- Email: [email protected]
Commentary: Postoperative analgesia after lumbar laminectomy: is there a role for single-shot epidural fentanyl?
The Spine Journal 12 (2012) 652–655
Commentary
Commentary: Postoperative analgesia after lumbar laminectomy: is there a role for single-shot epidural fentanyl? Hwan Ing Hee, MBBCH BAO (Ire), FRCA (UK)a, Yi Shuen Tracy Tan, MBBS, MMED (Singapore)a, Hwan Tak Hee, MBBS, FRCS (Ed), FRCS (Glas), FAMS (Ortho)b,* a Department of Paediatric Anaesthesia, KK Women’s and Children’s Hospital, 100 Bukit Timah Rd, Singapore 229899 Centre for Spine & Scoliosis Surgery, Paragon and Mount Elizabeth Medical Centre, 290 Orchard Rd, #09-09/10, Singapore 238859
b
Received 10 August 2012; accepted 19 August 2012
COMMENTARY ON: Guilfoyle MR, Mannion RJ, Mitchell P, Thomson S. Epidural fentanyl for postoperative analgesia after lumbar canal decompression: a randomized controlled trial. Spine J 2012;12:646–51 (in this issue).
Spine surgery may result in early severe pain with moderate pain lasting up to a week. Both epidural analgesia [1– 15] and intravenous patient-controlled analgesia are safe and effective techniques for postoperative analgesia after spine surgery. The practice of single bolus epidural (lumbar and thoracic) fentanyl has been used as postoperative analgesia for a variety of nonspinal surgeries ranging from abdominal, thoracic, perineal, and lower limb surgeries [16–22]. However, any information regarding use of bolus epidural fentanyl for spine surgery remains limited in literature. When an opioid is administered into the extradural space, its route of distribution [23] includes the following: moving through meninges into the cerebrospinal fluid (CSF); binding to opioid receptors and other nonspecific binding sites on the spinal cord; migrating rostrally via CSF to supraspinal sites; being absorbed into epidural and spinal vascular system; being taken into epidural fat. The vascular absorption of opioid is responsible for its systemic side effects, and the rostral spread accounts for delayed respiratory depression—the principal risk of epidural opioid.
DOI of original article: 10.1016/j.spinee.2012.07.007. FDA device/drug status: Not applicable. Author disclosures: HIH: Nothing to disclose. YSTT: Nothing to disclose. HTH: Nothing to disclose. * Corresponding author. Centre for Spine & Scoliosis Surgery, Paragon and Mount Elizabeth Medical Centre, 290 Orchard Rd, #09-09/10, Singapore 238859. Tel.: (65) 68875000; fax: (65) 68367617. E-mail address: [email protected] (H.T. Hee) 1529-9430/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spinee.2012.08.023
Compared with hydrophilic morphine, lipophilic fentanyl has reduced risks and less pronounced side effects mediated by the brainstem such as sedation and respiratory depression. The lipophilic nature of fentanyl limits rostral spread within the intrathecal space and also results in more rapid onset of action and greater potency [23,24]. As liposolubility is inversely proportional to spinal selectivity of opioid, fentanyl has a shorter duration of action [25,26]. This lack of selectivity for spinal cord is supported by pharmacokinetic studies, which show that lipophilic opioids display greater preferential partition into fat [24], larger systemic drug absorption [24], greater binding to myelin, and lower penetration into the gray matter [24,27]. The mechanism of action of epidural fentanyl is influenced largely by its mode of administration. Evidence shows that given as an epidural bolus, fentanyl binds predominantly at the spinal sites, resulting in segmental analgesia [25,26,28]. Given as an epidural infusion, fentanyl binds predominantly at supraspinal sites, resulting in systemic nonsegmental analgesic effect. Hence, epidural delivered by bolus has the value of greater potency (vs. intravenous route), greater analgesic effect at a lower plasma level, and lower systemic side effects. The effective regime of bolus epidural fentanyl can be extrapolated from previous published work [16–23,28] in which bolus epidural fentanyl was used effectively. A dose of 50 to 100 mcg in 6 to 10 mL was shown to provide effective and rapid onset of action within 10 to 15 minutes, which lasts for 2 to 4 hours [16,18,19,21,23,25,28]. This duration of action of a single dose of epidural fentanyl is disappointing. In the study by Lomessy et al. [17], a high
H.I. Hee et al. / The Spine Journal 12 (2012) 652–655
dose of 200 mcg at best extended the acceptable analgesia score to 3 hours, but the duration of analgesia for provoked pain remained at 2 hours. The study by Inagaki et al. [18] demonstrated dose-dependent effect with duration of analgesia increased from 130 to 239 minutes when 4 mcg/kg was administered. Caution should be exercised with large doses, as it can result in extensive systemic uptake [23] with consequent redistribution into the brain as well as rostral spread within the intrathecal space. Findings from the study by Birnbach et al. [29] showed a volume-dependent increase in duration of analgesia up to a volume of 20 mL with duration of action extended to 3 hours. In contrast, a single study by Shipton et al. [21] did show some promising results of excellent analgesia after lower abdominal, perineal, and lower limb surgery lasting at least 8 hours after a bolus of 100 mcg fentanyl was given as a 10-mL injectate. Given the lack of spread through CSF and segmental nature of the analgesia achieved with bolus fentanyl, it is logical that the catheter tip should be sited at the level of greatest nociceptive input [30–32], although this was not conclusively shown in several studies done [33–35]. Lower doses of epidural fentanyl have been reported to have no or only minor side effects [18], most commonly, pruritus [23,28]. Although less likely than morphine to produce ventilatory depression [23], reduction in respiratory rate, increase in PaCO2, and sedation have been reported with the use of higher doses of epidural fentanyl [17,18,23,28]. Profound respiratory depression has also been reported after epidural bolus of 100 mcg fentanyl [36,37]. Data on the incidence of urinary retention are limited by common postoperative practice of urinary catheterization. The article by Guilfoyle et al., in the current issue of The Spine Journal, evaluates the analgesic efficacy of bolus fentanyl 100 mcg given as a 10-mL injectate 10 cm rostral to the surgical site after lumbar decompression for spinal stenosis [38]. The authors concluded that their approach is beneficial as an adjunct for effective reduction of early postoperative pain. The epidural catheter was placed under direct vision by the surgeon. The dose regime (100 mcg) and volume of diluents (10 mL) used in his study had been used with success in previous nonspinal surgeries [16,18,19,21] in which dura was intact and placement of catheter performed by anesthetists. It may not be fair to extrapolate the nonspinal dose regime to spine surgery. Epidural delivery of fentanyl after a spine surgery may be affected by systemic absorption from the surgical site, dilutional effect from surgical site bleed, loss of opioids from surgical site drainage, or intrathecal spinal delivery because of the loss of integrity of dura during spinal surgery. It is also not known if the effect of the bolus fentanyl in Guilfoyle’s work is also attributed in part to supraspinal effect as a result of systemic absorption. The plasma fentanyl assay was not measured, neither was intravenous fentanyl used as a comparator. Guilfoyle’s target site of catheter tip is 10 cm rostral to laminectomy site and is slightly higher
653
than other reports [3–5,8,39,40] in which the tip of the catheter is placed 3 to 6 cm cephalic to the surgical site or within the mid-surgical field [9]. Surgical placement under direct vision has the advantage of greater accuracy with decreased risk of neurologic damage and inadvertent subarachnoid placement but does not guarantee correct placement. Misplaced catheter and variability in catheter tip have all been reported after catheter placement by surgeons [41]. Epidural opioid, especially fentanyl, offers numerous advantages over other techniques for elderly patients undergoing spine surgery. Epidural fentanyl acts on receptors in the dorsal horn instead of spinal nerve roots. This is of relevance after spine surgery, in which motor blockade [39,42] after epidural local anesthetic can interfere with the postoperative neurologic assessment. Motor blockade may mask symptoms of postoperative complications such as spinal epidural hematoma. Although the incidence of symptomatic spinal epidural hematoma is low at 0.1% to 4.5% [43,44], it has potential for devastating neurologic sequelae when diagnosis and treatment are delayed. Some authors have suggested that normal neurologic function should be demonstrated [14] or a day should lapse [40] before the initiation of epidural infusion of local anaesthetics to minimize interference with neurologic observation. Epidural opioid lacks sympathetic blockade unlike epidural local anesthetic and hence better tolerated in this patient group who often have concurrent cardiorespiratory comorbidities [45]. Furthermore, epidural opioid offers excellent analgesia and greater safety margin, especially central nervous system effects [46], compared with intravenous route. This benefits the elderly population who may have associated cognitive deficit that affects assessment and verbalization of pain. In contrast to morphine, fentanyl has a safer profile. Compared with fentanyl infusion, bolus fentanyl gives an effective segmental analgesia with less systemic effect. Compared with local anesthetic containing infusion, bolus fentanyl facilitates postoperative motor and sensory function monitoring in post–spine surgery. It is surprising that the duration of adequate analgesia in Guilfoyle’s study, represented by visual analog score (VAS) less than 5, extended beyond the limit of early postoperative period reported in previous studies into Day 1 after surgery. One can speculate that a concurrent postoperative analgesia regime could have explained the VAS observed. It is also interesting to note that a clinically significant proportion of patients (48% in the treatment group and 33% in the control group) were discharged on the first day of surgery. The average length of stay of 2 days reported in Guilfoyle’s study was comparable with that reported by Walcott et al. [47] but shorter than the average 3.6 days reported by Shabat et al. [48]. Patients in Guilfoyle’s study were notably younger than the octogenarians in Shabat’s study. The short hospital stay in the present study could possibly be attributed to patient selection with low morbidity, the surgical technique used, and the short spinal segments (1.5–2)
654
H.I. Hee et al. / The Spine Journal 12 (2012) 652–655
involved. The latter is important, as the number of vertebrae included in the operation and the degree of invasiveness are factors affecting the severity of pain [49]. Although not statistically significant, better early pain control (lower VAS) is demonstrated in the treatment group and may have contributed to the shorter hospital stay. There are some limitations in the present study design. A cause for concern is the omission of information on whether a concurrent postoperative analgesia regime was implemented. Time to first dose and total dose of supplementary analgesia are otherwise important measures that allowed meaningful comparison between treatment and control. Also lacking is information regarding type and dose of the intraoperative opioid used. Visual analog scale should be evaluated more frequently to give a better clinical comparison of efficacy. Guilfoyle also failed to qualify whether VAS was performed at rest or on movement. Other functional assessments such as time to ambulation and oral intake are important outcomes to be measured too. Although the incidence of side effects was similar between groups, no comments were made on severity and need for intervention. Perhaps future studies using intravenous fentanyl as a control will provide more useful data. In general, bolus epidural fentanyl produces rapid onset of good segmental analgesia that is brief, making it useful for early postoperative pain and in ambulatory surgery. It may not be the optimal primary approach in providing postoperative analgesia, but its systemic opioid sparing effect makes it a very useful adjunct. Although the incidence of respiratory depression is low, vigilant monitoring is still essential, especially in the early postoperative period. Guilfoyle’s work in extending its use to spinal surgery showed promising results, indicating that epidural bolus fentanyl may be useful in certain spine surgeries and in selected patients whose early discharge from hospital is anticipated. References [1] Ray CD, Bagley R. Indwelling epidural morphine for control of post-lumbar spinal surgery pain. Neurosurgery 1983;13:388–93. [2] Ozuna J, Burchiel KJ, Pencek T. Routine use of epidural morphine in patients following lumbar spine surgery. Clin J Pain 1988;4: 209–12. [3] Rechtine GR, Reinert CM, Bohlman HH. The use of epidural morphine to decrease postoperative pain in patients undergoing lumbar laminectomy. J Bone Joint Surg Am 1984;66:113–6. [4] Kundra P, Gurnani A, Bhattacharya A. Preemptive epidural morphine for postoperative pain relief after lumbar laminectomy. Anesth Analg 1997;85:135–8. [5] Sice PJA, Chan D, Macintyre PA. Epidural analgesia after spinal surgery via intervertebral foramen. Br J Anaesth 2005;94:378–80. [6] Lowry KJ, Tobias J, Kittle D, et al. Postoperative pain control using epidural catheters after anterior spinal fusion for adolescent scoliosis. Spine 2001;26:1290–3. [7] Arms DM, Smith JT, Osteyee J, Gartrell A. Postoperative epidural analgesia for pediatric spine surgery. Orthopedics 1998;21:539–44. [8] Shaw BA, Watson TC, Merzel DI, et al. The safety of continuous epidural infusion for postoperative analgesia in pediatric spine surgery. J Pediatr Orthop 1996;16:374–7.
[9] Joshi GP, McCarroll SM, O’Rourke K. Postoperative analgesia after lumbar laminectomy: epidural fentanyl infusion versus patientcontrolled intravenous morphine. Anesth Analg 1995;80:511–4. [10] Schenk MR, Putzier M, K€ugler B, et al. Postoperative analgesia after major spine surgery: patient-controlled epidural analgesia versus patient-controlled intravenous analgesia. Anesth Analg 2006;103: 1311–7. [11] Reynolds AF, Dautenhahn DL, Pollay M, Fagraeus L. Safety and efficacy of epidural analgesia in spine surgery. Ann Surg 1986;203: 225–7. [12] Cata JP, Noguera EM, Parke E, et al. Patient-controlled epidural analgesia (PCEA) for postoperative pain control after lumbar spine surgery. J Neurosurg Anesthesiol 2008;20:256–60. [13] Gottschalk A, Freitag M, Tank S, et al. Quality of postoperative pain using an intraoperatively placed epidural catheter after major lumbar spinal surgery. Anesthesiology 2004;101:175–80. [14] Tobias JD. A review of intrathecal and epidural analgesia after spinal surgery in children. Anesth Analg 2004;98:956–65. [15] Kumar RJ, Menon KV, Ranjith TC. Use of epidural analgesia for pain management after major spinal surgery. J Orthop Surg (Hong Kong) 2003;11:67–72. [16] Grass JA, Sakima NT, Schmidt R, et al. A randomized, doubleblind, dose response comparison of epidural fentanyl versus sufentanil analgesia after caesarean section. Anesth Analg 1997;85: 365–71. [17] Lomessy A, Magnin C, Viale JP, et al. Clinical advantages of fentanyl given epidurally for postoperative analgesia. Anesthesiology 1984;61:466–9. [18] Inagaki Y, Mashimo T, Yoshiya I. Segmental analgesic effect and reduction of halothane MAC from epidural fentanyl in humans. Anesth Analg 1992;74:856–64. [19] Harukuni I, Yamaguchi H, Sato S, Naito H. The comparison of epidural fentanyl, epidural lidocaine, and intravenous fentanyl in patients undergoing gastrectomy. Anesth Analg 1995;81:1169–74. [20] Privado MS, Issy AM, Lanchote VL, et al. Epidural versus intravenous fentanyl for postoperative analgesia following orthopedic surgery: randomized controlled trial. Sao Paulo Med J 2010;128:5–9. [21] Shipton EA, Hugo JM, Muller FO. Epidural fentanyl in the management of postoperative pain. S Afr Med J 1986;70:325–8. [22] Guinard JP, Carpenter RL, Chassot PG. Epidural and intravenous fentanyl produce equivalent effects during major surgery. Anesthesiology 1995;82:377–82. [23] Peng PW, Sandler AN. A review of the use of fentanyl analgesia in the management of acute pain in adults. Anesthesiology 1999;90: 576–99. [24] Ummenhofer WC, Arends RH, Shen DD, Bernards CM. Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil. Anesthesiology 2000;92:739–53. [25] Bujedo BM, Santos SG, Azpiazu AU. A review of epidural and intrathecal opioids used in the management of postoperative pain. J Opioid Manag 2012;8:177–92. [26] Ginosar Y, Riley ET, Angst MS. The site of action of epidural fentanyl in humans: the difference between infusion and bolus administration. Anesth Analg 2003;97:1428–38. [27] Herz A, Albus K, Metys J, et al. On the central sites for the antinociceptive action of morphine and fentanyl. Neuropharmacology 1970;9:539–51. [28] Coda BA, Brown MC, Schaffer R, et al. Pharmacology of epidural fentanyl, alfentanil, and sufentanil in volunteers. Anesthesiology 1994;81:1149–61. [29] Birnbach DJ, Johnson MD, Arcario T, et al. Effect of diluent volume on analgesia produced by epidural fentanyl. Anesth Analg 1989;68: 808–10. [30] Welchew EA, Breen DP. Patient-controlled on-demand epidural fentanyl. A comparison of patient-controlled on-demand fentanyl delivered epidurally or intravenously. Anaesthesia 1991;46:438–41.
H.I. Hee et al. / The Spine Journal 12 (2012) 652–655 [31] Salomaki TE, Laitinen JO, Nuutinen LS. A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for analgesia after thoracotomy. Anesthesiology 1991;75:790–5. [32] Sawchuk CW, Ong B, Unruh HW, et al. Thoracic versus lumbar epidural fentanyl for postthoracotomy pain. Ann Thorac Surg 1993;55:1472–6. [33] Guinard JP, Mavrocordatos P, Chiolero R, Carpenter RL. A randomized comparison of intravenous versus lumbar and thoracic epidural fentanyl for analgesia after thoracotomy. Anesthesiology 1992;77:1108–15. [34] Coe A, Sarginson R, Smith MW, et al. Pain following thoracotomy. A randomised, double-blind comparison of lumbar versus thoracic epidural fentanyl. Anaesthesia 1991;46:918–21. [35] Bouchard F, Drolet P. Thoracic versus lumbar administration of fentanyl using patient-controlled epidural after thoracotomy. Reg Anesth 1995;20:385–8. [36] Brockway MS, Noble DW, Sharwood-Smith GH, McClure JH. Profound respiratory depression after extradural fentanyl. Br J Anaesth 1990;64:243–5. [37] Wells DG, Davies G. Profound central nervous system depression from epidural fentanyl for extracorporeal shock wave lithotripsy. Anesthesiology 1987;67:991–2. [38] Guilfoyle MR, Mannion RJ, Mitchell P, Thomson S. Epidural fentanyl for postoperative analgesia after lumbar canal decompression: a randomized controlled trial. Spine J 2012;12:646–51. [39] O’Hara JF Jr, Cywinski JB, Tetzlaff JE, et al. The effect of epidural vs intravenous analgesia for posterior spinal fusion surgery. Paediatr Anaesth 2004;14:1009–15. [40] Kluba T, Hofmann F, Bredanger S, et al. Efficacy of post-operative analgesia after posterior lumbar instrumented fusion for degenerative disc disease: a prospective randomized comparison of epidural
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
655
catheter and intravenous administration of analgesics. Orthop Rev (Pavia) 2010;2:e9. Turner A, Lee J, Mitchell R, et al. The efficacy of surgically placed epidural catheters for analgesia after posterior spinal surgery. Anaesthesia 2000;55:370–3. Purnell RJ. Scoliosis correction and epidural analgesia. Prolonged block following Harrington rod insertion. Anaesthesia 1982;37: 1115–7. Aono H, Ohwada T, Hosono N, et al. Incidence of postoperative symptomatic epidural hematoma in spinal decompression surgery. J Neurosurg Spine 2011;15:202–5. Kaner T, Sasani M, Oktenoglu T, et al. Postoperative spinal epidural hematoma resulting in cauda equina syndrome: a case report and review of the literature. Cases J 2009;2:8584. Fanuele JC, Birkmeyer NJ, Abdu WA, Tosteson TD. The impact of spinal problems on the health status of patients: have we underestimated the effect? Spine 2000;25:1509–14. Wheeler M, Oderda GM, Ashburn MA, Lipman AG. Adverse events associated with postoperative opioid analgesia: a systematic review. J Pain 2002;3:159–80. Walcott BP, Hanak BW, Caracci JR, et al. Trends in inpatient setting laminectomy for excision of herniated intervertebral disc: populationbased estimates from the US nationwide inpatient sample. Surg Neurol Int 2011;2:7. Shabat S, Arinzon Z, Folman Y, Leitner J. Long-term outcome of decompressive surgery for lumbar spinal stenosis in octogenarians. Eur Spine J 2008;17:193–8. Ortiz-Cardona J, Bendo AA. Perioperative pain management in the neurosurgical patient. Anesthesiol Clin 2007;25:655–74.
Commentary
Commentary: Postoperative analgesia after lumbar laminectomy: is there a role for single-shot epidural fentanyl? Hwan Ing Hee, MBBCH BAO (Ire), FRCA (UK)a, Yi Shuen Tracy Tan, MBBS, MMED (Singapore)a, Hwan Tak Hee, MBBS, FRCS (Ed), FRCS (Glas), FAMS (Ortho)b,* a Department of Paediatric Anaesthesia, KK Women’s and Children’s Hospital, 100 Bukit Timah Rd, Singapore 229899 Centre for Spine & Scoliosis Surgery, Paragon and Mount Elizabeth Medical Centre, 290 Orchard Rd, #09-09/10, Singapore 238859
b
Received 10 August 2012; accepted 19 August 2012
COMMENTARY ON: Guilfoyle MR, Mannion RJ, Mitchell P, Thomson S. Epidural fentanyl for postoperative analgesia after lumbar canal decompression: a randomized controlled trial. Spine J 2012;12:646–51 (in this issue).
Spine surgery may result in early severe pain with moderate pain lasting up to a week. Both epidural analgesia [1– 15] and intravenous patient-controlled analgesia are safe and effective techniques for postoperative analgesia after spine surgery. The practice of single bolus epidural (lumbar and thoracic) fentanyl has been used as postoperative analgesia for a variety of nonspinal surgeries ranging from abdominal, thoracic, perineal, and lower limb surgeries [16–22]. However, any information regarding use of bolus epidural fentanyl for spine surgery remains limited in literature. When an opioid is administered into the extradural space, its route of distribution [23] includes the following: moving through meninges into the cerebrospinal fluid (CSF); binding to opioid receptors and other nonspecific binding sites on the spinal cord; migrating rostrally via CSF to supraspinal sites; being absorbed into epidural and spinal vascular system; being taken into epidural fat. The vascular absorption of opioid is responsible for its systemic side effects, and the rostral spread accounts for delayed respiratory depression—the principal risk of epidural opioid.
DOI of original article: 10.1016/j.spinee.2012.07.007. FDA device/drug status: Not applicable. Author disclosures: HIH: Nothing to disclose. YSTT: Nothing to disclose. HTH: Nothing to disclose. * Corresponding author. Centre for Spine & Scoliosis Surgery, Paragon and Mount Elizabeth Medical Centre, 290 Orchard Rd, #09-09/10, Singapore 238859. Tel.: (65) 68875000; fax: (65) 68367617. E-mail address: [email protected] (H.T. Hee) 1529-9430/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spinee.2012.08.023
Compared with hydrophilic morphine, lipophilic fentanyl has reduced risks and less pronounced side effects mediated by the brainstem such as sedation and respiratory depression. The lipophilic nature of fentanyl limits rostral spread within the intrathecal space and also results in more rapid onset of action and greater potency [23,24]. As liposolubility is inversely proportional to spinal selectivity of opioid, fentanyl has a shorter duration of action [25,26]. This lack of selectivity for spinal cord is supported by pharmacokinetic studies, which show that lipophilic opioids display greater preferential partition into fat [24], larger systemic drug absorption [24], greater binding to myelin, and lower penetration into the gray matter [24,27]. The mechanism of action of epidural fentanyl is influenced largely by its mode of administration. Evidence shows that given as an epidural bolus, fentanyl binds predominantly at the spinal sites, resulting in segmental analgesia [25,26,28]. Given as an epidural infusion, fentanyl binds predominantly at supraspinal sites, resulting in systemic nonsegmental analgesic effect. Hence, epidural delivered by bolus has the value of greater potency (vs. intravenous route), greater analgesic effect at a lower plasma level, and lower systemic side effects. The effective regime of bolus epidural fentanyl can be extrapolated from previous published work [16–23,28] in which bolus epidural fentanyl was used effectively. A dose of 50 to 100 mcg in 6 to 10 mL was shown to provide effective and rapid onset of action within 10 to 15 minutes, which lasts for 2 to 4 hours [16,18,19,21,23,25,28]. This duration of action of a single dose of epidural fentanyl is disappointing. In the study by Lomessy et al. [17], a high
H.I. Hee et al. / The Spine Journal 12 (2012) 652–655
dose of 200 mcg at best extended the acceptable analgesia score to 3 hours, but the duration of analgesia for provoked pain remained at 2 hours. The study by Inagaki et al. [18] demonstrated dose-dependent effect with duration of analgesia increased from 130 to 239 minutes when 4 mcg/kg was administered. Caution should be exercised with large doses, as it can result in extensive systemic uptake [23] with consequent redistribution into the brain as well as rostral spread within the intrathecal space. Findings from the study by Birnbach et al. [29] showed a volume-dependent increase in duration of analgesia up to a volume of 20 mL with duration of action extended to 3 hours. In contrast, a single study by Shipton et al. [21] did show some promising results of excellent analgesia after lower abdominal, perineal, and lower limb surgery lasting at least 8 hours after a bolus of 100 mcg fentanyl was given as a 10-mL injectate. Given the lack of spread through CSF and segmental nature of the analgesia achieved with bolus fentanyl, it is logical that the catheter tip should be sited at the level of greatest nociceptive input [30–32], although this was not conclusively shown in several studies done [33–35]. Lower doses of epidural fentanyl have been reported to have no or only minor side effects [18], most commonly, pruritus [23,28]. Although less likely than morphine to produce ventilatory depression [23], reduction in respiratory rate, increase in PaCO2, and sedation have been reported with the use of higher doses of epidural fentanyl [17,18,23,28]. Profound respiratory depression has also been reported after epidural bolus of 100 mcg fentanyl [36,37]. Data on the incidence of urinary retention are limited by common postoperative practice of urinary catheterization. The article by Guilfoyle et al., in the current issue of The Spine Journal, evaluates the analgesic efficacy of bolus fentanyl 100 mcg given as a 10-mL injectate 10 cm rostral to the surgical site after lumbar decompression for spinal stenosis [38]. The authors concluded that their approach is beneficial as an adjunct for effective reduction of early postoperative pain. The epidural catheter was placed under direct vision by the surgeon. The dose regime (100 mcg) and volume of diluents (10 mL) used in his study had been used with success in previous nonspinal surgeries [16,18,19,21] in which dura was intact and placement of catheter performed by anesthetists. It may not be fair to extrapolate the nonspinal dose regime to spine surgery. Epidural delivery of fentanyl after a spine surgery may be affected by systemic absorption from the surgical site, dilutional effect from surgical site bleed, loss of opioids from surgical site drainage, or intrathecal spinal delivery because of the loss of integrity of dura during spinal surgery. It is also not known if the effect of the bolus fentanyl in Guilfoyle’s work is also attributed in part to supraspinal effect as a result of systemic absorption. The plasma fentanyl assay was not measured, neither was intravenous fentanyl used as a comparator. Guilfoyle’s target site of catheter tip is 10 cm rostral to laminectomy site and is slightly higher
653
than other reports [3–5,8,39,40] in which the tip of the catheter is placed 3 to 6 cm cephalic to the surgical site or within the mid-surgical field [9]. Surgical placement under direct vision has the advantage of greater accuracy with decreased risk of neurologic damage and inadvertent subarachnoid placement but does not guarantee correct placement. Misplaced catheter and variability in catheter tip have all been reported after catheter placement by surgeons [41]. Epidural opioid, especially fentanyl, offers numerous advantages over other techniques for elderly patients undergoing spine surgery. Epidural fentanyl acts on receptors in the dorsal horn instead of spinal nerve roots. This is of relevance after spine surgery, in which motor blockade [39,42] after epidural local anesthetic can interfere with the postoperative neurologic assessment. Motor blockade may mask symptoms of postoperative complications such as spinal epidural hematoma. Although the incidence of symptomatic spinal epidural hematoma is low at 0.1% to 4.5% [43,44], it has potential for devastating neurologic sequelae when diagnosis and treatment are delayed. Some authors have suggested that normal neurologic function should be demonstrated [14] or a day should lapse [40] before the initiation of epidural infusion of local anaesthetics to minimize interference with neurologic observation. Epidural opioid lacks sympathetic blockade unlike epidural local anesthetic and hence better tolerated in this patient group who often have concurrent cardiorespiratory comorbidities [45]. Furthermore, epidural opioid offers excellent analgesia and greater safety margin, especially central nervous system effects [46], compared with intravenous route. This benefits the elderly population who may have associated cognitive deficit that affects assessment and verbalization of pain. In contrast to morphine, fentanyl has a safer profile. Compared with fentanyl infusion, bolus fentanyl gives an effective segmental analgesia with less systemic effect. Compared with local anesthetic containing infusion, bolus fentanyl facilitates postoperative motor and sensory function monitoring in post–spine surgery. It is surprising that the duration of adequate analgesia in Guilfoyle’s study, represented by visual analog score (VAS) less than 5, extended beyond the limit of early postoperative period reported in previous studies into Day 1 after surgery. One can speculate that a concurrent postoperative analgesia regime could have explained the VAS observed. It is also interesting to note that a clinically significant proportion of patients (48% in the treatment group and 33% in the control group) were discharged on the first day of surgery. The average length of stay of 2 days reported in Guilfoyle’s study was comparable with that reported by Walcott et al. [47] but shorter than the average 3.6 days reported by Shabat et al. [48]. Patients in Guilfoyle’s study were notably younger than the octogenarians in Shabat’s study. The short hospital stay in the present study could possibly be attributed to patient selection with low morbidity, the surgical technique used, and the short spinal segments (1.5–2)
654
H.I. Hee et al. / The Spine Journal 12 (2012) 652–655
involved. The latter is important, as the number of vertebrae included in the operation and the degree of invasiveness are factors affecting the severity of pain [49]. Although not statistically significant, better early pain control (lower VAS) is demonstrated in the treatment group and may have contributed to the shorter hospital stay. There are some limitations in the present study design. A cause for concern is the omission of information on whether a concurrent postoperative analgesia regime was implemented. Time to first dose and total dose of supplementary analgesia are otherwise important measures that allowed meaningful comparison between treatment and control. Also lacking is information regarding type and dose of the intraoperative opioid used. Visual analog scale should be evaluated more frequently to give a better clinical comparison of efficacy. Guilfoyle also failed to qualify whether VAS was performed at rest or on movement. Other functional assessments such as time to ambulation and oral intake are important outcomes to be measured too. Although the incidence of side effects was similar between groups, no comments were made on severity and need for intervention. Perhaps future studies using intravenous fentanyl as a control will provide more useful data. In general, bolus epidural fentanyl produces rapid onset of good segmental analgesia that is brief, making it useful for early postoperative pain and in ambulatory surgery. It may not be the optimal primary approach in providing postoperative analgesia, but its systemic opioid sparing effect makes it a very useful adjunct. Although the incidence of respiratory depression is low, vigilant monitoring is still essential, especially in the early postoperative period. Guilfoyle’s work in extending its use to spinal surgery showed promising results, indicating that epidural bolus fentanyl may be useful in certain spine surgeries and in selected patients whose early discharge from hospital is anticipated. References [1] Ray CD, Bagley R. Indwelling epidural morphine for control of post-lumbar spinal surgery pain. Neurosurgery 1983;13:388–93. [2] Ozuna J, Burchiel KJ, Pencek T. Routine use of epidural morphine in patients following lumbar spine surgery. Clin J Pain 1988;4: 209–12. [3] Rechtine GR, Reinert CM, Bohlman HH. The use of epidural morphine to decrease postoperative pain in patients undergoing lumbar laminectomy. J Bone Joint Surg Am 1984;66:113–6. [4] Kundra P, Gurnani A, Bhattacharya A. Preemptive epidural morphine for postoperative pain relief after lumbar laminectomy. Anesth Analg 1997;85:135–8. [5] Sice PJA, Chan D, Macintyre PA. Epidural analgesia after spinal surgery via intervertebral foramen. Br J Anaesth 2005;94:378–80. [6] Lowry KJ, Tobias J, Kittle D, et al. Postoperative pain control using epidural catheters after anterior spinal fusion for adolescent scoliosis. Spine 2001;26:1290–3. [7] Arms DM, Smith JT, Osteyee J, Gartrell A. Postoperative epidural analgesia for pediatric spine surgery. Orthopedics 1998;21:539–44. [8] Shaw BA, Watson TC, Merzel DI, et al. The safety of continuous epidural infusion for postoperative analgesia in pediatric spine surgery. J Pediatr Orthop 1996;16:374–7.
[9] Joshi GP, McCarroll SM, O’Rourke K. Postoperative analgesia after lumbar laminectomy: epidural fentanyl infusion versus patientcontrolled intravenous morphine. Anesth Analg 1995;80:511–4. [10] Schenk MR, Putzier M, K€ugler B, et al. Postoperative analgesia after major spine surgery: patient-controlled epidural analgesia versus patient-controlled intravenous analgesia. Anesth Analg 2006;103: 1311–7. [11] Reynolds AF, Dautenhahn DL, Pollay M, Fagraeus L. Safety and efficacy of epidural analgesia in spine surgery. Ann Surg 1986;203: 225–7. [12] Cata JP, Noguera EM, Parke E, et al. Patient-controlled epidural analgesia (PCEA) for postoperative pain control after lumbar spine surgery. J Neurosurg Anesthesiol 2008;20:256–60. [13] Gottschalk A, Freitag M, Tank S, et al. Quality of postoperative pain using an intraoperatively placed epidural catheter after major lumbar spinal surgery. Anesthesiology 2004;101:175–80. [14] Tobias JD. A review of intrathecal and epidural analgesia after spinal surgery in children. Anesth Analg 2004;98:956–65. [15] Kumar RJ, Menon KV, Ranjith TC. Use of epidural analgesia for pain management after major spinal surgery. J Orthop Surg (Hong Kong) 2003;11:67–72. [16] Grass JA, Sakima NT, Schmidt R, et al. A randomized, doubleblind, dose response comparison of epidural fentanyl versus sufentanil analgesia after caesarean section. Anesth Analg 1997;85: 365–71. [17] Lomessy A, Magnin C, Viale JP, et al. Clinical advantages of fentanyl given epidurally for postoperative analgesia. Anesthesiology 1984;61:466–9. [18] Inagaki Y, Mashimo T, Yoshiya I. Segmental analgesic effect and reduction of halothane MAC from epidural fentanyl in humans. Anesth Analg 1992;74:856–64. [19] Harukuni I, Yamaguchi H, Sato S, Naito H. The comparison of epidural fentanyl, epidural lidocaine, and intravenous fentanyl in patients undergoing gastrectomy. Anesth Analg 1995;81:1169–74. [20] Privado MS, Issy AM, Lanchote VL, et al. Epidural versus intravenous fentanyl for postoperative analgesia following orthopedic surgery: randomized controlled trial. Sao Paulo Med J 2010;128:5–9. [21] Shipton EA, Hugo JM, Muller FO. Epidural fentanyl in the management of postoperative pain. S Afr Med J 1986;70:325–8. [22] Guinard JP, Carpenter RL, Chassot PG. Epidural and intravenous fentanyl produce equivalent effects during major surgery. Anesthesiology 1995;82:377–82. [23] Peng PW, Sandler AN. A review of the use of fentanyl analgesia in the management of acute pain in adults. Anesthesiology 1999;90: 576–99. [24] Ummenhofer WC, Arends RH, Shen DD, Bernards CM. Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil. Anesthesiology 2000;92:739–53. [25] Bujedo BM, Santos SG, Azpiazu AU. A review of epidural and intrathecal opioids used in the management of postoperative pain. J Opioid Manag 2012;8:177–92. [26] Ginosar Y, Riley ET, Angst MS. The site of action of epidural fentanyl in humans: the difference between infusion and bolus administration. Anesth Analg 2003;97:1428–38. [27] Herz A, Albus K, Metys J, et al. On the central sites for the antinociceptive action of morphine and fentanyl. Neuropharmacology 1970;9:539–51. [28] Coda BA, Brown MC, Schaffer R, et al. Pharmacology of epidural fentanyl, alfentanil, and sufentanil in volunteers. Anesthesiology 1994;81:1149–61. [29] Birnbach DJ, Johnson MD, Arcario T, et al. Effect of diluent volume on analgesia produced by epidural fentanyl. Anesth Analg 1989;68: 808–10. [30] Welchew EA, Breen DP. Patient-controlled on-demand epidural fentanyl. A comparison of patient-controlled on-demand fentanyl delivered epidurally or intravenously. Anaesthesia 1991;46:438–41.
H.I. Hee et al. / The Spine Journal 12 (2012) 652–655 [31] Salomaki TE, Laitinen JO, Nuutinen LS. A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for analgesia after thoracotomy. Anesthesiology 1991;75:790–5. [32] Sawchuk CW, Ong B, Unruh HW, et al. Thoracic versus lumbar epidural fentanyl for postthoracotomy pain. Ann Thorac Surg 1993;55:1472–6. [33] Guinard JP, Mavrocordatos P, Chiolero R, Carpenter RL. A randomized comparison of intravenous versus lumbar and thoracic epidural fentanyl for analgesia after thoracotomy. Anesthesiology 1992;77:1108–15. [34] Coe A, Sarginson R, Smith MW, et al. Pain following thoracotomy. A randomised, double-blind comparison of lumbar versus thoracic epidural fentanyl. Anaesthesia 1991;46:918–21. [35] Bouchard F, Drolet P. Thoracic versus lumbar administration of fentanyl using patient-controlled epidural after thoracotomy. Reg Anesth 1995;20:385–8. [36] Brockway MS, Noble DW, Sharwood-Smith GH, McClure JH. Profound respiratory depression after extradural fentanyl. Br J Anaesth 1990;64:243–5. [37] Wells DG, Davies G. Profound central nervous system depression from epidural fentanyl for extracorporeal shock wave lithotripsy. Anesthesiology 1987;67:991–2. [38] Guilfoyle MR, Mannion RJ, Mitchell P, Thomson S. Epidural fentanyl for postoperative analgesia after lumbar canal decompression: a randomized controlled trial. Spine J 2012;12:646–51. [39] O’Hara JF Jr, Cywinski JB, Tetzlaff JE, et al. The effect of epidural vs intravenous analgesia for posterior spinal fusion surgery. Paediatr Anaesth 2004;14:1009–15. [40] Kluba T, Hofmann F, Bredanger S, et al. Efficacy of post-operative analgesia after posterior lumbar instrumented fusion for degenerative disc disease: a prospective randomized comparison of epidural
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
655
catheter and intravenous administration of analgesics. Orthop Rev (Pavia) 2010;2:e9. Turner A, Lee J, Mitchell R, et al. The efficacy of surgically placed epidural catheters for analgesia after posterior spinal surgery. Anaesthesia 2000;55:370–3. Purnell RJ. Scoliosis correction and epidural analgesia. Prolonged block following Harrington rod insertion. Anaesthesia 1982;37: 1115–7. Aono H, Ohwada T, Hosono N, et al. Incidence of postoperative symptomatic epidural hematoma in spinal decompression surgery. J Neurosurg Spine 2011;15:202–5. Kaner T, Sasani M, Oktenoglu T, et al. Postoperative spinal epidural hematoma resulting in cauda equina syndrome: a case report and review of the literature. Cases J 2009;2:8584. Fanuele JC, Birkmeyer NJ, Abdu WA, Tosteson TD. The impact of spinal problems on the health status of patients: have we underestimated the effect? Spine 2000;25:1509–14. Wheeler M, Oderda GM, Ashburn MA, Lipman AG. Adverse events associated with postoperative opioid analgesia: a systematic review. J Pain 2002;3:159–80. Walcott BP, Hanak BW, Caracci JR, et al. Trends in inpatient setting laminectomy for excision of herniated intervertebral disc: populationbased estimates from the US nationwide inpatient sample. Surg Neurol Int 2011;2:7. Shabat S, Arinzon Z, Folman Y, Leitner J. Long-term outcome of decompressive surgery for lumbar spinal stenosis in octogenarians. Eur Spine J 2008;17:193–8. Ortiz-Cardona J, Bendo AA. Perioperative pain management in the neurosurgical patient. Anesthesiol Clin 2007;25:655–74.