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Intrathecal addition of morphine to bupivacaine is not the cause of postoperative nausea and vomiting
Regional Anesthesia and Pain Medicine 23(1): 81-86, 1998
Intrathecal A d d i t i o n of M o r p h i n e to B u p i v a c a i n e Is n o t t h e Cause of P o s t o p e r a t i v e N a u s e a and V o m i t i n g Eric W.G. Weber, M.D., Robert Slappendel, M.D., Mathieu J.M. Gielen, M.D., Ph.D., and Ris Dirksen, M.D., Ph.D.
Background and Objectives. Postoperative nausea and vomiting after anesthesia is an distressing side effect. This study was undertaken to determine to what extent spinal opioids contribute to postoperative nausea and vomiting (PONV) and secondly to how effectively metodopramide can reduce the incidence of PONV after intrathecal administration of morphine. Methods. Patients were allocated to three groups all undergoing major joint surgery of the lower limb. In group 1 (n = 200), intrathecal anesthesia was assessed by administration of 20 mg bupivaca'fne and 0.2 mg morphine. In Group 2 (n = 100) intrathecal anesthesia was assessed in the same way and in addition, 20 mg metoclopramide intramuscular during maintenence of anesthesia and a second dose of 20 mg metoclopramide was administered intramuscular after arrival at the recovery room. Finally, in group 3 (n = 100), intrathecal anesthesia was assessed after administration of 20 mg bupivaca'fne. Results. The maximum PONV percentages were 41.1%, 32.7%, and 37% in groups 1, 2, and 3, respectively. The consumption of antiemetics was similar in all groups. The number of patients who needed one or more additional antiemetics during the first 24 hours after surgery was 112 (56.6%), 57 (58%), and 60 (60%) in groups 1, 2, and 3, respectively. Conclusions. Administration of metoclopramide did not reduce the overall incidence of PONV. Our study shows no relationship between the use of intrathecal morphine and the incidence of PONV during the first 24 hours postoperative. Reg Anesth Pain Med 1998: 23: 81-86. Key words: intrathecal morphine, postoperative nausea and vomiting, major joint surgery, metoclopramide.
Spinal opioids are frequently used for postoperative pain control in major orthopedic surgery of the lower limb (1-3). In our clinic, the intrathecal combination of a local anesthetic plus an opioid serves as an easy and inexpensive anesthetic technique to produce b o t h excellent surgical conditions a n d
postoperative pain relief. Moreover, the patients can ambulate quickly after surgery once the effect of the local anesthetic has w o r n off, as opioids do n o t impair m o t o r function. Despite the advantages of spinal opioids, bothersome side effects were described, including respiratory depression, urinary retention, postoperative nausea and vomiting (PONV), and pruritus. The (late) respiratory depression causes concern. However, it is extremely rare w h e n small doses of intrathecal m o r p h i n e are used (<0.3 rag). In contrast, nausea and vomiting occur far m o r e frequently i n
From the Department of Anesthesiology, 6500 GM Nijmegen, The Netherlands. Accepted for publication September 13, 1997. Reprint requests: Robert Slappendel, M.D., Sint Maartenskliniek, Department of Anesthesiology, P.O. Box 9011, 6500 GM Nijmegen, The Netherlands.
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the postoperative period. These two bothersome side effects are attributed to the intrathecal use of opioids and not to local anesthetics (4-6), although either symptom does occur in the absence of intrathecal opioids as well. We had two questions. First, to which extent do intrathecal opioids cause or contribute to PONV? Therefore, we investigated the relationship of PONV and intrathecal opioids by comparing the incidence of PONV after intrathecal bupivacaine to the incidence of PONV after bupivacaine plus morphine. Metoclopramide was found to reduce PONV after intrathecal anesthesia in orthopedic patients (7). The second question relates to how effectively can metoclopramide reduce the incidence of PONV after intrathecal morphine.
Methods The study was approved by the ethical committee of our hospital, and informed consent was obtained from all patients. Four hundred consecutive patients scheduled for major orthopedic surgery of the lower limb by intrathecal anesthesia were included in the study. All patients were premedicated with approximately 0.1 mg/kg midazolam (i.e., 5, 7.5, or 10 mg) orally 1 hour before spinal anesthesia. Patients were allocated to three groups. Group 1 consisted of the first 200 consecutive patients. Spinal anesthesia was produced in each of these patients by administering 20 mg bupivacaine plus 0.2 mg morphine in 4 mL intrathecal. Group 2 consisted of the next 100 patients and spinal anesthesia was produced by administering 20 mg bupivaca~ne and 0.2 mg morphine dissolved in 4 mL. In addition, each patient in group 2 was treated with 20 mg metoclopramide intramuscular during maintenence of anesthesia, and a second dose of 20 mg metoclopramide was administered intramuscular after arrival at the recovery room. Finally, group 3 consisted of the next 100 patients. Spinal anesthesia was produced by the intrathecal administration of 20 mg bupivacaYne only. Adequate sedation was provided to each patient during the procedure by means of 1 mg midazolam at the minimum interval of 5 minutes until the patient indicated that the desired sedation was produced. Noninvasive blood pressure, heart frequency (ECG), SpO 2, and respiratory frequency were continuously monitored during anesthesia and at the intensive care unit during the first 24 hours after surgery.
first step:
10 mg metoclopramide intramuscular
second step:
10 mg metoclopramide intramuscular
third step:
1.25 mg droperidol intravenously
fourth (final) step:
5 mg tropisetron intravenously
Fig. 1. Standardized treatment of PONV with antiemetics during 24 hours after surgery. Each step was initiated by the patient. The minimum interval between each step was 1 hour.
Pain In the postoperative period, all patients were treated with the analgesic, diclofenac, 2 mg/kg orally, three times a day. If diclofenac was contraindicated, oral paracetamol was given (50 mg/kg, four times a day). Pain was evaluated using visual analog scale WAS) scores (0-10; with 0 = no pain). If pain was present, 0.14 mg/kg morphine was administered intramuscular to a maximum of six doses of 10 mg/d.
Postoperative Nausea and Vomiting Postoperative nausea and vomiting (PONV) was treated according to the standard scheme (scheme 1). Each sequential step was completed at the interval of 1 hour. Step 1 was the administration of 10 mg metoclopramide intramuscular. When PONV persisted or recurred, the same dose of metoclopramide was administered intramuscular. If PONV still persisted, 1.25 mg droperidol was given intravenous. Finally, if step 1 through 3 had not reduced PONV satisfactory then 5 mg tropisetron was given intravenous (step 4; Fig. 1). Postoperative nausea and vomiting was evaluated from (a) the patient's subjective feeling (the presence or absence of subjective nausea or actual vomiting was noted at the interval of 3 hours during 24 hours postoperative); (b) the patient's request to be treated with an antiemetic; and (c) the actual consumption of antiemetics used.
Other Side Effects Other side effects measured in the postoperative period included itching, urinary retention (defined as absence of spontaneous voiding of urine at 7 hours after surgery, with the bladder volume at catheterization of >400 mL), hypotension (> 20% reduction of preoperative mean arterial blood pressures), and bradycardia (heart rate below 40 beat/ min). The presence or absence of these side effects was noted at a 3-hour interval during the 24-hour observation period. Also, the medication tor treat-
Intrathecal Morphine
•
Weber et al.
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Table 1. Demographic Data and Side Effects
n Intrathecal bupivacaine Intrathecal m o r p h i n e Intramuscular metoclopramide Mean age (SD) in years Site of operation (knee/hip %) Itching % Urinary retention % ( > 400 mL) Hypotension Bradycardia
Group 1
Group 2
Group 3
200 20 mg 0.2 mg -64.5 (11.1) 24.5%/75.5% 51.5% 63.8% 42 % 0%
100 20 mg 0.2 mg 40 mg 65.5 (12.5) 30%/70% 53% 64.3% 40 % 0%
100 20 mg --66.6 (10.9) 17%/83% 3%* 78.6% 35 % 16%*
* P < .001. n, n u m b e r of patients. For further explanation see text.
men+ of these side effects was registered at the same interval during the 2 4 - h o u r observation period.
Statistical Analysis Pain scores were analyzed using a o n e - w a y analysis of variance followed by Scheffd's post hoc analysis. The incidence of PONV was analyzed by Fisher's exact test. P value less t h a n .05 was considered significant.
Results Demographic data and the incidence of side effects are given in Table 1. The three groups did not differ for age, gender, and peroperative blood loss. Type and duration of the surgical procedures on the lower limb were similar for the three groups.
Pain As s h o w n w i t h the VAS scores in Table 2, excellent pain relief was p r e s e n t in the p o s t o p e r a tive p e r i o d for all patients in groups 1 and 2. Highest pain VAS scores (i.e., c o m p a r i n g the highest VAS score of each individual p a t i e n t in the 2 4 - h o u r period) and total pain VAS scores
[area u n d e r the curve (AUC) of VAS scores in the 2 4 - h o u r period] w e r e highest for group 3. These h i g h e r VAS scores o c c u r r e d e v e n t h o u g h a relev a n t l y and significantly h i g h e r c o n s u m p t i o n of systemic m o r p h i n e (Table 3) was n o t e d for patients t r e a t e d w i t h b u p i v a c a i n e alone (group 3) c o m p a r e d to those of groups 1 and 2 (bupivacMne plus m o r p h i n e ) .
Postoperative Nausea and Vomiting The subjective feeling of the patients m e a s u r e d e v e r y 3 h o u r s p o s t o p e r a t i v e s h o w e d n o statistical differences a m o n g groups. The m a x i m u m PONV p e r c e n t a g e s w e r e 4 1 . I % , 32.7%, and 37%, respectively, w h i c h all w e r e r e a c h e d 9 h o u r s after surgery (Fig. 2; Table 4). The c o n s u m p t i o n of antiemetics was similar in all groups. The n u m b e r of patients w h o n e e d e d one or m o r e antiemetics during the first 24 h o u r s after surgery was I12 (56.6%), 57 (58%), and 60 (60%) in groups 1, 2, a n d 3, respectively. The m e a n n u m b e r (doses) of antiemetics used in all patients was 1.1 (SD, 0.97), 1.i (SD, 0.86), and 1.2 (SD, 1.06), in groups 1, 2, and 3, respectively. The m e a n n u m ber of antiemetics used in patients w i t h PONV was 1.9, 1.9, and 2.0, respectively. The extra me-
T a b l e 2. M e a n V i s u a l A n a l o g S c a l e P a i n S c o r e s D u r i n g 2 4 H o u r s A f t e r S u r g e r y H o u r s After Surgery Group I Group 2 Group 3
3
6
9
12
I5
18
21
24
0.05 (0.35) 0.05 (0.29) 0.49 + (1.24)
0.31 (1.32) 0.38 (1.13) 2.14 + (2.27)
0.73 (1.63) 0.77 (1.51) 2.52 + (2.19)
0.81 (1,54) 0.82 (1.54) 2.27 + (1.98)
0.66 (1.53) 0.80 (1.65) 1.95 + (1.84)
0.72 (1.62) 0.40 (1.21) 0.86 (1.21)
0.66 (1.39) 0.66 (1.52) 1.03 + (1.27)
0.71 (1.39) 0.51 (1.17) 1.61 + (1.74)
HV 1.8 (0.2) 1.6 (0.2) 3.8* (0.2)
AUC 11.5 (1.2) 11.7 (2.0) 35.5* (2.4)
* Statistical difference b e t w e e n group 3 versus groups 1 and 2, P < .0001. t Statistical difference b e t w e e n group 3 versus groups 1 and 2, P < .001. Standard deviation b e t w e e n parentheses. HV, m e a n of highest individual VAS scores during 24 h o u r s postoperative. AUC, area u n d e r the curve of VAS scores in the 2 4 - h o u r period postoperative. Highest VAS scores: F (2.396) = 32.92, P < .001; Scheffe's post hoc: group 3 different from groups 1 and 2, and AUC VAS scores: F (2.396) = 54.14, P < .001; Scheff~'s post hoc: group 3 different from groups I and 2.
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Regional Anesthesia and Pain Medicine Vol. 23 No. 1 January-February 1998 T a b l e 3. Postoperative Systemic Morphine Consumption Group l
Group 2
Group 3
200 20 mg 0.2 mg
100 20 mg 0.2 mg
100 20 mg --
48 (24%)
23 (23%)
96 (96%)
64
27
303
0-3
0-2
0-6
2.35 (SD, 0.2)
2.2 (SD, 0.2)
29.7 (SD, 13.3)
n Intrathecal bupivacaine Intrathecal morphine No. of patients who needed intramuscular morphine injections during 24 hour postoperative Sum of intramuscular morphine injections during 24 hours postoperative Range of intramuscular morphine injections during 24 hours postoperative
Mean amount (my) of intramuscularmorphine during 24 hour postoperative SD, standard deviation.
toclopramide doses in group 2 are not included in these numbers.
Other Side Effects Itching mainly occurred in patients treated with intrathecal morphine. The incidence of this side effect was 51.5% (group 1) and 53% (group 2), in contrast to only 3% in group 3 (P < .001). The incidence of voiding dysfunction was 63.8%, 64.3%, and 78.6% in groups 1, 2, and 3, respectively. Hypotension was present in 42%, 40%, and 35% in groups 1, 2, and 3, respectively. As depicted in Table I, bradycardia presented in group 3 only and had the incidence of 16%, which was statistically different (P < .001). Typically, bradycardia presented in the very same period that motor function recovered.
Discussion The main finding of this study is that the incidence of PONV was not different among the three groups of patients. Thus, the notion that intrathecal morphine is a main cause for PONV is invalid.
Also, the present mode for treatment of PONV is ineffective. This study confirms that the combined administration of intrathecal morphine and bupivacaine results in optimal surgical conditions and produces excellent postoperative pain relief for at least 24 hours. However the only side effect exclusively attributable to intrathecal morphine is itching, which was easily treated. In earlier studies (1-4), the incidence of PONV after intrathecal morphine in major orthopedic surgery was between 50 and 65%. We confirmed this generally high incidence of PONV after orthopedic surgery (6) in all our groups. In prior reports, the various authors implied that the intrathecal morphine caused PONV. Our study shows no relationship between the use of intrathecal morphine and the high of the incidence of PONV, even though PONV occurred in high frequencies in all our groups, and the incidence was equal to these prior studies. Therefore, we propose that 0.2 mg intrathecal morphine does not significantly contribute to PONV. In a study by Carpenter et al. (8) several variables influenced the development of PONY, including gender, height, hypertension, history of carsick-
PONV
percentage
45 40 35 3O
Fig. 2. The incidence of PONV, postoperative nausea and vomiting.
g ~= 25
==group I ==group II
®
o 20 & 15 10 5 0
ngroup III
6
9
12
15
hours after surgery
18
21
24
Intrathecal Morphine
•
Weber et al.
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Table 4. Postoperative Nausea and Vomiting Percentages During 24 Hours After Surgery*
Group I Group 2 Group 3
3
6
9
11.7% 12.0% 7.0%
26.4% 29.3% 24.0%
41.1% 32.7% 37.0%
Hours After Surgery 12 15 28.3% 32.0% 25.0%
20.4% 2i.I% 21.6%
18
21
24
12.i% 15.2% i1.6%
9.2% 14.5% 20.5%
8.2% 11.1% 22.6%
* Patient's subjective feeling of PONV every 3 hours postoperative.
ness, baseline h e a r t rate, position for spinal p u n c ture, type of local anesthetic and dose of anesthetic. The highest f r e q u e n c y PONV in their study occurred 9 h o u r s after surgery, suggesting that intrathecal medications caused PONV. In our study, PONV was n o t induced b y intrathecal m o r p h i n e a n d was m o r e likely due to the type and dose of local anesthetic. L o w dosages of m e t o c l o p r a m i d e are ineffective in r e d u c i n g PONV after i n t r a t h e c a l a n e s t h e s i a in o r t h o p e d i c p a t i e n t s (7). In t h e h i g h e r dosages, m e t o c l o p r a m i d e was also ineffective in t r e a t i n g PONV, in c o n t r a s t to the s t u d y b y K n u d s e n et al. (2). T h e y f o u n d a r e d u c t i o n in t h e incidence of PONV f r o m 5 8 - 1 7 % after 40 m g m e t o c l o p r a m i d e i n t r a m u s c u l a r . H o w e v e r t h e p r e s e n c e of PONV w a s r e c o r d e d up to 5 h o u r s after surgery. The a n t i e m e t i c p r o p e r t i e s of m e t o c l o p r a m i d e result c e n t r a l l y f r o m its b l o c k of d o p a m i n e r e c e p t o r s of the c h e m o r e c e p t o r trigger zone, in h i g h e r doses a n t a g o n i s m of the c e n t r a l 5-HT 3 r e c e p t o r s a n d p e r i p h e r a l l y f r o m its s t i m u l a t i o n of gastric a n d small b o w e l motility, t h e r e b y p r e v e n t i n g the gastric stasis a n d dilation t h a t are p a r t of the v o m i t ing reflex (9). H o w e v e r , it is n o t e x p e c t e d t h a t i n t r a t h e c a l m o r p h i n e or b u p i v a c a i n e causes a decrease in gastric or small b o w e l m o t i l i t y (10). So, o n e can c o n c l u d e t h a t the c e n t r a l action of m e t o c l o p r a m i d e ( a n t a g o n i s m of d o p a m i n e a n d 5HT 3 r e c e p t o r ) did n o t r e d u c e PONV after intrathecal m o r p h i n e or b u p i v a c a i n e . In addition, d o p a m i n e a n d 5 HT 3 r e c e p t o r s a n d m u s c a r i n i c cholinergic a n d h i s t a m i n e r e c e p t o r s play a role in m e d i a t i n g the e m e t i c r e s p o n s e (1 i). Recently, o n e s t u d y (12) a n d o n e c o r r e s p o n d e n c e (13) suggested t h a t central a d m i n i s t r a t i o n of a n t i c h o l i n ergic drugs i n d e e d r e d u c e d PONV, after e p i d u r a l or i n t r a t h e c a l a n e s t h e s i a w i t h b u p i v a c a i n e a n d m o r p h i n e . Thus, w e c o n s i d e r e d w h e t h e r a n o t h e r t y p e of local anesthetic, a l o w e r dose of i n t r a t h e cal local anesthetic, l o w e r p e a k b l o c k heights, or c e n t r a l l y a d m i n i s t e r e d cholinergic drugs c a n h e l p p r o d u c e the l o w e r incidence of PONV. In conclusion, intrathecal m o r p h i n e added to b u -
pivacaine is superior to intrathecal bupivacafne alone for m a j o r orthopedic surgery. It is a costeffective t e c h n i q u e that minimizes the use of analgesics and disposables in the peri- and postoperative period. Also, there is no n e e d for catheters, infusion p u m p s , or patient-controlled analgesia p u m p s . Moreover, the excellent postoperative analgesia and h e m o d y n a m i c stability are reasons for selecting this anesthetic technique. Despite these benefits, one has to cope with occasional b o t h e r s o m e side effects. This study focused on the side effect PONV. There is a m p l e r e a s o n to question the relationship b e t w e e n PONV and intrathecal m o r p h i n e . Also, present t r e a t m e n t of PONV p r o v e d unsatisfactory a n d difficult.
References 1. T6rn K, Tuominen M, Tarkkila P, Lindgren L. Effects of sub-hypnotic doses of propofol on the side effects of intrathecal morphine. Br J Anaesth 1994: 73: 4 I I - 4 1 2 . 2. Knudsen K, Lisander B. Metodopramide decreases emesis after spinal anesthesia supplemented with subarachnoid morphine. Reg Anesth 1994:19 (6): 390-394. 3. Kalso E. Effects of intrathecal morphine, injected with bupivaca~ne, on pain after orthopedic surgery. Br J Anaesth 1983: 55: 415-421. 4. Morgan M. The rational use of intrathecal and extradural opioids. Br J Anaesth 1989: 63: 165-188. 5. Yaksh TL. Spinal opiate analgesia: Characteristics and principles of action. Pain 198I: l l: 293-346. 6. Quinn AC, Brown JI-I, Wallace PG, Asbury AJ. Studies in postoperative sequelae. Nausea and vomiting-still a problem. Anaesthesia 1994: 49(1): 62-65. 7. Spelina KR, Gerber HR, Pagels IL. Nausea and vomiting during spinal anaesthesia. Effect of metodopramide and dompiridone: A double blind trial. Anaesthesia 1984: 39: 132-137. 8. Carpenter RL, Caplan RA, Brown DL, Stephenson C, Wu R. Inddence and risk factors for side effects of spinal anesthesia. Anesthesiology 1992: 76: 906-916. 9. Schulze-Delrieu K. Drug therapy: Metodopramide. N Engl J Med 1981: 305: 28-33. 10. Rawal N, Sjostrand U, Christoffersson E. Comparison
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of intramuscular and epidural morphine for postoperative analgesia in the grossly obese: Influence on postoperative ambulation and p u l m o n a r y function. Anesth Analg 1984: 63: 583-592. 11. Watch FM, White PF. Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology 1992: 77: 162-184.
12. Moscovici R, Prego G, Schwartz M, Steinfeld O. Epidural scopolamine administration in preventing nausea after epidural morphine. J Clin Anesth 1995: 7: 4 7 4 - 4 7 6 . 13. Ramaioli F, De Amici D. Central antiemetic effect of atropine: Our personal experience. Can J Anaesth 1996: 43: 1079.
Intrathecal A d d i t i o n of M o r p h i n e to B u p i v a c a i n e Is n o t t h e Cause of P o s t o p e r a t i v e N a u s e a and V o m i t i n g Eric W.G. Weber, M.D., Robert Slappendel, M.D., Mathieu J.M. Gielen, M.D., Ph.D., and Ris Dirksen, M.D., Ph.D.
Background and Objectives. Postoperative nausea and vomiting after anesthesia is an distressing side effect. This study was undertaken to determine to what extent spinal opioids contribute to postoperative nausea and vomiting (PONV) and secondly to how effectively metodopramide can reduce the incidence of PONV after intrathecal administration of morphine. Methods. Patients were allocated to three groups all undergoing major joint surgery of the lower limb. In group 1 (n = 200), intrathecal anesthesia was assessed by administration of 20 mg bupivaca'fne and 0.2 mg morphine. In Group 2 (n = 100) intrathecal anesthesia was assessed in the same way and in addition, 20 mg metoclopramide intramuscular during maintenence of anesthesia and a second dose of 20 mg metoclopramide was administered intramuscular after arrival at the recovery room. Finally, in group 3 (n = 100), intrathecal anesthesia was assessed after administration of 20 mg bupivaca'fne. Results. The maximum PONV percentages were 41.1%, 32.7%, and 37% in groups 1, 2, and 3, respectively. The consumption of antiemetics was similar in all groups. The number of patients who needed one or more additional antiemetics during the first 24 hours after surgery was 112 (56.6%), 57 (58%), and 60 (60%) in groups 1, 2, and 3, respectively. Conclusions. Administration of metoclopramide did not reduce the overall incidence of PONV. Our study shows no relationship between the use of intrathecal morphine and the incidence of PONV during the first 24 hours postoperative. Reg Anesth Pain Med 1998: 23: 81-86. Key words: intrathecal morphine, postoperative nausea and vomiting, major joint surgery, metoclopramide.
Spinal opioids are frequently used for postoperative pain control in major orthopedic surgery of the lower limb (1-3). In our clinic, the intrathecal combination of a local anesthetic plus an opioid serves as an easy and inexpensive anesthetic technique to produce b o t h excellent surgical conditions a n d
postoperative pain relief. Moreover, the patients can ambulate quickly after surgery once the effect of the local anesthetic has w o r n off, as opioids do n o t impair m o t o r function. Despite the advantages of spinal opioids, bothersome side effects were described, including respiratory depression, urinary retention, postoperative nausea and vomiting (PONV), and pruritus. The (late) respiratory depression causes concern. However, it is extremely rare w h e n small doses of intrathecal m o r p h i n e are used (<0.3 rag). In contrast, nausea and vomiting occur far m o r e frequently i n
From the Department of Anesthesiology, 6500 GM Nijmegen, The Netherlands. Accepted for publication September 13, 1997. Reprint requests: Robert Slappendel, M.D., Sint Maartenskliniek, Department of Anesthesiology, P.O. Box 9011, 6500 GM Nijmegen, The Netherlands.
81
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Regional Anesthesia and Pain Medicine Vol. 23 No. 1 January-February 1998
the postoperative period. These two bothersome side effects are attributed to the intrathecal use of opioids and not to local anesthetics (4-6), although either symptom does occur in the absence of intrathecal opioids as well. We had two questions. First, to which extent do intrathecal opioids cause or contribute to PONV? Therefore, we investigated the relationship of PONV and intrathecal opioids by comparing the incidence of PONV after intrathecal bupivacaine to the incidence of PONV after bupivacaine plus morphine. Metoclopramide was found to reduce PONV after intrathecal anesthesia in orthopedic patients (7). The second question relates to how effectively can metoclopramide reduce the incidence of PONV after intrathecal morphine.
Methods The study was approved by the ethical committee of our hospital, and informed consent was obtained from all patients. Four hundred consecutive patients scheduled for major orthopedic surgery of the lower limb by intrathecal anesthesia were included in the study. All patients were premedicated with approximately 0.1 mg/kg midazolam (i.e., 5, 7.5, or 10 mg) orally 1 hour before spinal anesthesia. Patients were allocated to three groups. Group 1 consisted of the first 200 consecutive patients. Spinal anesthesia was produced in each of these patients by administering 20 mg bupivacaine plus 0.2 mg morphine in 4 mL intrathecal. Group 2 consisted of the next 100 patients and spinal anesthesia was produced by administering 20 mg bupivaca~ne and 0.2 mg morphine dissolved in 4 mL. In addition, each patient in group 2 was treated with 20 mg metoclopramide intramuscular during maintenence of anesthesia, and a second dose of 20 mg metoclopramide was administered intramuscular after arrival at the recovery room. Finally, group 3 consisted of the next 100 patients. Spinal anesthesia was produced by the intrathecal administration of 20 mg bupivacaYne only. Adequate sedation was provided to each patient during the procedure by means of 1 mg midazolam at the minimum interval of 5 minutes until the patient indicated that the desired sedation was produced. Noninvasive blood pressure, heart frequency (ECG), SpO 2, and respiratory frequency were continuously monitored during anesthesia and at the intensive care unit during the first 24 hours after surgery.
first step:
10 mg metoclopramide intramuscular
second step:
10 mg metoclopramide intramuscular
third step:
1.25 mg droperidol intravenously
fourth (final) step:
5 mg tropisetron intravenously
Fig. 1. Standardized treatment of PONV with antiemetics during 24 hours after surgery. Each step was initiated by the patient. The minimum interval between each step was 1 hour.
Pain In the postoperative period, all patients were treated with the analgesic, diclofenac, 2 mg/kg orally, three times a day. If diclofenac was contraindicated, oral paracetamol was given (50 mg/kg, four times a day). Pain was evaluated using visual analog scale WAS) scores (0-10; with 0 = no pain). If pain was present, 0.14 mg/kg morphine was administered intramuscular to a maximum of six doses of 10 mg/d.
Postoperative Nausea and Vomiting Postoperative nausea and vomiting (PONV) was treated according to the standard scheme (scheme 1). Each sequential step was completed at the interval of 1 hour. Step 1 was the administration of 10 mg metoclopramide intramuscular. When PONV persisted or recurred, the same dose of metoclopramide was administered intramuscular. If PONV still persisted, 1.25 mg droperidol was given intravenous. Finally, if step 1 through 3 had not reduced PONV satisfactory then 5 mg tropisetron was given intravenous (step 4; Fig. 1). Postoperative nausea and vomiting was evaluated from (a) the patient's subjective feeling (the presence or absence of subjective nausea or actual vomiting was noted at the interval of 3 hours during 24 hours postoperative); (b) the patient's request to be treated with an antiemetic; and (c) the actual consumption of antiemetics used.
Other Side Effects Other side effects measured in the postoperative period included itching, urinary retention (defined as absence of spontaneous voiding of urine at 7 hours after surgery, with the bladder volume at catheterization of >400 mL), hypotension (> 20% reduction of preoperative mean arterial blood pressures), and bradycardia (heart rate below 40 beat/ min). The presence or absence of these side effects was noted at a 3-hour interval during the 24-hour observation period. Also, the medication tor treat-
Intrathecal Morphine
•
Weber et al.
83
Table 1. Demographic Data and Side Effects
n Intrathecal bupivacaine Intrathecal m o r p h i n e Intramuscular metoclopramide Mean age (SD) in years Site of operation (knee/hip %) Itching % Urinary retention % ( > 400 mL) Hypotension Bradycardia
Group 1
Group 2
Group 3
200 20 mg 0.2 mg -64.5 (11.1) 24.5%/75.5% 51.5% 63.8% 42 % 0%
100 20 mg 0.2 mg 40 mg 65.5 (12.5) 30%/70% 53% 64.3% 40 % 0%
100 20 mg --66.6 (10.9) 17%/83% 3%* 78.6% 35 % 16%*
* P < .001. n, n u m b e r of patients. For further explanation see text.
men+ of these side effects was registered at the same interval during the 2 4 - h o u r observation period.
Statistical Analysis Pain scores were analyzed using a o n e - w a y analysis of variance followed by Scheffd's post hoc analysis. The incidence of PONV was analyzed by Fisher's exact test. P value less t h a n .05 was considered significant.
Results Demographic data and the incidence of side effects are given in Table 1. The three groups did not differ for age, gender, and peroperative blood loss. Type and duration of the surgical procedures on the lower limb were similar for the three groups.
Pain As s h o w n w i t h the VAS scores in Table 2, excellent pain relief was p r e s e n t in the p o s t o p e r a tive p e r i o d for all patients in groups 1 and 2. Highest pain VAS scores (i.e., c o m p a r i n g the highest VAS score of each individual p a t i e n t in the 2 4 - h o u r period) and total pain VAS scores
[area u n d e r the curve (AUC) of VAS scores in the 2 4 - h o u r period] w e r e highest for group 3. These h i g h e r VAS scores o c c u r r e d e v e n t h o u g h a relev a n t l y and significantly h i g h e r c o n s u m p t i o n of systemic m o r p h i n e (Table 3) was n o t e d for patients t r e a t e d w i t h b u p i v a c a i n e alone (group 3) c o m p a r e d to those of groups 1 and 2 (bupivacMne plus m o r p h i n e ) .
Postoperative Nausea and Vomiting The subjective feeling of the patients m e a s u r e d e v e r y 3 h o u r s p o s t o p e r a t i v e s h o w e d n o statistical differences a m o n g groups. The m a x i m u m PONV p e r c e n t a g e s w e r e 4 1 . I % , 32.7%, and 37%, respectively, w h i c h all w e r e r e a c h e d 9 h o u r s after surgery (Fig. 2; Table 4). The c o n s u m p t i o n of antiemetics was similar in all groups. The n u m b e r of patients w h o n e e d e d one or m o r e antiemetics during the first 24 h o u r s after surgery was I12 (56.6%), 57 (58%), and 60 (60%) in groups 1, 2, a n d 3, respectively. The m e a n n u m b e r (doses) of antiemetics used in all patients was 1.1 (SD, 0.97), 1.i (SD, 0.86), and 1.2 (SD, 1.06), in groups 1, 2, and 3, respectively. The m e a n n u m ber of antiemetics used in patients w i t h PONV was 1.9, 1.9, and 2.0, respectively. The extra me-
T a b l e 2. M e a n V i s u a l A n a l o g S c a l e P a i n S c o r e s D u r i n g 2 4 H o u r s A f t e r S u r g e r y H o u r s After Surgery Group I Group 2 Group 3
3
6
9
12
I5
18
21
24
0.05 (0.35) 0.05 (0.29) 0.49 + (1.24)
0.31 (1.32) 0.38 (1.13) 2.14 + (2.27)
0.73 (1.63) 0.77 (1.51) 2.52 + (2.19)
0.81 (1,54) 0.82 (1.54) 2.27 + (1.98)
0.66 (1.53) 0.80 (1.65) 1.95 + (1.84)
0.72 (1.62) 0.40 (1.21) 0.86 (1.21)
0.66 (1.39) 0.66 (1.52) 1.03 + (1.27)
0.71 (1.39) 0.51 (1.17) 1.61 + (1.74)
HV 1.8 (0.2) 1.6 (0.2) 3.8* (0.2)
AUC 11.5 (1.2) 11.7 (2.0) 35.5* (2.4)
* Statistical difference b e t w e e n group 3 versus groups 1 and 2, P < .0001. t Statistical difference b e t w e e n group 3 versus groups 1 and 2, P < .001. Standard deviation b e t w e e n parentheses. HV, m e a n of highest individual VAS scores during 24 h o u r s postoperative. AUC, area u n d e r the curve of VAS scores in the 2 4 - h o u r period postoperative. Highest VAS scores: F (2.396) = 32.92, P < .001; Scheffe's post hoc: group 3 different from groups 1 and 2, and AUC VAS scores: F (2.396) = 54.14, P < .001; Scheff~'s post hoc: group 3 different from groups I and 2.
84
Regional Anesthesia and Pain Medicine Vol. 23 No. 1 January-February 1998 T a b l e 3. Postoperative Systemic Morphine Consumption Group l
Group 2
Group 3
200 20 mg 0.2 mg
100 20 mg 0.2 mg
100 20 mg --
48 (24%)
23 (23%)
96 (96%)
64
27
303
0-3
0-2
0-6
2.35 (SD, 0.2)
2.2 (SD, 0.2)
29.7 (SD, 13.3)
n Intrathecal bupivacaine Intrathecal morphine No. of patients who needed intramuscular morphine injections during 24 hour postoperative Sum of intramuscular morphine injections during 24 hours postoperative Range of intramuscular morphine injections during 24 hours postoperative
Mean amount (my) of intramuscularmorphine during 24 hour postoperative SD, standard deviation.
toclopramide doses in group 2 are not included in these numbers.
Other Side Effects Itching mainly occurred in patients treated with intrathecal morphine. The incidence of this side effect was 51.5% (group 1) and 53% (group 2), in contrast to only 3% in group 3 (P < .001). The incidence of voiding dysfunction was 63.8%, 64.3%, and 78.6% in groups 1, 2, and 3, respectively. Hypotension was present in 42%, 40%, and 35% in groups 1, 2, and 3, respectively. As depicted in Table I, bradycardia presented in group 3 only and had the incidence of 16%, which was statistically different (P < .001). Typically, bradycardia presented in the very same period that motor function recovered.
Discussion The main finding of this study is that the incidence of PONV was not different among the three groups of patients. Thus, the notion that intrathecal morphine is a main cause for PONV is invalid.
Also, the present mode for treatment of PONV is ineffective. This study confirms that the combined administration of intrathecal morphine and bupivacaine results in optimal surgical conditions and produces excellent postoperative pain relief for at least 24 hours. However the only side effect exclusively attributable to intrathecal morphine is itching, which was easily treated. In earlier studies (1-4), the incidence of PONV after intrathecal morphine in major orthopedic surgery was between 50 and 65%. We confirmed this generally high incidence of PONV after orthopedic surgery (6) in all our groups. In prior reports, the various authors implied that the intrathecal morphine caused PONV. Our study shows no relationship between the use of intrathecal morphine and the high of the incidence of PONV, even though PONV occurred in high frequencies in all our groups, and the incidence was equal to these prior studies. Therefore, we propose that 0.2 mg intrathecal morphine does not significantly contribute to PONV. In a study by Carpenter et al. (8) several variables influenced the development of PONY, including gender, height, hypertension, history of carsick-
PONV
percentage
45 40 35 3O
Fig. 2. The incidence of PONV, postoperative nausea and vomiting.
g ~= 25
==group I ==group II
®
o 20 & 15 10 5 0
ngroup III
6
9
12
15
hours after surgery
18
21
24
Intrathecal Morphine
•
Weber et al.
85
Table 4. Postoperative Nausea and Vomiting Percentages During 24 Hours After Surgery*
Group I Group 2 Group 3
3
6
9
11.7% 12.0% 7.0%
26.4% 29.3% 24.0%
41.1% 32.7% 37.0%
Hours After Surgery 12 15 28.3% 32.0% 25.0%
20.4% 2i.I% 21.6%
18
21
24
12.i% 15.2% i1.6%
9.2% 14.5% 20.5%
8.2% 11.1% 22.6%
* Patient's subjective feeling of PONV every 3 hours postoperative.
ness, baseline h e a r t rate, position for spinal p u n c ture, type of local anesthetic and dose of anesthetic. The highest f r e q u e n c y PONV in their study occurred 9 h o u r s after surgery, suggesting that intrathecal medications caused PONV. In our study, PONV was n o t induced b y intrathecal m o r p h i n e a n d was m o r e likely due to the type and dose of local anesthetic. L o w dosages of m e t o c l o p r a m i d e are ineffective in r e d u c i n g PONV after i n t r a t h e c a l a n e s t h e s i a in o r t h o p e d i c p a t i e n t s (7). In t h e h i g h e r dosages, m e t o c l o p r a m i d e was also ineffective in t r e a t i n g PONV, in c o n t r a s t to the s t u d y b y K n u d s e n et al. (2). T h e y f o u n d a r e d u c t i o n in t h e incidence of PONV f r o m 5 8 - 1 7 % after 40 m g m e t o c l o p r a m i d e i n t r a m u s c u l a r . H o w e v e r t h e p r e s e n c e of PONV w a s r e c o r d e d up to 5 h o u r s after surgery. The a n t i e m e t i c p r o p e r t i e s of m e t o c l o p r a m i d e result c e n t r a l l y f r o m its b l o c k of d o p a m i n e r e c e p t o r s of the c h e m o r e c e p t o r trigger zone, in h i g h e r doses a n t a g o n i s m of the c e n t r a l 5-HT 3 r e c e p t o r s a n d p e r i p h e r a l l y f r o m its s t i m u l a t i o n of gastric a n d small b o w e l motility, t h e r e b y p r e v e n t i n g the gastric stasis a n d dilation t h a t are p a r t of the v o m i t ing reflex (9). H o w e v e r , it is n o t e x p e c t e d t h a t i n t r a t h e c a l m o r p h i n e or b u p i v a c a i n e causes a decrease in gastric or small b o w e l m o t i l i t y (10). So, o n e can c o n c l u d e t h a t the c e n t r a l action of m e t o c l o p r a m i d e ( a n t a g o n i s m of d o p a m i n e a n d 5HT 3 r e c e p t o r ) did n o t r e d u c e PONV after intrathecal m o r p h i n e or b u p i v a c a i n e . In addition, d o p a m i n e a n d 5 HT 3 r e c e p t o r s a n d m u s c a r i n i c cholinergic a n d h i s t a m i n e r e c e p t o r s play a role in m e d i a t i n g the e m e t i c r e s p o n s e (1 i). Recently, o n e s t u d y (12) a n d o n e c o r r e s p o n d e n c e (13) suggested t h a t central a d m i n i s t r a t i o n of a n t i c h o l i n ergic drugs i n d e e d r e d u c e d PONV, after e p i d u r a l or i n t r a t h e c a l a n e s t h e s i a w i t h b u p i v a c a i n e a n d m o r p h i n e . Thus, w e c o n s i d e r e d w h e t h e r a n o t h e r t y p e of local anesthetic, a l o w e r dose of i n t r a t h e cal local anesthetic, l o w e r p e a k b l o c k heights, or c e n t r a l l y a d m i n i s t e r e d cholinergic drugs c a n h e l p p r o d u c e the l o w e r incidence of PONV. In conclusion, intrathecal m o r p h i n e added to b u -
pivacaine is superior to intrathecal bupivacafne alone for m a j o r orthopedic surgery. It is a costeffective t e c h n i q u e that minimizes the use of analgesics and disposables in the peri- and postoperative period. Also, there is no n e e d for catheters, infusion p u m p s , or patient-controlled analgesia p u m p s . Moreover, the excellent postoperative analgesia and h e m o d y n a m i c stability are reasons for selecting this anesthetic technique. Despite these benefits, one has to cope with occasional b o t h e r s o m e side effects. This study focused on the side effect PONV. There is a m p l e r e a s o n to question the relationship b e t w e e n PONV and intrathecal m o r p h i n e . Also, present t r e a t m e n t of PONV p r o v e d unsatisfactory a n d difficult.
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