ABSTRACT

Corresponding Author:
Purba Haldar,
Flat: L-3, Block: IV,
Swabhumi Residency, P-12,
Motijheel Avenue,
Kolkata-74.
E-mail: purbahaldar@gmail.com

ABSTRACT

BACKGROUND

Epidural analgesia with local anaesthetics and opioids provide good control of postoperative pain in lower abdominal and lower extremity surgery.

AIM

To evaluate and compare the analgesic action and adverse effects of epidural bupivacaine, fentanyl and their combination in postoperative period.

METHODS

75 patients undergoing elective infraumbilical surgery were allocated in three groups in a randomized double blinded fashion. Postoperative analgesia was maintained with continuous infusion of epidural drug in the following manner: Group B: Injection Bupivacaine 0.125% @ 0.1mL/kg/hr through epidural route; Group F: Injection Fentanyl 4µg/mL @ 0.1mL/kg/hr through epidural route; Group BF: Injection Bupivacaine 0.0625% and Fentanyl 2µ/mL @ 0.1mL/kg/hr through epidural route.

RESULTS

VAS score were almost similar in all three groups at 00, 04, 08hrs and not clinically significant at that point of time. VAS score showed significant difference at 12, 20 and 24 hrs, being persistently lower in Gr BF than Gr B and Gr F. According to VRS Scale Score at 04 hrs majority of patients of all three groups had mild-to-moderate pain (p=0.278). At 08 hrs, 24% (p=0.082), 12 hrs 60% (<0.001), 16 hrs 68% (<0.001), 20 hrs 88% (<0.001) and 24 hrs 84% (<0.001) of Gr BF patients were pain free which are clinically significant. At the end of 08, 12, 16, 20, 24 postoperative hours, no patients of any groups had residual motor paralysis. Rescue analgesic needed in Gr BF patients were significantly less than other two groups.

CONCLUSION

Combined bupivacaine and fentanyl infusion through an epidural route provides better analgesia in comparison to bupivacaine and fentanyl alone. Total drug, rescue analgesic requirement and adverse effects are much lower in combined group.

KEYWORDS

Postoperative Analgesia, Epidural Infusion, Bupivacaine, Fentanyl, Combination.

INTRODUCTION

Acute post-operative pain is a complex physiologic reaction to tissue injury, visceral distention or disease, which results in patient specific unpleasant, unwanted sensory and subjective emotional experience.¹

The epidural route for analgesia has been used much more extensively for postoperative pain management. It provides the advantage of prolonging the analgesia with an epidural catheter using epidural local anaesthetic drug and

Chi square test 2- tailed p value < 0.001.

DISCUSSION

Analgesia delivered through an indwelling epidural catheter is a safe and effective method for management of acute postoperative pain. Studies have shown that the neuraxial administration of opioid provide profound analgesia with fewer central and systemic side effects than opioid administered systemically, particularly when local anaesthetic  (Morgan M, 1989) are used.

The duration of action of epidural fentanyl is short. Excellent results have been reported with continuous infusion of fentanyl postoperative analgesia. The choice of local anaesthetic drug play a role in regional anaesthesia. In this study, bupivacaine was chosen because fentanyl added to bupivacaine decreases the requirement of local anaesthetic. This advantage of fentanyl is lost if local anaesthetic used is lignocaine (Breen 1992). Continuous epidural infusion of drugs were used to provide the postoperative analgesia for twenty four hours and also continued where necessary. This made the patient more comfortable and also made the study less expensive.

At 4^th and 8^th postoperative hour HR in Gr F were greater than HR in Gr BF. At 20th hour HR of Gr B was greater than HR in Gr BF. Systolic blood pressure was consistently lower in Gr BF than other groups at all-time point from 08 hrs to 24hrs.

There were significant difference in systolic blood pressure at different point of time. Diastolic blood pressure in Gr BF was significantly lower than other two groups at 04, 08, 12, 20 and 24 hours. Difference was not significant at 16 hrs. VAS score were almost similar in all three groups at 00, 04, 08 hrs and they did not show any significant difference at these point of time. VAS score showed significant difference at 12, 20 and 24 hrs, being persistently lower in Gr BF than Gr B and Gr F. According to Verbal Rating Scale Score at 04 hrs majority of patients of all three groups had mild-to-moderate pain (p=0.278). At 08 hrs, 24% (p=0.082), 12 hrs 60% (<0.001), 16 hrs 68% (<0.001), 20 hrs 88% (<0.001) and 24 hrs 84% (<0.001) of Gr BF patients were pain free, which are clinically significant.

Rescue analgesic needed in Gr BF patients were significantly less in comparison to Gr B (P=0.002) and Gr F                      (P=0.001).

Milon D and Coworkers.⁴ In 1986 found bupivacaine-fentanyl provide better analgesia without any clinically significant respiratory depression in mother and foetus in epidural anaesthesia for caesarean section. Sintara RS et al.⁵ in 1991 in their study of labour analgesia concluded that epidurally administered fentanyl safely extend the duration of labour analgesia while reducing bupivacaine drug dose requirement and magnitude of motor block. Addition of fentanyl to extradural loading dose and subsequent infusion of local anaesthetic is a satisfactory alternative to giving higher doses of local anaesthetic alone. Copper D et al.⁶ in 1993 studied that in patient controlled extradural analgesia, bupivacaine and fentanyl combination provide better postoperative analgesia than either drug alone. Bander et al.⁷ in their study in 1994 concluded that bupivacaine improves continuous postoperative fentanyl analgesia after abdominal and thoracic surgery.

Oczan S and co-workers.⁸ in 2004 observed that pre-emptive administration of epidural fentanyl-bupivacaine combination reduces the postoperative pain and analgesic consumption in lower abdominal surgery. Continuous infusion provides effective analgesia, while reducing the side effects associated with bolus administration. El-Baz et al.⁹ in 1994 described that continuous epidural morphine (100µg/hr) provides equivalent analgesia and fewer side effects than after epidural boluses of either bupivacaine (0.5%) or morphine (5mg).

In our study, bupivacaine (0.0625%) and fentanyl (2µg/mL) combination provides adequate postoperative analgesia than either drug alone, which is consistent with all these previous studies. Continuous infusion of local anaesthetic drug with opioid has reduced the drug dose requirement, adverse effects and requirement of rescue analgesics.

Advantage of epidural administration of drugs, such as opioids and local anaesthetics include the reduced incidence of side effects and a diminished propensity for opioid induced ventilatory depression compared with the intrathecal route. When a drug is placed in the epidural space, it must first cross the dura before it can reach the spinal cord. Besides the physical barrier presented by the dura, the epidural space is highly vascularized and a significant redistribution of drug to the systemic circulation occurs. The epidural space also contains fat, connective tissues, a lymphatic network and the dorsal and ventral roots of the spinal nerves, all of which can serve as a repository for lipophilic agents.

Because the diffusion of drugs across the dura is both concentration and time dependent, it is necessary to administer significantly larger amounts of drugs than those that effectively saturate spinal opiate receptors. These higher doses are more likely to produce unwanted side effects from systemic and rostral distribution of drugs, but fewer than associated with equianalgesic intrathecal doses. When these factors are considered, the margin of therapeutic safety and the decrease in the side effects with epidural administration make this route preferred for postoperative analgesia.

Effective analgesia with epidural infusions administered at a continuous rate may take as long as 3 to 4 hours to achieve. Delay in onset of effective analgesia can be reduced by adjusting the infusion rate to provide the equivalent of a small (5 to 10mL) bolus of an epidural solution over 5 to 15 minutes before beginning the maintenance infusion. This allows an adequate concentration of the analgesic drugs to be present at their sites of action in a shorter time.

In addition to a reduction in adverse effects, another advantage of a continuous epidural infusion over an epidural bolus injection is the ability to titrate the amount of analgesia; particularly shorter acting opioid like fentanyl is used. Fentanyl has an onset of action within 4 to 5 minutes and a peak effect within 20 minutes.^{10, 11} Because of the rapid onset, it becomes much easier to adjust the dosage, to observe the desired effect, and titrate to an optimal intensity of analgesia.

The continuous infusion also maintains a more constant intensity of analgesia. It can provide analgesia avoiding the peaks and nadir of pain sensation seen with intermittent bolus dose.

Lipophilic drug such as fentanyl tend to provide more of a segmental analgesic effect. This may in part be the result of lipophilic compounds partitioning into lipid compartments in the spinal canal, such as epidural fat and spinal cord. This segmental nature of analgesia mandates the need to place an epidural catheter in a location to cover the dermatomes included in surgical field. For orthopaedic operations in the lower extremities and lower abdominal and gynaecologic surgery, catheter has to be placed at lumbar region. Alternatively, catheter placement should be approximately at the dermatomal level that corresponds to a point intersecting the upper one-third and lower two-thirds of the surgical incision.

Epidural co-administration of opioids with local anaesthetics takes advantage of the desirable properties of each drug. The desired result of these combinations are achievement of potentiated analgesia at lower opioid doses with diminished propensity for opioid induced ventilator depression.¹² and a concentration of local anaesthetic that does not produce significant motor blockade.

This potentiation may be a result of antinociception at different sites in the spinal cord.¹³ Opioids produce analgesia by binding to opiate receptors in the substantia gelatinosa, whereas local anaesthetics block transmission of afferent impulses at the nerve roots and dorsal root ganglia.¹⁴ Another advantage of the combination using reduced doses is the concomitant decrease in the incidence and severity of side effects. Despite wide acceptance, not all studies have demonstrated analgesic potentiation when bupivacaine and fentanyl have been used in combination.

CONCLUSION

In conclusion, this study shows that combined bupivacaine and fentanyl infusion through an epidural route provides better analgesia in comparison to bupivacaine and fentanyl alone. Total drug administered in combined group is much less than that of isolated drug group. Rescue analgesic required in combined bupivacaine and fentanyl group is also less than that required in the isolated drug group. Regarding adverse effects, epidural administration of bupivacaine along with fentanyl dose not show any increase in adverse effect. So continuous epidural infusion of bupivacaine and fentanyl can be safely considered for prolonged and improved quality of analgesia in patients undergoing lower abdominal and lower extremity surgery.

REFERENCES

1. Paul G Barash, Bruce F Cullen, Robert K. Stoelting clinical Anaesthesia. 5^th edition:691–692.
2. Kehlet H, Dhal JB. The value of multimodal or balanced analgesia in postoperative pain relief. Anaesth Analg 1993;77:1048-1056.
3. Prithvi Raj P. Textbook of Regional Anaesthesia. Page 218–219.
4. Milon D, Lavenac G, Noury D, et al. Epidural anaesthesia during labour: comparison of 3 combinations of fentanyl-bupivacaine and bupivacaine alone. Ann Fr. Anaesth Reanim 1986;5(1):18-23.
5. Sintara RS, Goldstein R, Sevarino FB. The clinical effectiveness of epidural bupivacaine, bupivacaine with lidocaine, and bupivacaine with fentanyl for labour analgesia. J Clin Anaesth 1991;3(3):219-24; discussion 214-5.
6. Copper D, Turner G. Patient controlled extradural analgesia to compare bupivacaine, fentanyl and bupivacaine with fentanyl in treatment of postoperative pain. Br J Anesthesia 1993;70:503-7.
7. Bander NH, Bhandari R, Komar WE. Bupivacaine 0.125% improves continuous postoperative epidural fentanyl analgesia abdominal or thoracic surgery. Can J Anesth 1994;41:387-92.
8. Ozcan S, Tabuk M, Baltaci B, et al. Is epidural pre-emptive analgesia effective in El-Baz NM, Faber LP, Jensik RJ, Continuous epidural infusion of morphine for treatment of pain after thoracic surgery: a new technique. Anaesth Analg 63:757,1984 lower abdominal surgery? Agri 2004;16(1):58-63.
9. El-Baz NM, Faber LP, Jensik RJ. Continuous epidural infusion of morphine, for treatment of pain after thoracic surgery: a new technique. Anaesth Analg 1984;63:757-64.
10. Cousins MJ, Mather LE. Intrathecal and epidural administration of opioids. Anaesthesiology 1984;61(3):276-310.
11. Rutter DV, Skewes DG, Morgan M. Extradural opioids for postoperative analgesia. A double blind comparison of pethidine, fentanyl and morphine. Br J Anaesth 1981;53(9):915-20.
12. Miller’s anaesthesia. Spinal, epidural and caudal anaesthesia, Acute postoperative pain. 6^th edition:pp 2738-39, 2741.
13. Akerman B, Arwenstorm E, Post C. Local anaesthetic potentiates spinal morphine nociception. Anaesth Anal 1988;67(10):943-8.
14. Solomon RE, Gebhart GF. Synergistic antinociceptive interaction among drugs administered to the spinal cord. Anaesth Analg 1994;78:1164-72.