Comparative study of continuous thoracic epidural infusion of ropivacaine-fentanyl v/s bupivacaine-fentanyl in upper abdominal surgery for post operative analgesia

 

 

Abstract              Background and Aim: This study was carried out to compare the efficacy and satisfaction level of continuous epidural infusion of ropivacaine and bupivacaine with fentanyl for postoperative analgesia in major upper abdominal surgeries. Material and Methods: A total of 50 patients scheduled for major upper abdominal surgery were randomized into two Groups BF and RF with 25 patients in each group. All patients were administered general anesthesia after placing epidural catheter. Patients received 0.25% bupivacaine with initial volume of 6-12 ml and for surgical procedures lasting more than 2 hrs additional dose of 5-8 ml of 0.25% bupivacaine was given via epidural catheter intraoperatively to maintain surgical analgesia. Postoperatively, they received 0.125% bupivacaine with 5 ug/ml fentanyl (Group BF) or 0.1% ropivacaine with 5 ug/ml fentanyl (Group RF) at the rate 0.1ml/kg/hr. Hemodynamic parameters, visual analog scale (VAS) at rest and movement, verbal ranking score (VRS) and degree of motor block and sedation were monitored for 24 h postoperatively. Results: Hemodynamic parameters, degree of motor block and sedation were comparable in the two groups (p value >0.05). The VAS at rest and movement and VRS were significantly lower in Gr. BF as compared to Gr. RF (p value <0.05). Conclusion: Both the groups are equally safe, with minimal motor block and are effective in providing postoperative analgesia during first 24 hrs but 0.125% bupivacaine with fentanyl 5 ug/ml produces better analgesia and satisfaction level among patients.

Key Words: Bupivacaine, Epidural Infusion, Postoperative Analgesia, Ropivacaine, Visual Analog Scale (VAS), Verbal Ranking Score (VRS)

 

INTRODUCTION

Pain is not merely a sensation which is perceived in direct relationship to stimulus intensity, but is also intimately connected with the emotional and the psychological state of the patient. Unrelieved pain after surgery increases heart rate, systemic vascular resistance and circulating catecholamines that may cause risk of myocardial ischemia, stroke, bleeding and other complications. The fear of pain delays ambulation, which leads to increase risk of deep vein thrombosis and embolism. Besides these detrimental effect, surgery involving the upper abdomen or thorax produces a number of pulmonary complication¹. Control of pathophysiologic processes associated with acute postoperative pain may attenuate the stress response, sympathetic and inhibitory spinal reflexes and may lead to improvements in morbidity². An effective pain therapy to block or modify the physiologic responses to stress has become an essential component of anaesthesia and surgical practice. Effective pain management is associated with patient satisfaction, earlier mobilization, early enteric nutrition, shortened hospital stay, and reduced costs. The analgesic benefits of controlling postoperative pain are generally maximized when multimodal strategy through the use of regional anaesthetic techniques² and a combination of analgesic agents³ to facilitate the patient’s convalescence is implemented ^4,5. Epidural infusion for postoperative analgesia has become a necessity as it provides sustained pain relief as compared to intermittent boluses. Local anaesthetic opioids mixture are preferred for epidural analgesia as this combination provides dynamic pain relief⁶. Fentanyl is commonly used adjuvants opioid as it is lipophillic, having rapid action and clearance and less delayed respiratory depression. Recently ropivacaine is popular local anaesthetic, as it is less toxic, safer than bupivacaine in pharmacodynamic profile and with less motor block because of selective blockade of A delta and C fibre which are involved in pain transmission. Assessment of pain relief not only at rest but also on moving and coughing is an essential component of studies analyzing pain relief methods. We therefore performed VAS scoring at rest and on coughing and movement. Fewer than 10% of studies of post-operative pain relief have examined this critical aspect. Thus in our study we have also attempted to improve the sensitivity of this study by use of more discriminating pain scoring methods. So in this prospective, randomized, comparativ study the analgesic effectiveness and side effects of thoracic epidural infusion of ropivacaine 0.1% with fentanyl 5 µg/ml (group RF) and bupivacaine 0.125% with fentanyl 5 µg/ml (group BF) was evaluated for 24 hrs after upper abdominal surgery.

 

MATERIAL AND METHODS

In this comparative study Patient of ASA grade I-II, 18-60 years of age, having weight not over 20% of ideal body weight, posted for elective upper abdominal surgery incision extending anywhere from upper abdomen to umbilicus with prior written permission were included. They were randomly allocated in two groups, 25 patients in each group.

Group RF:- Continuous thoracic epidural infusion of 0.1% ropivacaine + 5 µg/ml fentanyl at the rate of 0.1 ml/kg/ hr.

Group BF:- Continuous thoracic epidural infusion of 0.125% bupivacaine + 5 µg/ml fentanyl at the rate of 0.1 ml/kg/hr.

Patients with known hypersensitivity to drugs used, coagulopathy, shock, local infection, vertebral deformity, history of addiction to opiods or sedatives, Patient’s refusal for study and evidence of needle or catheter entry into epidural vein or CSF at the time of epidural catheter insertion were excluded from study. Preanesthetic evaluation performed and whenever necessary, specific investigations like ECG, Chest X-ray, Kidney, Liver, Respiratory function tests, serum electrolytes were done. Patients were explained about the procedure, pros and cons of the technique and drug to be used in the present study. Then a written consent was obtained. Patients were instructed to undergo overnight fasting before surgery. They were given tab ranitidine 150 mg and alprazolam 0.25 mg a night prior to surgery and same was repeated on the morning of surgery 1 hr before the schedule operation. On arrival in operation theatre, patient’s vital parameters were recorded and 15 ml/kg balanced salt solution infused prior to block. The procedure was again explained to the patient and asked to sit comfortably on the edge of table, the back was prepared, cleaned with antiseptic solution and was draped. Local infiltration with 2 – 5 ml of 2% lignocaine was done at selected thoracic intervertebral space and then 18 G Tuohy’s epidural needle was inserted with cephalic direction at the selected space and epidural space was identified by “Loss of Resistance” using LOR syringe with air. After identification of space epidural catheter was threaded keeping 4-5 cm of catheter in space. Epidural test dose of 60 mg of lignocaine and 15 µ gm of epinephrine was injected to eliminate intravascular or intrathecal epidural catheter placement.

Supplementation of Surgical Analgesia

Sensory block was provided with 0.25% bupivacaine with initial volume of 6-12 ml and for surgical procedures lasting more than 2 hrs additional dose of 5-8 ml of 0.25% bupivacaine was given via epidural catheter to maintain surgical analgesia.

General anaesthesia

After premedication with 0.05 mg/kg midazolam, 0.2 mg of glycopyrolate, 2µg/kg. fentanyl, patients was induced with propofol 2 mg/kg till the eyelash reflex disappear. The patient was intubated after administration of succinylcholine 1.5 mg/kg and intubated with oral cuffed endotracheal tube and tube was secured at proper place. Anesthesia was maintained with 100% oxygen with halothane (0.75 to 1.5%) and NDMR atracuricum 0.5 mg/kg and repeat 1/5 of initial dose as required. The patients were monitored for the following parameters intra operatively: Heart rate, Blood Pressure, (Systole, Diastole, Mean), ECG, SPO2. On completion of the procedure the residual effect of NDMR was reversed with neostigmine 0.05 mg/kg + glycopyrolate 0.01 mg/ kg and patient was extubated once the clinical signs of adequate recovery appear and patient having intact airway reflexes.The patient was shifted to recovery room and the study period was commence at the time of starting epidural infusion (Time 0 min.) and terminated at 24 hrs post operatively. All the parameters were recorded at 0.25, 0.50, 2, 4, 6, 8, 16, 24 hrs post operatively. The duration of post operative analgesia was measured from time of 0 min to a VAS (Visual analogue scale) score of 4. Top up doses of drugs was administered epidurally whenever the VAS score become more than 4.The following observations were made during post operative period (till 24 hrs.).

1. Analgesia (Degree of pain relief):-

Analgesia was assessed at (0.25, 0.50, 2, 4, 6, 8, 16, 24 hrs) using:

A. VAS (Visual Analogue Score) ranging from 0-10 cm, 0- No Pain 10-Severest possible pain. VAS of less than 4 cm was considered as effective analgesia, 4-7 cm considered as ineffective analgesia and VAS of 7 or more was considered as failure of technique.

B. Verbal Ranking Scale (VRS) as

1. No pain - not restricting any activities i.e. cough or turning into site
2. Mild pain - able to take deep breathe but movement and coughing slightly restricted by pain, physiotherapy effective.
3. Moderate pain - needs help to move to side, coughing and deep breathing restricted by pain, physiotherapy ineffective.
4. Severe pain - pain making turning to side impossible.

2. Changes in Hemodynamic:-

Pulse and mean arteria pressure (MAP) were recorded at (0.25, 0.50, 2, 4, 6, 8, 16, 24hrs) till the completion of study. Intervention for hypotension was not made until the reduction of mean arterial pressure ≥ 20% of base line. If systolic BP decreases to < 90 mm Hg on two readings, 250 ml of intravenous fluids or Inj. mephentermine 6 mg iv bolus was given as required. If systolic BP decreases to < 70 mm Hg the epidural infusion was switched off and patient was given 500 ml of colloid and inj. mephentermine 6 mg IV bolus was repeated as necessary and any intervention for episodes of hypotension was recorded on data collection sheet. Similarly if pulse rate decreases to <60/min, inj atropine 0.6 mg IV given and intervention was recorded.

3. Changes in Respiratory Rate

Respiratory rate was recorded hourly till the end of study. If at any time patient is found to be difficult to arouse or respiratory rate decreases to < 9 /min, the epidural infusion was switched off and patient was reassessed, infusion restarted only if respiratory rate return to > 9 /min.

4. Changes in Arterial Blood Saturation (SPO₂)

The SPO₂ was checked continuously and any patient having SPO₂ <90% was given O₂ via venti-mask at the rate of 5 L/min.

 5. Degree of Sedation:-( Ramsay Sedation Scale)⁷

1. anxious and agitated or restless, or both
2. co-operative, oriented, and calm
3. responsive to commands only
4. exhibiting brisk response to light glabellar tap or loud auditory stimulus
5. exhibiting a sluggish response to light glabellar tap or loud auditory stimulus
6. unresponsive

1. Degree of Motor Blockade (Modified Bromage score as used by Breen et al)⁸
2. Complete block (unable to move feet or knees)
3. Almost complete block (able to move feet only)
4. Partial block (just able to move knees)
5. Detectable weakness of hip flexion while supine (full flexion of knees)
6. No detectable weakness of hip flexion while supine
7. Able to perform partial knee bend

7. Side Effects

Side effect like nausea, vomiting, itching, urinary retention, respiratory depression, muscle rigidity etc was observed and treated accordingly.

8. Need for Rescue Analgesia

Frequency of demand for rescue analgesia was recorded in each group. Rescue analgesic Inj. Tramadol 100 mg IV slowly was injected when patient complains of inadequate analgesia.

9. Patients Satisfaction Regarding the Technique

Good -Patient very happy with the technique and will opt for the same in future if needed.

Fair -Patient satisfied but not very curious about the technique

Poor -Patient not at all happy with the technique

Statistical evaluation:

Group demographic data and adverse events were compared using unpaired t-test or chi-square test, whichever applicable. Comparison of block characteristics, duration of analgesia and haemodynamics were made using unpaired t-test. To compare intragroup variations from baseline, one-way ANOVA with Dunnett’s multiple com-parisons tests was used. The mean comparison between the two groups was done using unpaired t test, two group proportions were compared using Z test for two sample proportion. A P-value of <0.05 was taken as statistically significant. Statistical data were represented as Arithmetic mean, Standard Deviation (S.D.), Standard Error of Mean (S.E.M), Student T-Test and P- value.

DISCUSSION

The identification of opioid receptors in spinal cord by Martin⁹ (1967) opened a new door in the field of post operative pain relief. During spinal and epidural anaesthesia, the applied drugs diffuse directly into the spinal cord ¹⁰, particularly to superficial neurones in laminae I and II of the dorsal horn. Most fine calibre C- and A-fibres terminate within laminae I and II ^11,12 and are therefore considered to be a key element in the nociceptive processing system. Epidural 0.5% Bupivacaine with catheter placed in thoracic region results in effective analgesia after thoracotomy but is associated with unacceptable incidence of hypotension (Holte k 2004)¹³, but when bupivacaine is used as the sole epidural agent in lower concentration to avoid sympathetic blockade, analgesia was inadequate ( Le Coq G,1998)14 Concerning epidural administration of opioid/local anaesthetic mixtures, clinical studies have produced conflicting results. Badner et al ^15,16 reported no advantages to pain relief by adding Bupivacaine 0.1% to Fentanyl 0.001% for postoperative epidural analgesia. Others reported that low doses of epidural Morphine and Bupivacaine reduced pain more than Morphine alone during mobilization and coughing, but not at rest ¹⁶; while Cullen et al demonstrated that pain scores in patients receiving an epidural infusions of opioid local anaesthetic mixture were superior to those of patients receiving Bupivacaine alone ¹⁷. Fentanyl has emerged as a suitable opioid for infusion into epidural space because it is more lipophilic, easily crosses the lumber dura and quickly penetrates the lipid phase of underlying tissue of the cord. Thus analgesia is rapid, sharply segmented with few side effects resulting from migration of opioid in the rostral direction and no delayed respiratory depression. The infusion rate used in various studies also varied from 0.5-1.5 µg/kg /hr ^18,19,20. Many of the dose finding study used Fentanyl alone in concentration of 10 µg /ml, in a subsequent study in which fentanyl was combined with 0.125% levobupivacaine an optimal concentration of 4 µg/ml was recommended.²¹ Ropivacaine is newly introduced local anaesthetic, produces less motor block compared to same dose of bupivacaine but the role of ropivacaine alone in postoperative pain relief is unsatisfactory. A study comparing three doses of ropivacaine with fentanyl observed that motor block was less with 0.1% ropivacaine- 2 µg fentanyl and 0.05% ropivacaine- 1 µg fentanyl compared to 0.2% ropivacaine-4 µg fentanyl and concluded that concentration of local anaesthetics at low doses is a primary determinant of motor blockade in postoperative epidural analgesia.²² So we used 0.1% ropivacaine with 5 µg fentanyl in our study. A dose of 4-12 mg/hour of bupivacaine when combined with morphine 50 µg /ml, fentenyl 10 µg/ml, sufentanyl 1 µg/ml ²³, administered via a thoracic epidural catheter has been shown to provide effective dynamic pain relief. The Addition of opioids, therefore significantly reduces the hourly requirement of bupivacaine from 25-45 mg/hour when used alone. In a recent study, the two most effective regimens were bupivacaine 8 mg/hour and fentanyl 30 µg /hr or bupivacaine 13 mg/hour and fentanyl 25 µg/hour both infused at 9 ml/hour.²⁴ We have adopted a mid pathway and have used ropivacaine at a dose of 6 mg/hr (0.1% @0.1ml/kg/hr), bupivacaine at a dose of 7.5mg/hr (0.125% @0.1ml/kg/hr) and fentanyl at a dose of 30 µg/hr (5µg /ml) and have found that this combination of Local Anaesthetic and opioid also acts as a safe and effective one. By this combination the amount of Local Anaesthetic decreases further, hence the fluctuation in hemodynamic and degree of motor blockade can be minimized. Both the groups were comparable in regards to age, sex, height, weight, physical status according to ASA classification, nature of surgery, and technique of general anaesthesia etc.

The mean body weight of patients in group RF and BF was 59.48 and 59.68 kg. No significant difference in mean pulse rate between both the groups at 0.25, 0.50, 2, 4, 6, 8, 16 and 24 hrs was observed. None of the patient had tachycardia (pulse rate >120 min) or bradycardia (pulse rate <60 min). An insignificant change in pulse rate has also been observed by K. Laxmi et al²⁵. Decrease in mean arterial pressure of approximately 5% and 6% from base value was observed in group RF and BF respectively. Statistically there was no significant difference in mean MAP between the patients of both the groups in post-operative period. However, there was reduction in mean MAP in both the groups from pre-operative value i.e. 96.3± 5.69 mm Hg and 97.2±4.21 mm Hg in group RFand BF respectively to 92.50±4.31 mm Hg and 94.2±6.52 mm Hg in group RF and BF respectively at 0.25 hr after start of infusion in post-operative period.

RESULTS

 

Table 1: Patients characteristics

As shown in above table no. 1 the mean age, body weight and height was 41.48±7.14 and 43.12 ±6.80 yrs, 59.48±7.59 and 59.68±6.29, 165.00±7.8 and 164.00±8.72 cm in Gr. RF and Gr. BF respectively. Statistics showed insignificant difference in above parameters. (p>0.05) 18 patients were of ASA grade I, and 32 patients were of ASA grade II.

 

Table 2: Comparison of various parameters observed upto 24 hrs postoperatively and rescue analgesia

 Preoperative Mean pulse rate was 85.10±6.4 and 85.50±4.92, which decreased to 79.1±5.11 and 82.4±4.87 per min in Gr. RF and BF respectively at 24 hours post operatively. Similarly preoperative mean arterial pressure and respiratory rate was 96.3±5.69, 97.2 ±4.21 mm Hg and 16.2±1.58, 15.9±1.68 per min in Gr. RF and BF respectively and it remain almost unchanged thought out study period. The statistical analysis at regular interval was comparable between both the groups. Mean VAS, VAS on coughing and movement and VRS score was significantly lower in Gr.BF as compared to Gr.RF during most of the study period. Above table shows episodes of pain in both groups. Two patients in group RF at 0.50 hrs and one patient in group BF at 2 hrs had an episode of pain. . The observation was statistically insignificant between the two groups.

 

Table 3: Degree of sedation and motor blocks in postoperative period

Post operative sedation was either grade 2 or grade 3 in both group during most of the study period and it was statistically nonsignificant. No case of grade 1, 2, 3, 4 motor blockade was observed in group RF and BF. The observation was statistically insignificant between the two groups.

 

Table 4: Adverse effects

Adverse events like respiratory depression, itching, urinary retention, muscle rigidity did not occur in any patients. 5 patients suffered from nausea and two patients suffered from vomiting in Group RF and 1 patient in Group-BF suffered from nausea and vomiting. Incidence was not significant statistically.

Table 5: Patients Satisfaction level

Patients Satisfaction	Number of Patients
	Group RF	Group-BF
Good	18(72%)	20(80%)
Fair	5(20%)	5(20%)
Poor	2(8%)	0(0%)

 

 

 

 

 

 Above table shows 72% of group RF and 80% of group BF patients had good, 20% each of Group RF and BF had fair and 8 % of Group RF and none of Group BF had poor satisfaction.

Thereafter, there was slight decrease in mean MAP which remained almost at steady level throughout the observation period. The initial slight fall in mean MAP might be due to autonomic effects as observed by Marcus Vinicus et al²⁶.No significant changes in SPO2 were observed between two groups. Similar results were observed by Pouzeratte et al19 K. Laxmi et al²⁵Akifumi et al²⁷ Finucane et al²⁸ and Patil SS et al²⁹. No case of respiratory depression was observed in the study. Respiratory rate was 16:2±1.58 /min and 15.9±1.68 /min in group RF and BF respectively. In post-operative period respiratory rate remained almost unchanged with no statistical significance between both the groups of patients. Similarly, respiratory depression was not observed in either group by Antonio Macias et al30. Although Hays RL et al³¹ demonstrated mild to moderate respiratory depression with increased PaCO2 in few patients with epidural Fentanyl but the dosages used by them were high (1 µg/kg/hr-1.95 µg/hr), while in our study only 0.5 µg/kg/hr dose was used. The efficacy of the technique on VAS at rest was also qualitatively better in group BF. But it decreases steadily with the progression of infusion in both the groups. This is similar to the findings reported in earlier studies.^29,32,33,34 Mean VAS score during coughing or movement was statistically and comparatively much less in patients who received bupivacaine and fentanvl in comparison to patients who received ropivacaine and fentanyl. The mean VAS score during dynamic activity was 5.84 vs 4.4 cm, 5.84 vs 4.40cm, 5.08 vs 3.96cm, 4.60 vs 3.44cm, 3.76 vs 2.92cm, 3.32 vs 2.72cm, 3.12 vs 1.60cm and 2.72 vs 1.36cm in group RF and BF respectively at 0.25,0.50,2,4,6,8,16 and 24 hrs of observation suggesting that addition of bupivacaine to fentanyl provides better pain relief during movement. Our results are in accordance with findings of previous studies, Scott MB et al ²¹, Wie balack albrechte²³, H.Jorgenson³³, Torda T.A. et al³⁵, Cooper D.W. et al36, Crew J.C.³⁷ who founded that a mixture of local anaesthetic agents with opioid provide better pain relief particularly in terms of dynamic pain relief in comparison to epidural administration of local anaesthetic agents or opioids alone. In contrast to our study K. Laxmi et al²⁵ found better analgesia in ropivacaine fentanyl group which might be due to different doses used i.e. 0.2% bupivacaine with fentanyl 2µg /ml and 0.2%ropivacaine with fentanyl 2µg/ml. Similarly the verbal ranking score was lower in group BF as compared to RF which was statistically significant at all the specific time of observation. Our findings support the findings of Yvan Pouzeratte et al19, H Jorgensen et al³³. Two patients in group RF and one patient in group BF required rescue analgesia. Pouzeratte et al.19 , Jørgensen et al.³³, Casati et al.³⁸and Surabathuni et al³⁹ reported that the need for rescue analgesia was more in the ropivacaine group than the bupivacaine group, similar to our study. Majority of patients both groups were alert or mildly sedated, and as the time passed patients became more alert in both groups due to development of tolerance. Mild sedation may be beneficial as the patients remain anxiety free and less complaining. Sedation produced by epidural opioids may be the result of drug in CSF to receptors in thalamus, limbic system and cortex as well as systemic absorption. Due to high lipid solubility, rostral spread of drug through CSF is very less, this explains lower incidence of sedation in epidural fentanyl infusion. 2 patients at 0.25 hrs and 2 patients at 0.5 hrs and 1 patients at 2 hrs in Gr. BF having grade 5 motor blockade which might be due to continued effect of intraoperative 0.25% bupivacaine which resolved at later hrs but it was statistically non significant between both the groups. Similiar results are also reported by Patil SS et al²⁹. More incidences of nausea and vomiting were reported in group RF patients (28%) in comparison with group BF patients (8%) but the difference was statistically insignificant (P>0.1). Nausea and vomiting has easily controlled with injection ondensteron 4 mg I.V. Our results are comparable with the incidence observed by K. Laxmi et al²⁵, Patil SS et al²⁹ who also observed no significant difference in incidence of nausea and vomiting between the two groups. Opioids stimulate the chemoreceptor trigger zone in the area postrema of medulla. They also increase GI secretions, decrease GI tract activity and prolong emptying times. All these action promotes nausea and vomiting. Muscle rigidity can occur due to administration of fentanyl, large doses of fentanyl may pose this problem and older patients experienced a high incidence of rigidity after intravenous opioids. Since all the patients of our study were middle aged and fentanyl was used in small doses none of the patients suffered from this problem. Maximum number of patients of both the groups highly satisfied and happy to receive same technique of postoperative analgesia in future.

 

CONCLUSION

In our study, a continuous thoracic epidural infusion of 0.1 mL/kg/hr of 0.1% ropivacaine/fentanyl 5 μg/mL provides an adequate pain relief and similar analgesia to 0.125% bupivacaine/fentanyl 5 μg/mL during the first postoperative day after upper abdominal surgery without causing a concernable degree of hypotension or motor weakness. But patients receiving bupivacaine/fentanyl provides better analgesia with good satisfaction level among patients.

 

 

 

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