Comparative study of bupivacaine plus xylocaine with adrenaline versus bupivacaine plus xylocaine with adrenaline plus fentanyl in intrapleural block for post operative analgesia for modified radical mastectomy cases

Abstract 
Background: Postoperative pain plays a significant role in the pathogenesis of postoperative pulmonary complications after upper abdominal and thoracic opera¬tions. Diminishing lung volumes due to acute


Introduction
Effective postoperative analgesia is a very essential component of the care of the surgical patient. Inadequate pain controlmay result in increased rate of morbidity or mortality. Evidence suggests that surgery suppresses the immune system proportionate to the invasiveness of the surgery. Good analgesia can effectively reduce this deleterious effect. Various studies available indicate that afferent neural blockade with the help of local anaesthetics is the most effective a technique of analgesia. The advantages of effective postoperative pain management include patient comfort and therefore satisfaction, earlier mobilization, reduced pulmonary and cardiac complications, a lowered risk of deep vein thrombosis, faster recovery with less likelihood of the development of neuropathic pain, and reduced cost of care [1].
The adverse sequels of postoperative pain are numerous. Patients with significant postoperative pain may demonstrate anxiety, fright, insomnia which often exacerbate their pain perception rendering the postoperative recovery period an unpleasant and ominous experience. Other pain related stress responses include coagulation system activation, aggregation of platlets and fibrinolytic system alteration which may increase clotting leading to deep venous thrombosis and pulmonary embolism. Pain increases the sympatho-adrenal outflow of catecholamines leading to dysrhythmias, tachycardia and hypertension.
Postoperative pain is one of the major factor in postoperative pulmonary complication especially after upper abdominal and thoracic operations. Reduction of lung volumes due to acute restrictive pulmonary dysfunction secondary to pain may result in relative hypoxemia, major atelectasis and pulmonary consolidation.
Breast cancer surgeries are commonly performed under general anaesthesia which is the standard technique, but is associated with acute post-operative pain further aggravated by the arm and shoulder movements [2,3]. Concomitant use of regional blocks can not only help to minimize pain, but also improves the pulmonary function and reduce narcotic requirement during the perioperative period [4,5]. Among the regional techniques such as intercostal nerve block, thoracic epidural, thoracic paravertebral block (PVB), and inter pleural block (IPB), the last two are commonly being used to provide intra and post-operative analgesia in patient undergoing modified radical mastectomy [6,7]. Perioperative hypertension, tachycardia, headache, nausea, vomiting, and pain are frequently seen following breast surgery. This pain restricts shoulder movement postoperatively and may not be responding except for parenteral narcotics that have an emetogenic effect that needs further observation of these patients [8]. It is widely assumed that when postoperative patients are relatively pain free, their pulmonary functions are improved [9].
Intrapleural regional analgesia is a method of postoperative pain relief reported by Reiestad and Stromskug [10]. This technique provides a unique form of regional analgesia that has proven advantageous for upper abdominal surgical interventions and breast surgeries.

Subjects and Methods
After clearance from Institutional Ethics Committee, the study was carried out in patients undergoing Modified Radical Mastectomy (MRM). It was a randomized prospective double blind study. The observer and the patient were blinded for the study drug.
After careful pre-anaesthetic evaluation, 80 female patients diagnosed with Carcinoma of Breast in the age group of 20-69 years, American Society of Anaesthesiologist (ASA) physical status I, II or III who required MRM were included in the study.

Inclusion criteria
All the cases undergoing radical mastectomy of ASA grade I, II, III. Patients with emphysema and chronic obstructive pulmonary disease (as these respiratory pathologies may have hyper inflated lungs with air filled bullae, injury to which may be difficult to predict and prevent complications). • Previous or planned pleurectomy Informed consent for General anaesthesia as well as Intrapleural block (IPB) was obtained from the patients and care takers in the prescribed format. The patients were randomly allocated into two groups by computer generated random number sequence in 40 patients each. Odd numbers were given to group B (control group) and the even numbers were given to Group BF.
In this study, we use a posterior approach for giving interpleural block and perform injections with the patient in lateral position with affected side upwards before giving general anaesthesia. Consent for the procedure was obtained as per Institution protocol. The block was performed inside the Operation Theatre with an appropriate area which offered privacy, good lighting and ensures sterility, and with oxygen, monitoring and resuscitation drugs and equipment availablereadily. A senior anaesthetic assistant was always present to watch for procedure and full aseptic precautions observed (Photos 1-3).
The following parameters were noted 1. Time taken for onset of sensory blockade 2. Maximum level of sensory blockade attained 3. Intraoperative Hemodynamics. 4. Duration of sensory block 5. Duration of analgesia 6. Postoperative sedation 7. Postoperative pain score-Verbal Rating Scale (VRS) and Visual Analog Scale (VAS).

Postoperative Lung volumes and Peak Expiratory Flow
Rate (PEFR) 9. No. of rescue analgesia required in 24 hours.

Adverse effects
Onset of sensory blockade was taken as a time taken from the complete injection of study drug till the patient does not feel the pin prick at T4 level.
Duration of analgesia was considered as the time taken doi: 10.7243/2049-9752-8-1 from the completion of the injection of the study drug till the patient requests for analgesic in the post-operative period. Intravenous Diclofenac sodium 75mg was given as the rescue analgesic if the VAS pain score was ≥4. Same dose was repeated whenever patient complained pain afterwards and number of doses counted for 24 hours.

Statistical analysis
Data analysis has been done using the Microsoft excel software 2007. Sample size was calculated on assuming 80% statistical power and 5% α error. Sample size calculation was based on the presumption that post-operative requirement of inj. Diclofenac sodium as an analgesic drug as per VAS score and VRS taking the difference of 50 mg [among the total requirement] in 24 hours in both the group as (d) and Standard Deviation was taken 76.8 from the previous study. Considering dropouts total 40 patients in each group will be enrolled.
An unpaired t test was used to compare demographic variables, intra operative hemodynamic variables (heart rate, systolic blood pressure) oxygen saturation, and onset and duration of sensory and motor block between the groups. Sedation scores and pain scores were compared, while rescue analgesic requirements in both groups were compared by Chi square test. Inspiratory reserve volume, expiratory reserve volume, tidal volume and peak expiratory flow rate (PEFR) were also assessed. Intergroup comparison was done, using unpaired "t" Test and comparing mean and standard deviation.
A "p" value <0.05 was taken as significant and "p" value <0.001 was taken as highly significant. All the values were presented as Mean ± SD. Confidence Interval were calculated using Microsoft excel software 2007.

Results
Eighty patients were recruited. All the patients underwent radical mastectomy and received their allocated study drug. No assigned patients dropped out of the study. Demographic profile and surgical data were statistically comparable in both the groups (Tables 1 and 2). Mean Arterial pressure in group B and group BF before and after giving intrapleural block as well as intraoperatively and postoperatively were recorded. There were no statistical significant difference in both the groups throughout the procedure (Figure 1). Mean time of onset of sensory block in group B was higher (21.925±2.15 minutes) than in group BF (15.4±2.26 minutes) which was statistically significant {p<0.01} (Figure 2). Confidence interval of 95% cases of Group B is 22.592 to 21.258 min and Group BF is 16.10 to 14.69 min. Mean duration of sensory block in group B was 3.5125±0.51 hours and in group BF it was 6.45±1.13 hours which was significantly higher {p<0.01} in group BF than group B (Figure 3). Confidence interval of 95% cases of Group B is 7.95 to 6.70 hours and Group BF is 11.61 to 10.99 hours. Mean duration of analgesia was significantly higher in group BF (11.3±1.00 hours) than group B (7.95 to 6.70 hours)      6 shows mean VRS and VAS pain score in group B and group BF in postoperative period. There was no statistical significant difference in both the groups initially upto 240 minutes postoperatively. But after 240 minutes, the mean VRS and VAS score was consistently high in group B than group BF which was statistically significant {p>0.05}, which shows that addition of fentanyl had prolonged the duration of analgesia beyond 240 min.
Mean Peak Expiratory Flow Rate was comparable in both the groups preoperatively {p>0.05}. In postoperative period there was reduction in PEFR in both the groups in immediate postoperative period followed by gradual improvement in PEFR. The difference in both the groups was statistically not significant till 4 hrs postoperatively. But after 4 hr postoperatively there was statistically significant difference in PEFR in both the groups {p<0.05}. More improvement in PEFR was noted in group BF, suggesting early improvement in PEFR than group B. We noticed nausea, vomiting, chest   pain, coughing during procedure, pruritus in patients of both the groups. There was no incidence of any intra-operative or post-operative complications like convulsion, hypotension, bradycardia, pneumothorax and respiratory depression.

Discussion
Intrapleural analgesia consists of the injection of a local anaesthetic into the pleural space. Intrapleural blockade is the technique of giving local anaesthetic in between two pleurae (parietal and visceral) to produce ipsilateral somatic block of various thoracic dermatomes. It also helps to reduce the pain by spread of local anaesthetic bilaterally to block both the splanchnic nerves and the sympathetic chains. It is effective in treating unilateral surgical as well as non-surgical pain from upper abdomen and chest in both the acute and chronic settings. Local anaesthetic solutions can be given as single or intermittent doses, or as continuous infusions via an indwelling intrapleural catheter.
Intrapleural analgesia has gained popularity because of its low rate of complications. Local anaesthetics as well as opioid agents administered via a catheter placed inside the pleural cavity have been used to anesthetize intercostal nerves to relieve pain.
Opioids administered by various routes are still the mainstay of analgesia for various upper abdomen surgeries pain management. However, systemic opioids have the potential for good pain relief at rest with a lack of effective pain reduction when coughing or breathing deeply. In addition, opioids may cause adverse effects such as respiratory depression, somnolence, prolonged nausea or vomiting and pruritus, when administered via a systemic or epidural route. Patients receiving epidural narcotics may also need care in a setting that monitors their respiration. Adverse effects seen with systemic and epidural opioids may be avoided when using opioids intrapleurally [11].
Various authors have observed that, addition of adjuvant to local anaesthetic for IPB not only provides excellent analgesia but also reduces the hemodynamic response to surgery and the intraoperative anaesthetics and analgesic requirements with better emergence from anaesthesia with fewer side effects, a prolonged pain-free period, improving the respiratory performance and giving a rapid mobilization and overall better quality of postoperative recovery which is essential in the reduction of immediate postoperative complications. There was no statistical significant difference in heart rate (p>0.05) in both the groups throughout the procedure. It was noted that MAP was maintained at lower side in group BF throughout the procedure as compared to group B though not statistically significant (p>0.05 In their study, they noted that there was gradual improvement of PEFR in both the groups but that has no significant difference with bupivacaine alone group. Shideh Dabir, MD, Tahereh Parsa, MD et al [11] (2008) findings are also in favour of our findings. In their study "Intrapleural Morphine vs Bupivacaine for Post thoracotomy Pain Relief" (n=36) they came to the conclusion that, the number of patients who received intravenous morphine supplementation was significantly less in the morphine group than the bupivacaine group.
Complications in both the groups were statistically not significant, but few side effects specifically related to fentanyl, like pruritis was noted but needed no treatment, reassurance was sufficient. Bourke DL, Furman WR [16] (1993) studied, postoperative analgesia with morphine added to axillary block solution and concluded that, in study group where patients received morphine 0.1 mg/kg added to their axillary block solution, there were no major complications as compared to control group, who received saline added to their axillary block solution.

Conclusion
From this study we conclude that, when fentanyl was added as an adjuvant in intrapleural block, it fastens the onset of sensory block, prolongs duration of sensory bock, extends total duration of analgesia and has better preservation of respiratory functions compared to bupivacaine plus xylocaine-adrenaline alone. Intraoperatively hemodynamic stability was achieved in both the groups with no statistical significant difference in mean blood pressure and mean heart rate.