University of MN Medical Center, Fairview – I. Describe prescription drug interactions with common immunosuppressants, cholesterol-lowering agents, steroids, antivirals and Bactrim. medication interactions and which OTCs to avoid– III. Describe herbal medications that may be harmful and what interactions have been described in the literature. • Immunosuppressants • Steroids
07_hashemi.qxdAnesthesiology and Neurosurgery
ADDITION OF TRIAMCINOLONE OR PETHIDINETO EPIDURAL BUPIVACAINE CAN NOT IMPROVE POSTOPERATIVE PAIN RELIEF INLUMBAR DISCECTOMY SEYED J. HASHEMI* HASSAN A. SOLTANI*MITRA JABALAMELI*SEYED A. MIRHOSEYNI**BAHRAM SOLEYMANI*** SUMMARY: There is uncertainty as to whether addition of steroids or narcotics to epidural local anesthet- ics improves pain control in spine surgery. The aim of the current placebo-controlled, double blind study was to assess the postoperative pain score using a single epidural administration of bupivacaine alone, bupivacaine plus triamcinolone or bupivacaine plus pethidine after wound closure in patients underwent lumbar discectomy. 108 patients were included in this study. After closure of wound, patients were randomly assigned to receive bupivacaine 0.25% (group A), bupivacaine 0.25% plus triamcinolone 40 mg (group B), bupivacaine 0.25% plus pethidine 50 mg (group C) or saline (group D) via epidural catheter. 5 or 10ml of prepared med- ication was infiltrated in epidural space based on one or two segment procedures. Additional postoperative pain relief was provided using morphine. Patients were assessed with respect to pain score by visual analog scale (VAS), cumulative morphine requirement (mg), ambulation time (hour) and discharge time (day), at the postoperative period. Data were analyzed using chi-square, kruskal wallis, and ANOVA tests. Mean pain scores were higher in group D at recovery time, 6 and 24 hours postoperatively (P<0.05). The mean total morphine consumption up to 48 hours after operation in groups A, B, C, and D were 1.4±1.5, 1.4±1.3, 1.4±1.3 and 4.6±2.1 mg, respectively (P<0.05). The ambulation time and discharge time were higher in group D (P<0.05). There were not any statistically differences between group A, B and C in order to above variables. In conclusion, epidural administrations of bupivacaine 0.25% results in lower pain scores, opioid consumption and ambulation time and also discharge time when compared with placebo. Triamcinolone or pethidine added to bupivacaine could not improve these parameters. Key words: discectomy, postoperative pain, bupivacaine, triamcinolone, pethidine. Postoperative pain management results in lower rate of morbidity and mortality and also associated with shorter hospital stay, which reduces medical cost (1). Lumbar dis- *From Department of Anesthesiology and Critical Care Medicine, cectomy as a common elective surgery is painful for many Isfahan University of Medical Sciences, Isfahan, Iran.
patients. Opiates have been administered for postopera- **From Department of Neurosurgery, Isfahan University of MedicalSciences, Isfahan, Iran.
tive pain relief in patients undergoing discectomy but such ***From Department of Public Health, Islamic Azad University, Najaf pain control provides inadequate analgesia and may Medical Journal of Islamic World Academy of Sciences 19:3, 131-136, 2011 POSTOPERATIVE EPIDURAL ANALGESIA FOR LUMBAR DISCECTOMY HASHEMI, SOLTANI, JABALAMELI, MIRHOSEYNI, SOLEYMANI Table 1: Demographic Data and Operation Characteristics (NS).
Values are mean ± SD or the number (%) of patients, NS: Not significant.
result in nausea, vomiting, bradycardia, hypotension, res- and discharge time using single epidural administration piratory depression and addiction (2,3).
of bupivacaine alone, bupivacaine plus triamcinolone Epidural administration of local anesthetics is an and bupivacaine plus pethidine after wound closure in effective method for pain control in spinal surgeries (4,5) patients underwent lumbar discectomy.
but this technique can lead to some degree of sympa- thetic, sensory and motor block which associated with In this double blind, randomized prospective study, 108 unwanted effects (1). Injection of morphine as an opiate adult patients who were candidate for lumbar discectomy from analgesic in epidural space is another method for post- a dorsal approach, were enrolled in the study. The design for operative analgesia in spinal operations (6,7). However this study was approved by our institutional ethics committee some of the side effects such as late onset respiratory and written informed consent was obtained from all partici- depression, nausea, vomiting and pruritus limited its pants. This study was performed in Kashani Medical Center, widespread use (8). Most reports indicated that combi- Isfahan, Iran, during the period from March 2005 to December nation of local anesthetics and opioids for epidural anal- gesia may be result in need to lower doses of each Patients were selected if they met the following criteria: agents, effective analgesia and attenuation of some physical status (American Society of Anesthesiologists: ASA) I problems associated with the use of individual drugs or II; age 18-50 year; first disc surgery, and no history of drug abuse. The exclusion criteria were unwanted anesthesia or surgery intervention other than study protocol, known allergy to Corticosteroids have been used epidurally for local anesthetics, and using corticosteroids. Patients were ran- chronic pain relief (10,11). Infiltration of the wound site domized to 4 equal groups (n=27) by the sealed envelope by local anesthetics plus corticosteroids during lumbar technique as follows: group A; bupivacaine 0.25% alone, group discectomy can reduce postoperative pain (12,13).
B; bupivacaine 0.25% plus 40mg triamcinolone, group C; bupi- Pethidine as a narcotic analgesic with some local anes- vacaine 0.25% plus pethidine 50mg and group D; saline.
thetic property has been used epidurally for postopera- In preoperative period, patients' preparation was done tive pain relief after caesarean section and abdominal identically with intravenous infusion of crystalloid solution and 8-10 hours (none per oral) NPO time. Patients did not receive The aim of this study was to evaluate the postoper- any premedication. After preoxygenation, induction of anesthe- ative pain score, opioid requirement, ambulation time sia was performed using sodium thiopental 5 mg/kg, pancura- Medical Journal of Islamic World Academy of Sciences 19:3, 131-136, 2011 POSTOPERATIVE EPIDURAL ANALGESIA FOR LUMBAR DISCECTOMY HASHEMI, SOLTANI, JABALAMELI, MIRHOSEYNI, SOLEYMANI Table 2: Mean Pain Score and Frequency of Pain Occurrence in the First 48 Hours after Operation.
Values are mean ± SD for mean pain score, The number (%) of patients for frequency of pain occurrence, *Statistically significant.
nium bromide 0.1 mg/kg and fentanyl 2 μg/kg. Anesthesia was assumed as mild, 4-7 as moderate and 8-10 as severe pain.
maintained with oxygen 50%, nitrous oxide 50%, isoflurane 1- For postoperative pain relief, patients received morphine sul- 1.5% and fentanyl 1 μg/kg/30minutes. Following tracheal intu- fate 2mg iv as their request. Ambulation time and hospital dis- bation, mechanical ventilation was started with 10 ml/kg tidal charge time were determined in each patient. Ambulation time defined as the time that the patients can walking in ward with Patients were monitored using pulse oximetry, electrocar- or without help. The occurrence of nausea and vomiting diography, respiratory rate and non invasive blood pressure (PONV), urinary retention (need of bladder catheterization) and measurement. At the end of operation and before wound closure, respiratory depression (SPO2 <90% or RR<30% baseline) the surgeon inserted a number 8 French catheter with 5 pores at the distal part in epidural space of surgical field. Before dressing The sample size that was needed to detect a significant of surgical wound, 5 or 10ml of prepared and encoded medica- difference for pain score between 4 groups with a 1.5 unites of tion was infiltrated by surgeon in epidural space via inserted VAS, 0.90 powers and α error of 0.05 was calculated to be 108.
catheter based on one or two segment procedures, respectively Variables in study groups were compared using ANOVA for and then the catheter was removed. No surgical drains were quantitative variables like age, weight, operation time, SBP, used. All syringes were prepared similarly in two groups (5 and DBP, PR and RR, and chi-square test for nominal variables like 10ml) and enveloped in dark paper because triamcinolone when sex, ASA, type of operation, pain occurrence and side effects.
prepared for injection gives a white opaque solution. Kruskal Wallis test was used for comparison of pain intensity, All patients were operated in prone position by one sur- frequency of morphine demand, ambulation time, and dis- geon who was unaware of the medication and the assess- charge time between groups. For comparison of quantitative ments were performed by a blinded anesthesiologist. Systolic variables within groups in different situation and between two blood pressure (SBP), diastolic blood pressure (DBP), heart groups, such as pain score and total morphine consumption, rate (HR), and respiratory rate (RR) were recorded at the end ANOVA was used for repeated measurements, taking baseline of recovery time and in 3hours intervals until 24 hours and then values as covariate. Paired t-test was used to compare values in 12 hours intervals until 48 hours after operation.
in different time with baseline separately. Postoperative pain intensity was asked from the patients Values for quantitative variables were reported as mean ± before discharge from recovery room and at 6, 24 and also 48 standard deviation (SD), and for qualitative variables as count hours after operation using an 11-point visual analog scale and percent. For all tests, statistical significance was assumed (VAS), with 0 corresponding to "no pain" and 10 to "the worst if P<0.05. SPSS software version 16 was used for statistical imaginable pain". The number of VAS equal to 1-3 was Medical Journal of Islamic World Academy of Sciences 19:3, 131-136, 2011 POSTOPERATIVE EPIDURAL ANALGESIA FOR LUMBAR DISCECTOMY HASHEMI, SOLTANI, JABALAMELI, MIRHOSEYNI, SOLEYMANI Table 3:The frequency distribution of pain intensity at the end of recovery time.
Values are the number (%) of patients, P=0.003.
The number of patients who experienced PONV in All patients in 4 groups completed the study proto- groups A, B, C, and D were 4, 3, 4, and 5, respectively.
col. Demographic data and operation characteristics The number of patients who experienced urinary reten- tion were 3, 2, 4, and 3, respectively. No patients devel- Mean VAS score in group D was higher than the oped respiratory depression. There were no significant other groups up to 24 hours after surgery. At the time of differences in the incidence of PONV and urinary reten- 48 hours, no significant difference was reported among the groups. The patients in group D had a greater fre- quency of pain occurrence compared with other groups at the time of 24 hours after surgery (Table 2). Fre- The current randomized, placebo-controlled study quency distribution of moderate and severe pain inten- was performed to assess the postoperative pain score, sity were higher in group D only at the time of discharge opioid requirement, ambulation time and discharge time from recovery room (Table 3). All parameters related to in patients underwent lumbar discectomy using an intra- pain score, pain occurrence, and pain intensity were not operatively placed epidural catheter in surgical field with significantly different among groups A, B and C.
single administration of bupivacaine 0.25% alone, bupi- The numbers and percent of patients that requiring vacaine plus triamcinolone 40 mg and bupivacaine plus morphine sulphate after operation in groups A, B, C, pethidine 50 mg at the end of surgery.
and D were 6(23%), 7(26%), 7(26%) and 17(63%), In this study, the treated groups of lumbar discec- respectively (P=0.004). The mean total morphine con- tomy patients who received bupivacaine or bupiva- sumption after operation in 4 groups were 1.4 ± 1.5, 1.4 caine-triamcinolone or bupivacaine-pethidine showed ± 1.3, 1.4 ± 1.3 and 4.6 ± 2.1 mg, respectively (P=0.001).
significantly better results than the placebo group for The patients in group D received more morphine as an most parameters. The patients who treated with one of analgesic up to 48 hours after surgery. Mean ambula- three drug protocols, had lower postoperative pain in tion time and mean discharge time in 4 groups were recovery room and at the time of 24 after surgery, lower 25.8 ± 5.1, 23.1 ± 7.1, 25.9 ± 7.2, 33.3 ± 17.5 hour morphine requirements up to 48 hours after operation, (P=0.008) and 3.2 ± 0.4, 3.1 ± 0.3, 3.2 ± 0.4, 3.5 ± 0.5 shorter ambulation time and shorter discharge time from hospital. There were not any statistically differences There were also no significant differences among the between three drugs groups in order to above variables.
groups with respect to SBP, DBP, PR, and RR at the times Patients undergoing spinal surgery may suffer from of before operation, discharge from recovery and in post- significant postoperative pain. In previous studies, operative period up to 48 hours. The postoperative SBP, epidural analgesia has been shown to be safe and DBP, PR, and RR compared with that of baseline values effective and may confer some advantages over sys- (before operation) were not significant in each group. temic opioid-based analgesia. Gottschalk and co-work- Medical Journal of Islamic World Academy of Sciences 19:3, 131-136, 2011 POSTOPERATIVE EPIDURAL ANALGESIA FOR LUMBAR DISCECTOMY HASHEMI, SOLTANI, JABALAMELI, MIRHOSEYNI, SOLEYMANI ers demonstrated that in major lumbar spinal surgery, Although these studies are in line with our results, lack continuous epidural infusion 12 ml/h of ropivacaine of control groups in two later studies are important 0.1% after an initial bolus of 10 ml of drug during the methodologic difference with present study.
postoperative period, results in better pain control and Pethidine was chosen in our study as it has lower opioid requirement when compared with placebo lipophilic property in addition to a local anesthetic (4). In our study, bupivacaine 0.25% alone or combined action. Ruttar demonstrated that pethidine was more with opioid or steroid had similar results compared with effective than morphine when injected to epidural this study. Epidurally introduced local anesthetics in space, probably due to the use of larger dosages (25).
both studies can diminished significantly pain experi- So far no study compared the effect of local anesthetics supplementation with pethidine for better postoperative In present study, addition of triamcinolone to bupi- pain control after spinal surgery. In our study addition of vacaine had no significant effects on the postoperative pethidine to local anesthetics had no any effect on post- pain score, opioid requirement, ambulation time and operative pain compared with local anesthetic alone.
discharge time. Epidural steroid injection can improve Neuraxial administration of lipophilic narcotics tends to analgesia in chronic pain setting. Injection of steroids in provide shorter duration of analgesia than the narcotics epidural space was shown to be effective and safe in with hydrophilic property (1). Epidural pethidine 25 mg low back pain related to disc herniation (16,17). In two plus adrenaline 50 micrograms for analgesia after cae- study, extra-dural or intratechal triamcinolone were sarean section had only a median duration of analgesia effective in the relief of acute postdiscectomy pain to 196 min 26. Based on these data and like triamci- (18,19). In these studies, neuraxial steroid was admin- nolone, addition of pethidine 50 mg to bupivacaine istered without local anesthetics but in present investi- could not increase the duration or intensity of analgesia. gation, bupivacaine was supplemented with Postoperative pain at 48 hours after operation was triamcinolone 40 mg. For acute pain control, adding of not different between 4 groups. This may be due to ter- steroid to local anesthetic may not significantly change mination of bupivacaine or pethidine analgesic effect the potent and long acting analgesic property of bupiva- without beginning of anti inflammatory property of triam- caine. Addition of triamcinolone 40 mg to bupivacaine cinolone. The frequency of pain occurrence and pain 0.5% offers no advantage over plain bupivacaine when intensity in treated groups was lower than control group used for ilioinguinal block for postoperative pain relief only in one time after surgery. This is probably due to low sample size which may be inadequate to demon- Numerous studies have shown that the opiates strate a detectable difference of these variables in order alone or in combination with local anesthetics produce a postoperative analgesia after spinal surgeries when The lack of respiratory depression and hemody- namic instability in this study may be because of using Epidurally introduced morphine provides better low dose drugs. In addition, we completely avoided the analgesia and a reduction in early postoperative anal- administration of opiates as premedication. gesic requirement after spinal surgery (7,21).
In conclusion, this study demonstrated that In another study, continuous epidural infusion of epidural administration of bupivacaine 0.25% in fentanyl was superior to intravenous patient control patients, who undergo lumbar discectomy, effectively analgesia based morphine in the management of pain reduced pain scores, opioid consumption, ambulation after lumbar laminectomy (22). In two studies adminis- time, and hospital stay when compared with placebo.
tration of fentanyl plus local anesthetics to epidural Triamcinolone 40 mg or pethidine 50 mg added to bupi- space resulted in safe and effective control of postoper- vacaine provided similar postoperative pain control to ative pain after spine deformity surgery (23,24).
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What Are Nonprescription Pain Relievers? Nonprescription pain relievers are analgesics that can be bought without a doctor’s order (prescription). Sometimes they are called “over-the-counter” pain remedies. They include aspirin (Bufferin, Ascriptin, Ecotrin), acetaminophen (Anacin-3, Tylenol, Datril), and ibuprofen (Advil, Motrin, Nuprin). Many nonprescription pain relievers have diffe