Indian Journal of Anaesthesia

: 2009  |  Volume : 53  |  Issue : 1  |  Page : 57--63

Effect of Fentanyl Addition to Local Anaesthetic in Peribulbar Block

Mostafa Abdel Hamid Abo El Enin1, Ismail Ewis Amin1, Ahmed Sayed Abd El Aziz1, Mostafa Mohamed Mahdy2, Mohamed Abdel Hamid Abo El Enin3, Mostafa Mahmoud Mostafa3,  
1 Lecturer in Anaesthesia, Department of Anesthesia and Intensive Care and Ophthalmology, Facultyof Medicine, Al-Azhar University, Egypt
2 Prof. in Anaesthesia, Department of Anesthesia and Intensive Care and Ophthalmology, Facultyof Medicine, Al-Azhar University, Egypt
3 Lecturer in Ophthalmology, Department of Anesthesia and Intensive Care and Ophthalmology, Facultyof Medicine, Al-Azhar University, Egypt

Correspondence Address:
Mostafa Abdel Hamid Abo El Enin
Department of Anaesthesia & Intensive Care, Faculty of Medicine ,Al-Azhar Unversity


Forty patients ASAI, II undergoing vitrectomy due to vitreous hemorrhage not associated with retinal detach­ment were divided into two groups randomly, each of them with 20 patients. In Control group patients received local anaesthetic only, while Fentanyl group receive 20 mcg fentanyl added to local anaesthetic, the onset and duration of lid and globe akinesia were assessed at 1,3,5 and 10 min. Postoperative VAS was recorded each hour up to 6 th hour. The results show statistically significant difference between the two groups in the onset of lid akinesia. Fentanyl group had faster onset of lid akinesia and had significantly longer duration of akinesia (196.5 ± 14.24 min). There is statistically significant difference between the two groups in the onset of globe akinesia at 3, 5 min. Fentanyl group had faster onset than Control group and had longer duration of globe akinesia (294 ± 17.89 min). Fentanyl group had prolonged duration of analgesia 3.25+ 0.67 hr as compared to 1.85+ 0.67 in Control group, P=0.00 postoperatively. There were statistically significant differences between the two groups as regard the mean VAS in 1,2,3,4 hours, Fentanyl group had lower median pain score than Control group. Addition of fentanyl to local anaesthetic mixtures fasters the onset and prolong the duration of akinesia and improve quality of postoperative pain in peribulbar block.

How to cite this article:
Abo El Enin MA, Amin IE, Abd El Aziz AS, Mahdy MM, Abo El Enin MA, Mostafa MM. Effect of Fentanyl Addition to Local Anaesthetic in Peribulbar Block.Indian J Anaesth 2009;53:57-63

How to cite this URL:
Abo El Enin MA, Amin IE, Abd El Aziz AS, Mahdy MM, Abo El Enin MA, Mostafa MM. Effect of Fentanyl Addition to Local Anaesthetic in Peribulbar Block. Indian J Anaesth [serial online] 2009 [cited 2020 Feb 19 ];53:57-63
Available from:

Full Text


Fentanyl (N-phenyl-N-(1-Phenethyl-4-piperi­dinyl) propanamide) is anopioid analgesic with potency eighty times that of morphine.

Fentanylis extensively used for anaesthesia and analgesia in the operating room and intensive care unit. It is frequently given intrathecally as a part of spinal ana­esthesia or epidurally as apart of epidural anaesthesia and analgesia, it is also used as a sedative. [1] Addition of small amount of local anaestheics augments the effect of intrathecal opioids by increasing the duration of the block and speeding the onset of analgesia. [2]

Fentanyl is added commonly to local anaesthetic administrated in the extra dural space to improve anal­gesia in the postoperative period. [3] The addition of fen­tanyl produced only slight change in the quality and duration of analgesia after administration of 2% lidocaine with epinephrine for a short surgical procedure [4] or af­ter administration of 0.125% bupivacaine [5] , other stud­ies [6] in adults report improved and/or prolonged anal­gesia following the addition of fentanyl to lumbar extra ­dural bupivacaine for lower abdominal procedures, cae­sarean section and pain relief in labour. [7]

This study is designed to examine the effect of adding fentanyl to local anaesthetics in peribulbar block on the onset and duration of lid and globe akinesia and postoperative analgesia.


After institutional approval and informed consent, 40 adult patients of both sexes with ASA grade 1-2, scheduled for vitrectomy due to vitreous hemorrhage were divided into two groups each of them 20 patients randomly by using a table of random numbers and sealed closed envelopes in arandomized fashion.

Complete ophthalmological examination was done by the ophthalmologist as well as ophthalmic ultrasound and biometry was done for all cases to exclude com­plicated vitreous hemorrhage, diagnosis of any associ­ated disorders and diagnosis of posterior staphyloma if it was present, also the axial length was measured.

 Exclusion Criteria

Patients with impaired orbital/periorbital sensation.Patients having history of abnormal bleeding or al­lergy to local anaesthetics.Patients with complicated vitreous hemorrhage as retinal detachment, extensive epiretinal membranes, drooped nucleus or IOL, as such surgery takes a long time or when the surgeon expected prolonged surgery (= 2 hrs).Patients with posterior staphyloma. Patients with axial length more than 28 mm.

Control group: Volume of 6-10ml (5ml mepivacaine 3% + 1ml hyaluronidase (150mcg) + 3ml bupivacaine 0.5% + 1ml saline) was used.

Fentanyl group: Volume of 6-10ml (5ml mepivacaine 3% + 1ml hyaluronidase (150mcg) + 3ml bupivacaine 0.5% + 1ml saline containing 20 mcg fenta­nyl) was used.

After securing intravenous access, 1 mg midazolam was given intravenous with 25mcg fentanyl and topical anaesthesia in the form of tetracaine eyedrops 0.5 % applied to both groups. 2 mllidocaine 2% diluted with 13ml saline to form mixture for painless local injection [8] . 1ml from these mixture was given transconjunctival in the medial canthus in the tunnel (between the caruncle and the medial canthal angle) with insulin needle1cm length 27G, then 3-5 mlof local anaesthetic mixtures according to each group was injected with needle 27G and 3cm length with angle 45° between the caruncle and medial canthalangle till the tip of the needle touch the ethmoid bone then the direction of the needle changed to 90° with the hub of the needle at thelevel of the iris. Other 3-5ml from local anaesthetic mixture was injected in the extreme inferotemporal border of the orbit with the same needle 27G and 3cm length directed down­ward and medially below the globe. Light orbital compression for 1 minute then evaluation after 1minute, 3min, 5min, and 10 minute. The appearance of proptosis and chemosis was observed immediately after the block. The onset and duration of lid and globe akinesia were assessed every 1 minute until maximum blockade and then every 15 minutes after surgery until complete re­covery of the block.

 Evaluation Of The Block

Motor block evaluation include slid akinesia (lid closure by orbicularis and lid opening by the levator) and globe akinesia using 3 point scale for every muscle was done using the score system that shown in [Table 1].

For assessment of lid akinesia the patients were asked to open their eyelids and then squeeze them to­gether maximally. Orbicularis occuli muscle was as­sessed separately by using the score in [Table 1]. Also levator palpebrae muscle for opening eye lid was as­sessed by the score in [Table 1]. Globe akinesia was assessed at 1minute, then 3minute, 5minute, 10minute and 15 minute. These were scored using the move­ments of the extra ocular muscles in all 4 main direc­tions on a scale of 0 to 2 as shown in [Table 1]. The block was considered satisfactory when loss of at least two movement of the 4 cardinal direction. [10]

Arterial blood pressure, heart rate and oxygen saturation (SpO2) were checked every 15 minutes during the entire procedure and every 30minutes dur­ing the first two postoperative hours. Hypotension and bradycardia were defined as a 20% decrease in blood pressure and heart rate in relation to preblock value.

Postoperative analgesia was assessed by using Visual Analogue Score (VAS) every hour upto 6 hours postoperatively as 0 (no pain) to 10 (maximum pain imaginable). If the VAS was>5, injection of diclofenac 75mg intramuscular was given. Enquiry was made aboutany adverse effect such as nausea, vomiting, dry­ness of mouth, dizziness, diplopia and blindness.

 Statistical Analysis Of Data

Statistics were done by computerusing Epi- info.Software version 6.04. A word processing, database and statistics program (WHO, 2001). The tests used were: X(mean), SD (standard deviation): to measure the central tendency of data and the distribution of data around their mean value. Student's t test: for testing statistical significant difference between mean values of two samples. X 2 test (Chisquare test) to test for statis­tical significant relation between different variable or grades in qualitative data. ANOVA or F test:to test for significant difference between more than two samples mean values. Mann Whitney test: non parametric test for comparing two groups of data not normally distrib­uted or for small sample size. Fisher exact test: for com­paring two independent proportions when the expected observation in any cell of the table is below 5. Significant result is considered if P5 [Table 6].

• We did not observe any side effect during the study related to peribulbar block, there were no statis­tically significant differences in peripheral oxygen satu­ration, heart rate and non invasive blood pressure be­tween the two groups.


Opiates are widely known to have an antinociceptive effect at the central and/or spinal cord level [11]. However, evidence has begun to accumulate that opioid antinociception can be initiated by activation of peripheral opioid receptors [12]. The presence of periph­eral opioid receptors is shown in immune cells and pri­mary afferent neurons in animals. [13] If opioid adminis­tration improves regional anaesthesia without centrally mediated side effects, it would be useful in clinical prac­tice.

Study has demonstrated the presence of periph­eral opioid receptors that mediate analgesia by endogenous as well as exogenous opioid agonists. [14] It is specu­lated that the peripheral administration of opioids pro­vides tronger and longer lasting analgesia with a lower dose of opioid without central side effects such as respiratory depression, nausea, vomiting and pruritus. [15] A number of trials have examined the peripheral analge­sic effect of opioids in a large variety of surgical set­tings particularly arthroscopy and conduction nerve blocks. [16],[17]

The addition of opioids in brachial plexus block is reported to improve success rate and postoperative analgesia. [18] We postulate the possible mechanisms of action for the improved analgesia produced by the pe­ripheral application of fentanyl. First, fentanyl could act directly on the peripheral opioid receptor. Primary af­ferent tissues (dorsal roots) have been found to contain opioid binding sites [13] . Because the presence of bidi­rectional axonal transport of opioid binding protein has been shown [19] fentanyl may penetrate the nerve mem­brane and act at the dorsal horn. This could also ac­count for the prolonged analgesia. However, fentanyl is reported to have a local anaesthetic action. [20] Gormley et al [18] suggested that alfentanil also prolonged postop­erative analgesia by local anaesthetic action.

Second, fentanyl may potentiate local anaesthetic action via central opioid receptor-mediated analgesia by peripheral uptake of fentanyl to systemic circulation. [21]

Whether fentanyl diffuses from the peribulbar space to the subarachnoid space around theoptic nerve in the reterobulbar space or not to clarify this issue, the spinal fluid fentanyl concentrations should be measured.

A synergistic interaction between local anaesthetics and opioids with epidural administration has been re­ported. [22] It appears that local anaesthetics and opioids exert their action independently via different mechanisms. Local anaesthetics block propagation and generation of neuralaction potentials by a selective effecton so­dium channels, whereas opioids act on the opioid re­ceptors creating an increase in a potassium conductance. This action results in hyperpolarization of then erve cell membrane and a decrease in excitability [23] . Although sodium channel block is proposed to be the primary mode of action, local anaesthetics also have an effect on synaptic transmission [24] . Li et al [24] showed that lidocaine inhibited both substances P binding and sub­stance P-evoked increase in intracellular calcium. In contrast, in addition to the considered primary mode of action, opioids were found to directly suppress the action potential in nerve fibers [25] . Frazieret al [26] showed that morphine depressed both sodium and potassium currents associated with the action potential in squid giant axons. Therefore, the combination of local anaesthetics and opioids may effectively inhibit multiple areas of neuronal excitability.

The addition of hyaluronidase to local anaesthetic mixtures decreases the onset time of peribulbar block and quality of akinesia in most reported studies. [27]

The present study compares the effect of addi­tion of fentanyl to local anaesthetic mixtures in peribulbar block on the onset and duration of complete akinesia. The results of the present study showed that addition of fentanyl to local anaesthetic mixtures in peribulbar block fasten the onset of block (80% of patients get complete lid akinesia at 3 min and no patients remained to 5 min while in control group 15% get complete lid akinesia at 5 min and 5% at 10 min.). Also Fentanyl group had a short onset in globe akinesia 65% at 3min, 30% at 5 min and only 5% at 10 min but in Control group 15% at 3 min, 70% at 5 min and 15% at10 min. As regard duration of lid and globe akinesia Fentanyl group had longer duration than control group. The re­sults of the present study are in accordance with study done by Toshiharu et al [28] who studied the effect of ad­dition of fentanyl to mepivacaine in epidural block and found that addition of fentanyl to mepivacaine acceler­ate the onset of analgesia and enhances the analgesic effect of epidural block. Denizet al [29] found that addi­tion of fentanyl to bupivacaine in brachial plexus axil­lary approach prolong anaesthesia and analgesia, pro­long duration of sensory and motor block and prolong the duration of postoperative analgesia. In the present study the first time to require analgesia is prolonged in Fentanyl group, in which 75% of patients required res­cue analgesia 3 hour postoperative while in Control group 30% required it in first hour and 55% in second hour and 15% in the third hour. These results are simi­lar to the results of constant O et al [30] who studied the effect of addition fentanyl to local anaesthetic mixture in caudal block in children undergoing bilateral vesicoureteral reflex and they found that addition of fentanyl (1 -1 ) to bupivacaine 0.25% and lidocaine 1% prolong duration of surgical analgesia after single injection from start of injection to first re­quirement of analgesia from 174min in Control group to 253min in Fentanyl group. In the present study fen­tanyl group had lower pain score postoperatively than in Control group. In accordance with the study done by Vitaet al [31] who found that intraarticular injection of fentanyl improve postoperative pain and no difference between intraarticular morphine and fentanyl in post­operative pain relief.

Also Vijay et al [32] found that wound infiltration with fentanyl has lower VAS postoperatively and combina­tion of lidocaine with fentanyl for wound infiltration in cholecystectomy patients was associated with better postoperative analgesia, reduced analgesic consump­tion and better lung function. Saryazdietal [33] found that injection of fentanyl intraarticularly has better postop­erative pain less pain score and short time to walk were achieved by fentanyl orpethedine in comparison with dexamethasone when injected intraarticular.

The present study concluded that addition of fen­tanyl to local anaesthetic mixtures in peribulbar block fasters the onset and prolong duration of lid and globe akinesia, and improves quality of analgesia.


1Barr pharmaceuticals (2006-09-27). Barr Launches Generic ACTIQR Cancer pain management product press release. Retrived on 2006-09-30.
2Palmer CM, Van Maren G, Nogami WM, Alves D. Bupivacine augments intrathecal fentanyl for labour analgesia. Anesthesiology1999;91:84-9.
3Lejus C, Roussiere G,Testa S,Ganansia MF,Meignier M,Souran R. Postoperative extradural analgesia in children:comparison of morphine with fentanyl. Br J Anaesthesia1994;27:156-159.
4Jones RD,Gunawarden WM,Yeung CK: A comparison of lidocaine 2% with adrenaline 1:200,000 fentanyl as agents for caudal anaesthesia in children undergoing circumcision, Anaesthesia and Intensive Care 1990;18:194-199.
5Campbell FA, Yentis SM, Fean DW, Bissonnette B. Anal­gesic efficacy and safety of a caudal bupivacaine-fen­tanyl mixtures in children. Canadian Journal of Anaes­thesia1992:39:661-664.
6Morgan M. The rational use of intrathecal and extradu­ral opioids.Br JAnaesth1989;63: 165-88.
7Celleno D, Capogna G. Epidural fentanyl plus bupivacaine 0.125 per cent for labour analgesic effects. Can J Anaesth 1988;35:375-8.
8Farley JS, Hustead RF, Becker KE. Diluting lidocaine and mepivacaine in balanced salt solution reduces the pain of inradermal injection, Regional Anaesthesia 1994;19:48-51.
9Sarvela J, Nikki P, Paloheimo M. Orbicularis muscle aki­nesia inregional ophalmic anaesthesia with pH- adjusted bupivacaine; Effect of hyaluronidase and epinephrine, Can J Anaesth1993;40:1028-33.
10Dopfmer UR, Maloney DG, Gaynor PA, et al. Prilocaine 3% is superior to a mixture of bupivacaine and lidocaine for peribulbar anaesthesia Br J Anaesth1996;76-77-80.
11Yaksh KL. Multiple opioid receptor systems in brain and spinal cord. Eur J Anaesthesiol 1984;1:171-3.
12Stein C.Peripheral mechanisms of opioid analgesia.AnesthAnalg 1993;76:182-91.
13Fields HL, Emson PC, Leigh BK, et al. Multiple opiate receptor sites on primary afferent fibres. Nature (Lond) 1980;284:351-3.
14Stein C, Millan MJ, Shippenberg TS, Peter K, Herz A. Peripheral opioid receptors mediating antinociception in inflammation.Evidence for involvement of mu, delta and kappa receptors.Journal of Pharmacology and Ex­perimental Therapeutics1989;248: 1269-1275.
15Stein C.Peripheral mechanisms of opioid analgesia. AnesthAnalg1993;76:182-91.
16Nishikawa K, Kanaya N, Nakayama M, et al. Fentanyl improves analgesia but prolongs the onset of axillary brachial plexus block by peripheral mechanism. Anesth Analg2000;91: 384-7.
17Tverskoy M, BraslavskyA, Mazor A, Ferman R,Kissin 1. The peripheral effect of fentanyl on postoperative pain.AnesthAnalg1998; 87:1121-4.
18GormleyWP,MurrayJM,FeeJPH,Bower S.Effect of the addition of alfentanil to lignocaine during axillary bra­chial plexus anaesthesia.Br J Anaesth 1996;76:802-5.
19Laduron PM. Axonal transport of opiate receptors in capsaicin-sensitive neurones. Brain Res 1984;294:157- 60.
20GissenAJ, Gugino LD, DattaS, et al. Effects of fentanyl and sufentanil on peripheral mammalian nerves. Anesth Analg1987;66:1272-6.
21Nishikawa K, Kanaya N, Nakayama M, et al. Fentanyl improves analgesia but prolongs the onset of axillary brachial plexus block by peripheral mechanism. Anesth Analg2000;91:384-387.
22Vercauteren M, Meert TF. Isobolographic analysis of the interaction between epidural sufentanil and bupivacaine in rats. Pharmacol Biochem Behav 1997; 58:237-42.
23Duggan AW, North RA. Electrophysiology of opioids. Pharmacol Rev1984;35:219-81.
24Li YM, Wingrove DE, Too P, et al. Local anaesthetics inhibit substance P binding and evoked increases in intracellular Ca2+. Anesthesiology1995;82:166-73.
25Frank GB. Stereospecific opioid drug receptors on ex­citable cell membranes. Can J Physiol Pharmacol 1985; 63:1023-32.
26Frazier DT, Murayama K, Abbott NJ, et al. Effects of morphine on internally perfused squid axons. Proc Soc ExpBiolMed1972;139:434-8.
27Sarvela J, Nikki P. Hyaluronidase improves regional oph­thalamic anaesthesia with etidocaine. Can J Anaesth 1992; 39:920-924.
28Kasaba T, Yoshikawa G, Seguchi T, Takasaki M. Epidu­ral fentanyl improves the onset and spread of epidural mepivacaine analgesia, Canadian J Anesth 1996;43:12 1211-5.
29Karakaya D, Buyukgoz F, Bare S et al. Addition of fenta­nyl to bupivacaine prolongs anesthesia and analgesia in axillary brachial plexus block. Canadian J Anesth 2001;26:434-438.
30Consant O, Gall, L, Chawin and I.Mura. Addition of fenta­nyl to local anaesthetics prolongs the duration of surgi­cal analgesia after single shot caudal block in children. Br J Anaesthesia1998;80:294-298.
31Vita varkel, Gershon volpin, Bruce Ben David, Rayek said,Bernard Grimber,Kurt simon, Michael soudry. Intraarticular fentanyl compared with morphine for pain relief following arthroscopic knee surgery. Can J Anesth 1999;46:867-871.
32VijayKumar PT, Bhardwaj N, Sharma Kajal, BatraYK. Periperal analgesic effect of wound infilteration with lidocaine, fentanyl and combination of lignocaine-fen­tanyl on post operative pain. J Anaesth Clin Pharmacol 2006;22:161-167.
33Saryazdi H, Kashefi P, Heydari M, Kiani A. Analgesic effect of intraarticular fentanyl, pethedine and dexam­ethasone after knee arthroscopic surgery. Journal of Research in Medical Science2006;11:156-159.