The problem
Postoperative pain relief is often insufficient. Different
reasons may be taken into account:
· No or insufficient prescription of analgesics
· Need for strong analgesics
· Time gap between calling the doctor on duty and application
of the analgesic
· Intramuscular or intravenous injections require a nurse
or a doctor
Fentanyl transdermal system
Applied via a transdermal system fentanyl is released continuously
through the intact skin. This guarantees a long-lasting constant
pain relief. The concept of transdermal fentanyl seems to offer
good properties to overcome the major problems in postoperative
pain management.
More than 30 studies have been published applying transdermal fentanyl for postoperative pain relief. Predominantly patients who underwent abdominal surgery were included. All different sizes of transdermal fentanyl were used, predominantly 50 and 75 µg/h patches. In most cases transdermal systems were applied 2 hours before the onset of surgery. During the postoperative period the patients could ask for a further amount of an opioid, if they experienced insufficient pain relief. In this case, often morphine was applied, further opioids used were pethidine, piritramide or fentanyl. By providing a constant analgesia via transdermal fentanyl it is not surprising, that additional need for opioids was significantly reduced in the fentanyl groups in comparison with the placebo groups and that the amount of supplemental opioids was smaller in the groups with higher fentanyl dosages. However, results in pain relief were not uniform. Some studies demonstrated a better pain control with transdermal fentanyl compound to a conventional pain control with other opioids. In other studies the regime was not superior to the conventional regimes, though. However, side effects limit this strategy of postoperative pain control. Respiratory depression was noted in up to 10% of the patients. Continuous monitoring of respiratory rates or oxygen saturation was necessary. Opioid reversal with naloxone was performed in a few cases. This led to the following conclusion: transdermal fentanyl is contraindicated for treatment of acute pain which is also stated in the package insert.
Explanations for the drawbacks of transdermal fentanyl in the
treatment of acute pain are pharmacokinetic properties as well
as patient bound characteristics:
· Constant fentanyl delivery which cannot be influenced
-- Reduction of the dosage is not possible and, if the patch is
removed, there is a prolonged half-life time due to the dermal
depot of fentanyl.
- If pain relief is insufficient, an opioid must be applied using
a different route, e. g. intravenous or intramuscular injection.
· No data exist concerning the prognosis of postoperative
pain.
· Interindividual differences in the opioid response are
too large to guarantee an effective postoperative analgesia without
severe side effects by a preselected opioid dosage. Trials on
patient controlled analgesia demonstrated wide dosage ranges in
the patients opioid requirements.
Electrotransport system of fentanyl
A new possibility for transdermal opioid application in postoperative
pain might be the electrotransport therapeutic system (ETS) fentanyl.
Drug delivery via ETS is proportional to the applied current and
the time intervals. The pharmacokinetic profile of this formulation
is similar to i.v. application of fentanyl. Nominal dosages being
delivered over 10 minutes were 25 or 40 µg of fentanyl with
a maximum of 6 applications/h. More than 500 patients received
ETS fentanyl for postoperative pain relief. Excellent or good
pain control was reported by more than 90% of the patients. As
in PCA trials wide interindividual variations in the need of fentanyl
were recorded. Main side effects are nausea and vomiting with
an incidence up to 56%, respectively 36%. Due to these high incidences
antiemetic prophylaxis should be discussed. Hypoventilation was
reported in three patients, mild or moderate hypoxia probably
related to ETS fentanyl in 19 patients.
Overall the ETS fentanyl acts like a patient-controlled analgesia on a non invasive route and might be a future alternative for postoperative pain control possibly decreasing staffing requirements.
Conclusion
The fentanyl transdermal system which is marketed in over 30 countries,
is inappropriate and contraindicated for the treatment of acute
pain. It is reserved for patients with chronic pain. A transdermal
system delivering fentanyl through electroperation is under development.
The studies carried out up to now in healthy volunteers and patients
with postoperative pain demonstrated effective pain control. However
this system is not marketed yet. Consequently, at the moment transdermal
pain therapy is no option for the treatment of acute pain.