Acta Anaesthesiol &and 1992: 36: 5 16-5 18
A dose-range study of intrathecal meperidine combined with bupivacaine T. V. NGUYEN THI, G . ORLIAGUET, N. LIU, L. DELAUNAY and F. BONNET Service d'Anesthtsie Rtanimation, HBpital Henri Mondor Crtteil, France
Twenty-one patients were included in a randomized study to receive either 10 mg of 0.5% hyperbaric bupivacaine alone or combined with 0.05,O.1,0.2, 0.3,0.4or 0.5 mg .kg-' meperidine for spinal anaesthesia. Sensory blockade was assessed by pin prick, motor blockade by the Bromage scale, and postoperative analgesia by VAS scores and by the time before the first demand for analgesia. Spinal meperidine did not change the duration of sensory blockade, but induced a dose-related increase in postoperative efficient analgesia. Spinal meperidine might be considered as a means to obtain postoperative analgesia in the hours immediately following surgery. Recciutd 29 Juh,accepted for publication 13 Dtccmbtr 1991
K L words: ~ Anesthetic techniques: spinal anesthesia; opiates: meperidine.
Meperidine, a phenylpiperidine derivate, has a chemical structure close to the local anaesthetics, and produces peripheral nerve block ( 1, 2). Spinal anaesthesia has been achieved with meperidine as sole agent (3-5). Indeed, a dose of 1 mg-kg-' meperidine has been reported to induce spinal anaesthetic block effectively. However, respiratory depression has been observed with such a high dose (5-7). A smaller meperidine spinal dose has recently been reported to induce analgesia during labour (8,9) or minor surgical procedures (10, 11). We therefore performed a dose-effect study of spinal meperidine combined with bupivacaine, in order to determine to what extent meperedine could modify the anaesthetic block and postoperative analgesia.
PATIENTS AND METHODS Twenty-one ASA 1-11 patients scheduled for orthopaedic surgery of the foot or the knee (excluding total knee replacement) were included in this randomized, double-blind study after informed consent and ethics committee approval had been obtained. After oral premedication with 1 mg flunitrazepam P.o., spinal anaesthesia was performed with 10 mg of 0.5% hyperbaric bupivacaine. Patients were allocated randomly to receive either bupivacaine alone or 0.05, 0.1, 0.2, 0.3, 0.4 and 0.5 mg.kg-' 5% meperidine combined with bupivacaine. Therefore, each meperidine dose was administered to three patients, and three other patients received bupivacaine alone. No additional sedative or analgesic agent was administered during surgery. Arterial blood pressure and heart rate were monitored every 5 min using an automatic blood cuff (Dinamap@,Critikon), and arterial oxygen saturation with a pulse oximeter (Nellcor 2009. Patients received oxygen via a face mask or a nasal cannula. Sensory blockade was assessed by pin-prick and motor blockade was assessed on the Bromage scale every 5 min (12). Post-
operatively, pain was assessed on a visual analogue scale (VAS) ( 13). The VAS score was recorded at I , 2, 3 and 4 h after arrival in the recovery room. The time between the spinal injection of bupivacaine, with or without meperidine, and the first postoperative analgesic demand was considered as the duration of analgesia. Linear regressions were assessed by least-squares analysis, between meperidine dose and duration of sensory and motor blockades and duration of analgesia. The Kruskal-Wallis test was used for VAS score analysis. P < 0.05 was considered significant. Results are expressed as mean s.d.
RESULTS Seven men and 14 women were included in this study. The mean age was 56.6 f 10.8 years, the mean weight was 67.9 k 12.5 kg and the mean height 168.9 f 38.7 cm. The mean duration of surgery (from incision to skin closure) was 69 k 37 min. Spinal meperidine doses ranged between 0 and 48 mg. No significant correlation was documented between the duration of sensory blockade assessed at T12, L2 and S1 levels and the amount of spinal meperidine administered. The mean duration of sensory blockade at L2 was 156 f 50 min and the mean duration of grade 3 motor blockade was 73 k 55 min. A significant correlation was shown between the duration of grade 3 motor blockade and the meperidine dose (r = 0.49, P< 0.05). The duration of analgesia was also significantly correlated with the meperidine dose. For further analysis of the data, patients were allocated to three groups according to the meperidine dose administered. In the first group, patients had received 0.05 or 0.1 mg-kg-' meperidine (range: 3-8 mg), in the second group 0.2 or 0.3 mg.kg-' meperidine
517
MEPERIDINE WITH BUPIVACAINE
(extremes: 10-28 mg), and in the third group 0.4 or 0.5 mgekg-] meperidine (range: 22-48 mg). These three groups were equivalent for age, height, weight, duration of surgery and duration of sensory blockade. VAS scores at 2, 3 and 4 h postoperatively were significantly lower in patients who had received the highest meperidine dose (Table 1). The duration of analgesia was also significantly prolonged in patients in the third group (respectively: 307 f 80 min, 414 f 69 rnin and 472 f 108 min in groups 1, 2 and 3; *P< 0.05 difference between groups 1 and 3). No patient had documented arterial oxygen saturation < 93%. No patient complained of itching, nausea or vomiting. DISCUSSION This study points out that spinal meperidine in a dose range of 0.05 to 0.5 mgakg-' does not significantly prolong the sensory blockade induced by a 10-mg hyperbaric bupivacaine dose and measured by pinprick but induces a dose-related prolongation and improvement of postoperative analgesia evaluated by VAS. As previously mentioned, a dose of 1 mg-kg-' meperidine induces spinal anaesthetic blockade and efficient motor blockade (2, 3, 5). Both sensory and motor blockades are weaker after a dose of 0.5 mg*kg-' spinal meperidine (10, 11). The lack of prolongation of sensory blockade might be considered a surprising result of this study. Nevertheless, previous studies have documented a short anaesthetic action of meperidine, even when a dose of 1 mgakg-' was administered (3-6). For example, a 40-mg spinal dose of meperidine induced 46.6 f 6.3 min of sensory blockade at T10, corresponding to a less prolonged effect than a 40-mg spinal dose of lidocaine (6). In that study (6), the duration of complete motor blockade was less than 43 min. In another study (3), sensory blockade lasting 54.4f 18.7 min was observed after meperidine 1 mg * kg- ', while the duration of motor blockade was 54.5f 18.7 min. Finally, a dose of 0.5 mg-kg-' achieves roughly 25% of the duration of sensory blockade induced by a 8-12 mg tetracaine dose (14).
Thus it could be suggested that increasing the spinal meperidine dose from 0 to 0.5 mg-kg-' (maximum dose 48 mg) might have less effect than the addition of 5-10 mg of bupivacaine to the initial 10-mg dose, and that this effect could be difficult to document in the conditions of this study. However, despite its anaesthetic properties, meperidine as a means to strengthen the spinal blockade does not seem to provide any definite advantage over other solutions (increasing local anaesthetic dose, adding alpha 2 agonists, etc.). The main result of this study is a dose-related improvement in postoperative analgesia. A dose of 0.2-0.5 mg-kg-' meperidine gives 1-3 h longer analgesia compared to bupivacaine alone. In a previous study, Trivedy et al. reported 2-6 h duration of postoperative analgesia after a 0.5 mg * kg- spinal meperidine dose (1 1). Pate1 et al. have documented that 36% of patients had more than 24 h duration of anaesthesia after the same dose of meperidine compared to 20% in the group of patients receiving spinal lidocaine ( 10). A longer duration of analgesia has been reported with small doses of spinal morphine in previous studies (15-17), while the combination of fentanyl and bupivacaine produced a duration of effective analgesia comparable to the results of this study ( 18). Pharmacokinetic studies of morphine or meperidine performed in the CSF after spinal administration point to a more rapid disappearance of meperidine than morphine ( 19, 20), which may be explained by a difference in lipid solubility. Lipophilic opioids have a rapid penetration into the spinal cord and a correspondingly rapid removal from the spinal cord tissue, which results in a short time of onset of analgesia, but also in a short duration of action. Although no neurotoxicological study of meperidine has been published, more than 1035 patients have received spinal meperidine so far, including the patients in this study and 713 patients of Mircea et al. (4), without any documented neurotoxic effect. Meperidine has been administered via a spinal catheter for analgesia in labour, and has been documented
'
Table 1 VAS scores. Meperidine dose Group 1 (0.054.1 mg .kg- ') Group 2 ( 0 . 2 4 . 3 mg.kg-') Group 3 (0.4-0.5 mg.kg-')
*
Arrival in the recovery room
HI
H2
H3
H4
0.3 -f 5
1.7k1.5
4.3k1.8
6.0k0.9
6.0k2.7
o+o
0.5f1.2 0.7k1.2
3.8k3.7 1.2h1.3
5.0k4.5 1.8k2.0
6.5k4.0 3.0k2.4
0.5 f 1.2
P c 0 . 0 5 comparison between Group 1 and Group 3.
*
*
*
518
T. V. NGUYEN THI ET AL.
to provide efficient analgesia without toxicity (8, 9, 14). Respiratory depression has been reported with meperidine doses greater than 0.5 mg ekg-’, which might be related to a progressive increase in ventricular CSF concentration after vascular absorption of meperidine from the lumbar CSF (21). It is therefore our opinion that a dose greater than 0.5 mg’kg-’, which may provide a longer duration of analgesia, is not recommended. The safety margin of intrathecal meperidine appears to be narrow and the cost-benefit ratio seems to be low. We suggest that a dose lower than 0.5 mg-kg-’ of meperidine might be administered to obtain analgesia in the first postoperative hours spent in the recovery room. If more prolonged sedation of pain is required, morphine seems to be a more appropriate analgesic agent.
REFERENCES 1. Cousins M J, Mather L E. Intrathecal and epidural administration of opioids. Anesthesiology 1984: 61: 270-310.
2. Way E L. Studies on the local anesthetic properties of isonipercaine. 3 Am Pharm Assoc 1946: 35: 44-47. 3. Famewo C E, Naguib M. Spinal anaesthesia with meperidine as the agent. Can Anaesth SOCj 1985: 32: 533-537. 4. Mircea N, Constantinescu C, Jianu E et al. L‘anesthCsie sousarachnoydienne par la ptthidine. Ann F7 Anesth Reanim 1982: 1: 167- I 7 1. 5. Andrivet P, Ekherian J M, Lienhart A, Wars P. Bloc moteur induit par la pethidine intrarachidienne. Quantification et comparaison avec la lidocaine. Ann FY Anesthe Reanim 1987: 6: 419-422. 6. Sangarlangkarn S, Klaewtanong V, Jonglerttrakool P, Khankaew V. Meperidine as a spinal anesthetic agent: a comparison with lidocaine glucose. Anesthe Analg 1987: 66: 235-240. 7. Brownridge P, Wrobel J, Watt-Smith J. Respiratory depression following accidental subarachnoid pethidine. Anaesth Intensive Care 1983: 11: 237-240. 8. Swayze C R, Sholte F G, Walker E B, Sherman J H. Eflicacy of in trathecal meperidine during labor analgesia. Anesth Analg 1991: 72: S287. 9. Johnson M D, Hurley R J, Hilbertson L I, Datta S. Continuous
10.
11.
12.
13. 14.
15.
16.
17.
18.
19.
20.
21.
microcatheter spinal anaesthesia with subarachnoid meperidine for labor and delivery. Anesth Analg 1990: 70: 658-661. Patel D, Janardhan Y,Merai B, Robalino J, Shevde K. Intrathecal meperidine in endoscopic urologic procedures: a comparative study with a local anesthetic. Regional Anaesthesia 1989: 14: 49. Trivedi N S, Halpern M, Robalino J, Shevde K. Spinal anaesthesia with low dose meperidine for knee arthroscopy in ambulatory surgical patients. Regional Anaesthesia 1990: 15: 43. Bromage P R. A comparison of the hydrochloride and carbon dioxide salts of lidocaine and prilocaine and epidural anaesthesia. Acta Anaesthesiol Scand 1965: 16: 55-62. Huskisson E C. Measurement of pain. Lancet 1974: ii: 11271131. Talafre M L, Jacquinot P, Legagneux F, Jasson J, Conseiller C. Intrathecal administration of meperidine versus tetracaine for elective cesarean section. Anesthesiology 1987: 67: A620. Chadwick H S, Ready L B. Intrathecal and epidural morphine sulfate for post-cesarean analgesia. A clinical comparison. Anesthesiology 1988: 6 8 925-929. Abboud T K, Dror A, Mosaad P et al. Mini-dose intrathecal morphine for the reliefof post-cesarean section pain. Anesth Analg 1988: 67: 137-143. Abouleish E, Rawal N, Fallon K, Hernandez D. Combined intrathecal morphine and bupivacaine for cesarean section. Anesth Analg 1988: 67: 37Q-374. Hunt C 0, Naulty J S, Bader A M et al. Perioperative analgesia with subarachnoid fentanyl-bupivacaine for cesarean delivery. Anesthesiology 1989: 71: 535-540. Gustafsson L L, Post C, Edvardsen B, Ramsay C H. Distribution of morphine and meperidine after intrathecal administration in rat and mouse. Anesthesiology 1985: 63: 483-489. Sjostrom S, Tamsen A, Penson P, Hartvig P. Pharmacokinetics of intrathecal morphine and meperidine in humans. Anesthesiology 1987: 67: 889-895. Maurttte P, Tauzin-Fin P, VinGon G, Brachet-Lierman. Arterial and ventricular CSF pharmacokinetics after intrathecal meperidine in humans. Anesthesiology 1989: 70: 961-966.
Address: R Bonnet, M.D. Service d’Anesthtsie RCanimation Hbpital Henri Mondor 51, avenue du Martchal de Lattre de Tassigny 94010 Creteil France
A dose-range study of intrathecal meperidine combined with bupivacaine T. V. NGUYEN THI, G . ORLIAGUET, N. LIU, L. DELAUNAY and F. BONNET Service d'Anesthtsie Rtanimation, HBpital Henri Mondor Crtteil, France
Twenty-one patients were included in a randomized study to receive either 10 mg of 0.5% hyperbaric bupivacaine alone or combined with 0.05,O.1,0.2, 0.3,0.4or 0.5 mg .kg-' meperidine for spinal anaesthesia. Sensory blockade was assessed by pin prick, motor blockade by the Bromage scale, and postoperative analgesia by VAS scores and by the time before the first demand for analgesia. Spinal meperidine did not change the duration of sensory blockade, but induced a dose-related increase in postoperative efficient analgesia. Spinal meperidine might be considered as a means to obtain postoperative analgesia in the hours immediately following surgery. Recciutd 29 Juh,accepted for publication 13 Dtccmbtr 1991
K L words: ~ Anesthetic techniques: spinal anesthesia; opiates: meperidine.
Meperidine, a phenylpiperidine derivate, has a chemical structure close to the local anaesthetics, and produces peripheral nerve block ( 1, 2). Spinal anaesthesia has been achieved with meperidine as sole agent (3-5). Indeed, a dose of 1 mg-kg-' meperidine has been reported to induce spinal anaesthetic block effectively. However, respiratory depression has been observed with such a high dose (5-7). A smaller meperidine spinal dose has recently been reported to induce analgesia during labour (8,9) or minor surgical procedures (10, 11). We therefore performed a dose-effect study of spinal meperidine combined with bupivacaine, in order to determine to what extent meperedine could modify the anaesthetic block and postoperative analgesia.
PATIENTS AND METHODS Twenty-one ASA 1-11 patients scheduled for orthopaedic surgery of the foot or the knee (excluding total knee replacement) were included in this randomized, double-blind study after informed consent and ethics committee approval had been obtained. After oral premedication with 1 mg flunitrazepam P.o., spinal anaesthesia was performed with 10 mg of 0.5% hyperbaric bupivacaine. Patients were allocated randomly to receive either bupivacaine alone or 0.05, 0.1, 0.2, 0.3, 0.4 and 0.5 mg.kg-' 5% meperidine combined with bupivacaine. Therefore, each meperidine dose was administered to three patients, and three other patients received bupivacaine alone. No additional sedative or analgesic agent was administered during surgery. Arterial blood pressure and heart rate were monitored every 5 min using an automatic blood cuff (Dinamap@,Critikon), and arterial oxygen saturation with a pulse oximeter (Nellcor 2009. Patients received oxygen via a face mask or a nasal cannula. Sensory blockade was assessed by pin-prick and motor blockade was assessed on the Bromage scale every 5 min (12). Post-
operatively, pain was assessed on a visual analogue scale (VAS) ( 13). The VAS score was recorded at I , 2, 3 and 4 h after arrival in the recovery room. The time between the spinal injection of bupivacaine, with or without meperidine, and the first postoperative analgesic demand was considered as the duration of analgesia. Linear regressions were assessed by least-squares analysis, between meperidine dose and duration of sensory and motor blockades and duration of analgesia. The Kruskal-Wallis test was used for VAS score analysis. P < 0.05 was considered significant. Results are expressed as mean s.d.
RESULTS Seven men and 14 women were included in this study. The mean age was 56.6 f 10.8 years, the mean weight was 67.9 k 12.5 kg and the mean height 168.9 f 38.7 cm. The mean duration of surgery (from incision to skin closure) was 69 k 37 min. Spinal meperidine doses ranged between 0 and 48 mg. No significant correlation was documented between the duration of sensory blockade assessed at T12, L2 and S1 levels and the amount of spinal meperidine administered. The mean duration of sensory blockade at L2 was 156 f 50 min and the mean duration of grade 3 motor blockade was 73 k 55 min. A significant correlation was shown between the duration of grade 3 motor blockade and the meperidine dose (r = 0.49, P< 0.05). The duration of analgesia was also significantly correlated with the meperidine dose. For further analysis of the data, patients were allocated to three groups according to the meperidine dose administered. In the first group, patients had received 0.05 or 0.1 mg-kg-' meperidine (range: 3-8 mg), in the second group 0.2 or 0.3 mg.kg-' meperidine
517
MEPERIDINE WITH BUPIVACAINE
(extremes: 10-28 mg), and in the third group 0.4 or 0.5 mgekg-] meperidine (range: 22-48 mg). These three groups were equivalent for age, height, weight, duration of surgery and duration of sensory blockade. VAS scores at 2, 3 and 4 h postoperatively were significantly lower in patients who had received the highest meperidine dose (Table 1). The duration of analgesia was also significantly prolonged in patients in the third group (respectively: 307 f 80 min, 414 f 69 rnin and 472 f 108 min in groups 1, 2 and 3; *P< 0.05 difference between groups 1 and 3). No patient had documented arterial oxygen saturation < 93%. No patient complained of itching, nausea or vomiting. DISCUSSION This study points out that spinal meperidine in a dose range of 0.05 to 0.5 mgakg-' does not significantly prolong the sensory blockade induced by a 10-mg hyperbaric bupivacaine dose and measured by pinprick but induces a dose-related prolongation and improvement of postoperative analgesia evaluated by VAS. As previously mentioned, a dose of 1 mg-kg-' meperidine induces spinal anaesthetic blockade and efficient motor blockade (2, 3, 5). Both sensory and motor blockades are weaker after a dose of 0.5 mg*kg-' spinal meperidine (10, 11). The lack of prolongation of sensory blockade might be considered a surprising result of this study. Nevertheless, previous studies have documented a short anaesthetic action of meperidine, even when a dose of 1 mgakg-' was administered (3-6). For example, a 40-mg spinal dose of meperidine induced 46.6 f 6.3 min of sensory blockade at T10, corresponding to a less prolonged effect than a 40-mg spinal dose of lidocaine (6). In that study (6), the duration of complete motor blockade was less than 43 min. In another study (3), sensory blockade lasting 54.4f 18.7 min was observed after meperidine 1 mg * kg- ', while the duration of motor blockade was 54.5f 18.7 min. Finally, a dose of 0.5 mg-kg-' achieves roughly 25% of the duration of sensory blockade induced by a 8-12 mg tetracaine dose (14).
Thus it could be suggested that increasing the spinal meperidine dose from 0 to 0.5 mg-kg-' (maximum dose 48 mg) might have less effect than the addition of 5-10 mg of bupivacaine to the initial 10-mg dose, and that this effect could be difficult to document in the conditions of this study. However, despite its anaesthetic properties, meperidine as a means to strengthen the spinal blockade does not seem to provide any definite advantage over other solutions (increasing local anaesthetic dose, adding alpha 2 agonists, etc.). The main result of this study is a dose-related improvement in postoperative analgesia. A dose of 0.2-0.5 mg-kg-' meperidine gives 1-3 h longer analgesia compared to bupivacaine alone. In a previous study, Trivedy et al. reported 2-6 h duration of postoperative analgesia after a 0.5 mg * kg- spinal meperidine dose (1 1). Pate1 et al. have documented that 36% of patients had more than 24 h duration of anaesthesia after the same dose of meperidine compared to 20% in the group of patients receiving spinal lidocaine ( 10). A longer duration of analgesia has been reported with small doses of spinal morphine in previous studies (15-17), while the combination of fentanyl and bupivacaine produced a duration of effective analgesia comparable to the results of this study ( 18). Pharmacokinetic studies of morphine or meperidine performed in the CSF after spinal administration point to a more rapid disappearance of meperidine than morphine ( 19, 20), which may be explained by a difference in lipid solubility. Lipophilic opioids have a rapid penetration into the spinal cord and a correspondingly rapid removal from the spinal cord tissue, which results in a short time of onset of analgesia, but also in a short duration of action. Although no neurotoxicological study of meperidine has been published, more than 1035 patients have received spinal meperidine so far, including the patients in this study and 713 patients of Mircea et al. (4), without any documented neurotoxic effect. Meperidine has been administered via a spinal catheter for analgesia in labour, and has been documented
'
Table 1 VAS scores. Meperidine dose Group 1 (0.054.1 mg .kg- ') Group 2 ( 0 . 2 4 . 3 mg.kg-') Group 3 (0.4-0.5 mg.kg-')
*
Arrival in the recovery room
HI
H2
H3
H4
0.3 -f 5
1.7k1.5
4.3k1.8
6.0k0.9
6.0k2.7
o+o
0.5f1.2 0.7k1.2
3.8k3.7 1.2h1.3
5.0k4.5 1.8k2.0
6.5k4.0 3.0k2.4
0.5 f 1.2
P c 0 . 0 5 comparison between Group 1 and Group 3.
*
*
*
518
T. V. NGUYEN THI ET AL.
to provide efficient analgesia without toxicity (8, 9, 14). Respiratory depression has been reported with meperidine doses greater than 0.5 mg ekg-’, which might be related to a progressive increase in ventricular CSF concentration after vascular absorption of meperidine from the lumbar CSF (21). It is therefore our opinion that a dose greater than 0.5 mg’kg-’, which may provide a longer duration of analgesia, is not recommended. The safety margin of intrathecal meperidine appears to be narrow and the cost-benefit ratio seems to be low. We suggest that a dose lower than 0.5 mg-kg-’ of meperidine might be administered to obtain analgesia in the first postoperative hours spent in the recovery room. If more prolonged sedation of pain is required, morphine seems to be a more appropriate analgesic agent.
REFERENCES 1. Cousins M J, Mather L E. Intrathecal and epidural administration of opioids. Anesthesiology 1984: 61: 270-310.
2. Way E L. Studies on the local anesthetic properties of isonipercaine. 3 Am Pharm Assoc 1946: 35: 44-47. 3. Famewo C E, Naguib M. Spinal anaesthesia with meperidine as the agent. Can Anaesth SOCj 1985: 32: 533-537. 4. Mircea N, Constantinescu C, Jianu E et al. L‘anesthCsie sousarachnoydienne par la ptthidine. Ann F7 Anesth Reanim 1982: 1: 167- I 7 1. 5. Andrivet P, Ekherian J M, Lienhart A, Wars P. Bloc moteur induit par la pethidine intrarachidienne. Quantification et comparaison avec la lidocaine. Ann FY Anesthe Reanim 1987: 6: 419-422. 6. Sangarlangkarn S, Klaewtanong V, Jonglerttrakool P, Khankaew V. Meperidine as a spinal anesthetic agent: a comparison with lidocaine glucose. Anesthe Analg 1987: 66: 235-240. 7. Brownridge P, Wrobel J, Watt-Smith J. Respiratory depression following accidental subarachnoid pethidine. Anaesth Intensive Care 1983: 11: 237-240. 8. Swayze C R, Sholte F G, Walker E B, Sherman J H. Eflicacy of in trathecal meperidine during labor analgesia. Anesth Analg 1991: 72: S287. 9. Johnson M D, Hurley R J, Hilbertson L I, Datta S. Continuous
10.
11.
12.
13. 14.
15.
16.
17.
18.
19.
20.
21.
microcatheter spinal anaesthesia with subarachnoid meperidine for labor and delivery. Anesth Analg 1990: 70: 658-661. Patel D, Janardhan Y,Merai B, Robalino J, Shevde K. Intrathecal meperidine in endoscopic urologic procedures: a comparative study with a local anesthetic. Regional Anaesthesia 1989: 14: 49. Trivedi N S, Halpern M, Robalino J, Shevde K. Spinal anaesthesia with low dose meperidine for knee arthroscopy in ambulatory surgical patients. Regional Anaesthesia 1990: 15: 43. Bromage P R. A comparison of the hydrochloride and carbon dioxide salts of lidocaine and prilocaine and epidural anaesthesia. Acta Anaesthesiol Scand 1965: 16: 55-62. Huskisson E C. Measurement of pain. Lancet 1974: ii: 11271131. Talafre M L, Jacquinot P, Legagneux F, Jasson J, Conseiller C. Intrathecal administration of meperidine versus tetracaine for elective cesarean section. Anesthesiology 1987: 67: A620. Chadwick H S, Ready L B. Intrathecal and epidural morphine sulfate for post-cesarean analgesia. A clinical comparison. Anesthesiology 1988: 6 8 925-929. Abboud T K, Dror A, Mosaad P et al. Mini-dose intrathecal morphine for the reliefof post-cesarean section pain. Anesth Analg 1988: 67: 137-143. Abouleish E, Rawal N, Fallon K, Hernandez D. Combined intrathecal morphine and bupivacaine for cesarean section. Anesth Analg 1988: 67: 37Q-374. Hunt C 0, Naulty J S, Bader A M et al. Perioperative analgesia with subarachnoid fentanyl-bupivacaine for cesarean delivery. Anesthesiology 1989: 71: 535-540. Gustafsson L L, Post C, Edvardsen B, Ramsay C H. Distribution of morphine and meperidine after intrathecal administration in rat and mouse. Anesthesiology 1985: 63: 483-489. Sjostrom S, Tamsen A, Penson P, Hartvig P. Pharmacokinetics of intrathecal morphine and meperidine in humans. Anesthesiology 1987: 67: 889-895. Maurttte P, Tauzin-Fin P, VinGon G, Brachet-Lierman. Arterial and ventricular CSF pharmacokinetics after intrathecal meperidine in humans. Anesthesiology 1989: 70: 961-966.
Address: R Bonnet, M.D. Service d’Anesthtsie RCanimation Hbpital Henri Mondor 51, avenue du Martchal de Lattre de Tassigny 94010 Creteil France
