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Use of IONSYS in clinical practice

Anna Spacek MD
10 August, 2017  
Effective management of acute pain is a very important to ensure the optimal care of all patients undergoing surgery. Although current technologies can effectively relieve acute pain, the management of postoperative pain remains a significant problem. Several surveys have shown that still around one-third of patients experience discomfort and moderate to severe pain after surgical procedures.1 Thus there is still a need for some improvements in postoperative pain management. Insufficient pain control may cause several negative physiological reactions such as an increase in sympathetic activity, with subsequent risk of myocardial ischaemia. Certain respiratory problems may occur and lead to hypoxia and pneumonia. Endocrinologic effects as a stress reaction during the perioperative period can release a number of hormones. 
 
Last, but not least, the immobilisation due to pain is associated with the risk of thrombosis and thromboembolism. Due to insufficient postoperative pain control, morbidity and mortality can increase, as well as the duration and cost of the hospital stay. There is conclusive evidence that the improvement of postoperative pain therapy is not only desirable for humanitarian reasons, but it also has dramatic effects on patient outcomes and economics. Moreover, early and appropriate therapy of acute pain prevents the development of chronic pain.2 So postoperative pain management should be adapted to the needs of each individual patient.
 
The choice of the method of analgesia depends on the localisation of pain, its severity, assessed using one of the pain scales, character, and last, but not least, on the surgical procedure itself. Generally we can differentiate between systemic application of analgesic drugs, local and regional analgesia procedures including epidural or intrathecal analgesia. In properly selected patients, it is also possible to additionally use complementary medicine techniques, for example, acupuncture and transcutaneous electrical nerve stimulation. Postoperative pain management may vary considerably among different countries; however, the ‘old’ modalities of intermittent analgesic administration via intramuscular, subcutaneous and intravenous (IV) injections, and continuous IV infusion have been improved by using patient-controlled analgesia (PCA) modalities. This kind of therapy includes utilising the IV (IV PCA) and epidural (EPCA) routes of administration and offers benefits not provided by conventional therapies.3
 
IV PCA
The most elegant and efficient therapy is pain control using the PCA pump. The pump delivers on-demand doses of opioid – small enough to minimise adverse effects, but large enough to achieve, when given repeatedly – the desired analgesic efficacy. It is known that the risk of respiratory depression by IV PCA used for postoperative pain – in bolus mode only – is very low. The advantages of IV PCA include improved pain relief and therefore the great satisfaction of patients who are independent from medical staff. This method provides minimal adverse effects that can result from strong opioids. Nevertheless, this device is not suitable for every patient and, of course, a proper IV line is necessary. However, it is possible that some problems may occur due to errors regarding the preparation of reservoir of the pump (wrong substance, wrong concentration) or with the programming of the device (additional basal rate, incorrect dose) and problems caused by an improper IV line. The IV PCA equipment may also impair patients’ mobility.4
 
IONSYS
The new transdermal fentanyl PCA device, IONSYS, offers a number of clinical advantages over existing PCA modalities because it is a non-invasive, needle-free option for PCA. IONSYS is pre-programmed and pre-filled to deliver a dose of 40µg fentanyl on demand using iontophoresis to actively transport fentanyl through the skin into the bloodstream.5 Therefore this method of drug delivery avoids the risk of complications from needle-related injuries and infection. The pre-filled device eliminates preparation errors and the pre-programmed electronic eliminates programming errors and excessive dosing. The compact size of the device attached to the skin without any lines allows unrestricted mobility postoperatively.
 
A simple version of IONSYS (an integrated one-piece system) was first launched in 2008. Due to corrosion caused by unseparated packed components of the device (drug unit with hydrogels together with the electronic component), a small number of devices became activated in storage. Therefore IONSYS was withdrawn from the market. An improved version of IONSYS was relaunched in 2016 (Figure 1).
 
Figure 1: The IONSYS system
 
IONSYS is delivered now in a box with two components (that are packed separately) – one part (the drug unit) contains anode hydrogel with 9.7mg fentanyl chloride and a cathode hydrogel without fentanyl. The second part (the controller) includes the electronics and a control system. This piece has a recessed dosing button that may guard against inadvertent dosing. The control system with audio and visual cues confirms the dose activation, shows the number of delivered doses and monitors the system function. The electronics provide a ten-minute lockout system and is pre-programmed – this eliminates risk of programming errors during the setup.6
 
Before using IONSYS, both components must be assembled by medical staff.
 
The IONSYS is an iontophoretic system using a low level of electric current to move ionised molecules of fentanyl through the skin to the blood vessels on activation by the patient. The current level used by IONSYS is imperceptible to the patients (170µA).7 Passive absorption of fentanyl from IONSYS is shown to be negligible (2.3µg/hour (0.4 µg/10 min).8 Fentanyl pharmacokinetics from a IONSYS dose are similar to those of the same doses of IV fentanyl infused over ten minutes. Systemic absorption increases as a function of time independent of frequency of dosing. The initially absorbed dose after first application of 40µg fentanyl is around 16µg and the steady state (absorption of 40µg) occurs after 10–12 hours.9 So the patient may activate the IONSYS more often during this time. Studies have shown that absorption of fentanyl delivered by IONSYS is unaffected by age, gender, body mass index or race.10,11
 
Fentanyl was chosen for iontophoretic PCA because it is a strong opioid, approximately 80–100-times more potent than morphine. A lipophilic opioid fentanyl has a quicker onset than morphine (5 vs. 10 minutes after IV administration) and an intermediate duration of action (t½ 2–5 hours). Small, positively charged molecules (373 Daltons), such as fentanyl HCl are ideal for active diffusion (through iontophoresis). Fentanyl has no active metabolites so it causes less sedation and pharmacokinetics are minimally affected by hepatic/renal impairment.12
 
IONSYS is indicated for the management of acute moderate to severe postoperative pain in adult patients in hospital settings only. Most studies were performed in patients after abdominal, gynaecologic/urologic surgery with laparatomy or after orthopaedic/trauma surgery on hip, knee, shoulder or spine.13
 
Treatment with IONSYS should be initiated by, and remain under control of, physicians experienced in the management of opioid therapy. Due to the well-known addictive potential of fentanyl, physicians should evaluate patients for a history of drug misuse. The appropriate selection and education of patients on how to correctly use IONSYS is very important. 
 
There are some contraindications, including a hypersensitivity to active substance, severe respiratory depression or cystic fibrosis, or chronic therapy with strong opioids.
 
IONSYS should be removed before magnetic resonance imaging, cardioversion, defibrillation, X-ray, computed tomography or diathermy procedures.
 
Use of IONSYS
IONSYS is an easy-to-use device. Before it can be attached to the skin, it is necessary to assemble both its components. After assembly – the parts should snap together – a self-test occurs (acoustic signal, red light flash (once), digital display shows 88). When the self-test is completed, the digital display shows 0 and the green light flashes quickly, indicating that the IONSYS is ready to use and may be applied to the skin of patient.
 
The application site should be easy to reach, such as on the chest or the upper outer arm (noting that there is approximately 20% less resorption at the inside of the forearm) (Figure 2).
 
Figure 2: The application site should be easy to reach
 
The skin at the application site should be prepared – wiped with an alcohol swab and wiped dry – and, if necessary, the hair should be clipped. The skin at the application area should be intact (not radiated, no scar, no exanthema).
 
The IONSYS must be held firmly in place for at least 15 seconds after application. If necessary, the edges can be attached with an additional adhesive plaster. 
 
Patients should be titrated to an acceptable level of analgesia (visual analogue scale <4) prior to initiating use of IONSYS. To activate the device, it is necessary to press the dosing button twice within three seconds – the acoustic signal and flashing green light confirms the proper use. IONSYS provides 40µg fentanyl on-demand dose, delivered over ten minutes with a maximum of six doses available per hour. The device is set for 24 hours’ activity or a maximum of 80 doses delivered. Whichever limit occurs first inactivates the device (no green light, flashing display with the number of given doses). The device should be removed and a new one (if necessary) placed at a different location.
 
The drug depot should be removed from the rest of the device and disposed of according to the rules for opioid medicinal products. The electronic component should be switched off by pressing the button for six seconds and disposed of according to the rules for electronics.
 
The maximum treatment duration with IONSYS is restricted for up to 72 hours (three consecutive used devices).14
 
Clinical data
Several studies have shown that IONSYS produces comparable pain relief to morphine IV PCA. However, more patients treated with IONSYS rated their pain control as excellent at 24-, 48-, and 72-hour time points as the patients treated with IV morphine PCA.15 The data show significantly fewer analgesic gaps in the therapy with IONSYS versus morphine IV PCA.16 Regarding adverse events, there were similar rates for IONSYS and IV morphine PCA. The possible opioid adverse effects including nausea and emesis, which should be treated properly with anti-emetics, sedation, hypotension and dizziness rarely occur. However, application site reactions such as erythema and pruritus (mostly mild; Figure 3) are relatively common and can be effectively treated with ointment, and are not considered to be serious or have a demonstrated systemic impact.17,18 
 
Figure 3: Application site reactions are mostly mild
 
Studies have demonstrated the ease of care of IONSYS. Significantly more nurses favoured IONSYS over morphine IV PCA on a satisfaction subscale and found IONSYS less time consuming. The same was demonstrated for physical therapists.19 Studies have further demonstrated that significantly more IONSYS patients reported no interference with mobility versus morphine IV PCA.20 The greater mobility with IONSYS is a very important aspect of the postoperative management of patients.   
 
Conclusions
IONSYS is a novel, transdermal iontophoretic fentanyl PCA device. This is a pre-filled and pre-programmed, non-invasive needle-free system. It allows 24-hour analgesic coverage and unrestricted mobility and independence from medical staff. IONSYS is easy to use and safe. Adverse effects and analgesic effectivity are comparable to morphine IV PCA. A non-invasive method of delivery of fentanyl for management of acute pain offers logistic advantages for patients and healthcare staff. Therefore IONSYS provides optimal individual pain control to patients after surgical procedures and may effectively serve as an alternative therapy option in the management of postoperative pain.
 
References
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