- Email: [email protected]
Fentanyl for Acute Pain Management
PAIN CARE
Fentanyl for Acute Pain Management Chris Pasero, MS, RN, FAAN THE OPIOID ANALGESIC fentanyl has long been used as an anesthetic analgesic1 and is rapidly gaining in popularity for the management of acute pain.2 The impetus for this may have been generated over 10 years ago when the Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality) Acute Pain Management Clinical Practice Guideline Panel advised clinicians to find alternatives to meperidine, which was the most common parenteral opioid analgesic administered for moderate to severe acute pain at that time.3 The panel cautioned that meperidine produces a metabolite (normeperidine) that can readily accumulate and cause central nervous system (CNS) toxicity. The American Pain Society has warned that meperidine doses greater than 600 mg/24 hours and for more than 48 hours places the patient at especially high risk.4 It is particularly dangerous in individuals with renal insufficiency, such as older adults and patients with sickle cell disease. Fentanyl, along with morphine and hydromorphone, was recommended as one alternative to meperidine.3,4 Fentanyl is considered a valuable analgesic in the pain management arena because it can be given by a variety of routes of administration for many different types of pain.1 It has been administered intraspinally for many years to manage postoperative pain,1,5 IV and intranasally for procedural pain,1,6 and the transdermal formulation is indicated for chronic pain management.5 Oral transmucosal fentanyl has been used for both procedural pain and breakthrough chronic pain treatment.1,5 The most recent surge in interest focuses on the use of IV fentanyl for rapid pain relief in the PACU and emergency department (ED) and to manage Journal of PeriAnesthesia Nursing, Vol 20, No 4 (August), 2005: pp 279-284
moderate to severe postoperative pain after transfer to the clinical unit.2
Pharmacology of Fentanyl Fentanyl is a semisynthetic agonist opioid with strong affinity for the mu opioid receptor site. Mu opioid receptor binding produces analgesia as well as opioid adverse effects, such as nausea, sedation, and respiratory depression. By the IV route, fentanyl has a rapid onset of analgesia (1 to 5 minutes) and a short duration of action (less than 1 hour).1,6 Peak effect occurs within 3 to 5 minutes. Fentanyl’s rapid onset of analgesia is related to its lipophilic properties (attraction to fatty tissue), which cause it to penetrate the CNS and bind with mu opioid receptor sites quickly after administration.2,5 This characteristic also causes the drug to be rapidly redistributed from blood to other body tissues, such as muscle and fat, rather than to hepatic and renal elimination, thus, its short duration of action.1,7 Because it is lipophilic, fentanyl is well absorbed by the oral mucosa and capable of providing analgesia within 5 minutes via the oral transmucosal route.5 After epidural administration, fentanyl moves quickly across the meninges into the cerebrospinal fluid and then into the spinal cord for binding with the opioid receptor sites. There is also rostral spread of the drug to supraspinal
Chris Pasero is a pain management educator and clinical consultant in El Dorado Hills, CA. Address correspondence to Chris Pasero, MS, RN, FAAN, 1252 Clearview Dr, El Dorado Hills, CA 95762; e-mail address: [email protected]. © 2005 by American Society of PeriAnesthesia Nurses. 1089-9472/05/2004-0008$30.00/0 doi:10.1016/j.jopan.2005.03.007 279
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binding sites and uptake of the drug by epidural fat and vasculature for distribution to the systemic circulation.1,5 Onset of analgesia following an epidural fentanyl bolus is rapid (5 to 15 minutes) compared with the hydrophilic opioids morphine (30 to 90 minutes) and hydromorphone (15 to 30 minutes).5 Likewise, duration is short at 1 to 3 hours after a single bolus dose.5 Little is known about the pharmacokinetics of intrathecal (spinal) fentanyl; however, it is thought that intrathecal administration results in less systemic absorption of fentanyl than does epidural administration.1 Like other opioids, fentanyl is metabolized by the liver and undergoes extensive biotransformation.8 Its primary metabolite, norfentanyl, is pharmacologically inactive and eliminated by the renal system.9 The elimination half-life (reduction of plasma concentration by 50%) of fentanyl ranges from 3 to 12 hours and is influenced by the extent of storage in fatty tissue.7
should be delivered over a 2- to 5-minute period and may be repeated about every 10 minutes based on patient response.6 A maximum of 150 mcg during conscious sedation in adults is recommended.10 Increments of 0.5 to 1 mcg/kg given over 2 to 5 minutes to a maximum of 4 mcg/kg/hour are recommended in infants and children.6,10 When fentanyl is used for procedural pain management, clinicians must plan ahead to provide postprocedure analgesia for pain that is expected to continue after the procedure. For example, a nonopioid, such as IV ketorolac or oral celecoxib, can be administered before procedures or on admission to the PACU or ED.6
IV PCA
Fentanyl’s fast onset of analgesia makes it an ideal analgesic when rapid pain relief is needed, such as for severe, escalating pain.2 It is being used with increasing frequency in PACUs and EDs for this purpose. Its short duration of action makes fentanyl an appropriate first choice for IV analgesia when a goal of care is short recovery time, such as following ambulatory surgical procedures and during painful procedures.6
Morphine is the primary drug prescribed for IV PCA and is often used as a comparison for other opioid analgesics.5 The most common starting PCA bolus dose of morphine in adults is 1 mg. As mentioned, 1 mg of IV morphine is thought to be roughly equal to 25 mcg of IV fentanyl5,7; however, research suggests that this may be a conservative estimate for opioid-naïve patients receiving IV PCA, although no direct comparison studies could be found. A study evaluating the effects of 3 different IV PCA bolus doses of fentanyl in opioid-naïve patients found that a 20-mcg dose did not provide adequate pain relief, a 60-mcg dose produced respiratory depression, and a 40-mcg dose was most appropriate.11 Another study examined the use of IV PCA in 60 adults during burn dressing changes and found a 30-mcg PCA bolus dose to be optimal.12 Others have suggested PCA bolus doses between 20 mcg and 50 mcg for acute pain management.1
Fentanyl is often diluted (10 mcg/mL) for IV titration, and doses range from 0.5 to 2 mcg/kg in adults.2 Very slow IV administration is critical to prevent serious adverse effects (see later discussion of adverse effects). For example, IV bolus dose increments of 12.5 to 100 mcg
Fentanyl’s short duration is a primary consideration when prescribing the PCA delay (lockout) interval. Although the most common delay interval for IV PCA morphine is 8 minutes, a shorter delay interval of 5 to 6 minutes is warranted in patients receiving IV PCA fentanyl for
Fentanyl is thought to be 80 times more potent than parenteral morphine for acute pain in opioid-naïve patients (those who are not taking opioids regularly).7 Clinically, 25 mcg/hour of parenteral fentanyl is reported to be roughly equal to 1 mg/hour of parenteral morphine.5,7
Short-Term IV Analgesia
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Table 1. IV PCA Fentanyl Prescription Ranges for Opioid-Naı¨ve Patients4,5,11,12,20 Patient Population
Loading Dose
PCA Bolus Dose
Delay (Lockout)
Basal Rate
Adult Pediatric
25 mcg repeat PRN 1.0 mcg/kg/dose repeat PRN
5-40 mcg 0.5-1 mcg/kg/dose
4-8 min 6-10 min
0-10 mcg/h 0-1 mcg/kg/h
h, hour; kg, kilogram; mcg, microgram; min, minute; PRN, as needed.
acute pain management.1,12 It may need to be as short as 4 minutes in patients who experience unrelieved pain with a longer interval.2
Table 1 shows the IV PCA fentanyl prescription ranges for opioid-naïve patients.
Transdermal PCA Because of its short duration, a background continuous infusion (basal rate) with IV PCA fentanyl may be necessary.1,6 Without a basal rate, patients may find it necessary to self-administer frequent bolus doses to maintain adequate pain control.2 Peng and Sandler1 reported that fentanyl background infusion rates during IV PCA for acute pain management range from 4 to 60 mcg/hour.1 There is controversy over the use of basal rates with IV PCA, and they must be administered with caution in opioid-naïve patients.4,13 Research and clinical practice have shown that this practice is both effective and safe when the starting basal rate is low (0.5 mg/hour of morphine or equivalent), starting PCA bolus doses are 1 mg or less of morphine or equivalent per dose, nurses monitor sedation and respiratory status every 1 to 2 hours during continuous infusion, and the opioid dose is decreased when excessive sedation is noted and as the patient recovers and pain lessens.13 A conservative approach is to start IV PCA therapy without a basal rate and add one if the patient is tolerating IV PCA well but is having difficulty maintaining satisfactory pain control or is unable to rest and sleep adequately because of pain. If careful nurse monitoring of sedation and respiratory status is not possible, the use of continuous opioid infusions in opioid-naïve patients is discouraged.13 Regardless of the mode used, patients receiving IV PCA require systematic assessment and prescription adjustments, as needed, based on their response to treatment.5
A patient-controlled transdermal fentanyl system (IONSYS), the size of a credit card and designed to adhere to a patient’s arm, is currently under development.14 Patients can press a small button on the device to self-administer up to 6 preprogrammed PCA doses of 40 mcg of fentanyl each per hour; each bolus is infused over a 10-minute period via iontophoresis through the skin (electrotransport technology). Each transdermal PCA unit can deliver analgesia for 24 hours and a maximum of 80 PCA doses then must be replaced with a new unit if therapy is to be continued. The device does not allow for a basal rate. PCA transdermal fentanyl appears to be comparable with morphine in efficacy and safety. More than 600 patients who underwent major surgery were randomly assigned to receive PCA transdermal fentanyl (40 mcg PCA bolus, delay 10 minutes) or IV PCA morphine (1 mg PCA bolus, delay 5 minutes).15 Patients’ global assessments of method of pain control during the first 24 hours postoperatively were good or excellent for 73.7% of patients receiving fentanyl and 76.9% of those receiving morphine. Adverse effects were similar among the groups; 1 episode of clinically significant confusion occurred in a patient receiving fentanyl, and 1 patient receiving morphine required naloxone for treatment of clinically significant respiratory depression. Discontinuation of therapy for a variety of reasons occurred in 25% of the patients in both groups; withdrawals due to inad-
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Table 2. Intraspinal Fentanyl Dose Ranges for Opioid Naı¨ve Adults1,5,20 Route
Single Dose
Continuous Infusion
Patient-Controlled Analgesia
Intrathecal Epidural
5-25 mcg 50-100 mcg
0.8 mcg/h 25-100 mcg/h
ND PCEA bolus dose: 10-20 mcg Delay: 6-10 min Basal rate: 0-30 mcg/h
h, hour; kg, kilogram; mcg, microgram; min, minute; PCEA, patient-controlled epidural analgesia; ND, no data.
equate analgesia were more common but not statistically significant in the fentanyl group. Another randomized study compared PCA transdermal fentanyl and placebo in 205 patients following major abdominal, thoracic, or orthopedic surgery.16 Patients receiving fentanyl had lower visual analogue pain ratings and higher global satisfaction scores. There were no incidences of clinically relevant respiratory depression. One quarter of the patients receiving fentanyl withdrew from the study because of inadequate analgesia compared with 40.4% in the placebo group. Further research is needed to determine the cost-effectiveness of this method of analgesic delivery.
Intraspinal Fentanyl Intraspinal (intrathecal and epidural) fentanyl has an extensive history of safe and efficacious administration for acute pain management.1,5,17-20 Although fentanyl can be given as a sole agent intraspinally, it is most often combined with the local anesthetic bupivacaine or ropivacaine for a synergistic effect.5,20 The combination produces better analgesia at lower doses of each drug than would be possible with 1 drug alone. A major benefit of this approach is that lower doses result in fewer or less severe adverse effects.5,21 Table 2 shows the intraspinal fentanyl dose ranges for opioid-naïve adults. Benefits of a lipophilic opioid such as fentanyl and local anesthetic spinal administration include enhanced quality of anesthesia, more rapid return of motor function, and a better adverse effect profile compared with hydrophilic morphine and local anesthetic.21 Patients
(N ⫽ 50) undergoing ambulatory arthroscopy surgery were randomized to receive spinal anesthesia with dilute (0.177%) bupivacaine alone or bupivacaine plus low-dose (10 mcg) fentanyl.22 Those who received the combination of bupivacaine and fentanyl experienced a more intense and longer lasting sensory blockade without interfering with recovery milestones, such as urination, ambulation, and time of discharge. Similarly, a study of women (N ⫽ 54) receiving continuous epidural infusions of 0.1% ropivacaine plus fentanyl 16 mcg/hour or 0.2% ropivacaine alone following abdominal hysterectomy revealed both groups experienced similar pain relief and adverse effects.23 However, those who received ropivacaine and fentanyl consumed less supplemental morphine than those who received ropivacaine alone. Because of its short duration, fentanyl is usually administered postoperatively by continuous epidural infusion and is increasingly used for patient-controlled epidural analgesia (PCEA) with excellent outcomes.1,5 For example, thoracic fentanyl and bupivacaine (0.05%) PCEA was a key component of a multimodal approach to the management of 56 patients following neartotal esophagectomy.24 Patients in this study were extubated in the operating room, first ambulated an average of 1.6 days after surgery, and had a median stay in the ICU of 1 day. Pain ratings on a scale of 0 to 10 averaged 2 or less during rest and 4 or less during movement; adverse effects were minimal.
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Adverse Effects
A lack of clinically relevant metabolites makes fentanyl an acceptable opioid for patients with renal failure or renal insufficiency, such as the elderly and patients with sickle cell disease.2,25 However, caution is recommended in patients with renal insufficiency5 and chronic kidney disease because clearance of the drug may be altered in these patients.8,9 Reduced clearance can result in accumulation of the drug, which would be evidenced by increased sedation and subsequent respiratory depression.9 The extent to which fentanyl is removed by dialysis or continuous renal replacement therapy is not clear8; however, Dean claims that no dose adjustments are necessary for dialysis patients.9 Fentanyl is also preferred for patients with hepatic failure because of its high potency; analgesic effect is achieved with a small number of molecules, which minimizes metabolic load.25 Fentanyl dose requirements are very small, and the drug appears to be less affected by changes in hepatic function than other opioids.25 Other desirable effects of fentanyl are no histamine release, a lack of myocardial depressant effects, and hemodynamic stability, all of which make the drug a good choice for patients with cardiac disease.25 Minimal adverse hemodynamic effects also facilitate management of pain in hypotensive patients.
Fentanyl can produce all of the usual opioidinduced adverse effects, such as nausea, constipation, pruritus, sedation, and respiratory depression.1,5 When used in combination with other CNS depressants, such as midazolam or diazepam, during procedures it is wise to decrease initial doses to prevent excessive sedation and respiratory depression and monitor patients closely.6 With repetitive dosing or continuous infusion of fentanyl, a steady state (the rate of excretion of a drug equals the rate at which the drug enters the system) is achieved. At steady state, slow release of fentanyl from tissue storage sites can result in a long terminal half-life (up to 12 hours). Consequently, all patients, and particularly those who are obese or older adults, should be monitored for fentanyl accumulation and late or possibly prolonged duration of sedation and respiratory depression.5 Nurse monitoring of sedation level and respiratory status every 1 to 2 hours during the first 24 hours of parenteral or intraspinal opioid therapy in opioid-naïve patients is recommended, regardless of the opioid administered.5 Bradycardia, severe respiratory depression, and chest wall rigidity can occur with rapid, highdose IV bolus administration.2,5,10 This usually occurs within minutes of administration and is treated with low-dose naloxone, a depolarizing muscle relaxant, such as succinylcholine, and intubation. Fentanyl is not recommended in patients who have taken monoamine oxidase inhibitors, such as phenelzine, within 14 days of administration.10
References 1. Peng PWH, Sandler AN: A review of the use of fentanyl analgesia in the management of acute pain in adults. Anesthesiology 90:576-599, 1999 2. Pasero C, Montgomery R: IV fentanyl. Am J Nurs 102:73, 75, 76, 2002 3. Agency for Health Care Policy and Research (AHCPR) Acute Pain Management Guideline Panel: Acute Pain Management: Operative or Medical Procedures and Trauma, Clinical Practice Guideline, AHCPR Pub. No. 92-0032. Rock-
ville, MD, Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1992 4. American Pain Society: Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain (ed 5). Glenview, IL, The Society, 2003 5. Pasero C, Portenoy RK, McCaffery M: Opioid analgesics, in McCaffery M, Pasero C: Pain: Clinical Manual (ed 2), St. Louis, MO, Mosby, 1999, pp 161-299
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6. Pasero C, McCaffery M: Procedural pain management, in McCaffery M, Pasero C: Pain: Clinical Manual (ed 2), St. Louis, MO, Mosby, 1999, pp 362-398 7. Hanks G, Cherny N, Fallon M: Opioid analgesics, in Doyle D, Hanks G, Cherny NI (eds): Oxford Textbook of Palliative Medicine (ed 3), New York, NY, Oxford University Press, 2004, pp 316-341 8. Kurella M, Bennett WM, Chertow GM: Analgesia in patients with ESRD: A review of available evidence. Am J Kidney Dis 42:217-228, 2003 9. Dean M: Opioids in renal failure and dialysis patients. J Pain Symptom Manage 28:497-504, 2004 10. Youmans L: Conscious sedation, in Hankins J, Waldman Londsway R-A, Hedrick C, et al (eds): Infusion Therapy in Clinical Practice (ed 2), St. Louis, MO, Saunders, 2001, pp 604-614 11. Camu F, Van Aiken H, Bovill JG: Postoperative analgesic effects of three demand-dose sizes of fentanyl administered by patient-controlled analgesia. Anesth Analg 87:890-895, 1998 12. Prakash S, Fatima T, Pawar M: Patient-controlled analgesia with fentanyl for burn dressing changes. Anesth Analg 99:552-555, 2004 13. Pasero C, McCaffery M: Safe use of continuous infusion with IV PCA. J PeriAnesth Nurs 19:42-45, 2004 14. Ortho-McNeil: Subanalysis finds patient-controlled, transdermal pain management system may be comparable to IV PCA morphine after gynecologic surgery. Available at: www. orthomcneil.com. Accessed February 2005 15. Viscusi ER, Reynolds L, Chung F: Patient-controlled transdermal fentanyl hydrochloride vs intravenous morphine pump for postoperative pain. JAMA 291:1333-1347, 2004 16. Chelly JE, Grass J, Houseman TW, et al: The safety and efficacy of a fentanyl patient-controlled transdermal system for
CHRIS PASERO acute postoperative analgesia: A multicenter, placebo-controlled trial. Anesth Analg 98:427-433, 2004 17. Liu S, Carpenter RL, Neal JM: Epidural anesthesia and analgesia. Anesthesiology 82:1474-1506, 1995 18. Scott DA, Beilby DSN, McClymont C: Postoperative analgesia using epidural infusions of fentanyl with bupivacaine. Anesthesiology 83:727-737, 1995 19. Ballantyne JC, McKenna JM, Ryder E: Epidural analgesia—Experience of 5628 patients in a large teaching hospital derived through audit. Acute Pain 4:89-97, 2003 20. Wu CL: Acute postoperative pain, in Miller RD (ed): Miller’s Anesthesia (ed 6), St. Louis, MO, Elsevier, 2005, pp 2729-2762 21. Hamber EA, Viscomi CM: Intrathecal and lipophilic opioids as adjuncts to surgical spinal anesthesia. Reg Anesth Pain Med 24:255-263, 1999 22. Ben-David B, Solomon E, Levin H, et al: Intrathecal fentanyl with small-dose dilute bupivacaine: Better anesthesia without prolonging recovery. Anesth Analg 85:560-565, 1997 23. Thienthong S, Krisanaprakornkit W, Horatanaruang D, et al: Motor blockade associated with continuous epidural infusion after abdominal hysterectomy: A randomized controlled trial comparing 0.1% ropivacaine-plus-fentanyl versus 0.2% ropivacaine-alone. Acute Pain 6:15-21, 2004 24. Neal JM, Wilcox RT, Allen HW, et al: Near-total esophagectomy: The influence of standardized multimodal management and intraoperative fluid restriction. Reg Anesth Pain Med 28:328-334, 2003 25. Sinatra RS: Pain management in patients suffering from major organ failure, in Sinatra RS, Hord AH, Ginsberg B, et al (eds): Acute Pain: Mechanisms and Management, St. Louis, MO, Mosby-Year Book, 1992, pp 399-411
Fentanyl for Acute Pain Management Chris Pasero, MS, RN, FAAN THE OPIOID ANALGESIC fentanyl has long been used as an anesthetic analgesic1 and is rapidly gaining in popularity for the management of acute pain.2 The impetus for this may have been generated over 10 years ago when the Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality) Acute Pain Management Clinical Practice Guideline Panel advised clinicians to find alternatives to meperidine, which was the most common parenteral opioid analgesic administered for moderate to severe acute pain at that time.3 The panel cautioned that meperidine produces a metabolite (normeperidine) that can readily accumulate and cause central nervous system (CNS) toxicity. The American Pain Society has warned that meperidine doses greater than 600 mg/24 hours and for more than 48 hours places the patient at especially high risk.4 It is particularly dangerous in individuals with renal insufficiency, such as older adults and patients with sickle cell disease. Fentanyl, along with morphine and hydromorphone, was recommended as one alternative to meperidine.3,4 Fentanyl is considered a valuable analgesic in the pain management arena because it can be given by a variety of routes of administration for many different types of pain.1 It has been administered intraspinally for many years to manage postoperative pain,1,5 IV and intranasally for procedural pain,1,6 and the transdermal formulation is indicated for chronic pain management.5 Oral transmucosal fentanyl has been used for both procedural pain and breakthrough chronic pain treatment.1,5 The most recent surge in interest focuses on the use of IV fentanyl for rapid pain relief in the PACU and emergency department (ED) and to manage Journal of PeriAnesthesia Nursing, Vol 20, No 4 (August), 2005: pp 279-284
moderate to severe postoperative pain after transfer to the clinical unit.2
Pharmacology of Fentanyl Fentanyl is a semisynthetic agonist opioid with strong affinity for the mu opioid receptor site. Mu opioid receptor binding produces analgesia as well as opioid adverse effects, such as nausea, sedation, and respiratory depression. By the IV route, fentanyl has a rapid onset of analgesia (1 to 5 minutes) and a short duration of action (less than 1 hour).1,6 Peak effect occurs within 3 to 5 minutes. Fentanyl’s rapid onset of analgesia is related to its lipophilic properties (attraction to fatty tissue), which cause it to penetrate the CNS and bind with mu opioid receptor sites quickly after administration.2,5 This characteristic also causes the drug to be rapidly redistributed from blood to other body tissues, such as muscle and fat, rather than to hepatic and renal elimination, thus, its short duration of action.1,7 Because it is lipophilic, fentanyl is well absorbed by the oral mucosa and capable of providing analgesia within 5 minutes via the oral transmucosal route.5 After epidural administration, fentanyl moves quickly across the meninges into the cerebrospinal fluid and then into the spinal cord for binding with the opioid receptor sites. There is also rostral spread of the drug to supraspinal
Chris Pasero is a pain management educator and clinical consultant in El Dorado Hills, CA. Address correspondence to Chris Pasero, MS, RN, FAAN, 1252 Clearview Dr, El Dorado Hills, CA 95762; e-mail address: [email protected]. © 2005 by American Society of PeriAnesthesia Nurses. 1089-9472/05/2004-0008$30.00/0 doi:10.1016/j.jopan.2005.03.007 279
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binding sites and uptake of the drug by epidural fat and vasculature for distribution to the systemic circulation.1,5 Onset of analgesia following an epidural fentanyl bolus is rapid (5 to 15 minutes) compared with the hydrophilic opioids morphine (30 to 90 minutes) and hydromorphone (15 to 30 minutes).5 Likewise, duration is short at 1 to 3 hours after a single bolus dose.5 Little is known about the pharmacokinetics of intrathecal (spinal) fentanyl; however, it is thought that intrathecal administration results in less systemic absorption of fentanyl than does epidural administration.1 Like other opioids, fentanyl is metabolized by the liver and undergoes extensive biotransformation.8 Its primary metabolite, norfentanyl, is pharmacologically inactive and eliminated by the renal system.9 The elimination half-life (reduction of plasma concentration by 50%) of fentanyl ranges from 3 to 12 hours and is influenced by the extent of storage in fatty tissue.7
should be delivered over a 2- to 5-minute period and may be repeated about every 10 minutes based on patient response.6 A maximum of 150 mcg during conscious sedation in adults is recommended.10 Increments of 0.5 to 1 mcg/kg given over 2 to 5 minutes to a maximum of 4 mcg/kg/hour are recommended in infants and children.6,10 When fentanyl is used for procedural pain management, clinicians must plan ahead to provide postprocedure analgesia for pain that is expected to continue after the procedure. For example, a nonopioid, such as IV ketorolac or oral celecoxib, can be administered before procedures or on admission to the PACU or ED.6
IV PCA
Fentanyl’s fast onset of analgesia makes it an ideal analgesic when rapid pain relief is needed, such as for severe, escalating pain.2 It is being used with increasing frequency in PACUs and EDs for this purpose. Its short duration of action makes fentanyl an appropriate first choice for IV analgesia when a goal of care is short recovery time, such as following ambulatory surgical procedures and during painful procedures.6
Morphine is the primary drug prescribed for IV PCA and is often used as a comparison for other opioid analgesics.5 The most common starting PCA bolus dose of morphine in adults is 1 mg. As mentioned, 1 mg of IV morphine is thought to be roughly equal to 25 mcg of IV fentanyl5,7; however, research suggests that this may be a conservative estimate for opioid-naïve patients receiving IV PCA, although no direct comparison studies could be found. A study evaluating the effects of 3 different IV PCA bolus doses of fentanyl in opioid-naïve patients found that a 20-mcg dose did not provide adequate pain relief, a 60-mcg dose produced respiratory depression, and a 40-mcg dose was most appropriate.11 Another study examined the use of IV PCA in 60 adults during burn dressing changes and found a 30-mcg PCA bolus dose to be optimal.12 Others have suggested PCA bolus doses between 20 mcg and 50 mcg for acute pain management.1
Fentanyl is often diluted (10 mcg/mL) for IV titration, and doses range from 0.5 to 2 mcg/kg in adults.2 Very slow IV administration is critical to prevent serious adverse effects (see later discussion of adverse effects). For example, IV bolus dose increments of 12.5 to 100 mcg
Fentanyl’s short duration is a primary consideration when prescribing the PCA delay (lockout) interval. Although the most common delay interval for IV PCA morphine is 8 minutes, a shorter delay interval of 5 to 6 minutes is warranted in patients receiving IV PCA fentanyl for
Fentanyl is thought to be 80 times more potent than parenteral morphine for acute pain in opioid-naïve patients (those who are not taking opioids regularly).7 Clinically, 25 mcg/hour of parenteral fentanyl is reported to be roughly equal to 1 mg/hour of parenteral morphine.5,7
Short-Term IV Analgesia
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Table 1. IV PCA Fentanyl Prescription Ranges for Opioid-Naı¨ve Patients4,5,11,12,20 Patient Population
Loading Dose
PCA Bolus Dose
Delay (Lockout)
Basal Rate
Adult Pediatric
25 mcg repeat PRN 1.0 mcg/kg/dose repeat PRN
5-40 mcg 0.5-1 mcg/kg/dose
4-8 min 6-10 min
0-10 mcg/h 0-1 mcg/kg/h
h, hour; kg, kilogram; mcg, microgram; min, minute; PRN, as needed.
acute pain management.1,12 It may need to be as short as 4 minutes in patients who experience unrelieved pain with a longer interval.2
Table 1 shows the IV PCA fentanyl prescription ranges for opioid-naïve patients.
Transdermal PCA Because of its short duration, a background continuous infusion (basal rate) with IV PCA fentanyl may be necessary.1,6 Without a basal rate, patients may find it necessary to self-administer frequent bolus doses to maintain adequate pain control.2 Peng and Sandler1 reported that fentanyl background infusion rates during IV PCA for acute pain management range from 4 to 60 mcg/hour.1 There is controversy over the use of basal rates with IV PCA, and they must be administered with caution in opioid-naïve patients.4,13 Research and clinical practice have shown that this practice is both effective and safe when the starting basal rate is low (0.5 mg/hour of morphine or equivalent), starting PCA bolus doses are 1 mg or less of morphine or equivalent per dose, nurses monitor sedation and respiratory status every 1 to 2 hours during continuous infusion, and the opioid dose is decreased when excessive sedation is noted and as the patient recovers and pain lessens.13 A conservative approach is to start IV PCA therapy without a basal rate and add one if the patient is tolerating IV PCA well but is having difficulty maintaining satisfactory pain control or is unable to rest and sleep adequately because of pain. If careful nurse monitoring of sedation and respiratory status is not possible, the use of continuous opioid infusions in opioid-naïve patients is discouraged.13 Regardless of the mode used, patients receiving IV PCA require systematic assessment and prescription adjustments, as needed, based on their response to treatment.5
A patient-controlled transdermal fentanyl system (IONSYS), the size of a credit card and designed to adhere to a patient’s arm, is currently under development.14 Patients can press a small button on the device to self-administer up to 6 preprogrammed PCA doses of 40 mcg of fentanyl each per hour; each bolus is infused over a 10-minute period via iontophoresis through the skin (electrotransport technology). Each transdermal PCA unit can deliver analgesia for 24 hours and a maximum of 80 PCA doses then must be replaced with a new unit if therapy is to be continued. The device does not allow for a basal rate. PCA transdermal fentanyl appears to be comparable with morphine in efficacy and safety. More than 600 patients who underwent major surgery were randomly assigned to receive PCA transdermal fentanyl (40 mcg PCA bolus, delay 10 minutes) or IV PCA morphine (1 mg PCA bolus, delay 5 minutes).15 Patients’ global assessments of method of pain control during the first 24 hours postoperatively were good or excellent for 73.7% of patients receiving fentanyl and 76.9% of those receiving morphine. Adverse effects were similar among the groups; 1 episode of clinically significant confusion occurred in a patient receiving fentanyl, and 1 patient receiving morphine required naloxone for treatment of clinically significant respiratory depression. Discontinuation of therapy for a variety of reasons occurred in 25% of the patients in both groups; withdrawals due to inad-
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Table 2. Intraspinal Fentanyl Dose Ranges for Opioid Naı¨ve Adults1,5,20 Route
Single Dose
Continuous Infusion
Patient-Controlled Analgesia
Intrathecal Epidural
5-25 mcg 50-100 mcg
0.8 mcg/h 25-100 mcg/h
ND PCEA bolus dose: 10-20 mcg Delay: 6-10 min Basal rate: 0-30 mcg/h
h, hour; kg, kilogram; mcg, microgram; min, minute; PCEA, patient-controlled epidural analgesia; ND, no data.
equate analgesia were more common but not statistically significant in the fentanyl group. Another randomized study compared PCA transdermal fentanyl and placebo in 205 patients following major abdominal, thoracic, or orthopedic surgery.16 Patients receiving fentanyl had lower visual analogue pain ratings and higher global satisfaction scores. There were no incidences of clinically relevant respiratory depression. One quarter of the patients receiving fentanyl withdrew from the study because of inadequate analgesia compared with 40.4% in the placebo group. Further research is needed to determine the cost-effectiveness of this method of analgesic delivery.
Intraspinal Fentanyl Intraspinal (intrathecal and epidural) fentanyl has an extensive history of safe and efficacious administration for acute pain management.1,5,17-20 Although fentanyl can be given as a sole agent intraspinally, it is most often combined with the local anesthetic bupivacaine or ropivacaine for a synergistic effect.5,20 The combination produces better analgesia at lower doses of each drug than would be possible with 1 drug alone. A major benefit of this approach is that lower doses result in fewer or less severe adverse effects.5,21 Table 2 shows the intraspinal fentanyl dose ranges for opioid-naïve adults. Benefits of a lipophilic opioid such as fentanyl and local anesthetic spinal administration include enhanced quality of anesthesia, more rapid return of motor function, and a better adverse effect profile compared with hydrophilic morphine and local anesthetic.21 Patients
(N ⫽ 50) undergoing ambulatory arthroscopy surgery were randomized to receive spinal anesthesia with dilute (0.177%) bupivacaine alone or bupivacaine plus low-dose (10 mcg) fentanyl.22 Those who received the combination of bupivacaine and fentanyl experienced a more intense and longer lasting sensory blockade without interfering with recovery milestones, such as urination, ambulation, and time of discharge. Similarly, a study of women (N ⫽ 54) receiving continuous epidural infusions of 0.1% ropivacaine plus fentanyl 16 mcg/hour or 0.2% ropivacaine alone following abdominal hysterectomy revealed both groups experienced similar pain relief and adverse effects.23 However, those who received ropivacaine and fentanyl consumed less supplemental morphine than those who received ropivacaine alone. Because of its short duration, fentanyl is usually administered postoperatively by continuous epidural infusion and is increasingly used for patient-controlled epidural analgesia (PCEA) with excellent outcomes.1,5 For example, thoracic fentanyl and bupivacaine (0.05%) PCEA was a key component of a multimodal approach to the management of 56 patients following neartotal esophagectomy.24 Patients in this study were extubated in the operating room, first ambulated an average of 1.6 days after surgery, and had a median stay in the ICU of 1 day. Pain ratings on a scale of 0 to 10 averaged 2 or less during rest and 4 or less during movement; adverse effects were minimal.
FENTANYL FOR ACUTE PAIN MANAGEMENT
Fentanyl in Patients With Major Organ Failure
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Adverse Effects
A lack of clinically relevant metabolites makes fentanyl an acceptable opioid for patients with renal failure or renal insufficiency, such as the elderly and patients with sickle cell disease.2,25 However, caution is recommended in patients with renal insufficiency5 and chronic kidney disease because clearance of the drug may be altered in these patients.8,9 Reduced clearance can result in accumulation of the drug, which would be evidenced by increased sedation and subsequent respiratory depression.9 The extent to which fentanyl is removed by dialysis or continuous renal replacement therapy is not clear8; however, Dean claims that no dose adjustments are necessary for dialysis patients.9 Fentanyl is also preferred for patients with hepatic failure because of its high potency; analgesic effect is achieved with a small number of molecules, which minimizes metabolic load.25 Fentanyl dose requirements are very small, and the drug appears to be less affected by changes in hepatic function than other opioids.25 Other desirable effects of fentanyl are no histamine release, a lack of myocardial depressant effects, and hemodynamic stability, all of which make the drug a good choice for patients with cardiac disease.25 Minimal adverse hemodynamic effects also facilitate management of pain in hypotensive patients.
Fentanyl can produce all of the usual opioidinduced adverse effects, such as nausea, constipation, pruritus, sedation, and respiratory depression.1,5 When used in combination with other CNS depressants, such as midazolam or diazepam, during procedures it is wise to decrease initial doses to prevent excessive sedation and respiratory depression and monitor patients closely.6 With repetitive dosing or continuous infusion of fentanyl, a steady state (the rate of excretion of a drug equals the rate at which the drug enters the system) is achieved. At steady state, slow release of fentanyl from tissue storage sites can result in a long terminal half-life (up to 12 hours). Consequently, all patients, and particularly those who are obese or older adults, should be monitored for fentanyl accumulation and late or possibly prolonged duration of sedation and respiratory depression.5 Nurse monitoring of sedation level and respiratory status every 1 to 2 hours during the first 24 hours of parenteral or intraspinal opioid therapy in opioid-naïve patients is recommended, regardless of the opioid administered.5 Bradycardia, severe respiratory depression, and chest wall rigidity can occur with rapid, highdose IV bolus administration.2,5,10 This usually occurs within minutes of administration and is treated with low-dose naloxone, a depolarizing muscle relaxant, such as succinylcholine, and intubation. Fentanyl is not recommended in patients who have taken monoamine oxidase inhibitors, such as phenelzine, within 14 days of administration.10
References 1. Peng PWH, Sandler AN: A review of the use of fentanyl analgesia in the management of acute pain in adults. Anesthesiology 90:576-599, 1999 2. Pasero C, Montgomery R: IV fentanyl. Am J Nurs 102:73, 75, 76, 2002 3. Agency for Health Care Policy and Research (AHCPR) Acute Pain Management Guideline Panel: Acute Pain Management: Operative or Medical Procedures and Trauma, Clinical Practice Guideline, AHCPR Pub. No. 92-0032. Rock-
ville, MD, Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1992 4. American Pain Society: Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain (ed 5). Glenview, IL, The Society, 2003 5. Pasero C, Portenoy RK, McCaffery M: Opioid analgesics, in McCaffery M, Pasero C: Pain: Clinical Manual (ed 2), St. Louis, MO, Mosby, 1999, pp 161-299
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6. Pasero C, McCaffery M: Procedural pain management, in McCaffery M, Pasero C: Pain: Clinical Manual (ed 2), St. Louis, MO, Mosby, 1999, pp 362-398 7. Hanks G, Cherny N, Fallon M: Opioid analgesics, in Doyle D, Hanks G, Cherny NI (eds): Oxford Textbook of Palliative Medicine (ed 3), New York, NY, Oxford University Press, 2004, pp 316-341 8. Kurella M, Bennett WM, Chertow GM: Analgesia in patients with ESRD: A review of available evidence. Am J Kidney Dis 42:217-228, 2003 9. Dean M: Opioids in renal failure and dialysis patients. J Pain Symptom Manage 28:497-504, 2004 10. Youmans L: Conscious sedation, in Hankins J, Waldman Londsway R-A, Hedrick C, et al (eds): Infusion Therapy in Clinical Practice (ed 2), St. Louis, MO, Saunders, 2001, pp 604-614 11. Camu F, Van Aiken H, Bovill JG: Postoperative analgesic effects of three demand-dose sizes of fentanyl administered by patient-controlled analgesia. Anesth Analg 87:890-895, 1998 12. Prakash S, Fatima T, Pawar M: Patient-controlled analgesia with fentanyl for burn dressing changes. Anesth Analg 99:552-555, 2004 13. Pasero C, McCaffery M: Safe use of continuous infusion with IV PCA. J PeriAnesth Nurs 19:42-45, 2004 14. Ortho-McNeil: Subanalysis finds patient-controlled, transdermal pain management system may be comparable to IV PCA morphine after gynecologic surgery. Available at: www. orthomcneil.com. Accessed February 2005 15. Viscusi ER, Reynolds L, Chung F: Patient-controlled transdermal fentanyl hydrochloride vs intravenous morphine pump for postoperative pain. JAMA 291:1333-1347, 2004 16. Chelly JE, Grass J, Houseman TW, et al: The safety and efficacy of a fentanyl patient-controlled transdermal system for
CHRIS PASERO acute postoperative analgesia: A multicenter, placebo-controlled trial. Anesth Analg 98:427-433, 2004 17. Liu S, Carpenter RL, Neal JM: Epidural anesthesia and analgesia. Anesthesiology 82:1474-1506, 1995 18. Scott DA, Beilby DSN, McClymont C: Postoperative analgesia using epidural infusions of fentanyl with bupivacaine. Anesthesiology 83:727-737, 1995 19. Ballantyne JC, McKenna JM, Ryder E: Epidural analgesia—Experience of 5628 patients in a large teaching hospital derived through audit. Acute Pain 4:89-97, 2003 20. Wu CL: Acute postoperative pain, in Miller RD (ed): Miller’s Anesthesia (ed 6), St. Louis, MO, Elsevier, 2005, pp 2729-2762 21. Hamber EA, Viscomi CM: Intrathecal and lipophilic opioids as adjuncts to surgical spinal anesthesia. Reg Anesth Pain Med 24:255-263, 1999 22. Ben-David B, Solomon E, Levin H, et al: Intrathecal fentanyl with small-dose dilute bupivacaine: Better anesthesia without prolonging recovery. Anesth Analg 85:560-565, 1997 23. Thienthong S, Krisanaprakornkit W, Horatanaruang D, et al: Motor blockade associated with continuous epidural infusion after abdominal hysterectomy: A randomized controlled trial comparing 0.1% ropivacaine-plus-fentanyl versus 0.2% ropivacaine-alone. Acute Pain 6:15-21, 2004 24. Neal JM, Wilcox RT, Allen HW, et al: Near-total esophagectomy: The influence of standardized multimodal management and intraoperative fluid restriction. Reg Anesth Pain Med 28:328-334, 2003 25. Sinatra RS: Pain management in patients suffering from major organ failure, in Sinatra RS, Hord AH, Ginsberg B, et al (eds): Acute Pain: Mechanisms and Management, St. Louis, MO, Mosby-Year Book, 1992, pp 399-411