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CLINICAL INVESTIGATION
Year : 2008  |  Volume : 52  |  Issue : 2  |  Page : 164-169 Table of Contents     

Acute Post Mastectomy Pain: A Double Blind Randomised Controlled Trial: Intravenous Tramadol Vs Bupivacaine Irrigation through Surgical Drains


1 Senior Consultant and Coordinator, Department of Anesthesiology, ICU, Pain & Palliative Care Medicine, Jaipur, India
2 Consultant Anaesthesiologist, Department of Anesthesiology, ICU, Pain & Palliative Care Medicine, Jaipur, India
3 Senior Consultant, S.K. Soni Hospital, Jaipur, India
4 Senior Consultant and Coordinator, Department of Surgical Oncology Bhagwan Mahaveer Cancer Hospital & Research Centre , Jaipur, India

Date of Acceptance12-Feb-2008
Date of Web Publication19-Mar-2010

Correspondence Address:
Anjum S KhanJoad
Senior Consultant & Coordinator, Department of Anesthesiology, ICU and Pain & Palliative medicine, Bhagwan Mahaveer Cancer Hospital and Research Centre, J.L.N. Marg, Malviya Nagar, Jaipur-302017
India
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Source of Support: None, Conflict of Interest: None


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Clinical experience suggests that acute postoperative pain after radical surgery for breast cancer can be managed by bupivacaine irrigation. This prospective randomized double blind controlled study was designed to test the hypothesis that bupivacaine irrigation will reduce the 24 hour requirement of tramadol (400 mg + 100 mg) by one fourth (100+25mg).
Forty six patients were allocated randomly to receive intravenous tramadol (Group T) (0.25mg.kg -1 .hr -1 ) and bupivacaine drain irrigation(Group B) (0.4% 20 ml 8 hourly) for postoperative pain. Pain was monitored independently by the APS and PACU nursing staff. APS residents were allowed to give intravenous boluses of tramadol of 50 mg on complaints of pain. Pain scores, nausea, vomiting, sedation, urinary retention ECG and haemodynamic changes were monitored for 24 hours and analysed by Mann-Whitney u test and Fisher's exact test.
Both groups had good pain relief. The T group had significantly more nausea (P<0.007). The T group patients had a higher incidence of vomiting, catheterisation and delayed oral intake, but this was not significant statistically. Bupivacaine administered through the surgical drain offered equivalent postoperative pain relief to intravenous tramadol, with significantly less nausea.

Keywords: Local anaesthetic; Acute;Post-mastectomy pain; Randomised controlled trial.


How to cite this article:
KhanJoad AS, Gupta P, Tiwari M, Patni S. Acute Post Mastectomy Pain: A Double Blind Randomised Controlled Trial: Intravenous Tramadol Vs Bupivacaine Irrigation through Surgical Drains. Indian J Anaesth 2008;52:164-9

How to cite this URL:
KhanJoad AS, Gupta P, Tiwari M, Patni S. Acute Post Mastectomy Pain: A Double Blind Randomised Controlled Trial: Intravenous Tramadol Vs Bupivacaine Irrigation through Surgical Drains. Indian J Anaesth [serial online] 2008 [cited 2020 Dec 4];52:164-9. Available from: https://www.ijaweb.org/text.asp?2008/52/2/164/60615


   Introduction Top


Conventionally, breast surgery is performed under general anaesthesia and intravenous opioids are admin­istered for acute post mastectomy pain. Our acute pain service conducted an observational study [1] in which af­ter surgery under a general anaesthetic, local anaesthetics were instilled through the surgical drains during the post­operative period. Patients had access to intravenous tramadol. Eighteen patients (of twenty) had good pain relief with no side effects during the first twenty-four hours after surgery. We therefore planned a randomized double blind controlled trial to evaluate the efficacy and safety of this regimen.


   Methods Top


We conducted a randomized, double blind, con­trolled trial in 45 patients (ASA Grade I& II) who were posted for modified radical mastectomy from August 2005 to June 2006. Our institutional Ethics Committee and Infection Control Committee approved the study. All patients posted for modified radical mastectomy were screened during the preanaesthetic assessment. Exclu­sion criteria included pregnancy, history of allergy to lo­cal anaesthetics, regular consumption of analgesics, val­vular heart disease (congenital / rheumatic), coronary artery disease, arrhythmias, conduction blocks and liver disease. All patients gave informed consent.

All patients were tested for sensitivity to bupivacaine by an intradermal skin test after the pre - anaesthetic as­sessment, one day prior to surgery. A standard anaes­thetic technique was adopted. Oral diazepam (10 mg) was given one hour before surgery and ondansetron (4 mg) was given intravenously just before induction. Fentanyl (2 mcg.kg -1 ) and a sleep dose of propofol (2-2.5 mg.kg -1 ) was given for induction and neuromuscular blockade was achieved with vecuronium (0.1 mg.kg -1 ) to facilitate tra­cheal intubation. Anaesthesia was maintained with fenta­nyl, vecuronium, isoflurane in nitrous oxide and oxygen as required. Neuromuscular blockade was reversed with neo­stigmine (2.5 mg) and glycopyrrolate (0.5 mg). The inter-costobrachial nerve was preserved in all cases. At the completion of surgery the surgeon placed one drain reaching high up in the axilla and one along the chest incision. The terminal six inches of the drains (16 french) had 50 holes of 2 mm diameter. After closure both drains were con­nected to a closed wound drainage system under negative pressure. After extubation and recovery the drains were checked for collection. The surgeon instilled 10 ml of in­jection A in each drain (see flow chart). The T (tramadol) group of patients received a continuous intravenous tramadol infusion (0.25mg.kg -1 .hr -1 ) and dummy (Normal Saline) intermittent irrigation of the surgical drains. The B (bupivacaine) group received intermittent (8 hourly) drain irrigation (0.4% bupivacaine) with 20 ml bupivacaine and a dummy intravenous infusion of normal saline. The drains were then clamped for twenty minutes. Injection A was instilled in both drains at 8 hourly intervals (with aseptic precautions) by the surgical resident on duty. When the clamp was released excess solution was removed by the negative pressure drains. The intravenous infusion (B) was continued for a period of 24 hours.

[Additional file 1]

Randomization was done by opening numbered sealed envelopes. For trial purposes patients were sub­sequently referred to by their trial numbers. All individu­als involved in the pain assessments of the patients were blinded to the patients treatment group. Three 20 ml sy­ringes and one 50 ml syringe of treatment solutions A and B respectively were prepared for each patient in a sterile fashion by an operating theatre nurse who played no further role in the assessment or treatment of these patients. All the patients were given ondansetron 4 mg at 8 hourly intervals.

The patients were kept under close observation of the anaesthesiologists in the PACU, to assess pain relief and to rule out any immediate side effects. Pulse, blood pressure, electrocardiogram (lead II) and oxygen satu­ration (SpO2) were monitored for twenty four hours by PACU nurses and residents.

Pain was evaluated every two hour by the Acute Pain Service (APS) team. Pain was recorded on a 4 point verbal rating scale - no pain / mild / moderate / severe pain (VRS : none = 0; mild = 1; moderate = 2; severe = 3) [2]. The APS Resident was instructed to ad­minister an intravenous dose of tramadol (50 mg) when­ever the patient complained of pain of moderate inten­sity or greater. Dose restrictions were as follows - Not more than 2 boluses of tramadol (50 mg each) in one hour, and 4 injections in twenty four hours. If a patient needed more than 4 injections i.e. 200 mg in the study period she was to be given supplemental NSAIDS and taken out of the study. The PACU nurses independently recorded pain scores at rest and on movement every 6 hours. Movement was defined as sitting up in bed and flexing the arm on the side of surgery.

Nausea, vomiting, pruritus, sedation [3] respiratory depression, urinary retention, hypotension, ECG changes and other untoward events were monitored. [Table 1] The total dose of analgesics and supplemental anti-emet­ics administered in the day was recorded. Incidence of post operative fever, wound infection/dehiscence and date of discharge and date of suture removal were noted.

The primary objective was to evaluate the pain relief i.e. effectiveness. The secondary outcome was to com­pare side effects and safety profiles.

Statistical methods

Baseline pain scores and mean post treatment pain scores in the bupivacaine and tramadol groups were compared using a Mann-Whitney U test. A 95% confi­dence interval for the difference in medians was calcu­lated using the distribution-free method of Moses [4] .

Incidences of side-effects (nausea, vomiting, uri­nary retention, sedation score > 1, and presence of any of the aforementioned side-effects) were compared us­ing Fisher's exact test.

For all statistical tests, a 2-tailed P-value of less than 0.05 was considered as evidence of a treatment difference. Statistical analyses were carried out using Stata version 9.2 software (Stata Corporation, College Station, TX).

It was determined that 22 patients per group would provide 80% power to detect a difference in mean pain scores of 0.9 of a standard deviation unit, at a 2-tailed type I error of 0.05.


   Results Top


Demographics of patients in both groups were com­parable. At zero hour i.e. on the operation table after extubation the pain scores of both groups were similar (P=0.37). One patient's syringe pump malfunctioned and volume of drug delivered was more than twice the set rate for about 3 hours. This patient was taken out of the trial.

Pain scores were comparable[Table 2]& [Table 3]. There was no significant difference between bupivacaine and tramadol groups in mean pain at rest (P = 0.86) or on movement (P = 0.72). The 95% confidence interval for the difference between median scores in bupivacaine and tramadol groups was -0.25 to +0.25, for both pain at rest and pain on movement[Figure 1]. Rescue doses of tramadol 50 mg were as follows: 23 doses in the "B" Group and 22 doses in the "T" Group. Tramadol con­sumption was 388.63 mg (+ 53.54 ) and 41.3 mg (+38.03) in the T and B group respectively. The "T" Group had a mandatory tramadol consumption of 0.25mg.kg -1 . Only one patient was given 150 mg i.e. 3 boluses as rescue analgesia. No patient needed supplemental non steroidal anti-inflammatory drugs.

The data on side effects is tabulated in [Table 4]. Complaints of nausea. vomiting and uninary retention were more common in Group T. No patients had hy­potension, pruritis or respiratory depression. In all pa­tients the incision and scar were healthy and there was no difference in the date of suture removal and discharge in both groups. Patients in group T had a significantly higher complaint of nausea(P=0.007).


   Discussion Top


There is a lot of emotional and physical pain asso­ciated with mastectomy. The common management of pain is a continuous/PCA opioid infusion [5] . At our centre tramadol is used as a continuous infusion for post mas­tectomy pain. Tramadol is a µ-agonist and norepineph­rine and serotonin reuptake inhibitor [6] . Patients have good pain relief but often complain of nausea, vomiting and occasionally have urinary retention. We conducted an observational study based on a regimen described by Talbot et al [5] with satisfactory results. We therefore planned a double blind randomized controlled trial com­paring two regimens - local anaesthetic irrigation and intravenous tramadol infusion.

The Acute Pain Service monitored the patient ev­ery two hours. This ensured that patients were evalu­ated by trained personnel and there was a reliable pain record for the first 24 hrs. The APS residents were in­structed to give tramadol as specified for all complaints of pain of moderate / severe intensity. This was the clos­est equivalent to a PCA pump that we could devise. The PACU nurses independently recorded pain scores at rest and on movement at 6 hourly intervals. The PACU nurses scores correlated well with the APS scores.

The anaesthesia regimen and operating technique were standard in all patients. All patients were given ondansetron to cover post operative nausea and vomiting(PONV), because this is a high risk patient popu­lation [7] . PONV consensus Guidelines have identified a number of risk factors for postoperative nausea and vom­iting in this population apart from postoperative opioid use i.e. non-smoking, female patients, breast surgery and the use of halogenated agents, nitrous oxide and neo­stigmine [7] . Bupivacaine was instilled after the patient was awake so that any side effects would be apparent im­mediately. The patient was kept under close observation in the PACU. No side effects were seen attributable to bupivacaine in any patient in twenty four hours. No pa­tient complained of paresthesias /numbness / dysaesthesias. No patient had hypotension, ECG changes or respiratory depression.

There was no significant difference between bupivacaine and tramadol groups in mean pain at rest (P = 0.86) or on movement (P = 0.72).

The bupivacaine irrigation decreased the 24 hours requirement of tramadol by more than one fourth. How­ever in Talbot's [5] study PCA morphine consumption in the study and control groups was not significantly differ­ent This could be because they irrigated only the axillary drain based on the premise that this was the source of most pain after a modified radical mastectomy. Accord­ing to Talbot [5] malpositioned drains, blockage of some holes in a multisite drain and the influence of gravity may have prevented infiltration of drug in some cases. He cited patients (not part of their study) in their own practice in whom this technique was effective. He con­cluded that since the technique had worked well for some patients further refinement in the technique was neces­sary.

Perfusion of local anaesthetics for postoperative analgesia through drains /catheters have been described after cholecystectomy [8] and mastectomy [9] caesarian sec­tion [10] and cardiac surgery [11] In fact, abdominal wound perfusion after cholecystectomy can also improve forced vital capacity [8] .

Moiniche et al [12] conducted a qualitative system­atic review of incisional local anaesthesia for postop­erative pain relief. But, they reviewed only single doses in abdominal surgery. Analyzing data from 26 studies (1211 patients) they concluded that in abdominal surger­ies there was lack of evidence for effect (rather than evidence for a lack of effect) of this intervention except for repairs of inguinal hernias.

Fourteen patients in the tramadol group vomited compared to nine patients in the bupivacaine group. But, this difference was not statistically significant. This was despite prophylaxis with ondansetron. Only one patient in the tramadol group was drowsy (but easily a roused). All patients in the bupivacaine group were able to eat six hours after surgery but four patients in the tramadol group had excessive nausea or could not tolerate oral feeds six hours after surgery. Seven patients needed an intervention to pass urine in the tramadol group com­pared to four in the bupivacaine group. Again this was not statistically significant. Significant reduction of post­operative opioid use and nausea have been reported af­ter incisional infiltration in patients undergoing hysterec­tomies [12] and joint replacement [13] . A recent meta-analy­sis [14] showed a significant decrease in postoperative nau­sea and vomiting due to the morphine sparing effect of NSAIDs - For each milligram of morphine spared by NSAIDs the incidence of postoperative nausea and vom­iting decreased by 0.9% and 0.3% respectively. A re­gression analysis indicated that decreased morphine con­sumption due to perioperative use of NSAIDs will sig­nificantly impact on the incidence of nausea, vomiting and sedation. But the decreased consumption of mor­phine due to NSAIDs does not significantly have de­crease urinary retention and respiratory depression [15]. Similar data on tramadol sparing was not available.

In our study four patients in the bupivacaine group vomited soon after rescue intravenous tramadol (within 30 minutes). Studies may be planned using NSAIDs as rescue analgesics.

Safety profile - None of the patients (B and T Groups) had hypotension, respiratory depression or ECG Changes. The maximum single dose of bupivacaine for infiltration is 175mg [16] . The dose we used was 80 mg. which was well within safe limits. Talbot et al [5] used 100 mg.

Animal and in vitro studies have shown that inhibi­tion of healing appears to be a property of all local an­aesthetic drugs [17] . It is a matter of concern in patients who are at a higher risk of wound complications eg. aged, diabetic, obese patients, those with vascular disease [18] , especially in surgeries where there is a risk of an incisional hernia.

From an exhaustive review of acute pain service audits Dolin et al [19] proposed standards of care for the tolerability of acute postoperative pain management - nausea 25%, vomiting 20%, minor sedation 24%, exces­sive sedation 2.6%, pruritus 14.7% and urinary retention requiring catheterization 23%. In our study the bupivacaine regimen satisfies these standards but the tramadol based regimen does not.

The study did have shortcomings. PCA was not available. Most of our patients were unable to rate pain on the visual analogue scale and we had to depend on the verbal rating score.

To conclude, there was no clinically important dif­ference in pain scores between the groups, Tramadol consumption was 388.63 mg (± 53.54 ) and 41.3 mg (±38.03) in the T and B groups respectively and there was a significantly higher incidence of nausea in the tramadol group.

Measurement of quality of recovery unlike "tradi­tional" outcomes of mortality and major morbidity de­pends on the patient's subjective assessment. In a re­cent survey Macario [20] noted that several patients pre­ferred to have less vomiting (associated with decreased opioid use) to less pain. The bupivacaine regimen is effective, but, we need studies adequately powered to detect adverse effects to confirm that this regimen is indeed associated with less morbidity.

 
   References Top

1.Khan-Joad A, Gupta.P, Tiwari M. Efficacy and safety of post­incisional local Anaesthetic for Acute Post-Mastectomy Pain, Indpain 2007 ; 21:21-27.  Back to cited text no. 1      
2.Perttunen K, Nilson E and Kalso E. IV diclofenac and ketorolac for pain after thoracoscopic surgery. Br J Anaesth 1999;82: 221.  Back to cited text no. 2      
3.Ready L. Brian - Regional Analgesia with intraspinal opioids in the management of pain. In Management of pain, second edi­tion Editors John J. Bonica, 1990, Lea and Febiger, Philadel­phia, 1967-80.  Back to cited text no. 3      
4.Hollander M, Wolfe DA. Nonparametric Statistical Methods, 2nd ed. 1999 John Wiley& Sons, Inc, New York,165.  Back to cited text no. 4      
5.Talbot H, Hutchinson S P., Edbrooke DL, et al. Evaluation of a local anaesthesia regimen following mastectomy. Anaesthesia, 2004; 59:664- 667.  Back to cited text no. 5      
6.Bailey Peter L., Talmage D Egan, and Theodore H. Stanley - Intravenous opioid anaesthetics, in Anaesthesia, fifth edition, Editor - Ronald D. Miller, - 2000. Churchill Livingstone, Phila­delphia 273-376.  Back to cited text no. 6      
7.Gan TJ, Meyer T, Apfel CC, Chung F, Pavis PJ, Eubanks S, et al. Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analgesia 2003; 97: 62-71.  Back to cited text no. 7      
8.Levack ID, Holmes JD, Robertson GS: Abdominal wound per­fusion for the relief of postoperative pain. Br J Anaesth 1986; 58: 615-9.  Back to cited text no. 8      
9.Shah K, Shah B, Patel BM. Subcutaneous injection of bupivacaine with or without buprenorphine for post operative analgesia in modified radical mastectomy Surgery. Indpain 2005; vol 19, no. 1, .  Back to cited text no. 9      
10.Gibbs P, Purushottam A, Auld C, et al. Continuous wound perfusion with bupivacaine for postoperative wound pain. Br J Surg 1988; 75 : 923 - 4.  Back to cited text no. 10      
11.White PF. Rawal S, Satham P, et al. Use of a continuous local anaesthetic infusion for pain management after median sterno­tomy. Anesthesiology 2003; 99 : 918 - 23.  Back to cited text no. 11      
12.Moiniche S, Mikkelsen S, Wettersley J, et al. A qualitative systematic review of incisional local anaesthesia for postop­erative pain relief after abdominal operations. Br Journal of Anaesth 1998; 81: 377 - 383.  Back to cited text no. 12      
13.Zohar E. Fredman B, Phillipov A, et al. The analgesic efficacy of patient controlled bupivacaine wound instillation after total abdominal hysterectomy with bilateral salpingo -ophorectomy. Anesth Analg 2001; 93 : 482 - 7.  Back to cited text no. 13      
14.Biranconi M, Ferraro L, Traina G.C, et al. Pharmacokinetics and efficacy of ropivacaine continuous wound instillation after joint replacement surgery. Br J Anaesth 2003;91:830- 5.  Back to cited text no. 14      
15.Marret E, Kurdi O. Zufferey. P, et al. Effects of Non-steroidal Anti-inflammatory drugs on patient controlled analgesia mor­phine side effects. Anaesthesiology 2005;102:1249-1260.  Back to cited text no. 15      
16.Tucker GT, Mather LE. Clinical pharmacokineties of local anaestheties. Clin. Pharmacokinet 1979; 4:241-8.  Back to cited text no. 16      
17.Rawal Narinder. Ambulatory wound and intra articular infu­sions. Indpain 2006; 20:2-17.  Back to cited text no. 17      
18.Brower MC, Johnson ME. Adverse effects of local anaesthetic infiltration on wound healing. Reg Anesth Pain Med 2003; 28:233 - 240.  Back to cited text no. 18      
19.Dolin S.J and Cashman J N Tolerability of acute postoperative pain management: nausea, vomiting, sedation, pruritus, and urinary retention. Evidence from published data. Br Anaesthe­sia 2005;95:584-91.  Back to cited text no. 19      
20.Macario. A. Weinger M, Carney S, et al. Which clinical anaes­thesia outcomes are important to avoid? The perspective of patients. Anesth Analg 1999;89:652-658.  Back to cited text no. 20      


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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