ORIGINAL ARTICLE
Tramadol Added to Bupivacaine Does Not Prolong Analgesia of Continuous Psoas Compartment Block Mukesh Kumar, MD*; Yatindra Kumar Batra, MD, MNAMS, FAMS*; Nidhi Bidyut Panda, MD*; Subramanyam Rajeev, MD, DNB, MNAMS*; Onkar Nath Nagi, MS, FAMS† Departments of *Anaesthesia and Intensive Care; †Orthopaedic Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
䊏 Abstract: The primary aim of our study was to evaluate the quality and duration of analgesia when tramadol was added to 0.25% bupivacaine for continuous psoas compartment block (CPCB) using visual analog pain scores. Thirty patients were prospectively randomized into two equal groups (n = 15). Visual analog scale pain score was not significantly different between the groups during the 48-hour follow-up period. Rescue analgesic consumption, nausea and vomiting, and the satisfaction scores were comparable between the groups (P > 0.05). Success with catheter placement adjacent to the lumbar plexus was 100%, and none of the patients developed any catheter-related complications. In conclusion, tramadol does not provide a clinically significant analgesic action as an adjunct to 0.25% bupivacaine for CPCB. 䊏
Address correspondence and reprint requests to: Yatindra Kumar Batra, MD, MNAMS, FAMS, Department of Anaesthesiology and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India. E-mail:
[email protected]. Submitted: March 27, 2008; Accepted: July 29, 2008 DOI. 10.1111/j.1533-2500.2008.00243.x
© 2008 World Institute of Pain, 1530-7085/09/$15.00 Pain Practice, Volume 9, Issue 1, 2009 43–50
Key Words: continuous psoas compartment block, pain, tramadol, postoperative analgesia, total hip arthroplasty
INTRODUCTION Hip and femoral shaft surgeries often give rise to severe postoperative pain. Following total hip arthroplasty (THA), 50% of patients consider postoperative pain to be severe at rest and exacerbated during physical therapy.1 Inadequate analgesia may impede physical therapy and rehabilitative efforts, and delay discharge from hospital.2 Peripheral nerve blockade of the lumbosacral plexus has emerged as an alternative approach to intravenous patient-controlled analgesia or epidural analgesia.2 These techniques may be a desirable analgesic method following total joint arthroplasty with few adverse effects.2 Psoas compartment block (PCB), a technique associated with a complete block of the lumbar plexus (LP) (forming the femoral nerve, obturator nerve, and lateral femoral cutaneous nerve), has been demonstrated to be effective for postoperative analgesia following THA3 with minimal side effects.4 Although bupivacaine 0.25% alone produces analgesia and motor blockade, large volumes (30 to 40 mL) of
44 • kumar et al.
local anesthetic solution may be needed to fill the psoas compartment to ensure a reliable postoperative analgesia.4 Various adjuvants, including clonidine, epinephrine, and opioids, are used with local anesthetics to enhance the duration and quality of anesthesia and postoperative analgesia.5–7 Tramadol may be an advantageous adjunct to regional anesthesia because it is an analgesic that acts at both central and peripheral m-opioid and monoaminergic receptors.8 The addition of tramadol to local anesthetics purportedly prolongs pain relief after peripheral nerve block.9,10 Tramadol further displays a peripheral local anesthetic effect, suggesting its use in peripheral nerve blocks.11 Clinical studies evaluating the benefits of tramadol as an adjuvant in brachial plexus block have shown promising results with reduced incidence of side effects.9–11 However, studies evaluating the benefits of tramadol in epidural anesthesia and in peripheral nerve blocks, other than the brachial plexus blockade, have yielded contradictory results.12–14 Mannion et al. studied the role of tramadol as an adjunct in PCB, and concluded that tramadol neither prolongs nor augments analgesia.15 With a continuous block recommendable for analgesia after THA, conflicting evidence as to the use of tramadol as an adjunct to local anesthesia, and a lack of studies evaluating the addition of tramadol for continuous PCB (CPCB), we performed a prospective, randomized study in patients undergoing unilateral THA. The primary aim of the study was to investigate the analgesic efficacy of tramadol added to 0.25% bupivacaine compared with bupivacaine alone for CPCB using visual analog scale (VAS) pain scores. The secondary aim of the study was to investigate rescue analgesic requirements and other side effects with the use of this combination.
METHODS Approval from institutional ethical committee and informed written consent from each patient were obtained. We performed a prospective, randomized, double-blind study with 30 patients of American Society of Anesthesiologists physical status I to II scheduled for unilateral THA. Exclusion criteria included the following: patients aged 80 years, pre-existing neurological deficits, morbid obesity, inability to comprehend pain scales, and contraindications for regional anesthetic technique (eg, coagulation abnormality, local infection, and sepsis). The patients were randomly assigned to one of two groups according to a computer-generated randomiza-
tion schedule. Fifteen patients were included in each group. All patients were premedicated with oral diazepam 0.2 mg/kg 1 hour before surgery. The patients were monitored with electrocardiogram, noninvasive blood pressure, and SpO2 in the operating room. CPCB was placed, after which subarachnoid block was administered. CPCB was performed using a modified Winnie’s technique16 under moderate sedation achieved with propofol infusion (25 to 100 mg/kg/min). Propofol was provided only for the performance of the block. After aseptic preparation of the area, an 18G Tuohy needle was advanced at the desired point perpendicular to the skin until it contacted the transverse process of L4. The nerve stimulator with a current of 2 mA (frequency, 1 Hz; pulse width, 100 seconds) was attached to the needle, and the needle advanced beyond the transverse process of L4 in cephalic direction until quadriceps muscle twitches were elicited. The position was judged proper when quadriceps twitches were still elicited with a current of 0.5 mA. The depth of the LP and the distance between the skin and the L4 transverse process, as measured by needle markings, were noted. The psoas compartment was distended with 5 mL saline, and a catheter was introduced 5 to 8 cm distal to the needle tip. One milliliter of 0.9% sodium chloride was injected through the catheter to ensure its patency. The time taken to perform the block, length of catheter inserted, and ease of insertion were also noted. Subarachnoid block with 0.5% bupivacaine in 8% dextrose at L3–L4 interspace was administered in all patients following the placement of PCB catheter. At the end of the surgery, the position of the catheter was verified by injecting 3 to 5 mL of a nonionic iodinated contrast medium (Iohexol 300 mg I/mL; Omnipaque, Amersham Health, Cork, Ireland) through the catheter. An anteroposterior radiograph of the combined pelvis and lumbar region was taken to verify the position of the catheter. Following surgery, motor block of lower extremities during the regression phase of the spinal anesthetic was measured according to modified Bromage scale (0, no paralysis; 1, ability to raise extended leg but inability to flex ankle joint and first digit; 2, just able to move the knees; 3, inability to flex ankle joint and first toe).17 After completion of the surgery, the loading dose of test drug was given in 5 mL-increments following aspiration while observing cardiovascular parameters. After the patients were transferred to postanesthesia care unit (PACU), continuous infusion of test drug through the catheter was started and continued for 24 hours. Arrival in the PACU was recorded as time zero.
Efficacy of Tramadol Added to Bupivacaine for CPCB • 45
The infusion protocol included: •
•
Group B: 0.4 mL/kg (loading dose) of 0.25% bupivacaine, followed by continuous infusion of 0.25% bupivacaine at 0.15 mL/kg/hour for 24 hours. Group BT: 1.5 mg/kg of tramadol added to 0.4 mL/kg loading dose of 0.25% bupivacaine, followed by continuous infusion of 0.15 mg/kg tramadol (50 mg/mL) added to 0.25% bupivacaine at 0.15 mL/kg/hour for 24 hours.
The drug solutions were prepared by an anesthesiologist who was not involved in performing the nerve blocks, in patients’ care, or in data collection. The catheters were removed at 24 hours. Postoperative assessments were made at 0, 0.5, 2, 4, 6, 12, 24, 36, and 48 hours for pain score (VAS), rescue analgesic requirement, hemodynamics (heart rate, systolic blood pressure, and diastolic blood pressure), emesis score, anti-emetic requirement, and other adverse events and complications. The severity of postoperative pain, both at rest and with movement, was assessed by an 11-point numerical VAS score, ranging from 0 to 10 cm (0 = no pain, 10 = worst possible pain). Ketorolac 30 mg iv was administered as the rescue analgesic for 48 hours in the postoperative period when VAS 3 4. The incidence of nausea and vomiting was assessed using a 4-point Postoperative Nausea and Vomiting scale (0 = none, 1 = nausea only, 2 = nausea and/or occasional vomiting, and 3 = frequent vomiting). Ondansetron 0.1 mg/kg iv
was administered for an emesis score 32. At the end of the study period, total rescue analgesic requirement, total anti-emetic requirement, the occurrence of postanesthetic complications including injection site infection, hematoma, and any catheter-related problems were noted. The acceptance of the analgesic technique by the patients was assessed using a 3-point satisfaction score at the end of the study period (B, bad [1]; G, good [2]; E, excellent [3]). The primary end point of the study was considered as the number of patients having a VAS pain score >4 at any time during the 48-hour follow-up period. To demonstrate a 50% reduction in the incidence of pain score, a sample of 14 patients in each group was required with an a value of 0.05 and 80% power. Statistical analysis was performed using SPSS 15.0 software for Windows (SPSS software GmbH, Munich, Germany). Parametric data were analyzed by independent student’s t-test, while Mann–Whitney U-test was used to analyze nonparametric data such as VAS and satisfaction scores. Time for first rescue analgesic medication was analyzed using survival analysis and Cox regression analysis, and is represented by Kaplan–Meier survival curves. A value of P < 0.05 was considered significant.
RESULTS Thirty patients were enrolled, and all patients completed the study successfully (Figure 1). The demographic data, hemodynamic parameters, duration of the surgery, dosage of propofol, average time taken to perform the
Assessed for eligibility (n=35) Excluded (n=5) Did not agree to participate (n=3) Technical errors (n=2)
Randomized (n=30)
Continuous psoas compartment block
0.25% bupivacaine alone (n=15)
Analyzed (n=15)
0.25% bupivacaine with tramadol (n=15)
Analyzed (n=15)
Figure 1. Consort diagram.
46 • kumar et al.
Table 1. Demographic and Continuous Psoas Compartment Block-Related Data Variable Age (year) Male/female American Society of Anesthesiologists class (I/II) Weight (kg) Height (m) BMI (kg/m2) Duration of surgery (minute) Propofol dosage during performing block (mg) Time taken to perform the block (minute) Distance between the skin and the transverse process of L4 (cm) Distance between skin and lumbar plexus (cm) Length of catheter inserted (cm) Ease of catheter insertion
Group B (n = 15)
Group BT (n = 15)
P value
58.2 1 13.3 9/6 7/8 59.4 1 9.7 1.6 1 0.1 22.8 1 3.1 138.3 1 24.7 54.3 1 7.4 11.8 1 3.1 4.0 1 0.5 6.9 1 0.7 12.1 1 0.8 15/0
51.5 1 13.2 12/3 8/7 63.6 1 12.8 1.6 1 0.1 22.6 1 3.9 156.0 1 24.0 56.8 1 6.3 12.8 1 3.4 4.2 1 0.5 7.0 1 0.8 12.7 1 1.0 15/0
0.180 0.247 0.726 0.326 0.224 0.862 0.570 0.542 0.381 0.348 0.551 0.11 1
BMI, body mass index.
Table 2. Number of Patients with VAS 3 4, Rescue Analgesic Use, and Other Parameters
VAS 3 4, rest: n (%) VAS 3 4, movement: n (%) Ketorolac (mg/48 hours) (mean 1 SD) Nausea/vomiting, n (%) Rescue anti-emetic, n (%) Satisfaction score (mean 1 SD)
after 15 days. No evidence of any neurological sequel attributable to peripheral nerve blocks was detected.
Group B (n = 15)
Group BT (n = 15)
P value
4 (26.7) 5 (33.3) 30.1 1 14.9
2 (13.3) 4 (26.7) 29.5 1 15.2
0.569 0.695 0.76
3 (20) 3 (20) 1.93 1 0.59
3 (20) 2 (13) 2.06 1 0.5
1 0.651 0.203
blocks, and the length and ease of catheter inserted were comparable between both groups (P > 0.05) (Table 1). The sensory and motor block levels were comparable between both groups, and no block failures were noted in the study. The primary end point (number of patients having a VAS pain score >4) revealed no significant differences between group B and group BT during rest and movement at any recorded time interval during the study period (Table 2; Figure 2a,b). The estimated postoperative pain-free interval was comparable (P = 0.1) between both groups (Figure 3). The rescue analgesic requirement and time for first rescue were also comparable between both groups (P > 0.05). The number of episodes of nausea and vomiting, anti-emetic used, and complications during the performance of the blocks was not significantly different between the groups (Table 2). Radiographic analysis confirmed that 80% of the catheters were located in the psoas major muscle, and 20% between psoas and quadratus lumborum muscles (psoas compartment). The level of satisfaction with the analgesic technique was similar in both groups. The patients were reviewed by personal visit, at 48 hours and again
DISCUSSION In patients undergoing unilateral THA, the primary outcome, VAS pain scores, was similar with the addition of tramadol to bupivacaine and bupivacaine alone for CPCB. Hence, this study demonstrates that the addition of tramadol to 0.25% bupivacaine in CPCB does not improve either the quality or the duration of postoperative analgesia following THA. This is further supported by the notion that time to first-dose rescue analgesic, total rescue analgesic requirements, and patient satisfaction were not significantly different between both groups. Adjuncts added to local anesthetic solution potentially offer the ability to spare local anesthetic, reduce motor and sensory block, and improve the quality of analgesia.18 The use of tramadol as an adjunct for peripheral nerve blocks can be supported by various rationales. Tramadol increases serotonin (5-HT) concentrations by both inhibiting reuptake and stimulating release. The presence of serotonin subtype 3 (5-HT3) receptors on peripheral nerve endings and in the dorsal laminae of the spinal cord indicates possible peripheral sites of analgesic action for tramadol.19 Tramadol and lidocaine produce approximately the same level of conduction block. Tramadol may block the Na+ channels following the hydrophilic pathway, like lidocaine, and blocks the K+ channels more intensely than lidocaine, which may account for the local anesthetic-like effects of tramadol.20 Explanations for the local anesthetic action of tramadol remain hypothetical. 5-HT3 receptors are present on the peripheral and spinal terminal of the nociceptive primary afferent fibers (PAF) and on the superficial laminae of the dorsal horn, but serotonin
Efficacy of Tramadol Added to Bupivacaine for CPCB • 47
a
6
VAS pain score (mm)
5
4
3
2
GROUP 1 B BT
0 .0
.5
2.0
4.0
6.0
12.0
24.0
36.0
48.0
Assessment time in hours (p>0.05) b
7
VAS pain score (mm)
6
5
4
3
2
GROUP 1
B BT
0 .0
.5
2.0
4.0
6.0
12.0
24.0
36.0
Assessment time in hours (p>0.05)
agonists at the presynaptic level, in regard to the PAF, mediate a pronociceptive action. As mentioned, although lidocaine inhibits Na channels, it has been suggested that tramadol also inhibits K channels.9 Despite its long use, the understanding and prediction of the time course of tramadol’s pharmacological effects are still hampered by the presence of active metabolites and the coexistence of multiple mechanisms.21 The administration of tramadol into a compartment may cause physical dispersal of solution with a reduction in direct neural effects, in contrast to deposi-
48.0
Figure 2. (a) VAS pain score at rest. (b) VAS pain score with movement. The box represents the 25th to 75th percentiles; the dark line is the median. The extended bars represent the 10th to 90th percentiles; the circles represent the values outside this range.
tion within the sheath of the brachial plexus, which may alter the drug concentrations.15 Second, it is possible that the lipophilic properties of tramadol resulted in rapid diffusion of the drug out of the psoas compartment similar to that seen in subarachnoid space.22 Third, the dose of tramadol used in this study could have been too small for a clinically relevant analgesic effect to be detected. Increasing the dose may, however, increase the incidence of side effects.10 The benefit of a larger dose of tramadol in prolonging the duration and quality of analgesia remains to be determined. Lastly, there is a wide
48 • kumar et al.
Figure 3. Kaplan–Meier survival curve comparing the postoperative painfree interval between groups.
interpatient variability in the clearance of tramadol, as exemplified by the high coefficient of variation of total clearance rates.23 Studies of tramadol as adjunct in peripheral nerve blocks are few and have investigated tramadol’s effects when combined with a local anesthetic. The results of studies using tramadol in compartment blocks and peripheral nerve blocks are conflicting. Mannion et al.15 studied the effect of tramadol as an adjunct to singleshot PCB with levobupivacaine 0.5%. There were no differences in verbal rating pain scores between groups at any of the four time points except at 20 and 24 hours after the block, and they concluded that tramadol as adjunct to levobupivacaine 0.5% in PCB neither prolongs nor augments analgesia. The long duration of analgesia provided by levobupivacaine might have obscured the beneficial effects of tramadol. We performed this study to construct one narrow aspect of the dose–response curve, which entails the 0.25% bupivacaine concentration and in the context of a continuous infusion, given the cited failure of the 0.5% levobupivacaine to show any benefit with tramadol. Studies using tramadol in peripheral nerve blocks have demonstrated an advantage with the addition of tramadol.9,11 In a recent study by Kesimci et al., however, the addition of 100 mg of tramadol to 7.5 mg/mL of ropivacaine for axillary brachial plexus block did not prolong the duration of motor and sensory block and analgesia determined by VAS scores.24 Clonidine is a commonly used adjunct in peripheral nerve block and shares some mechanisms of action with tramadol.11 Similar to tramadol, the effect of clonidine on PNB has yielded conflicting data. In spite of the well-documented benefits of clonidine in prolonging
analgesia in the brachial plexus block, it was found that it did not prolong the action of 0.5% levobupivacaine in PCB. The vasoconstrictive properties of levobupivacaine may negate clonidine’s vasoconstrictor activity, and explain levobupivacaine’s longer duration of sensory block compared with racemic bupivacaine.25 The physical dispersal of clonidine may affect local neural concentrations within the psoas compartment, consequently reducing the direct neural effects of clonidine,26 and a similar mechanism may be involved for not producing a beneficial effect with tramadol in our study. The CPCB was chosen as the analgesic technique in our study as it results in a more reliable blockade of obturator nerve in comparison with “3-in-1” nerve block, and the duration of analgesia provided with a single-shot PCB is limited. CPCB provides optimal analgesia following THA with few side effects and a low failure rate.16 Single-shot PCB produces analgesia for approximately 16 hours; hence, we used a continuous block to assess the duration of analgesia provided by infusions up to 24 hours, and monitored the patients for pain and analgesic requirements for 48 hours in the postoperative period. The success rate of PCB was 100% in the study performed by Dadure et al., in which 15 children underwent major hip or femoral shaft surgery.27 In our adult population, we also had a success rate of 100% for the placement of catheter adjacent to the LP, and there was no failure of block in any of the patients. This indicates the ease of catheter placement with a PCB, and that this block may practically be employed to provide a prolonged duration of analgesia. We confirmed the position of catheter tip with an anteroposterior radiograph of the combined pelvis and lumbar region within 3 minutes of injection of contrast medium. We found that
Efficacy of Tramadol Added to Bupivacaine for CPCB • 49
24 catheters (80%) were located in the psoas major muscle, and the remaining 6 (20%) catheters were located between psoas and quadratus lumborum muscles. In another study,1 a similar location was observed in 74% and 22%, respectively, while three patients had their catheter in an improper position. In that study, the spread of injectate was evaluated with magnetic resonance imaging. It was observed that the most common pattern spread was within the body of the psoas muscle around the lumbar branches (L2–L4) with cephalad spread to the lumbar nerve roots. One catheter resulted in injectate between psoas and quadratus lumborum muscles.28 Biasi et al. evaluated the benefits of using the LP catheter to help avoid inadvertent epidural spread of the local anesthetic, and they recommended radiographic assessment as a complement to careful clinical practice and surveillance only when an unusual catheter location is suspected.29 We agree with the findings of Biasi et al. in that routine radiographic confirmation of catheter tip is not always necessary. Although we used traditional dosing (0.4 mL/kg of bupivacaine), lower volumes may be more appropriate in the interest of improving the already good PCB safety profile.28 The number of episodes of nausea and vomiting, and rescue anti-emetic use was not significantly different between groups. None of the major complications described with the use of PCB, including peridural blockade, total spinal anesthesia,30 renal subcapsular hematoma,1 and psoas hematoma with lumbar plexopathy,31 were observed in our study. None of our patients suffered any nerve injury. Severe nerve injuries after regional anesthesia techniques remain infrequent and probably underreported. To date, there is only one report of reversible femoral nerve injury following PCB.32 One of the drawbacks in our study was that the assessment of LP block onset could not be established as the infusion was started pre-emptively at the end of the surgery. However, radiographic confirmation revealed all the catheters to be in appropriate positions. We conclude that tramadol, as an adjunct to 0.25% bupivacaine in CPCB for postoperative analgesia, neither improves the quality nor prolongs the duration of analgesia. Routine radiographic examination of catheter tip is not necessary and should be reserved for situations when an unusual catheter location is suspected.
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