopental-fentanyl and thiopentalmorphine hypnotic synergism also have been demonstrated in animal experiments.4 The aim of the present study was to compare the effects of alfentanil on hypnotic and antinociceptive components of thiopental anesthesia. The authors suggest that the addition of alfentanil to thiopental would result in different
outcomes
for
these
2 components.
Materials and Methods Eighty unpremeditated, ASA physical status I or II adult female patients scheduled for various surgeries participated in the study that was approved by the Institutional Review Board for Human Use of the University of Alabama at Birmingham. Patients’ ages ranged from 18 to 60 years, with a weight range of 50 to 90 kg. Those who had received opioids or sedatives within 1 month of the investigation were excluded from the study. The following 3 endpoints of anesthesia were determined: Eye opening in the response to voice command (EOVC) was determined 1 minute after injection of thiopental sodium. Absence of the response to 2 consecutive voice commands was regarded as a positive response to the agent(s). If the EOVC was blocked, the next endpoint was tested. Eye opening in the response to noxious stimulation (EONS). Pressure on the trapezius muscle was used as the stimulation.5.” With the use of a Pressure Threshold Meter (Pain Diagnostics and Thermography Co., Great Neck, NY), the pressure of 10 kg/cm2 was held against the muscle for 30 seconds (this pressure was well above the pain threshold for this area, 4.2 -+ 1.2 kg/cm’). If the eyes were opened, the application of pressure was stopped. Purposeful movement in the response to noxious stimulation (PMNS). Any purposeful movement with closed eyes during the pressure on the trapezius muscle was considered a positive response to the stimulation.
Patients were assigned to 1 of 2 groups: salinethiopental and alfentanil-thiopental. The patients of each group were divided into 8 subgroups of 5 patients with predetermined doses of drug(s) in each subgroup. The thiopental dose range was from 2 mg/ kg to 6 mg/kg in the saline-thiopental group, and from 1 mg/kg to 5 mg/kg in the alfentanil-thiopental group, with an alfentanil fixed dose of 0.01 mg/kg. Dose selection was made randomly with blocked allocation of patients. The person who determined the responses was blinded to the patient group or subgroup. Drugs were injected intravenously in a volume of 10 ml into a rapidly flowing intravenous (IV) infusion via the port nearest the IV catheter over 15 seconds. In the saline-thiopental group, saline (10 ml) was injected first, followed 1 minute later by thiopental. The response to the verbal command was determined 1 minute after the injection, followed by the determination of the responses to the pressure. In the alfentanil-thiopental group, alfentanil was injected first, followed 1 minute later by thiopental. The responses were determined at the same time intervals as in the first group. After the endpoints were determined, all patients received additional doses of thiopental, if needed, to assure that anesthesia was adequate before injection of succinylcholine chloride for intubation. For each of the 3 endpoints, the percentages of patients unable to respond was converted into probit values and plotted against logarithmic values for the respective doses. Dose-response curves and EDs0 values were determined with the use of probit analysis.7 Differences between the ED5o values were compared by using pairwise t-test on the log ED5o values.
Results The study groups were comparable with respect to age and weight (Table 1). Figure 1 represents the thiopental dose-response curves for the 3 endpoints with and without the addition of 0.01 mg/kg alfentanil. The thiopental ED,, values obtained from these curves are presented in Table 2. For EOVC, the ED,, value
Table
1.
Characteristics
Variable
of Patients
Saline-Thiopental Group
AlfentanilThiopental Group
40 31 k 7*
n (all females) Age (years) Weight (kg) Race (Black/White)
65 ? 11* 26114
40 32 k 5 69 k 12
22118
*Mean k SD.
J. Clin.
Anesth.,
vol. 3, July/August
1991
281
I
I
I
I
I
I
1
1.5
2
3
4
6
THIOPENTAL (mg - kg-l) 1. Thiopental dose-response curves for different endpoints of anesthesia with and without the addition of alfentanil. Shown along the vertical axis are the percentage of patients (on a probit scale) that reached the specified endpoints; along the horizontal axis, the dose of thiopental (on a log scale). EOVC (circles) represents eye opening response to verbal command; EONS (squares) represents eye opening response to noxious stimulation (pressure on the trapezius muscle); and PMNS (triangles) represents purposeful movement response to noxious stimulation. Each symbol (circle, square, or triangle) represents the effect in a subgroup of 5 patients at the indicated dosage. Arrows superimposed on symbols indicate that their actual locations are higher or lqwer (restriction due to probit scale of the figure). Broken lines represent dose-response curves with the addition of alfentanil 0.01 mg/kg. Figure
was 2.6 mglkg (95% confidence limits, 2.2 and 2.8 mgl kg); for EONS, the ED,,, was 3.2 (2.8, 3.5) mg/kg; and for PMNS, the ED-,,, was 4.2 (3.8, 4.7) mg/kg. The addition of alfentanil shifted the thiopental dose-response curves for all 3 endpoints to the left along the dose axis. As a result, the ED,, values were decreased to 1.9 mg/kg (p < 0.02) for EOVC, 1.9 mg/kg (p < 0.0005) for EONS, and 2.4 mg/kg (p < 0.0001) for PMNS. The increase in the thiopental potency for PMNS was significantly greater than that for EOVC (75% 7~s 36%; p = 0.02, Figure 21, which indicates that alfen282
.J. Clin. Anesth.. vol. 3, .July/August 1991
tanil potentiates the suppression of the nociceptive reflexes by thiopental to a greater extent than does the hypnotic effect of thiopental.
Discussion Thiopental ED,,, values obtained in this study are comparable to those reported in the literature. The thiopental ED,,, value for the loss of consciousness, 2.6 mg/kg, is close to the ED,,, values for the same endpoint reported by Stella et aLx and Tverskoy et al.,”
Alfentanil-thiopental anesthetic interactions: Mehta et al. Table 2.
Effect
of Alfentanil
(0.01
EOVC
EONS
PMNS
ED,,,
2.0 (1.5, 2.4)
ED,,, ED,,,
2.6 (2.2, 3.1 (2.8,
2.8) 4.1)
1.6 (1.1, 1.9 (1.6, 2.4 (2.1,
1.8) 2.2) 3.2)
ED,,, ED,,, ED,,
2.5 (1.9, 3.2 (2.8, 4.0 (3.6,
2.8) 3.5) 5.2)
1.5 (1.1, 1.9 (1.6, 2.4 (2.1,
1.8) 2.2) 3.2)
ED,,
3.2 (2.4, 4.2 (3.8, 5.6 (5.0,
3.6) 4.7) 7.4)
1.8 (1.3, 2.4 (2.1, 3.2 (2.8,
2.1) 2.8) 4.2)
EOVC
= blockade of eye opening response to verbal command. = blockade of eye opening response to noxious
PMNS
= blockade of purposeful indicate
95% confidence
& f 80 t? 1 58 40 E l.: 20 P 2 PMNS
$ p = 0.02 from EOVC t p = 0.06 from EOVC
2. Comparison
of the alfentanil-induced
changes
in thiopental potency regarding different endpoints of anesthesia. EOVC, eye opening response to verbal command; and
EONS, PMNS,
eye opening purposeful
response
to noxious
movement
response
stimulation; to
noxious
stimulation.
2.2 mg/kg and 2.9 mg/kg, respectively.
stimulation.
movement response to noxious stimulation.
~80
EONS
Potency
Alfentanil
EONS
EOVC
Anesthetic
Saline
ED,,, ED,,,
Numbers in parentheses
Figure
on Thiopental
Thiopental (mg/kg)
Level of Response
Endpoint
*0
mg/kg)
The thiopental EDSo value of 4.2 mg/kg for prevention of movement response to the painful pressure on the trapezius muscle correlates well with the thiopental ED,o value of 3.7 mg/kg for loss of movement response to trapezius muscle squeeze reported by Brett and Fisher.” The present thiopental ED,, value of 3.2 mg/kg for loss of the eye opening response to the painful pressure of
limits.
the trapezius muscle was less than that for the movement of extremities in response to the pressure (4.2 mg/kg), indicating that the eye opening reflex to noxious stimulation is more sensitive to thiopental. Alfentanil strengthened both the hypnotic and antinociceptive components of thiopental anesthesia, although to a different degree: it strengthened the antinociceptive component more so than the hypnotic. With the addition of alfentanil, the thiopental potency for blockade of the eye opening response to verbal command (hypnosis) was increased by 36% at a time when thiopental potency value for blockade of purposeful movement response to noxious stimulation was increased to a greater degree, 75% (p = 0.02 for the difference). Alfentanil strengthened the effects of thiopental in a dose of 0.01 mg/kg. This dose constitutes only l/13 of the alfentanil ED,,, value for the loss of consciousness, 130 pg/kg.lO At the same time, 0.01 mg/kg of alfentanil is already a borderline analgesic dose. In a previous study,” alfentanil was found to increase the pain threshold to pressure on the trapezius muscle starting with a dose of 0.01 mg/ kg. Therefore, the more distinct contribution of alfentanilO.0 1 mg/kg to the antinociceptive component of anesthesia compared with the hypnotic component seems logical. At the same time, it should be taken into consideration that the antianalgesic effect of thiopentallz,ls might decrease, at least to some degree, the antinociceptive contribution of alfentanil. Alfentanil has been found to profoundly potentiate the hypnotic effect of midazolam.” In comparison to this effect, alfentanil-induced potentiation of the hypnotic action of thiopental is rather mild. Compare a J. Clin. Anesth., vol. 3, July/August 1991
283
Table 3. Thiopental
No ALF
ALF
hI;wtitl DE, Rosenberg H. I\ukbtlrg SJ. et al: l.o\~(Io\t. lent;~t~vl bluiitb c-irculaton resporises to tidw~l i~iti~txttion. .-\twd~ .\rulg 3982;61:680-4. 3. Dundee JW’. Hallida\ F,!, MCMUI-ray ‘I:], Harper Kit’: l‘he effect on thiopelltal Pi-etreatriient with opioitis. intluc tion ;uitl on the onset oi action of niida/ol;iirl. ‘) _.
Potentiatiorl of’ the Hypnotic Ef’frc 15 of and Midazolam by Alfenranil
Increase in Potency (%)
, \~u~.\/ku\icrI CC-if;41: 1,!I!)-ti 1. MidaLolam t E&, (mg/kg) Thiopental$ ED-,,, (mg/kg)
0.270
0.125”
116
2.6
1.9**
36
ALF = Alfentanil. * = ti mcgikg alferltanil. ** = 10 mcg/kg alfentanil.
tlkr.
II.
$This study.
116% alfentanil-induced increase in the midazolam hypnotic potency with a 36% increase in the thiopental hypnotic potency (Table ?). Enhancement of the hypnotic effect of thiopental by opioids was reported in several studies.“,” In one of the studies,” alfentanil in a small dose of 300 kg (per patient) reduced the titrated dose of thiopental required to abolish the eyelash reflex by 18%, which is comparable to the decrease of the thiopental ED,,, for the hypnotic effect reported here. The effect of alfentanil on the antinociceptive component of thiopental anesthesia is more significant and, therefore, has an important clinical implication: the decrease in the dose of thiopental necessary for blockade of movement response to noxious stimulation (from ED,, of 5.6 mgikg to 3.2 mg/ kg) suggests the possibility of a faster and more complete recovery from anesthesia. In conclusion, alfentanil enhances both the antinociceptive and hypnotic components of thiopental anesthesia but to a different degree, its contribution to antinociception was more pronounced.
References 1. Dahlgren
N, Messeter K: Treatment of stress response to laryngoscopy and intubation with fentanyl. Anaesthesis 1981;36: 1022-6.
284
J. Clin. Anesth.,
vol. 3, July/August
1991
-I. Kissin 1, Masor~.JO, Hradlev EL Jr.: Morphine and tenrar~yl hypnotic interactions with thiopental. .4~rc/kr\& o’q I9H7:67:331-5. 5. Becker KE: Plasma levels of thiopental necessar) tor anesthesia. ,4n~cthesiolo~q 1978349: 192-6. 6. Brett CM, Fisher DM: Thiopental dose-response relations in nnpremedicated infants, children, and adults. .-\,~#i At$g 1987;66: 1024-27. 7. bhiey (Iambridge DJ: !‘r(Jhil L~r~ct/y.ri.c, 3rd rd. London: CJni\ersity Press, 197 1.. 8. St& I,, Torri (;. Castiglioni CL: ‘I‘he relative potencies of’thiopentone. ketamine, propanidid, alphaxalone and diazepani. HI- / Artcr~tfh 1979;5 1: 119-22. 9. l‘verskoy M, ‘Fleyshman G, Bradley EL. Jr, Kissin I: ~lida~ol;lm-thiopental anesthetic interac&ns in IXtients. ,4t~& .4~ulg 1988;67:342-5. 0. \‘inik HR, Hradlev EL .Jr, Kissin I: Midazolam-alfentanil synergism for anesthetic induction in patients.
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