|Year : 2008 | Volume
| Issue : 2 | Page : 164-169
Acute Post Mastectomy Pain: A Double Blind Randomised Controlled Trial: Intravenous Tramadol Vs Bupivacaine Irrigation through Surgical Drains
Anjum S KhanJoad1, Pushplata Gupta2, Malati Tiwari3, Sanjeev Patni4
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 Acceptance||12-Feb-2008|
|Date of Web Publication||19-Mar-2010|
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
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 2013 May 22];52:164-9. Available from: http://www.ijaweb.org/text.asp?2008/52/2/164/60615
| Introduction|| |
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  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|| |
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) . 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  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.
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  .
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|| |
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|| |
There is a lot of emotional and physical pain associated with mastectomy. The common management of pain is a continuous/PCA opioid infusion  . 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  . 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  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  . 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  . 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  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  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  and mastectomy  caesarian section  and cardiac surgery  In fact, abdominal wound perfusion after cholecystectomy can also improve forced vital capacity  .
Moiniche et al  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  and joint replacement  . A recent meta-analysis  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 . 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  . The dose we used was 80 mg. which was well within safe limits. Talbot et al  used 100 mg.
Animal and in vitro studies have shown that inhibition of healing appears to be a property of all local anaesthetic drugs  . 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  , especially in surgeries where there is a risk of an incisional hernia.
From an exhaustive review of acute pain service audits Dolin et al  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  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.
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[Table 1], [Table 2], [Table 3], [Table 4]