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A new needle-free PCA system: The fentanyl iontophoretic transdermal system
Acute Pain (2006) 8, 151—153
EDITORIAL
A new needle-free PCA system: The fentanyl iontophoretic transdermal system PCA has proved popular with patients, who appreciate their being given control and access to selfadministered rapidly acting pain relief. Although trials show that intermittent nurse-administered opioid boluses can achieve equivalent pain relief to PCA, this is unlikely to be attainable in the nontrial, challenging environment of a busy surgical ward. The main drawback of our current PCA systems is their dependence on intravenous access (a dedicated line, or the use of an anti-syphon valve) and expensive, dedicated pumps. A novel self-contained, transdermal patient controlled analgesia system has recently been approved in both Europe and the USA. It is a selfadhesive, battery-driven device which employs the active process of iontophoresis to accelerate the delivery of the ionised fentanyl molecules across intact skin into the systemic circulation. The imperceptible, iontophoretic (electric) current significantly enhances the penetration rate of fentanyl through the stratum corneum of the epidermis relative to passive diffusion [1,2]. In this way, a sufficient dose can be administered rapidly enough to be appropriate for the acute pain post-operative setting. Having activated the device by two presses of the button within 3 s, the pre-programmed, fixed dose of 40 is delivered over 10 min, during which time the system is ‘locked-out’, and will not respond to further pressing of the button. The iontophoretic transdermal system (ITS) is therefore able to deliver up to 240 h−1 , up to a capacity of 80 doses over 24 h. At 24 h (or if 80 doses are reached sooner), the device automatically shuts down. If continued PCA is required, a new ITS has to be applied for the next 24 h period. Fentanyl has a number of advantages over morphine for this method and route of administra-
tion, being a small, charged, lipophilic molecule. It is amenable to being driven actively by the iontophoretic mechanism and with its high penetration into the central nervous system, once it has reached the bloodstream, has a more rapid time to peak analgesia. With a relative potency of 100:1, a proportionately smaller mass of drug is required to cross the poorly permeable skin barrier. In addition, fentanyl has some general advantages over morphine including pharmacokinetics unaffected by renal impairment, and no active metabolites. However, fentanyl’s shorter duration of action may need to be compensated (relative to an equipotent dose morphine) by more or larger boluses of fentanyl. Hence, the 40 dose in the fentanyl PCA ITS. Clearly the departure from a needle-based system may confer some advantages, and these need to be weighed against potential limitations and drawbacks, but first we need to be reassured that patients receive at least equivalent analgesic benefit to conventional intravenous, opioid based PCA. The efficacy of the fentanyl ITS is supported by data from one active-controlled study and three placebo-controlled studies of adult patients following major abdominal, orthopaedic, or thoracic surgery [3—6]. Results of the placebo-controlled studies demonstrated that fentanyl ITS was superior to placebo in providing postoperative pain relief, as measured by the number of patient withdrawals from the study due to inadequate analgesia, and by patient ratings of pain intensity and the method of pain control [3—5]. Additional outcome measures were evaluated using patient questionnaires in the largest of the placebo-controlled studies [5].
1366-0071/$ — see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.acpain.2006.08.044
152 A larger percentage of patients (61.5%) in the fentanyl ITS group than in the placebo group (32.1%) were very satisfied with their method of pain management, and the majority of patients found the fentanyl ITS to be very convenient (79.8%) and very easy to use (87.0%). The fentanyl ITS was shown to be an equivalent method of pain control compared to a standard regimen of morphine IV PCA in a large study of adult patients following major abdominal, orthopaedic, or thoracic surgery [6]. A similar percentage of patients in each treatment group (>73%) reported a rating of success (‘‘excellent’’ or ‘‘good’’) on the global assessment of the method of pain control in the first 24 h, and >80% of patients in each group reported a rating of success on this measure in the second and third 24-h periods of continued treatment. Turning to the pros and cons of the new device, some of the advantages are obvious, such as the avoidance of being dependent on patent intravenous access, and the potential benefit in enhanced mobilisation, unencumbered by lines, wires and heavy pumps with no mains connection or battery charging. Minimal nurse training is required for the comparatively quick and simple set-up, consisting of the self-adhesive device being placed on the upper outer arm or chest. However, the procedures and checks remain for prescription and administration of a strong opioid substance, and similarly, on cessation of use, the local procedures must be followed for the disposal of opioids, as there is a substantial reservoir of fentanyl in the device. However the fixed dose is a double-edged sword: while, importantly, prescription, dispensing and pump-programming errors are eliminated, there is no possibility to adjust the bolus dose or lock-out time for individual patient titration. One size does not fit all, and it would not be possible therefore to offer a comprehensive PCA service with only this fixed performance device. Similarly, it is only suitable (and only licensed) for adults. New devices with smaller bolus doses would be required for paediatric use, and it is to be hoped that these will be produced and tested in the near future. Unlike the electronic PCA pumps, the ITS cannot provide a detailed history of demands, successful or otherwise and no facility for a printed output/record. However a small diode does give an indication of usage by the number of light flashes, one per five successful dose demands/ deliveries. In common with all transdermal devices, the adhesive produces a reaction in a number of
Editorial patients. In most it is short-lived erythema with no discomfort, but a few longer term skin reactions have been reported up to one month in duration. For those responsible for running the acute pain service in the hospital, there may be advantage in not having to provide the large capital outlay, maintenance costs and rolling replacement programme associated with running expensive, precision technology in the clinical workplace. The cost of the new needle-free ITS PCA will need to be weighed against this and the small potential saving in intravenous equipment, set-up time, and the risk-management benefit of avoiding prescription errors. Further data is now required to compare intravenous PCA with needle-free ITS with respect to actual resource utilisation. It is vital to maintain the high level of education for the nurses and ward doctors regarding pain management and for the patients regarding correct use of PCA. Indeed, many patient management aspects pertain to the class of drug and the clinical scenario and not the system, so despite it appearing simple and innocuous, it is important that the ITS remains only for in-patient use in a medically supervised environment. It, nevertheless, offers an alternative strategy for PCA with some unique potential advantages.
References [1] 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. [2] Striebel HW, Touissant S, Raab C, Klocker N. Noninvasive methods for PCA in pain management. Acute Pain 1999;2:36—40. [3] Brown CR, Moodie JE, Bisley EJ. Safety and efficacy of Transfenta in the treatment of post-operative pain: a doubleblind, single-center, placebo-controlled trial. In: 17th Annual Scientific Meeting of the American Pain Society. 1998. p. 192 [abstract 886]. [4] Chelly JE, Grass J, Houseman TW, Minkowitz H, Pue A. The safety and efficacy of a fentanyl patient-controlled transdermal system for acute postoperative analgesia: a multicenter, placebo-controlled trial. Anesth Analg 2004;98:427—33. [5] Viscusi ER, Reynolds L, Tait S, Melson T, Irani H, Atkinson LE. An iontophoretic fentanyl patient-controlled analgesic delivery system for postoperative pain: a double-blind, placebocontrolled trial. Anesth Analg 2006;102:188—94. [6] Viscusi ER, Reynolds L, Chung F, Atkinson LE, Khanna S. Patient-controlled transdermal fentanyl hydrochloride vs intravenous morphine pump for postoperative pain: a randomized controlled trial. JAMA 2004;291:1333—41.
Richard M. Langford ∗ Anaesthetic Laboratory, St. Bartholomew’s Hospital, London, United Kingdom
Editorial
153
Narinder Rawal Department of Anaesthesiology and Intensive ¨ ¨ Care, Orebro University Hospital, Orebro, Sweden ∗ Corresponding
author. Tel.: +44 20 7601 7524; fax: +44 20 7601 7524.
E-mail address: [email protected] (R.M. Langford) 25 August 2006 Available online 17 October 2006
EDITORIAL
A new needle-free PCA system: The fentanyl iontophoretic transdermal system PCA has proved popular with patients, who appreciate their being given control and access to selfadministered rapidly acting pain relief. Although trials show that intermittent nurse-administered opioid boluses can achieve equivalent pain relief to PCA, this is unlikely to be attainable in the nontrial, challenging environment of a busy surgical ward. The main drawback of our current PCA systems is their dependence on intravenous access (a dedicated line, or the use of an anti-syphon valve) and expensive, dedicated pumps. A novel self-contained, transdermal patient controlled analgesia system has recently been approved in both Europe and the USA. It is a selfadhesive, battery-driven device which employs the active process of iontophoresis to accelerate the delivery of the ionised fentanyl molecules across intact skin into the systemic circulation. The imperceptible, iontophoretic (electric) current significantly enhances the penetration rate of fentanyl through the stratum corneum of the epidermis relative to passive diffusion [1,2]. In this way, a sufficient dose can be administered rapidly enough to be appropriate for the acute pain post-operative setting. Having activated the device by two presses of the button within 3 s, the pre-programmed, fixed dose of 40 is delivered over 10 min, during which time the system is ‘locked-out’, and will not respond to further pressing of the button. The iontophoretic transdermal system (ITS) is therefore able to deliver up to 240 h−1 , up to a capacity of 80 doses over 24 h. At 24 h (or if 80 doses are reached sooner), the device automatically shuts down. If continued PCA is required, a new ITS has to be applied for the next 24 h period. Fentanyl has a number of advantages over morphine for this method and route of administra-
tion, being a small, charged, lipophilic molecule. It is amenable to being driven actively by the iontophoretic mechanism and with its high penetration into the central nervous system, once it has reached the bloodstream, has a more rapid time to peak analgesia. With a relative potency of 100:1, a proportionately smaller mass of drug is required to cross the poorly permeable skin barrier. In addition, fentanyl has some general advantages over morphine including pharmacokinetics unaffected by renal impairment, and no active metabolites. However, fentanyl’s shorter duration of action may need to be compensated (relative to an equipotent dose morphine) by more or larger boluses of fentanyl. Hence, the 40 dose in the fentanyl PCA ITS. Clearly the departure from a needle-based system may confer some advantages, and these need to be weighed against potential limitations and drawbacks, but first we need to be reassured that patients receive at least equivalent analgesic benefit to conventional intravenous, opioid based PCA. The efficacy of the fentanyl ITS is supported by data from one active-controlled study and three placebo-controlled studies of adult patients following major abdominal, orthopaedic, or thoracic surgery [3—6]. Results of the placebo-controlled studies demonstrated that fentanyl ITS was superior to placebo in providing postoperative pain relief, as measured by the number of patient withdrawals from the study due to inadequate analgesia, and by patient ratings of pain intensity and the method of pain control [3—5]. Additional outcome measures were evaluated using patient questionnaires in the largest of the placebo-controlled studies [5].
1366-0071/$ — see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.acpain.2006.08.044
152 A larger percentage of patients (61.5%) in the fentanyl ITS group than in the placebo group (32.1%) were very satisfied with their method of pain management, and the majority of patients found the fentanyl ITS to be very convenient (79.8%) and very easy to use (87.0%). The fentanyl ITS was shown to be an equivalent method of pain control compared to a standard regimen of morphine IV PCA in a large study of adult patients following major abdominal, orthopaedic, or thoracic surgery [6]. A similar percentage of patients in each treatment group (>73%) reported a rating of success (‘‘excellent’’ or ‘‘good’’) on the global assessment of the method of pain control in the first 24 h, and >80% of patients in each group reported a rating of success on this measure in the second and third 24-h periods of continued treatment. Turning to the pros and cons of the new device, some of the advantages are obvious, such as the avoidance of being dependent on patent intravenous access, and the potential benefit in enhanced mobilisation, unencumbered by lines, wires and heavy pumps with no mains connection or battery charging. Minimal nurse training is required for the comparatively quick and simple set-up, consisting of the self-adhesive device being placed on the upper outer arm or chest. However, the procedures and checks remain for prescription and administration of a strong opioid substance, and similarly, on cessation of use, the local procedures must be followed for the disposal of opioids, as there is a substantial reservoir of fentanyl in the device. However the fixed dose is a double-edged sword: while, importantly, prescription, dispensing and pump-programming errors are eliminated, there is no possibility to adjust the bolus dose or lock-out time for individual patient titration. One size does not fit all, and it would not be possible therefore to offer a comprehensive PCA service with only this fixed performance device. Similarly, it is only suitable (and only licensed) for adults. New devices with smaller bolus doses would be required for paediatric use, and it is to be hoped that these will be produced and tested in the near future. Unlike the electronic PCA pumps, the ITS cannot provide a detailed history of demands, successful or otherwise and no facility for a printed output/record. However a small diode does give an indication of usage by the number of light flashes, one per five successful dose demands/ deliveries. In common with all transdermal devices, the adhesive produces a reaction in a number of
Editorial patients. In most it is short-lived erythema with no discomfort, but a few longer term skin reactions have been reported up to one month in duration. For those responsible for running the acute pain service in the hospital, there may be advantage in not having to provide the large capital outlay, maintenance costs and rolling replacement programme associated with running expensive, precision technology in the clinical workplace. The cost of the new needle-free ITS PCA will need to be weighed against this and the small potential saving in intravenous equipment, set-up time, and the risk-management benefit of avoiding prescription errors. Further data is now required to compare intravenous PCA with needle-free ITS with respect to actual resource utilisation. It is vital to maintain the high level of education for the nurses and ward doctors regarding pain management and for the patients regarding correct use of PCA. Indeed, many patient management aspects pertain to the class of drug and the clinical scenario and not the system, so despite it appearing simple and innocuous, it is important that the ITS remains only for in-patient use in a medically supervised environment. It, nevertheless, offers an alternative strategy for PCA with some unique potential advantages.
References [1] 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. [2] Striebel HW, Touissant S, Raab C, Klocker N. Noninvasive methods for PCA in pain management. Acute Pain 1999;2:36—40. [3] Brown CR, Moodie JE, Bisley EJ. Safety and efficacy of Transfenta in the treatment of post-operative pain: a doubleblind, single-center, placebo-controlled trial. In: 17th Annual Scientific Meeting of the American Pain Society. 1998. p. 192 [abstract 886]. [4] Chelly JE, Grass J, Houseman TW, Minkowitz H, Pue A. The safety and efficacy of a fentanyl patient-controlled transdermal system for acute postoperative analgesia: a multicenter, placebo-controlled trial. Anesth Analg 2004;98:427—33. [5] Viscusi ER, Reynolds L, Tait S, Melson T, Irani H, Atkinson LE. An iontophoretic fentanyl patient-controlled analgesic delivery system for postoperative pain: a double-blind, placebocontrolled trial. Anesth Analg 2006;102:188—94. [6] Viscusi ER, Reynolds L, Chung F, Atkinson LE, Khanna S. Patient-controlled transdermal fentanyl hydrochloride vs intravenous morphine pump for postoperative pain: a randomized controlled trial. JAMA 2004;291:1333—41.
Richard M. Langford ∗ Anaesthetic Laboratory, St. Bartholomew’s Hospital, London, United Kingdom
Editorial
153
Narinder Rawal Department of Anaesthesiology and Intensive ¨ ¨ Care, Orebro University Hospital, Orebro, Sweden ∗ Corresponding
author. Tel.: +44 20 7601 7524; fax: +44 20 7601 7524.
E-mail address: [email protected] (R.M. Langford) 25 August 2006 Available online 17 October 2006