Patient-controlled Transdermal System Research Articles

Studies on local anesthetic lidocaine hydrochloride delivery via photo-triggered implantable polymeric microneedles as a patient-controlled transdermal analgesia system

This study aimed to develop photo-triggered implantable polymeric microneedles (MNs) for successful drug delivery in a transdermal analgesia system. The prepared iron oxide nanoparticles (Fe3O4NPs) were coated with polydopamine (PDA) followed by polyvinylpyrrolidone (PVP) and polycaprolactone (PCL). While the PCL/PVP-Fe3O4NPs synthesis, the absorption band of PVP at 1656 cm−1 shifted to 1665 cm−1 which indicate the presence of interaction between Fe+ and C = O groups. The size and morphology of PCL/PVP-Fe3O4NPs were examined by scanning electron microscope and transmission electron microscope (SEM and TEM) analysis. The results confirmed that the prepared PCL/PVP-Fe3O4NPs were spherical with sizes ranging from 9 to 11 nm. The lidocaine hydrochloride content in the microneedles was 3.72 ± 0.31 mg and A + 2.2S ≤ L representing that the drug was uniformly distributed. The insertion ability of lidocaine hydrochloride@PCL/PVP-Fe3O4NPs-DMNs was tested by porcine skin. The results demonstrated outstanding insertion ability and potential for drug delivery. In addition, near-infrared (NIR) irradiation has the potential to penetrate the skin and enhance lidocaine hydrochloride-releasing activity. The in vivo experimental data confirmed that lidocaine hydrochloride@PCL/PVP-Fe3O4NPs-DMNs allowed for painless drug delivery by breaking the barrier of the stratum corneum. To conclude, lidocaine hydrochloride can be safely delivered through the transdermal analgesic system, with a quick onset time.

Sublingual, transdermal and intravenous patient-controlled analgesia for acute post-operative pain: systematic literature review and mixed treatment comparison

Objective: To conduct a systematic literature review (SLR) and quantitative analysis to assess the comparative efficacy and safety of the sufentanil sublingual tablet system (SSTS) against other available patient controlled analgesia (PCA) options for post-operative analgesia.Methods: An SLR was conducted for studies published between 2004 and 2016. Due to study heterogeneity, subgroup analyses were conducted controlling for differences in imputation methods for missing values, baseline pain severity, and type of surgery. Where sufficient data was available, a mixed treatment comparison (MTC) was performed.Results: The MTC and subgroup analyses used 13 studies. In direct meta-analysis, there was a statistically significant difference in favor of SSTS compared with intravenous (IV) PCA (morphine) at 24 hours for the patient global assessment (PGA) scores of “good” or “excellent”. For the Pain Intensity Score, there were numerical but not statistically significant differences in favor of the SSTS versus IV PCA (morphine) and the patient controlled transdermal system (PCTS) (fentanyl) in the MTC at 6 hours (standardized mean difference −0.27 [credible interval −2.78, 2.09] and −0.36 [−3.89, 3.03], respectively). The onset of pain relief was earlier with the SSTS versus IV PCA (morphine) as shown by the Pain Intensity Difference. Likewise, the onset was earlier compared with PCTS (fentanyl) where data was available. There was a significant difference in favor of SSTS compared with IV PCA (morphine) and with PCTS (fentanyl) for any adverse event, and numerical improvements for withdrawals due to adverse events.Conclusions: This meta-analysis shows that SSTS is an option for non-invasive management of moderate-to-severe post-operative pain which can be more effective, faster in onset and better tolerated than IV PCA (morphine) and PCTS (fentanyl).

Indirect treatment comparison of two non-invasive patient-controlled analgesia treatments for acute post-operative pain management

Objectives: To evaluate the relative clinical efficacy, safety, and tolerability associated with two non-invasive patient-controlled analgesia (PCA) treatments, sufentanil sublingual tablet system (SSTS) and fentanyl iontophoretic patient-controlled transdermal system (PCTS). These two treatments have recently been approved in the EU for the management of acute moderate-to-severe post-operative pain in adult patients.Methods: As no head-to-head trials comparing SSTS and PCTS currently exist, indirect treatment comparison (ITC) analyses were conducted to evaluate SSTS or PCTS versus intravenous (IV) morphine PCA.Results: Five studies, four assessing PCTS and one assessing SSTS, were included in this analysis. SSTS had statistical or numerical advantages over PCTS for both patient global assessment (PGA) and healthcare professional global assessment (HPGA) outcomes at all time points investigated. SSTS was also associated with greater patient ease of use (weighted mean difference [WMD]: 0.13; 95% confidence interval [CI]: −0.02–0.28) and a higher patient satisfaction score (WMD: 0.31; 95% CI: 0.05–0.57; p = .019) compared with PCTS. In terms of tolerability, all-cause withdrawals from treatment were reported to be less likely with SSTS (risk ratio: 0.65; 95% CI: 0.42–1.02). No significant differences were observed between SSTS and PCTS in terms of safety and adverse events.Conclusions: In the absence of direct head-to-head data, the combination of promising phase III trial results compared to IV morphine PCA, a SLR comparison against other opioid treatments, and the results of this exploratory analysis present a strong rationale in support of SSTS as a key option for management of post-operative pain.

Implantable polymeric microneedles with phototriggerable properties as a patient-controlled transdermal analgesia system.

Adequate pain control can be achieved using a patient-controlled drug delivery system that can provide analgesia to patients as needed. To achieve this objective, we developed a phototriggered microneedle (MN) system that enables the on-demand delivery of pain medications to the skin under external near-infrared (NIR) light stimulation. In this system, polymeric MNs, containing NIR absorbers and analgesics, are combined with a poly(l-lactide-co-d,l-lactide) supporting array. A "removable design" of the supporting array enables the quick implantation of the MNs into the skin to act as a drug depot, thus shortening the patch application time. Upon irradiation with NIR light, the NIR absorbers in the implanted MNs can absorb light energy and induce a phase transition in the MNs to activate drug release. We demonstrated that lidocaine release can be modulated or repeatedly triggered by varying the duration of irradiation and controlling the on and off status of the laser. Lidocaine delivered by the implanted MNs can be rapidly absorbed into the blood circulation within 10 min and has a bioavailability of at least 95% relative to the subcutaneous injection, showing that the proposed system has the potential to provide a rapid onset of pain relief. Such an implantable device may allow pain sufferers receiving the painkiller without the need for multiple needle injections, and may enable controlling pain more conveniently and comfortably.

Iontophoretic transdermal fentanyl for the management of acute perioperative pain in hospitalized patients

ABSTRACTIntroduction: Intravenous (I.V.) morphine administered through a patient-controlled system currently represents the gold standard treatment for moderate to severe acute postoperative pain. To fix the limitations showed by the available I.V. patient-controlled analgesia (PCA) systems that may restrict its use in the clinical practice a needle-free, iontophoretic, fentanyl patient-controlled transdermal system has been developed and recently approved by the United States Food and Drug Administration (FDA) and by the European Medicines Agency (EMA).Areas covered: This review aims at describing the technology, pharmacology and clinical efficacy of fentanyl iontophoretic transdermal system (ITS) in the treatment of acute pain. A literature search was conducted in the PUBMED database using the term ‘fentanyl iontophoretic transdermal system’ through September 2015 and results from the main clinical trials are discussed.Expert opinion: In 2015, the appropriate treatment of acute pain after surgery is still a challenge and it represents a primary goal in the care of the surgical patient. When regional analgesia techniques are not applicable and systemic analgesia is required, patient controlled systems represent the standard of care for opioid administration. The fentanyl ITS presents several potential advantages compared to the currently used PCA devices. In particular, it does not require intravenous lines and eliminates the potential for drug administration errors, observed with manually programmed standard PCA devices. Nevertheless, further studies are needed to address eventual inter-individual variability especially for opioid tolerant patients.

Pharmacodynamics and clinical efficacy of fentanyl iontophoretic transdermal system for post-operative pain in hospitalized patients

Introduction: The fentanyl iontophoretic transdermal system (ITS) is a patient-controlled transdermal system allowing needle-free administration of on-demand doses of Fentanyl of 40 µg over a 10-min period up to 80 doses or over a 24-h period. It is indicated in opioid naïve patients for the treatment of acute postoperative pain in the hospitalized patients for up to 72 h.Areas covered: It has been demonstrated to be effective and safe in randomized trials and to provide comparable analgesia versus morphine intravenous (i.v.) patient-controlled analgesia (PCA) with adverse events similar between groups.Expert opinion: Fentanyl ITS has shown high patient satisfaction rates, and was described by patients and investigators as easy and convenient to use. These properties make this technology interesting when considering perioperative pain management. In the present health care environment additional data are required to establish the cost-benefit ratio of this technology in optimizing patient’s recovery from surgery.

Patient-controlled analgesia:patient and nurse satisfaction with intravenous delivery systems and expected satisfaction with transdermal delivery systems

ABSTRACTObjective: To compare patient and nurse satisfaction with intravenous patient-controlled analgesia (IV-PCA) to their prospective satisfaction with patient-controlled transdermal delivery system (PCTS) technology.Methods: Nationwide samples of 301 nurses (200 medical-surgical, 101 post-anesthesia care units) and 500 surgery patients (192 abdominal, 119 gynecological, 189 orthopedic) completed self-administered, Internet-based questionnaires. Respondents indicated satisfaction with attributes of IV‐PCA and, after reading a description of PCTS, indicated prospective satisfaction with comparable attributes. Within patient and nurse samples, half rated IV-PCA first (and later re-rated overall satisfaction) and half rated PCTS first. Paired comparison t-tests were used to determine significant differences in satisfaction for IV‐PCA and PCTS attributes.Results: Nurses reported significantly higher satisfaction with PCTS for patient and nurse ease of use, safety, and tolerability ( p < 0.001 for all); and higher satisfaction with IV‐PCA for the ability to vary drugs ( p < 0.001) and doses ( p < 0.001), deliver basal doses ( p < 0.001), and dose tracking accessibility ( p = 0.003) and quality ( p = 0.002). Patients reported significantly higher satisfaction with PCTS for pain relief ( p < 0.001), safety ( p = 0.027), self-control ( p < 0.001), and patient ( p < 0.001) and nurse ease of use ( p < 0.001); and higher satisfaction with IV‐PCA for correct set-up and programming ( p = 0.002). Overall satisfaction did not differ significantly among nurses, but among patients satisfaction with IV‐PCA declined after considering PCTS ( p < 0.001). Nurses placed greater importance on safety to their overall satisfaction than patients did.Limitations: Only respondents with Internet access were included. PCTS satisfaction is hypothetical and may not reflect true product satisfaction.Conclusion: PCTS is a novel delivery system for postoperative pain and has the potential to improve patient and nurse satisfaction over IV‐PCA.

The Effect of Dosing Frequency on the Pharmacokinetics of a Fentanyl HCl Patient-Controlled Transdermal System (PCTS)

The fentanyl HCl patient-controlled transdermal system (PCTS) is a noninvasive, needle-free, credit card-sized drug delivery system designed for the on-demand management of acute pain in a medically supervised setting. The objective of these studies was to determine the effect of dosing frequency on the pharmacokinetics of fentanyl delivered by the PCTS. All three studies were single-centre, open-label, randomised, crossover studies. The fentanyl HCl PCTS was applied to the upper outer arm of all participants. In the first study, participants (n = 30) received three fentanyl HCl PCTS 25 microg treatments: two sequential doses hourly for 23.33 hours, six sequential doses every 3 hours for 22 hours, and 72 doses continuously over 12 hours. Participants (n = 31) in the second study received three fentanyl HCl PCTS 40 microg treatments: two sequential doses hourly over 23.33 hours, six sequential doses every 3 hours over approximately 10 hours, and 80 doses continuously over 13.33 hours. In the third study, participants (n = 28) received four fentanyl HCl PCTS 40 microg treatments: 6, 18, 36 and 80 doses over 1, 3, 6 and 13.33 hours, respectively. Naltrexone was used to block the opioid effects of fentanyl. Pharmacokinetic parameters, including maximum serum fentanyl concentration (Cmax), time to Cmax (tmax), area under the serum concentration-time curve (AUC) and terminal half-life (t(1/2)) were determined. In the first study, the dose-normalised AUC (AUCn) values for the 2- and 6-dose sequence treatments were not significantly different (p = 0.937), suggesting that the frequency of dosing has little effect on the amount of fentanyl absorbed; however, the AUCn for the 72-dose treatment was significantly lower than that of the other treatments (p = 0.001), which were of longer duration. The results of the second study paralleled those from the first, suggesting that the bioavailability of fentanyl delivered by the PCTS increases as a function of time and is likely to be independent of dosing frequency. Results from the third study suggested that approximately 40% of the nominal 40 microg fentanyl dose is absorbed during the first hour of treatment, with the full nominal dose absorbed after approximately 10 hours. The fentanyl HCl PCTS was well tolerated. The amount of fentanyl absorbed from the PCTS increases as a function of time and is independent of both dosing frequency and total number of doses delivered. The fentanyl HCl PCTS is generally safe and well tolerated.

Characterisation of the Pharmacokinetics of the Fentanyl HCl Patient-Controlled Transdermal System (PCTS)

The fentanyl HCl patient-controlled transdermal system (PCTS) is a self-contained, preprogrammed, noninvasive analgesic delivery system for acute pain management. We carried out three studies with the following objectives: study I to evaluate the relationship between fentanyl absorption and the magnitude of current applied to the system; study II to determine dose-proportionality for the fentanyl HCl PCTS (25 and 40 microg); and study III to describe the effects of single- and multiple-day administration on the pharmacokinetics of fentanyl delivered by the PCTS. All studies were open-label, crossover studies with washout periods between treatments. In study I, randomised participants (n = 36) received three of a potential five fentanyl HCl PCTS prototypes, each of which used a different current magnitude, and each of which was evaluated for 24 hours. In study II, participants (n = 40) received fentanyl (25 microg) from the PCTS for 23.33 hours, followed by fentanyl (40 microg) from the PCTS for 23.33 hours. Intravenous (IV) fentanyl (80 microg/h) was administered intermittently over 24 hours as a reference treatment in Studies I and II. In study III, participants (n = 28) received fentanyl (40 microg) from the PCTS for 20 hours, followed by fentanyl (40 microg) from the PCTS for 68 hours. Pharmacokinetic parameters, including maximum serum fentanyl concentration (Cmax), time to Cmax (tmax), area under the serum concentration-time curve (AUC) and terminal half-life (t(1/2)), were determined for each treatment. The amount of fentanyl absorbed from the PCTS was linearly dependent on the magnitude of current applied to the system, with a current of 170 microA resulting in the absorption of 39.5 microg of fentanyl at hour 23. Mixed-effect ANOVA indicated no significant difference (p > 0.1) in the dose-normalised pharmacokinetics of the fentanyl HCl PCTS 25 and 40 microg. No significant difference existed between the corrected AUC(0-5) of the fentanyl HCl PCTS during the single- and multiple-day treatment periods (0.40 and 0.54 microg x h/L, respectively; p = 0.133). The system was well tolerated, with headache and mild application site erythema being the most common treatment-related adverse events. A linear relationship exists between the amount of current applied to the fentanyl HCl PCTS and the amount of fentanyl absorbed. There is dose-proportionality in the pharmacokinetics of the fentanyl HCl PCTS 25 and 40 microg. Multiple-day administration does not affect the pharmacokinetics of the fentanyl HCl PCTS 40 microg. The system was well tolerated, even after repeated application.

Effects of Application Site and Subject Demographics on the Pharmacokinetics of Fentanyl HCl Patient-Controlled Transdermal System (PCTS)

The fentanyl HCl patient-controlled transdermal system (PCTS) is a self-contained, preprogrammed, needle-free system currently in development for acute pain management in a medically supervised setting. The objectives of these studies were to evaluate skin application sites for the fentanyl HCl PCTS and to evaluate the effect of patient demographics on its pharmacokinetics. The first study was a randomised, open-label, single-centre, 3-treatment, crossover study in which the fentanyl HCl PCTS was applied to the upper outer arm, lower inner arm or chest of healthy volunteers. Fentanyl 25 microg was then delivered via this system twice during the first 20 minutes of every hour for 24 hours. The pharmacokinetics of fentanyl were determined and analysed for each application site using ANOVA. The second study was a nonrandomised, nonblind, multicentre, sequential treatment study. Healthy volunteers received fentanyl HCl 40 microg via the PCTS three times during the first 30 minutes of each hour for 3 hours. After a 5- to 10-day washout period, fentanyl HCl 120 microg was administered intravenously during the first 30 minutes of each hour for 3 hours as a reference treatment. Pharmacokinetic parameters were determined for the fentanyl HCl PCTS, and results were analysed using ANOVA. Safety and tolerability were evaluated in both studies. Application of the system to the upper outer arm or chest resulted in similar maximum serum concentrations (Cmax; 1.193 and 1.176 microg/L, respectively) and areas under the serum concentration-time curve (AUC24-25; 1.033 and 1.015 microg h/L). However, both Cmax and AUC24-25 were less when the system was applied to the lower inner arm (0.859 microg/L and 0.757 microg x h/L). Subject age, bodyweight, sex and ethnicity had no significant effect on pharmacokinetic parameters. No serious adverse events were reported in either study during or after administration of the fentanyl HCl PCTS. Fentanyl HCl is comparably absorbed from the PCTS when it is applied to the upper outer arm or chest. The pharmacokinetics of fentanyl HCl delivered by the PCTS are unaffected by sex, age, race or weight.

The Fentanyl HCl Patient-Controlled Transdermal System (PCTS)

Inadequate pain control in the postoperative period not only contributes to patient discomfort, but also causes physiological changes that may result in increased risk of myocardial ischaemia, deep vein thrombosis and pulmonary embolism. These events complicate postoperative recovery and may lead to longer hospital stays as well as increased healthcare costs. Patient-controlled analgesia (PCA) has emerged as an effective way for patients to manage their pain, allowing self-administration of small doses of analgesics to maintain a certain level of pain control. PCA is most commonly delivered via an intravenous (IV) or epidural route, and while patient satisfaction is higher with PCA than with conventional methods of analgesic administration, the invasiveness, costs and risk of errors associated with currently available modalities may limit their utility. These systems also require significant healthcare resources, as nurses must manually program the pumps to deliver the correct amount of medication. Several new PCA modalities are being developed to address these limitations. These systems deliver drug through a variety of routes, including nasal transmucosal and transdermal. Most notably, a self-contained, credit card-sized, transdermal PCA system is currently in the final stages of development. The fentanyl HCl patient-controlled transdermal system (PCTS; IONSYS, Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ) uses an imperceptible, low-intensity direct current to transfer fentanyl on demand across the skin into the systemic circulation. This compact system is patient-activated, can be applied to the patient's upper arm or chest, and is designed to manage moderate-to-severe pain requiring opioid analgesia. The system delivers a preprogrammed amount of fentanyl HCI over 10 minutes, for a total of 80 doses, or for 24 hours, whichever occurs first. The on-demand dosing and pharmacokinetics of this system differentiate it from the passive transdermal formulation of fentanyl designed for the management of chronic pain. Clinical studies have shown that the fentanyl HCl PCTS is effective in the management of acute postoperative pain. These studies have also demonstrated that the system is safe and well tolerated by patients.

Patient-controlled Modalities for Acute Postoperative Pain Management

Although numerous clinical practice guidelines for pain management have been published throughout the last 12 years, inadequate pain relief remains a significant health care issue. Several patient-controlled analgesia (PCA) modalities are currently available for the treatment of acute postoperative pain, including intravenous (IV) PCA, epidural (PCEA), and oral PCA. Although PCEA and IV PCA are both commonly used modalities, IV PCA is considered the standard of care for postoperative pain management. Limitations of this modality do exist, however. Consequently, noninvasive PCA systems are under development to circumvent many of these limitations, including the fentanyl hydrochloride patient-controlled transdermal system (PCTS); (IONSYS Ortho-McNeil Pharmaceutical, Raritan, NJ) and a number of patient-controlled intranasal analgesia (PCINA) delivery systems. The objective of this article is to review the PCA modalities currently in use and to discuss those in development for the treatment of acute postoperative pain.

Postoperative pain management with a patient-controlled transdermal delivery system for fentanyl

The efficacy and safety of fentanyl hydrochloride patient-controlled trans-dermal system (PCTS) for management of acute postoperative pain are discussed. Fentanyl hydrochloride PCTS is a self-contained, needle-free, credit-card-sized fentanyl-delivery system that is worn on the patient's arm or chest. The system uses iontophoretic technology to actively deliver preprogrammed doses of fentanyl into the systemic circulation when activated by the patient on demand. PCTS is as safe and effective as i.v. morphine patient-controlled analgesia and superior to placebo for managing acute postoperative pain. Fentanyl absorption from PCTS is clinically insignificant when the device is not activated. This contrasts with the transdermal fentanyl patch, which delivers fentanyl continuously for 72 hours via passive absorption and is indicated only for use in the management of chronic pain. Fentanyl hydrochloride PCTS is a self-contained iontophoretic fentanyl-delivery system that provides patients control over pain management and consistent management of pain without analgesic peaks and troughs.

An iontophoretic, fentanyl HCl patient-controlled transdermal system for acute postoperative pain management

Patient-controlled modalities using intravenous or epidural routes have dramatically improved postoperative pain management. However, acute post-operative pain continues to be undermanaged. Intravenous patient-controlled analgesia (PCA), the current standard of care for acute postoperative pain management, requires the patient to be attached to a staff-programmed pump apparatus via an intravenous catheter and tubing, rendering it invasive and mobility-limiting. An innovative, needle-free, iontophoretic, fentanyl HCl patient-controlled transdermal system (PCTS) is being developed for acute postoperative pain management. Fentanyl HCl PCTS is a compact, self-contained system that is easily applied to the upper outer arm or chest. It provides pain relief therapeutically equivalent to that of a standard regimen of morphine intravenous PCA, with pharmacokinetics similar to those of intravenous fentanyl infusion. Fentanyl HCl PCTS may be an effective, non-invasive alternative to currently available PCA modalities.

Protocol design: a fentanyl HCl patient-controlled transdermal system (PCTS) vs. IV morphine patientcontrolled analgesia for post-surgical pain management in 11 European countries

Protocol design: a fentanyl HCl patient-controlled transdermal system (PCTS) vs. IV morphine patientcontrolled analgesia for post-surgical pain management in 11 European countries

Comparison of the safety and efficacy of an iontophoretic Patient-Controlled Transdermal fentanyl HCl delivery System (PCTS) versus an intravenous patient-controlled morphine pump for the treatment of acute post-operative pain after general surgery

Acute postoperative pain is commonly managed with intravenous administration of morphine via patient-controlled analgesia (IV PCA) devices. The iontophoretic fentanyl HCl patient-controlled transdermal system (PCTS) is a non-invasive, preprogrammed, credit card-sized system applied to the upper arm or chest. This subanalysis of a randomized, multicenter study that compared the safety and efficacy of morphine IV PCA with the fentanyl PCTS was performed to assess the efficacy of each modality in the subset of patients who had undergone general surgery.

Validity of a patient-reported assessment of methods of pain control

As new pain control methods are developed, clinicians and patients must be able to distinguish among those having similar efficacy. Singleitem measures of efficacy have been used extensively in pain assessment; however, new measures require evidence of validity before they can contribute to informed decision-making. This analysis provides evidence of validity of the single-item measure, patient global assessment (PGA) of the pain control method. The validity of PGA as an efficacy measure was assessed using data from 5 clinical trials (1572 patients) comparing the new, iontophoretic fentanyl HCl patient-controlled transdermal system (PCTS) with intravenous patient-controlled analgesia (IV PCA) morphine or placebo for postoperative analgesia. Different trial designs prevented assessment of each of the following 4 proposed validity hypotheses within the same trial: PGA ratings of “excellent” or “good” will be associated with 1) lower pain intensity levels (3 trials), 2) greater satisfaction with pain relief (2 trials), 3) future intention to select the assigned pain control method (2 trials), and 4) pain management goal achievement (1 trial). Pain intensity, satisfaction with pain relief, and future intention were assessed by visual-analog or categorical-rating scales. Support for validity of the measure was inferred when data supported the hypotheses. As hypothesized, positive PGAs were associated with lower pain intensity. Satisfaction with pain relief and future intention to use the assigned pain control method were strongly associated with positive PGAs (Kendall’s tau b .001). Among 47% (n 484) who met their pain management goal, 91.0% rated their pain control method as “good” or “excellent.” Only 30.4% not meeting their goal reported similar ratings. New pain control methods having similar efficacy require assessment methods that help clinicians and patients differentiate among them. The PGA provides a simple assessment of pain control method. Findings support the validity of this single-item measure.

The Safety and Efficacy of a Fentanyl Patient-Controlled Transdermal System for Acute Postoperative Analgesia

Survey of Anesthesiology: October 2004 - Volume 48 - Issue 5 - p 265 doi: 10.1097/01.sa.0000140557.62084.f8

Patient-controlled analgesia: A randomized multicenter trial comparing the safety and efficacy of a patient-controlled transdermal fentanyl HCl delivery system versus an intravenous patient-controlled morphine pump for the treatment of acute post-operative pain

Intravenous administration of morphine via patient-controlled analgesia (IV PCA) devices is a common method of managing acute postoperative pain. The fentanyl HCl patient-controlled transdermal system (PCTS) is a non-invasive, credit card-sized system using the E-TRANS® delivery platform (ALZA Corp.) that can be applied to the upper arm or chest. This randomized, multicenter study compared the safety and efficacy of these two pain control modalities. After major surgical procedures, 636 adults were titrated to comfort with opioids and randomized 1:1 to fentanyl HCl PCTS or IV PCA morphine. Fentanyl HCl PCTS delivered 40 μg fentanyl on demand, up to 6 doses/hour. The IV PCA delivered 1 mg morphine, up to 10 mg/hour. Visual Analog Scale (VAS) pain intensity scores were recorded before randomization and thereafter for 72 hours. The primary efficacy endpoint was the proportion of patients who rated their method of pain control as excellent or good during the first 24 hours (patient global assessment-PGA). Investigator global assessments, withdrawal due to inadequate analgesia, withdrawal for any reason, and last pain intensity score were also recorded. Demographic data was similar between groups. PGA was comparable between groups, with 233/316 (73.7%) patients receiving fentanyl HCl PCTS rating their method of pain control as excellent or good, compared with 246/320 (76.9%) IV PCA morphine patients.. All secondary efficacy endpoints had comparable outcomes between groups. One occurrence of respiratory depression was reported (in the IV PCA morphine group). The most frequent systemic adverse events in both groups were headache, nausea, pruritus, vomiting, constipation, and dizziness. Mild, self-limiting erythema at the application site was observed in 54% of patients receiving fentanyl HCl PCTS. Fentanyl HCl PCTS, a non-invasive patient-controlled fentanyl HCl system, provided control of acute post-operative pain similar to standard IV PCA morphine. Fentanyl HCl PCTS was well tolerated. Intravenous administration of morphine via patient-controlled analgesia (IV PCA) devices is a common method of managing acute postoperative pain. The fentanyl HCl patient-controlled transdermal system (PCTS) is a non-invasive, credit card-sized system using the E-TRANS® delivery platform (ALZA Corp.) that can be applied to the upper arm or chest. This randomized, multicenter study compared the safety and efficacy of these two pain control modalities. After major surgical procedures, 636 adults were titrated to comfort with opioids and randomized 1:1 to fentanyl HCl PCTS or IV PCA morphine. Fentanyl HCl PCTS delivered 40 μg fentanyl on demand, up to 6 doses/hour. The IV PCA delivered 1 mg morphine, up to 10 mg/hour. Visual Analog Scale (VAS) pain intensity scores were recorded before randomization and thereafter for 72 hours. The primary efficacy endpoint was the proportion of patients who rated their method of pain control as excellent or good during the first 24 hours (patient global assessment-PGA). Investigator global assessments, withdrawal due to inadequate analgesia, withdrawal for any reason, and last pain intensity score were also recorded. Demographic data was similar between groups. PGA was comparable between groups, with 233/316 (73.7%) patients receiving fentanyl HCl PCTS rating their method of pain control as excellent or good, compared with 246/320 (76.9%) IV PCA morphine patients.. All secondary efficacy endpoints had comparable outcomes between groups. One occurrence of respiratory depression was reported (in the IV PCA morphine group). The most frequent systemic adverse events in both groups were headache, nausea, pruritus, vomiting, constipation, and dizziness. Mild, self-limiting erythema at the application site was observed in 54% of patients receiving fentanyl HCl PCTS. Fentanyl HCl PCTS, a non-invasive patient-controlled fentanyl HCl system, provided control of acute post-operative pain similar to standard IV PCA morphine. Fentanyl HCl PCTS was well tolerated.

Patient-controlled analgesia: A double-blind, multicenter, placebo-controlled trial incorporating the JCAHO pain management standards in the evaluation of a patient-controlled transdermal fentanyl delivery system for acute postoperative pain management

The undertreatment of pain is recognized as a major public health problem, and JCAHO standards were developed in response to this issue. These standards may be applied when evaluating innovative pain management systems, such as the fentanyl HCl patient-controlled transdermal system (PCTS), a needle-free, credit card-sized system designed to be applied to the upper arm or chest. This study compared its safety and efficacy with placebo for acute postoperative pain. Patients were randomized 1:1 to receive fentanyl HCl PCTS 40 μg or placebo systems for 24 hours post-surgery. Pursuant to JCAHO standards, patients were educated regarding postoperative pain, pain assessment, and goals of pain control prior to and after surgery. The primary efficacy parameter was the percentage of patients discontinuing because of inadequate pain control three or more hours after system application. Pain intensity, patient global assessment (PGA), investigator global assessment (IGA), patient satisfaction, ease of use, and convenience were also evaluated. 244 subjects were randomized to fentanyl HCl PCTS, and 240 to placebo. Significantly fewer patients on fentanyl HCl PCTS discontinued due to inadequate analgesia compared to placebo (28.7% versus 60.0%; P<0.0001), and last pain intensity score was 3.5 (fentanyl HCl PCTS) versus 5.4 (placebo). A majority of fentanyl HCl PCTS patients (65%) met or exceeded their pain management goal versus placebo (37%; P<0.001). Patients (76.2%, PGA) and investigators (74.9%, IGA) also considered the fentanyl HCl PCTS a good or excellent method of pain control, and 64% of patients receiving the active treatment were very satisfied with the system versus 37% on placebo (P<0.001). Study medication was well tolerated. The fentanyl HCl PCTS 40 mcg was superior to placebo for patient-controlled analgesia after major surgery and was well tolerated. Patients considered fentanyl HCl PCTS convenient and easy to use.