Anesth Analg 2000;91:585-588
© 2000 International Anesthesia Research Society
AMBULATORY ANESTHESIA
Retrobulbar Versus Systemic Application of Morphine During Titratable Regional Anesthesia via Retrobulbar Catheter in Intraocular Surgery
Thomas M. Hemmerling, MD, DEAA*,
Wido M. Budde, MD
,
Wolfgang Koppert, MD*, and
Jost B. Jonas, MD
Departments of
*Anesthesiology and
Ophthalmology and Eye Hospital, University of Erlangen-Nuremberg, Germany
Address correspondence and reprint requests to Dr. T. M. Hemmerling, Department of Anesthesiology, University of Erlangen-Nuremberg, Krankenhausstr. 12, D-91054 Erlangen, Germany. Address e-mail to thomashemmerling{at}hotmail.com
 |
Abstract
|
|---|
Implications: We investigated the effects of morphine on postoperative pain in patients undergoing intraocular surgery using a new indwelling catheter. Although morphine produced central analgesic effects, there was no evidence for the involvement of peripheral opioid receptors in the modulation of ocular pain.
|
Introduction
|
|---|
The use of single-shot regional anesthesia for intraocular surgery (1) can be limited by the difficulty in predicting the length of the operation. Postoperative pain extending more than 6 h after surgery can be a problem, especially after cyclodestructive and vitreoretinal procedures.
In view of the growing evidence of antinociceptive effects of opioids on peripheral sensory nerve fibers and their terminal endings (2–4), we used a recently developed technique of titratable retrobulbar (RB) anesthesia (5) to determine if RB opioid administration offers an advantage over subcutaneous (SC) administration for postoperative pain management after intraocular surgery.
|
Methods
|
|---|
After we obtained approval by the local ethics committee and patients’ formal consent, 36 patients undergoing antiglaucomatous cyclodestructive or vitreoretinal surgery were included in this prospective, randomized, double-blinded study. Exclusion criteria were an axial length of the globe longer than 26 mm, myopia of more than -6 diopters, and disability of the patient to lie down for the operation for more than 2.5 h. One day before surgery, all patients were instructed in the use of the pain assessment tool, a numeric rating scale (NRS) with 0 = "no pain" and 10 = "maximal imaginable pain."
Before surgery, all patients received RB anesthesia with 5 mL mepivacaine 2% mixed with hyaluronidase by using a custom-made 23-gauge RB needle. A 28-gauge catheter was then introduced into the RB space (Fig. 1), the needle withdrawn, and the catheter attached to the skin to avoid displacement. A bacterial filter with 0.20-micron pores was adapted to minimize risk of infection during reinjections; 1 mL of mepivacaine 2% was injected through the catheter to remove air. Patients were asked every 10 min during surgery to assess the pain (NRS). If the score was more than 3, reinjections of 2 mL of mepivacaine 2% were applied. The number of reinjections was recorded.
View larger version (45K):
[in this window]
[in a new window]
|
Figure 1. Drawing showing the retrobulbar catheter inserted through a commercially available 23-gauge, single-use retrobulbar needle.
|
|
After surgery, patients were randomly assigned to one of three treatment groups by a nurse not involved in the study. In one group, 2 mg (2 mL) of morphine was injected in the RB space and 2 mL of saline was administered SC (morphine RB, n = 12). In another group, 2 mg (2 mL) of morphine was injected SC and 2 mL saline into the RB space (morphine SC, n = 12). In a third group, 2 mL of saline was injected in the RB space and SC (control, n = 12).
Postoperatively, the first occurrence of clinically significant ocular pain (NRS > 3) was noted. All patients were asked hourly to assess the ocular pain. If the score was higher than 3, one mL of mepivacaine 2% was reinjected, and the total number of injections was determined. Side effects related to the catheter, e.g., swelling, inflammation, decreased ocular motility, as well as to morphine, e.g., nausea, vomiting, pruritus, were recorded.
The group size was chosen to create a power of more than 80%. Patient data, duration of surgery, and number of reinjections were analyzed by using the Student’s paired t-test and 
2 test. Pain ratings were compared by using analysis of variance (ANOVA) in a two-way within-subjects (repeated measures) model. The values of repeated measures ANOVA were expressed as F values and, in parentheses, degrees of freedom for effect and error planned comparison was performed where suitable. The mepivacaine consumption was evaluated by using the Kruskal-Wallis ANOVA, followed by Mann-Whitney U-tests. Multiple testing was corrected with the Bonferroni procedure. Two-sided P values 
0.05 were considered significant. All data were expressed as the mean ± SD, except for figures (mean ± SEM). The STATISTICA software package (Statsoft, NC) was used for statistical analysis.
|
Results
|
|---|
Patient data, duration of surgery, and the number of reinjections did not reveal any differences among the three groups (Table 1). The first occurrence of ocular pain after surgery (NRS > 3) was not statistically different in the three groups (morphine RB: 136 ± 91 min, morphine SC: 105 ± 69 min, and control: 100 ± 98 min). In all patients, injection of 1 mL mepivacaine 2% stopped the pain within 1–2 min. Pain scores in all three groups significantly decreased during the observation period (time effect: F(11,121) = 7.83, P < 0.001). This decrease was different in the three groups (group x time interaction: F(22,242) = 1.86, P < 0.01). Post hoc tests showed higher pain scores during the first 3 h in the control group when compared with the morphine-treated groups (Fig. 2).
View larger version (21K):
[in this window]
[in a new window]
|
Figure 2. Time courses of mean pain scores assessed hourly by numeric rating scale (NRS) during the observation period of 12 h after finishing the ophthalmosurgical procedure. Values are expressed as mean ± SEM. *P < 0.05 by repeated measures analysis of variance and post hoc tests. r.b. = retrobulbar, s.c. = subcutaneous.
|
|
Mepivacaine consumption was significantly less in both morphine groups (Fig. 3) during the first 3 h (morphine RB: 0.9 ± 0.7 mL, morphine SC: 1.1 ± 0.9 mL, and control: 1.9 ± 1.2 mL; P < 0.05). At 12 h after surgery, however, no differences among groups were determined (morphine RB: 3.3 ± 2.0 mL, morphine SC: 3.4 ± 2.1 mL, and control: 3.9 ± 1.5 mL).
View larger version (60K):
[in this window]
[in a new window]
|
Figure 3. Cumulative mepivacaine consumption during the observation period of 12 h after finishing the ophthalmosurgical procedure. If indicated, 1 mL of mepivacaine 2% was injected. Values are expressed as mean ± SEM. *P < 0.05 by Kruskal-Wallis analysis of variance and Mann-Whitney U-tests. r.b. = retrobulbar, s.c. = subcutaneous.
|
|
Postoperative diplopia or other ocular motility problems were not detected. The catheter stayed in place for 13.4 ± 0.4 h. Removal of the catheter and inspection of the catheter entry were unremarkable. No local or systemic infections were detected. There were no side effects attributable to morphine.
|
Discussion
|
|---|
Catheters have been used for intraoperative RB sub-Tenon analgesia (6) by introduction through a blunt dissection of the conjunctiva and for RB administration of medication such as interferon (7). Recently, a new technique for regional anesthesia using an indwelling catheter-through-needle-technique was introduced for RB anesthesia in potentially long-lasting intraocular surgery (5); the thin, flexible 28-gauge catheter has not caused any detected damage in the RB space or infection with excellent patient acceptance. This new technique offers the possibility to use regional anesthesia for long ophthalmic procedures as well as postoperative pain control. The possibility of accidental globe perforation and other complications (8–12) during the reinjection is eliminated because the catheter is not moved when the anesthetic is injected. In all patients in the current study, the repetitive injections of mepivacaine were painless and relieved the patients from ocular or orbital pain within one to two minutes with no complications.
One may argue that longer-acting local anesthetics could have been used to render reinjections unnecessary. Our primary goal, however, was to examine the involvement of local opioid receptors in prolonging local anesthesia. Peripheral analgesic effects of opioids have been observed mainly under inflammatory-induced pain, e.g., knee surgery or arthritis (13,14). These studies also demonstrated that intraarticularly applied opioids are effective a few hours after the induction of an inflammation. This could be caused by an enhancement of the permeability of the perineurium and by activation of opioid receptors in the terminal nerve endings, which may undergo structural changes in the acidic environment of the inflammation (4,15). The presence of each of the three subtypes of opioid receptors has been demonstrated in the optic nuclei of the rat (16). They are found to contain exceedingly high levels of µ-opioid receptors, which were significantly decreased after monocular enucleation (16). This led to the hypothesis that µ agonists might play an important role in the peripheral modulation of pain during ocular surgery.
In the present study, no peripheral antinociceptive effects of morphine were observed. During intraocular surgery, pain is mediated via the ciliary nerves. Given that the concentration of the µ agonists was sufficient, the missing peripheral effect might be caused by missing opioid receptors in these nerves. If they do exist, the absence of inflammation during retinal and vitreoretinal interventions might exclude conformational changes of preformed opioid receptors. However, the central effects of morphine were evident during the first three hours after the administration of 2 mg of morphine RB or SC. The morphine-induced enhancement of postoperative analgesia may be related, in part, to a mild sedative effect. The mean age of our patients was greater than 60 years, and pharmacokinetic changes in morphine’s breakdown characterized by reduced distribution volumes and increased terminal elimination half-times (17–20) may have contributed to enhancing the analgesic effect of 2 mg morphine.
The absence of side effects in comparison with our traditional analgesia of administering oral nonsteroidal antiinflammatory drugs or orally applied opioids make this novel technique a viable alternative for postoperative pain control. However, small doses of morphine administered with local anesthetics in the RB space did not differ from systemic administration.
In conclusion, using a RB indwelling catheter allows the postoperative reinjections of an opioid analgesic and local anesthetic for prolonged analgesia. However, peripheral opioid effects were not observed in the RB space.
|
Acknowledgments
|
|---|
Supported by Deutsche Forschungsgemeinschaft (Grant SFB 539).
|
References
|
|---|
-
Feibel RM. Current concepts in retrobulbar anesthesia. Surv Ophthalmol 1985; 30: 102–10.[ISI][Medline]
-
Stein C, Hassan AHS, Przewlocki R, et al. Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation. Proc Natl Acad Sci USA 1990; 87: 5935–9.[Abstract/Free Full Text]
-
Coggeshall RE, Zhou S, Carlton SM. Opioid receptors on peripheral sensory axons. Brain Res 1997; 764: 126–32.[ISI][Medline]
-
Stein C. The control of pain in peripheral tissue by opioids. N Engl J Med 1995; 332: 1685–90.[Free Full Text]
-
Jonas JB, Hemmerling TM, Budde WM, Dinkel M. Postoperative analgesia by re-injections through an indwelling retrobulbar catheter. Am J Ophthalmol 2000; 129: 54–8.[ISI][Medline]
-
Dantas PE, Nishiwaki-Dantas MC, Henrique MJ, de-Almeida GV. Retrobulbar anesthesia with a flexible catheter. Ophthalmic Surg Lasers 1996; 27: 275–8.[ISI][Medline]
-
Lincoff H, Kreissig I. A catheter to deliver retrobulbar medication. Arch Ophthalmol 1996; 114: 634–5.[ISI][Medline]
-
Ramsay RC, Knobloch WH. Ocular perforation following retrobulbar anesthesia for retinal detachment surgery. Am J Ophthalmol 1978; 86: 61–4.[ISI][Medline]
-
Pautler SE, Grizzard WS, Thompson LN, et al. Blindness from retrobulbar injection into the optic nerve. Ophthalmic Surg 1986; 17: 334–7.[ISI][Medline]
-
Javitt JC, Addiego R, Friedberg HL, et al. Brain stem anesthesia after retrobulbar block. Ophthalmology 1987; 94: 718–24.[ISI][Medline]
-
Morgan CM, Schatz H, Vine AK, et al. Ocular complications associated with retrobulbar injections. Ophthalmology 1988; 95: 660–5.[ISI][Medline]
-
Duker JS, Belmont JB, Benson WE, et al. Inadvertent globe perforation during retrobulbar and peribulbar anesthesia: patient characteristics, surgical management, and visual outcome. Ophthalmology 1991; 98: 519–26.[ISI][Medline]
-
Stein C, Comisel K, Haimerl F, et al. Analgesic effect of intraarticular morphine after arthroscopic knee surgery. N Engl J Med 1991; 325: 1123–6.[Abstract]
-
Likar R, Schäfer M, Paulak F, et al. Intraarticular morphine analgesia in chronic patients with osteoarthritis. Anesth Analg 1997; 84: 1313–7.[Abstract]
-
Antonijevic I, Mousa SA, Schäfer M, Stein C. Perineural defect and peripheral opioid analgesia in inflammation. J Neurosci 1995; 15: 165–72.[Abstract]
-
Giolli RA, Blanks RH, Torgoe Y, et al. Opioid receptors in the accessory optic system of the rat: effects of monocular enucleation. Vis Neurosci 1990; 5: 497–506.[ISI][Medline]
-
Kaiko RF. Age and morphine analgesia in cancer patients with postoperative pain. Clin Pharmacol Ther 1980; 28: 823–6.[ISI][Medline]
-
Owen JA, Sitar DS, Berger L, et al. Age-related morphine kinetics. Clin Pharmacol Ther 1983; 34: 364–8.[ISI][Medline]
-
Chauvin M, Sandouk P, Scherrmann JM, et al. Morphine pharmacokinetics in renal failure. Anesthesiology 1987; 66: 327–31.[ISI][Medline]
-
Osborne RJ, Joel SP, Trew D, et al. Morphine and metabolite behaviour after different routes of administration: demonstration of the importance of the active metabolite morphine-6-glucuronide. Clin Pharmacol Ther 1990; 47: 12–9.[ISI][Medline]
Accepted for publication May 5, 2000.
Top
Abstract
Introduction
