- Email: [email protected]
Effects of fentanyl on pain and hemodynamic response after retrobulbar block in patients having phacoemulsification
Effects of fentanyl on pain and hemodynamic response after retrobulbar block in patients having phacoemulsification ¨ mit U ¨ beyt Inan, MD, Remziye Gu¨l Sivaci, MD, Sı˙tkı˙ Samet Ermis, MD, Faruk O ¨ ztu¨rk, MD U Purpose: To determine the effects of systemic fentanyl analgesia in preventing the pain related to the administration of retrobulbar anesthesia and cataract surgery. Setting: Departments of Ophthalmology and Anesthesiology, School of Medicine, Kocatepe University, Afyon, Turkey. Methods: One hundred twenty patients with American Society of Anesthesiologists physical status I to III scheduled for cataract surgery were evaluated in a single-blind randomized study. Patients with a history of hypertension, hyperthyroidism, or neurologic or psychiatric disorders were excluded. In the study (fentanyl) group, an intravenous bolus of fentanyl 2 g/kg was slowly given 5 minutes before retrobulbar anesthesia was administered. In the control group, fentanyl was not given. There were 60 patients in each group. Demographic data were not statistically different between the 2 groups. The intensity of pain during injection and intraoperatively was measured by verbal pain scores. Hemodynamic stability was assessed by the heart rate (HR) and mean arterial pressure (MAP). End-tidal carbon dioxide concentrations and oxygen saturations were also recorded. Results: The changes in HR and MAP at 0, 10, 20, and 30 minutes were statistically significant between the fentanyl and control groups (P⬍.05). Fentanyl reduced pain scores significantly at all evaluations (P⬍.05). Conclusion: The results suggest that fentanyl preemptively decreases injection and intraoperative hyperalgesia and provides hemodynamic stability without affecting patient cooperation, resulting in cataract surgery with retrobulbar anesthesia that is comfortable for both surgeon and patient. J Cataract Refract Surg 2003; 29:1137–1142 © 2003 ASCRS and ESCRS
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ataract surgery is the most commonly performed operation in the older population. Today, phacoemulsification is the preferred method of cataract extraction and can be safely performed using local or topical anesthesia.1,2 However, patients, especially older ones, can experience discomfort perioperatively that is related to concomitant systemic disorders such as cardiovascular, pulmonary, and metabolic diseases.3 Patient discomfort can produce hemodynamic instability and thus Accepted for publication November 15, 2002. ¨ mit U ¨ beyt Inan, MD, Dumlupinar Mh Turabi Reprint requests to U Cadessi, Tutuncu Apartment, B Blok 4/7, 03200, Afyon, Turkey. E-mail: [email protected]. © 2003 ASCRS and ESCRS Published by Elsevier Inc.
more discomfort. Surgical pain can also make patients become agitated. In addition, some patients find it difficult to remain motionless for a certain amount of time, especially under topical anesthesia during cataract surgery.4 Topical anesthesia has gained growing popularity among experienced surgeons. However, patient cooperation and vocal anesthesia are required to achieve patient relaxation. Therefore, some patients may need local anesthesia to cooperate with the surgeon. In addition, mentally incompetent or anxious patients may not be good candidates for topical anesthesia.3–5 Local anesthesia with retrobulbar or peribulbar injection causes anxiety and pain in most patients. As a result, they may 0886-3350/03/$–see front matter doi:10.1016/S0886-3350(02)02053-9
FENTANYL ANALGESIA IN CATARACT SURGERY
remain agitated throughout the procedure.6 Some patients also feel pain from the wire speculum or experience discomfort caused by factors such as variations in intraocular pressure (IOP), compression by the blood pressure cuff, and uncomfortable positioning. Preventing perioperative pain and discomfort is necessary to allow comfortable surgery for both surgeon and patient. Maintenance of sedation by medication given before surgery may compromise the patient’s consciousness and cooperation. Several techniques are used to produce sedation for placement of a retrobulbar or peribulbar block and to ensure the patient has no discomfort during surgery.7–14 Fentanyl, a commonly used agent for systemic analgesia given during general anesthesia, is an opioid of the phenalpiperidine group that is 100 times more potent an analgesic than morphine. Its use in cataract surgery may help prevent pain and discomfort during retrobulbar injection and surgery without hindering patient cooperation.15–18 Our study evaluated the effectiveness of the induction and maintenance of systemic analgesia by intravenous (IV) fentanyl given before the retrobulbar block and during surgery on patient pain and discomfort during the injection and intraoperatively. We also assessed whether fentanyl provides hemodynamic stability during surgery.
Patients and Methods One hundred twenty patients aged 40 to 78 years with American Society of Anesthesiologists physical status I to III scheduled for cataract were evaluated in a single-blind randomized study. Patients with a history of hypertension, hyperthyroidism, or neurologic or psychiatric disorders were excluded. The Institutional Human Investigation Committee approved the study. Patients were prospectively randomized to receive local anesthesia (control group) or local anesthesia combined with fentanyl analgesia (fentanyl group). There were 60 patients in each group. The patients’ demographic data and the duration of surgery are shown in Table 1; there were no statistically significant differences between groups in any parameter (P⬎.05)
Preoperative Routine A few weeks before surgery, patients came to the clinic for a preoperative assessment. The patients were questioned about general health and current medications. Systemic diseases (eg, cardiovascular conditions, hypertension, respiratory 1138
Table 1. Patients’ demographics and duration of surgery. Mean ⴞ SD Fentanyl Group
Control Group
65.76 ⫾ 6.10
65.21 ⫾ 7.82
Height (m)
164.08 ⫾ 6.87
163.91 ⫾ 8.68
Weight (kg)
67.85 ⫾ 7.20
68.00 ⫾ 7.43
Duration of surgery (min)
31.05 ⫾ 4.30
29.66 ⫾ 3.35
Parameter Age (y)
dysfunction, diabetes, previous or current ocular disease) were recorded. Laboratory examination included blood tests, an electrocardiogram, and a chest x-ray. Patients with abnormal laboratory results and uncontrolled systemic disease were referred to an internist before surgery.
Anesthesia Administration No premedication was given so the full effect of the fentanyl could be ascertained. Patients were given an IV of 500 cc electrolyte solution (Isolyte威 S) using a 22-gauge needle. Both groups received 4 L/min–1 of oxygen through a nasal cannula; expired air was suctioned through a Y-piece system. In the fentanyl group, an IV bolus of fentanyl 2 g/kg was slowly administered 5 minutes before the retrobulbar block and repeated 30 minutes after the first dose. In the control group, fentanyl was not given before the retrobulbar block. The block was given by 1 of 3 experienced surgeons using the Atkinson retrobulbar injection approach. A 23-gauge sharp needle (Rhein Medical) was inserted at the inferior lateral junction of the skin of the lower lid. A mixture of 1 mL (5 mg/mL) bupivacaine and 1.5 mL (20 mg/mL) of lidocaine 2% were injected. Orbital compression was not done because sufficient ocular hypotony was achieved by fentanyl administration.
Surgical Technique Surgeries were performed by 1 of 3 surgeons. Mydriasis was obtained with 3 to 4 drops of topical phenylephrine hydrochloride 2.5% (Mydfrin威), tropicamide 0.5% (Mydriacyl威), and cyclopentolate hydrochloride 1% (Siklomid威). Topical anesthetic drops of proparacaine hydrochloride (Alcaine威) were instilled a few minutes apart preceding surgery. After standard aseptic preparation, a wire speculum was inserted. A 3.2 mm clear corneal tunnel was made. Cataract extraction comprised a continuous curvilinear capsulorhexis, bimanual endocapsular phacoemulsification, and aspiration of remaining cortical lens material. In half the patients, a foldable acrylic (AR40, Allergan) or silicone (SI-40, Allergan) intraocular lens (IOL) was implanted using an Unfolder (Allergan) without widening the corneal incision. In the other half, the tunnel was widened to 4.0 mm and a foldable acrylic (AcrySof威 MA30BM, Alcon, or Softec威, Lenstec Inc.) or silicone (CeeOn威 911, Pharmacia & Upjohn, or Siltec威, Lens-
J CATARACT REFRACT SURG—VOL 29, JUNE 2003
FENTANYL ANALGESIA IN CATARACT SURGERY
tec Inc.) IOL was implanted. At the end of surgery, a subconjunctival injection of a gentamicin and dexamethasone mixture was given.
Table 2. Verbal pain scores. Mean ⴞ SD Fentanyl Group
Control Group
P Value
Monitoring
Scoring Time
All patients were monitored with an anesthesia machine (Datex-Ohmeda ADU AS/3 or Cicero EM). In both groups, the mean arterial pressure (MAP), heart rate (HR), and endtidal carbon dioxide concentration (EtCO2) were recorded at 1-minute intervals throughout the perioperative period. The MAP and HR were evaluated at baseline, during the injection, and 10, 20, and 30 minutes after initiation of the surgery. An anesthetist performed the intraoperative monitoring and intervened medically when necessary.
During RB injection
0.06 ⫾ 0.25 1.60 ⫾ 0.52 .000
5 minutes after RB injection
0.05 ⫾ 0.21 1.01 ⫾ 0.32 .000
During surgery
0.08 ⫾ 0.27 1.06 ⫾ 0.25 .000
Postoperatively
0.01 ⫾ 0.12 0.11 ⫾ 0.32 .031
Duration of Surgery The exact duration of all surgical procedures was recorded. A stopwatch was started when the surgeon sat down by the operating microscope and stopped when he ended the operation and rose from the chair. The total time included focusing the microscope, opening the draping, placing the speculum, performing phacoemulsification, and removing the draping.
Pain Assessment Patients’ pain was evaluated by verbal pain scores (VPS) using a 4-point scale (0 ⫽ no pain, 1 ⫽ mild pain, 2 ⫽ moderate pain, and 3 ⫽ severe pain).The scores were recorded during the injection, 5 minutes after the retrobulbar injection, during the surgical procedure, and immediately after surgery.
Statistical Analysis Statistical analysis was done using SPSS 10.0 software (SPSS Inc.). Demographic data and comparisons between the groups at each evaluation were by an unpaired t test. Multiple comparisons of hemodynamic parameters within the groups were done using an analysis of variance. Statistical comparisons of VPS values between groups were by the Pearson chisquare test. The Fisher exact test was used to compare VPS values postoperatively. A P value less than 0.05 was considered statistically significant.
Results The VPS in the fentanyl group were lower than in the control group. During retrobulbar injection, 56 patients in the fentanyl group had a pain score of 0 and 4 of 1. In the control group, 25 patients had a pain score of 1, 34 of 2, and 1 of 3. Table 2 and Figure 1 show the mean pain scores. The fentanyl group had statistically significantly lower pain scores than the control group at all evaluations (P⬍.05).
RB ⫽ retrobulbar
There were no significant changes in oxygen saturation and EtCO2 between the 2 groups. Significant hemodynamic changes occurred at 0, 10, 20, and 30 minutes in the control group while hemodynamic parameters in the fentanyl group remained stable (Figures 2 and 3). The HR during the retrobulbar injection and at 10, 20, and 30 minutes increased significantly over baseline values in the control group. The MAP during the retrobulbar injection and at 20 minutes increased significantly over baseline values in the control group. There were no statistically significant differences between baseline and subsequent HR and MAP measurements in the fentanyl group. The HR and MAP values at all points except at baseline were statistically different between the 2 groups. The fentanyl group had a statistically significantly lower hemodynamic response to the local anesthetic injection and surgery than the control group (P⬍.001). Five patients in the control group developed systemic hypertension and required an antihypertensive drug (IV enalapril 10 mg).
Discussion In our study, fentanyl analgesia reduced perioperative pain and stabilized the hemodynamic response during cataract surgery under retrobulbar block. Ophthalmic pain after uneventful extracapsular cataract surgery has been reported. Koay et al.6 found that although nearly half the patients having ophthalmic surgery in their study had no pain or discomfort postoperatively, 32% reported slight discomfort, 8% mild pain, and 5% moderate to severe pain. Many ophthalmic procedures can be performed using a retrobulbar regional anesthetic technique. However, the block is painful and patients often express anxiety over the procedure. The pain can make patients
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FENTANYL ANALGESIA IN CATARACT SURGERY
Figure 1. (Inan) Verbal pain scores at 4 stages (P⬍.05 between groups at all stages).
Figure 2. (Inan) Heart rate (P⬍.05 during injection and 10, 20, and 30 minutes after initiation of surgery).
Figure 3. (Inan) Mean arterial pressure (P⬍.05 during injection and 10, 20, and 30 minutes after initiation of surgery).
move their eyes, increasing the risk for complications. In an attempt to prevent complications, patients can be sedated before the block is administered. However, sedated patients may be uncooperative and feel pain that makes them move.4,5 Surgical pain can also cause intraoperative anxiety. Anxiety and stress are associated with systemic problems such as tachycardia, hypertension, and dysrhythmia.19,20 Preventing pain and anxiety may increase the patient’s tolerance of surgery. There is a difference between North American practice, in which IV sedation appears to be used routinely, and northern European practice, in which sedation is used less frequently. The routine use of sedation is sometimes avoided because of risks such as airway obstruction and a rise or drop in blood pressure. Kallio and coauthors5 report that sudden unexpected head or body
movements during surgery occur more often with IV sedation than without, making its use relatively more dangerous to patients’ vital functions and the surgery less safe. Keeping the patient cooperative under IV sedative sedation is a challenge. The risk of respiratory depression necessitates the presence of experienced anesthesia personnel. Opioid drugs can be used for both sedation and analgesia. Producing good preemptive analgesia can also provide hemodynamic stability and reduce IOP.21 Fewer side effects and more successful surgery can also be obtained. As a result of improvements in surgical and anesthetic techniques, topical anesthesia has become more popular in recent years. Painless cataract surgery using only topical anesthesia is possible and desirable. How-
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ever, phacoemulsification with topical anesthesia alone is painful for some patients. Differences in pain sensitivity among individuals or the need for increased intraocular manipulation can cause pain.1,3,5,22 In such cases, systemic analgesia might be sufficient to relieve patients without adding peribulbar or retrobulbar anesthesia. Hyperalgesia produced by C-fiber-strength electrical stimulation of a nerve can be prevented by a relatively low dose of an analgesic drug when a much higher dose is required to suppress established hyperalgesia.23 The concept that analgesia given before the painful stimulus has effects that long outlast the presence of the analgesic in the body created the basis for the preemptive treatment of pain. Preemptive analgesia eliminates painful mechanical stimulation during surgery. Opioids are central receptor-mediated analgesics. The finding of opioid receptors in the peripheral systems prompted studies using opioids for regional analgesia and peripheral analgesic actions.24,25 The process of pain emphasizes the role of the primary mediators of the cytokine cascade—tumor necrosis factor ␣ and interleukin (IL) 1b—in hyperalgesia. Hyperalgesia induced by IL-1b depends partly on induction of bradykinin-1 receptors. Nerve growth factor modulates the production of substance P and is key to understanding the phenomenon of hyperalgesia.26,27 Opioids are highly effective in suppressing substance P. Fentanyl prevents production of cytokines indirectly without causing an algesia process. “Sustained hyperexcitability” is caused not only by direct surgical stimulation but also by the action of proteolytic and inflammatory processes in the wound tissue that last longer than the surgery.25 Fentanyl has qualities that make it promising for ophthalmic use. It has a rapid onset and short duration of action, and it lacks active metabolites. The higher lipophilicity of fentanyl may be responsible for the lower incidence of side effects and allows less free fentanyl to migrate into the cerebrospinal fluid, causing less rostral spread to the brain.28 Possible harmful effects can easily be reversed with naloxone. When fentanyl is given for analgesia in half-hourly IV injections of 2 to 3 g/kg, there is no increase in the incidence of respiratory depression. Fentanyl also reduces postoperative pain without producing respiratory depression.29,30 Optimal efficacy and safety depend on a dose that is small enough to minimize adverse effects but
large enough to achieve analgesic efficacy. The dose in our study was 2 g/kg. The fentanyl IV titration phase, treatment period, and number and frequency of doses during surgery must be individualized. Side effects of fentanyl, such as myocardial and respiratory depression, hypotension, consciousness, and parasympathetic activation (nausea, vomiting, pruritis, urticheria), can occur at doses exceeding 5 g/kg. The effective minimal dose for sufficient analgesia of fentanyl used alone is 2 g/kg. The effects of fentanyl may be heightened when combined with other drugs such as hypnotics, sedatives, and muscle-relaxing agents. Doses lower than 2 g/kg may contribute to sedation but not provide adequate analgesia. Surgical pain and stress can cause increased agitation. Therefore, patients with less pain and stress during surgery may be significantly more comfortable. An increase in systemic blood pressure and heart rate during the retrobulbar block and surgery indicates the hemodynamic responses to pain.4,7 McHardy et al.31 report that alfentanyl minimizes the hemodynamic response and reduces pain scores in the first postoperative hour and that the use of alfentanyl is more advantageous in ambulatory patients having ophthalmic surgery than midazolam and propofol sedation. Hodgkins et al.32 report that IV neuroleptanalgesia combined with a facial nerve block achieves satisfactory ocular analgesia and akinesia during cataract extraction without the use of a periocular injection. In conclusion, our study indicates that fentanyl is safe and effective for the management of moderate to severe pain during cataract surgery. Based on safety and efficacy, an IV fentanyl dose of 2 g/kg seems optimal for ophthalmic surgery. Fentanyl alone can be used to prevent painful stimulation during the placement of a local anesthesia block and to provide cooperative, comfortable intraocular surgery.
References 1. Crandall AS. Anesthesia modalities for cataract surgery. Curr Opin Ophthalmol 2001; 12:9 –11 2. Hamilton RC. Regional anaesthesia of the eye. Curr Opin Anaesth 1990; 3:740 –744 3. Suzuki R, Kawata K, Kuroki S, et al. A comparison of blood pressure changes in phacoemulsification surgery with topical and retrobulbar block local anesthesia: part II. Ophthalmologica 1997; 211:327–331
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4. Yee JB, Schafer PG, Crandall AS, Pace NL. Comparison of methohexital and alfentanil on movement during placement of retrobulbar nerve block. Anesth Analg 1994; 79:320 –323 5. Kallio H, Uusitalo RJ, Maunuksela E-L. Topical anesthesia with or without propofol sedation versus retrobulbar/ peribulbar anesthesia for cataract extraction; prospective randomized trial. Cataract Refract Surg 2001; 27:1372– 1379 6. Koay P, Laing A, Adams K, et al. Ophthalmic pain following cataract surgery: a comparison between local and general anaesthesia. Br J Ophthalmol 1992; 76:225–227 7. Schwall B, Jakob W, Sessler DI, et al. Less adrenergic activation during cataract surgery with total intravenous than with local anesthesia. Acta Anaesthesiol Scand 2000; 44:343–347 8. Salmon JF, Mets B, James MFM, Murray ADN. Intravenous sedation for ocular surgery under local anaesthesia. Br J Ophthalmol 1992; 76:598 –601 9. Weindler J, Kiefer RT, Rippa A, et al. Low-dose oral clonidine as premedication before intraocular surgery in retrobulbar anesthesia. Eur J Ophthalmol 2000; 10:248 – 256 10. Kiefer RT, Weindler J, Ruprecht KW. Oral low-dose midazolam as premedication for intraocular surgery in retrobulbar anesthesia: cardiovascular effects and relief of perioperative anxiety. Eur J Ophthalmol 1997; 7:185– 192 11. Wong DH, Merrick PM. Intravenous sedation prior to peribulbar anaesthesia for cataract surgery in elderly patients. Can J Anaesth 1996; 43:1115–1120 12. Kost M, Emerson D. Propofol–fentanyl versus midazolam–fentanyl: a comparative study of sedation techniques for cataract surgery. CRNA 1992; 3:7–15 13. Virkkila ME, Ali-Melkkila TM, Kanto JH. Premedication for outpatient cataract surgery: a comparative study of intramuscular alfentanyl, midazolam and placebo. Acta Anaesthesiol Scand 1992; 36:559 –563 14. Ferrari LR, Donlon JV. A comparison of propofol, midazolam, and methohexital for sedation during retrobulbar and peribulbar block. J Clin Anesth 1992; 4:93–96 15. Wine NA. Sedation with neuroleptanalgesia in cataract surgery. Am J Ophthalmol 1966; 61:456 –460 16. White PF, Coe V, Shafer A, Sung ML. Comparison of alfentanil with fentanyl for outpatient anesthesia. Anesthesiology 1986; 64:99 –106 17. Mostafa SM, Lockhart A, Kumar D, Bayoumi M. Comparison of effects of fentanyl and alfentanil on intra-ocular pressure. Anaesthesia 1986; 41:493–498 18. Stead SW, Northfield KM. Effects of alfentanil analgesia for ophthalmic nerve blocks [abstract]. Anesthesiology 1990; 73:A769
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19. Foggitt PS. Anxiety in cataract surgery: pilot study. J Cataract Refract Surg 2001; 27:1651–1655 20. Kiefer RT, Weindler J, Ruprecht KW. The endocrine stress response after oral premedication with low-dose midazolam for intraocular surgery in retrobulbar anaesthesia. Eur J Ophthalmol 1998; 8:239 –245 21. Juckenhofel S, Feisel C, Schmitt HJ, Biedler A. TIVA mit Propofol/Remifentanil oder balancierte Anesthesie mit Sevoflurane/Fentanyl bei laparoskopischen Operationen. Hamodynamik, Aufwachchverhalten und Nebenwirkungen. Anaesthesist 1999; 48:807–812 22. Mo¨ nestam E, Kuusik M, Wachtmeister L. Topical anesthesia for cataract surgery: a population-based perspective. J Cataract Refract Surg 2001; 27:445–451 23. Han T, Kim D, Kil H, Inagaki Y. The effects of plasma fentanyl concentrations on propofol requirement, emergence from anesthesia, and postoperative analgesia in propofol-nitrous oxide anesthesia. Anesth Analg 2000; 90:1365–1371 24. Pang WW, Mok MS, Huang S, Hwang MH. The analgesic effect of fentanyl, morphine, meperidine, and lidocaine in the peripheral veins: a comparative study. Anesth Analg 1998; 86:382–386 25. Tverskoy M, Oz Y, Isakson A, et al. Preemptive effect of fentanyl and ketamine on postoperative pain and wound hyperalgesia. Anesth Analg 1994; 78:205–209 26. Sheeran P, Hall GM. Cytokines in anaesthesia. Br J Anaesth 1997; 78:201–219 27. Hall GM, Desborough JP. Interleukin-6 and metabolic response to surgery. Br J Anaesth 1992; 69:337–338 ¨ zalp G, Gu¨ ner F, Kuru N, Kadiogullari N. Postopera28. O tive patient-controlled epidural analgesia with opioid bupivacaine mixtures. Can J Anaesth 1998; 45:938 –942 29. Guinard JP, Carpenter RL, Chassot PG. Epidural and intravenous fentanyl produce equivalent effects during major surgery. Anesthesiology 1995; 82:377–382 30. Camu F, Van Aken H, Bovill JG. Postoperative analgesic effects of three demand-dose sizes of fentanyl administered by patient-controlled analgesia. Anesth Analg 1998; 87:890 –895 31. McHardy FE, Fortier J, Chung F, et al. A comparison of midazolam, alfentanil and propofol for sedation in outpatient intraocular surgery. Can J Anaesth 2000; 47:211– 214 32. Hodgkins PR, Teye-Botchway L, Morrell AJ, et al. Neuroleptanalgesia and extracapsular cataract extraction. Br J Ophthalmol 1992; 76:153–156 ¨ ztu¨ rk) and From the Departments of Ophthalmology (Inan, Ermis, O Anesthesiology (Sivaci), School of Medicine, Kocatepe University, Afyon, Turkey. None of the authors has a financial or proprietary interest in any material or method mentioned.
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ataract surgery is the most commonly performed operation in the older population. Today, phacoemulsification is the preferred method of cataract extraction and can be safely performed using local or topical anesthesia.1,2 However, patients, especially older ones, can experience discomfort perioperatively that is related to concomitant systemic disorders such as cardiovascular, pulmonary, and metabolic diseases.3 Patient discomfort can produce hemodynamic instability and thus Accepted for publication November 15, 2002. ¨ mit U ¨ beyt Inan, MD, Dumlupinar Mh Turabi Reprint requests to U Cadessi, Tutuncu Apartment, B Blok 4/7, 03200, Afyon, Turkey. E-mail: [email protected]. © 2003 ASCRS and ESCRS Published by Elsevier Inc.
more discomfort. Surgical pain can also make patients become agitated. In addition, some patients find it difficult to remain motionless for a certain amount of time, especially under topical anesthesia during cataract surgery.4 Topical anesthesia has gained growing popularity among experienced surgeons. However, patient cooperation and vocal anesthesia are required to achieve patient relaxation. Therefore, some patients may need local anesthesia to cooperate with the surgeon. In addition, mentally incompetent or anxious patients may not be good candidates for topical anesthesia.3–5 Local anesthesia with retrobulbar or peribulbar injection causes anxiety and pain in most patients. As a result, they may 0886-3350/03/$–see front matter doi:10.1016/S0886-3350(02)02053-9
FENTANYL ANALGESIA IN CATARACT SURGERY
remain agitated throughout the procedure.6 Some patients also feel pain from the wire speculum or experience discomfort caused by factors such as variations in intraocular pressure (IOP), compression by the blood pressure cuff, and uncomfortable positioning. Preventing perioperative pain and discomfort is necessary to allow comfortable surgery for both surgeon and patient. Maintenance of sedation by medication given before surgery may compromise the patient’s consciousness and cooperation. Several techniques are used to produce sedation for placement of a retrobulbar or peribulbar block and to ensure the patient has no discomfort during surgery.7–14 Fentanyl, a commonly used agent for systemic analgesia given during general anesthesia, is an opioid of the phenalpiperidine group that is 100 times more potent an analgesic than morphine. Its use in cataract surgery may help prevent pain and discomfort during retrobulbar injection and surgery without hindering patient cooperation.15–18 Our study evaluated the effectiveness of the induction and maintenance of systemic analgesia by intravenous (IV) fentanyl given before the retrobulbar block and during surgery on patient pain and discomfort during the injection and intraoperatively. We also assessed whether fentanyl provides hemodynamic stability during surgery.
Patients and Methods One hundred twenty patients aged 40 to 78 years with American Society of Anesthesiologists physical status I to III scheduled for cataract were evaluated in a single-blind randomized study. Patients with a history of hypertension, hyperthyroidism, or neurologic or psychiatric disorders were excluded. The Institutional Human Investigation Committee approved the study. Patients were prospectively randomized to receive local anesthesia (control group) or local anesthesia combined with fentanyl analgesia (fentanyl group). There were 60 patients in each group. The patients’ demographic data and the duration of surgery are shown in Table 1; there were no statistically significant differences between groups in any parameter (P⬎.05)
Preoperative Routine A few weeks before surgery, patients came to the clinic for a preoperative assessment. The patients were questioned about general health and current medications. Systemic diseases (eg, cardiovascular conditions, hypertension, respiratory 1138
Table 1. Patients’ demographics and duration of surgery. Mean ⴞ SD Fentanyl Group
Control Group
65.76 ⫾ 6.10
65.21 ⫾ 7.82
Height (m)
164.08 ⫾ 6.87
163.91 ⫾ 8.68
Weight (kg)
67.85 ⫾ 7.20
68.00 ⫾ 7.43
Duration of surgery (min)
31.05 ⫾ 4.30
29.66 ⫾ 3.35
Parameter Age (y)
dysfunction, diabetes, previous or current ocular disease) were recorded. Laboratory examination included blood tests, an electrocardiogram, and a chest x-ray. Patients with abnormal laboratory results and uncontrolled systemic disease were referred to an internist before surgery.
Anesthesia Administration No premedication was given so the full effect of the fentanyl could be ascertained. Patients were given an IV of 500 cc electrolyte solution (Isolyte威 S) using a 22-gauge needle. Both groups received 4 L/min–1 of oxygen through a nasal cannula; expired air was suctioned through a Y-piece system. In the fentanyl group, an IV bolus of fentanyl 2 g/kg was slowly administered 5 minutes before the retrobulbar block and repeated 30 minutes after the first dose. In the control group, fentanyl was not given before the retrobulbar block. The block was given by 1 of 3 experienced surgeons using the Atkinson retrobulbar injection approach. A 23-gauge sharp needle (Rhein Medical) was inserted at the inferior lateral junction of the skin of the lower lid. A mixture of 1 mL (5 mg/mL) bupivacaine and 1.5 mL (20 mg/mL) of lidocaine 2% were injected. Orbital compression was not done because sufficient ocular hypotony was achieved by fentanyl administration.
Surgical Technique Surgeries were performed by 1 of 3 surgeons. Mydriasis was obtained with 3 to 4 drops of topical phenylephrine hydrochloride 2.5% (Mydfrin威), tropicamide 0.5% (Mydriacyl威), and cyclopentolate hydrochloride 1% (Siklomid威). Topical anesthetic drops of proparacaine hydrochloride (Alcaine威) were instilled a few minutes apart preceding surgery. After standard aseptic preparation, a wire speculum was inserted. A 3.2 mm clear corneal tunnel was made. Cataract extraction comprised a continuous curvilinear capsulorhexis, bimanual endocapsular phacoemulsification, and aspiration of remaining cortical lens material. In half the patients, a foldable acrylic (AR40, Allergan) or silicone (SI-40, Allergan) intraocular lens (IOL) was implanted using an Unfolder (Allergan) without widening the corneal incision. In the other half, the tunnel was widened to 4.0 mm and a foldable acrylic (AcrySof威 MA30BM, Alcon, or Softec威, Lenstec Inc.) or silicone (CeeOn威 911, Pharmacia & Upjohn, or Siltec威, Lens-
J CATARACT REFRACT SURG—VOL 29, JUNE 2003
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tec Inc.) IOL was implanted. At the end of surgery, a subconjunctival injection of a gentamicin and dexamethasone mixture was given.
Table 2. Verbal pain scores. Mean ⴞ SD Fentanyl Group
Control Group
P Value
Monitoring
Scoring Time
All patients were monitored with an anesthesia machine (Datex-Ohmeda ADU AS/3 or Cicero EM). In both groups, the mean arterial pressure (MAP), heart rate (HR), and endtidal carbon dioxide concentration (EtCO2) were recorded at 1-minute intervals throughout the perioperative period. The MAP and HR were evaluated at baseline, during the injection, and 10, 20, and 30 minutes after initiation of the surgery. An anesthetist performed the intraoperative monitoring and intervened medically when necessary.
During RB injection
0.06 ⫾ 0.25 1.60 ⫾ 0.52 .000
5 minutes after RB injection
0.05 ⫾ 0.21 1.01 ⫾ 0.32 .000
During surgery
0.08 ⫾ 0.27 1.06 ⫾ 0.25 .000
Postoperatively
0.01 ⫾ 0.12 0.11 ⫾ 0.32 .031
Duration of Surgery The exact duration of all surgical procedures was recorded. A stopwatch was started when the surgeon sat down by the operating microscope and stopped when he ended the operation and rose from the chair. The total time included focusing the microscope, opening the draping, placing the speculum, performing phacoemulsification, and removing the draping.
Pain Assessment Patients’ pain was evaluated by verbal pain scores (VPS) using a 4-point scale (0 ⫽ no pain, 1 ⫽ mild pain, 2 ⫽ moderate pain, and 3 ⫽ severe pain).The scores were recorded during the injection, 5 minutes after the retrobulbar injection, during the surgical procedure, and immediately after surgery.
Statistical Analysis Statistical analysis was done using SPSS 10.0 software (SPSS Inc.). Demographic data and comparisons between the groups at each evaluation were by an unpaired t test. Multiple comparisons of hemodynamic parameters within the groups were done using an analysis of variance. Statistical comparisons of VPS values between groups were by the Pearson chisquare test. The Fisher exact test was used to compare VPS values postoperatively. A P value less than 0.05 was considered statistically significant.
Results The VPS in the fentanyl group were lower than in the control group. During retrobulbar injection, 56 patients in the fentanyl group had a pain score of 0 and 4 of 1. In the control group, 25 patients had a pain score of 1, 34 of 2, and 1 of 3. Table 2 and Figure 1 show the mean pain scores. The fentanyl group had statistically significantly lower pain scores than the control group at all evaluations (P⬍.05).
RB ⫽ retrobulbar
There were no significant changes in oxygen saturation and EtCO2 between the 2 groups. Significant hemodynamic changes occurred at 0, 10, 20, and 30 minutes in the control group while hemodynamic parameters in the fentanyl group remained stable (Figures 2 and 3). The HR during the retrobulbar injection and at 10, 20, and 30 minutes increased significantly over baseline values in the control group. The MAP during the retrobulbar injection and at 20 minutes increased significantly over baseline values in the control group. There were no statistically significant differences between baseline and subsequent HR and MAP measurements in the fentanyl group. The HR and MAP values at all points except at baseline were statistically different between the 2 groups. The fentanyl group had a statistically significantly lower hemodynamic response to the local anesthetic injection and surgery than the control group (P⬍.001). Five patients in the control group developed systemic hypertension and required an antihypertensive drug (IV enalapril 10 mg).
Discussion In our study, fentanyl analgesia reduced perioperative pain and stabilized the hemodynamic response during cataract surgery under retrobulbar block. Ophthalmic pain after uneventful extracapsular cataract surgery has been reported. Koay et al.6 found that although nearly half the patients having ophthalmic surgery in their study had no pain or discomfort postoperatively, 32% reported slight discomfort, 8% mild pain, and 5% moderate to severe pain. Many ophthalmic procedures can be performed using a retrobulbar regional anesthetic technique. However, the block is painful and patients often express anxiety over the procedure. The pain can make patients
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Figure 1. (Inan) Verbal pain scores at 4 stages (P⬍.05 between groups at all stages).
Figure 2. (Inan) Heart rate (P⬍.05 during injection and 10, 20, and 30 minutes after initiation of surgery).
Figure 3. (Inan) Mean arterial pressure (P⬍.05 during injection and 10, 20, and 30 minutes after initiation of surgery).
move their eyes, increasing the risk for complications. In an attempt to prevent complications, patients can be sedated before the block is administered. However, sedated patients may be uncooperative and feel pain that makes them move.4,5 Surgical pain can also cause intraoperative anxiety. Anxiety and stress are associated with systemic problems such as tachycardia, hypertension, and dysrhythmia.19,20 Preventing pain and anxiety may increase the patient’s tolerance of surgery. There is a difference between North American practice, in which IV sedation appears to be used routinely, and northern European practice, in which sedation is used less frequently. The routine use of sedation is sometimes avoided because of risks such as airway obstruction and a rise or drop in blood pressure. Kallio and coauthors5 report that sudden unexpected head or body
movements during surgery occur more often with IV sedation than without, making its use relatively more dangerous to patients’ vital functions and the surgery less safe. Keeping the patient cooperative under IV sedative sedation is a challenge. The risk of respiratory depression necessitates the presence of experienced anesthesia personnel. Opioid drugs can be used for both sedation and analgesia. Producing good preemptive analgesia can also provide hemodynamic stability and reduce IOP.21 Fewer side effects and more successful surgery can also be obtained. As a result of improvements in surgical and anesthetic techniques, topical anesthesia has become more popular in recent years. Painless cataract surgery using only topical anesthesia is possible and desirable. How-
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ever, phacoemulsification with topical anesthesia alone is painful for some patients. Differences in pain sensitivity among individuals or the need for increased intraocular manipulation can cause pain.1,3,5,22 In such cases, systemic analgesia might be sufficient to relieve patients without adding peribulbar or retrobulbar anesthesia. Hyperalgesia produced by C-fiber-strength electrical stimulation of a nerve can be prevented by a relatively low dose of an analgesic drug when a much higher dose is required to suppress established hyperalgesia.23 The concept that analgesia given before the painful stimulus has effects that long outlast the presence of the analgesic in the body created the basis for the preemptive treatment of pain. Preemptive analgesia eliminates painful mechanical stimulation during surgery. Opioids are central receptor-mediated analgesics. The finding of opioid receptors in the peripheral systems prompted studies using opioids for regional analgesia and peripheral analgesic actions.24,25 The process of pain emphasizes the role of the primary mediators of the cytokine cascade—tumor necrosis factor ␣ and interleukin (IL) 1b—in hyperalgesia. Hyperalgesia induced by IL-1b depends partly on induction of bradykinin-1 receptors. Nerve growth factor modulates the production of substance P and is key to understanding the phenomenon of hyperalgesia.26,27 Opioids are highly effective in suppressing substance P. Fentanyl prevents production of cytokines indirectly without causing an algesia process. “Sustained hyperexcitability” is caused not only by direct surgical stimulation but also by the action of proteolytic and inflammatory processes in the wound tissue that last longer than the surgery.25 Fentanyl has qualities that make it promising for ophthalmic use. It has a rapid onset and short duration of action, and it lacks active metabolites. The higher lipophilicity of fentanyl may be responsible for the lower incidence of side effects and allows less free fentanyl to migrate into the cerebrospinal fluid, causing less rostral spread to the brain.28 Possible harmful effects can easily be reversed with naloxone. When fentanyl is given for analgesia in half-hourly IV injections of 2 to 3 g/kg, there is no increase in the incidence of respiratory depression. Fentanyl also reduces postoperative pain without producing respiratory depression.29,30 Optimal efficacy and safety depend on a dose that is small enough to minimize adverse effects but
large enough to achieve analgesic efficacy. The dose in our study was 2 g/kg. The fentanyl IV titration phase, treatment period, and number and frequency of doses during surgery must be individualized. Side effects of fentanyl, such as myocardial and respiratory depression, hypotension, consciousness, and parasympathetic activation (nausea, vomiting, pruritis, urticheria), can occur at doses exceeding 5 g/kg. The effective minimal dose for sufficient analgesia of fentanyl used alone is 2 g/kg. The effects of fentanyl may be heightened when combined with other drugs such as hypnotics, sedatives, and muscle-relaxing agents. Doses lower than 2 g/kg may contribute to sedation but not provide adequate analgesia. Surgical pain and stress can cause increased agitation. Therefore, patients with less pain and stress during surgery may be significantly more comfortable. An increase in systemic blood pressure and heart rate during the retrobulbar block and surgery indicates the hemodynamic responses to pain.4,7 McHardy et al.31 report that alfentanyl minimizes the hemodynamic response and reduces pain scores in the first postoperative hour and that the use of alfentanyl is more advantageous in ambulatory patients having ophthalmic surgery than midazolam and propofol sedation. Hodgkins et al.32 report that IV neuroleptanalgesia combined with a facial nerve block achieves satisfactory ocular analgesia and akinesia during cataract extraction without the use of a periocular injection. In conclusion, our study indicates that fentanyl is safe and effective for the management of moderate to severe pain during cataract surgery. Based on safety and efficacy, an IV fentanyl dose of 2 g/kg seems optimal for ophthalmic surgery. Fentanyl alone can be used to prevent painful stimulation during the placement of a local anesthesia block and to provide cooperative, comfortable intraocular surgery.
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