Fentanyl (Duragesic, Actiq, and others)

Even though fentanyl and its derivatives are heavily used for pain relief, both in surgery and as highly dangerous and addictive time-release skin patches, there is amazingly little research comparing fentanyl to non-narcotic pain relievers.  Large numbers of studies compare it to other narcotics or against placebo, but manufacturers have been very careful not to fund studies comparing it to non-narcotic alternatives.  Fentanyl has been a very popular drug of abuse among anesthesiologists, who have by far the highest rate of narcotic abuse of any branch of medicine.  It is definitely a very dangerous drug which should be banned until there is some evidence than it is better for something that non-narcotic alternatives.  Cephalon's brand is Actiq in an oral transmucosal form.  Janssen pushes Duragesic patches, and generic injections are available as well. 

In the 14 studies I was able to find for pain, sedation, and/or anesthetic induction, compared to non-narcotic pain relievers, fentanyl was inferior six times, equally effective but with more side-effects twice, and equally effective six times.  Fentanyl has never been shown to be better than non-narcotic alternatives.  Thus, fentanyl's box score is 0 wins, 9 ties, and 11 losses.  Fentanyl is a loser.  Fentanyl did sometimes help as an add-on in epidural anesthesia compared to placebo, but many other studies found it of no added value and the added value, if present, was relatively minor.  It and other narcotics don't ever appear necessary for surgery.  It is immoral to needlessly subject another human being to highly addictive narcotics. 

In the insane rush to reap profits from pushing narcotics, the Alza Corporation (Johnson & Johnson) has resubmitted an application to the FDA (11/30/05) for a iontophoretic fentanyl HCl patient-activated transdermal system.  Johnson and Johnson hopes to rush through the application under the Prescription Drug User Fee Act (PDUFA) in just six months.  Johnson & Johnson has been very careful not to compare its patch to non-narcotic pain relievers.  It is almost certainly inferior and carries with it a real risk of leading patients into addiction.  

Johnson & Johnson is also pushing more narcotics into Europe, convincing the lackadaisacal European Committee for Medicinal Products for Human Use of the European Medicines Agency for a positive response in October, 2005.  Wall Street is closely following the developments with reports on CNN Money, Morningstar, Forbes, and elsewhere.  The fentanyl patch is unethical since it provides inferior analgesia, has never been compared to non-narcotics, and is highly addictive.  Also, medical schools like Thomas Jefferson University and the University of Pittsburgh have completed unethical research for Johnson & Johnson by comparing this highly addictive drug only to narcotics even though numerous non-narcotic pain treatments have been proven to relieve pain post-op pain very effectively and often better than narcotics.  

I have found the Thomas Jefferson lead anesthesiologist, Dr. Viscusi, open-minded, but poorly informed.  In his practice, he actually uses non-narcotics very frequently along with narcotics to reduce the amount of narcotics used.  Since narcotics are poor pain relievers, this is a very effective strategy and worthy of some praise.  However, Viscusi has never researched nor apparently used non-narcotics alone, despite extensive research showing that they do very well without any added narcotics.  

For Johnson & Johnson, it's all about money.  The FDA will allow placebo comparaison and that's the easiest way to make sure that Johnson & Johnson gets its narcotic drug license.  Narcotics is a dirty business.  Shame on the people at Johnson & Johnson for being involved.

How IRBs and the university research ethics boards approved these studies is beyond me.  They have either been negligent in failing to do a literature search on double-blind studies involving fentanyl or must realize that the manufacturer refuses to allow a non-narcotic comparator in order not to make their narcotic look bad.  A literature search takes about two hours worth of work and should be done by every IRB and ethics board for every research proposal as a check on the diligence or honesty of the physicians wanting to do any study.  Obviously, this website should prove to you, if you had any doubt, that physicians can't be trusted until each has earned that trust and no one should ever be completely trusted.  IRBs should know about the many studies showing non-narcotics as good or better.  If they don't know, why don't they know?  They deprive physicians and their patients of the knowledge on how this highly addictive narcotic matches up to non-narcotic alternatives and, thus, will considerably increase narcotic use and narcotic addiction.  The FDA and the many in Congress sold out long ago to the pharmaceutical industry.  

If a doctor wants to give you fentanyl (Duragesic and others), print out this webpage and give it to him.  If he still insists on giving you a narcotic, get another doctor.  If a doctor gave you fentanyl and you became addicted and suffered some unfortunate consequence, the doctor and the narcotic manufacturer could be liable for malpractice.  Also, consider whether you should report the doctor to the state licensing board.  In view of the research, prescribing fentanyl is or at least should be ruled malpractice.  I have had one recent patient turned into a fentanyl addict by a physician giving it to her for back pain.  She was lucky being successful after an expensive, taxpayer-funded rehab program.  I average one patient a month turned into narcotic addicts by Pennsylvania physicians.  

Doctors are responsible for knowing whether or not narcotics are necessary.  This research is readily available to anyone with a computer and an internet connection.  Just go to Pubmed, and enter "fentanyl and double-blind."  

Bronchoscopy: Patient-Controlled Propofol Sedation with Ketamine is Superior to with Alfentanil: In a DB study of 276 patients undergoing fiberoptic bronchoscopy, patient-controlled sedation with propofol and ketamine resulted in a more stable systolic arterial pressure than with PCS with propofol and alfentanil for whom pressure decreased. Propofol/ketamin resulted in more patient satisfaction (9.5 vs. 9.0, P < 0.05) and amnesia (82% vs. 61%, P < 0.01). Comparison of alfetanil and ketamine in combination with propofol for patient-controlled sedation during fiberoptic bronchoscopy. Hwang J, et al. Seoul National University Bundang Hospital, Sungnam, South Korea. Acta Anesthes Scand 2005 Oct;49(9):1334-8.

Children: Dental Extraction Surgery: Sufentanil No Better than Non-Narcotic Ketamine: In a DB study of 50 children ages 5-7 having 6 or more teeth extracted, intranasal sufentanil and intranasal midazolam before anesthesia did no better for ease of administration, speed of onset, degree of sedation, or postoperative analgesia, when compared with intranasal ketamine and intranasal midazolams. Intranasal sufentanil/midazolam versus ketamine/midazolam for analgesia/sedation in the pediatric population prior to undergoing multiple dental extractions under general anesthesia: a prospective, double-blind, randomized comparison. Roelofse JA, et al. University of Stellenbosch. Anest Prog 2004;51(4):114-21.

Children: Hypospadias Surgery: Alfentanil Inferior to Ketamine and No Value as Add-On Either: In a DB study of 109 boys ages 1-9 undergoing hypospadias repair, single dose alfentanil (20 microg/kg) given caudally was not as good as a single dose of ketamine (0.5 mg/kg) alone for pain relief and sedation with alfentanil requiring more and earlier additional analgesia with paracetanol 15 mg/kg (p<0.001 and p=0.009).  Adding alfentanil to ketamine did not improve the benefits of ketamine alone. The comparison of caudal ketamine, alfentanil and ketamine plus alfentanil administration for postoperative analgesia in children. Ozbek H, et al. Cukurova University, Adana, Turkey. . Pediatr Anesth 2002 Sep;12(7):610-6.

Children: Out-Patient Surgery: Ketamine as Good as Remifentanil Before Anesthetic Induction: In a DB study of 75 children ages 1-7 undergoing out-patient surgery, IV remifentanil 1 mcg/kg was compared to IV ketamine 0.7 mg/kg or placebo before anesthetic induction. Anesthesia was induced with propofol and maintained with O2-N2O-sevoflurane. The required induction dose of propofol was lower for remifentanil and ketamine compared to placebo. After tracheal intubation, heart rate and blood pressure were better attenuated with remifentanil than with ketamine or placebo. In the recovery room, children in the placebo group received more doses of oxycodone than the other two groups but this did not reach statistical significance. There were no differences between the groups in achieving predetermined recovery end-points, attaining full points on the Steward score or in the well being at home. Comparison of remifentanil versus ketamine for paediatric day case adenoidectomy. Tarkkila P, et al. Helsinki University Central Hospital, Finland. Acta Anaesthesiol Belg. 2003;54(3):217-22. Ed: Oxycodone was used as the rescue medication in this study.  However, extensive research suggests that several non-narcotics would have done better.

Children: Urologic or Abdominal Surgery: Fentanyl Not Needed for Epidural Anesthesia: In a DB study of perioperative epidural levobupivacaine with and without fentanyl in 120 children ages 6-months to 12 years undergoing urologic or abdominal surgery with epidural solutions as a continuous infusion for 24 h of 0.125% levobupivacaine; 0.0625% levobupivacaine; 1 mug/ml fentanyl; or the combination, 0.0625 levobupivacaine and 1 mug/ml fentanyl, the time to the first dose of rescue analgesia in the first 10 h was less in the plain fentanyl group (P < 0.044). All other effects were similar among the four groups. The plasma concentration of levobupivacaine increased during the infusion period, reaching a maximum of 0.76 mug/ml in the 0.125% group and 0.48 mug/ml in the 0.0625% group by 24 h. The plasma concentration of fentanyl also increased steadily, reaching a maximum concentration of 0.37 ng/ml by 24 h. The authors conclude that 0.0625% levobupivacaine without fentanyl is an effective perioperative epidural solution in children. Efficacy, safety, and pharmacokinetics of levobupivacaine with and without fentanyl after continuous epidural infusion in children: a multicenter trial. Lerman J, et al. Children's Hospital of Buffalo, New York. . Anesthesiology. 2003 Nov;99(5):1166-74. Ed: An opiate was used in this study as the rescue medication, but research suggests that non-narcotics would have done better.

Children: Tonsillectomy: Ketorolac as Good as Fentanyl for Pain: In a DB study of 57 children, IV ketorolac (1 mg/kg) was as effective at pain control as fentanyl (2 microg/kg) during a standardized general anaesthetic with propofol infusion. The incidence of PONV was low and equal in both groups. Postoperative pain scores were equal at all stages of followup. Intraoperative ketorolac is an effective substitute for fentanyl in children undergoing outpatient adenotonsillectomy. Keidan I, et al. Sackler Faculty of Medicine, Tel Aviv University, Israel. . Pediatr Anesth 2004 Apr;14(4):318-23.

Epidural in Arthroscopy: Fentanyl Epidural Improves Speed of Sensory/Motor Block by Only 4-5 Minutes with More Side-Effects: In a DB study of 45 young adults undergoing knee arthroscopic surgery, those given 100 mcg epidural fentanyl with their epidural 15 mL of 1% ropivacaine had slightly faster onset of sensory block compared to 100 mcg of IV fentanyl or normal saline control (13 min. vs. 16 min, vs. 17.7 min, p<.05) at T10. The onset times of motor block were also a little faster (12 and 24 min) vs. IV fentanyl (17 and 31 min, P < 0.05) or Control (18 and 33 min, P < 0.05). There was no difference in the incidence of shivering among the three groups. Pruritus occurred 20% with epidure and 7% with IV fentanyl. Onset of sensory and motor blocks during epidural ropivacaine anesthesia without significant fentanyl-related side effects. Epidural fentanyl speeds the onset of sensory and motor blocks during epidural ropivacaine anesthesia. Cherng CH, et al. Tri-Service General Hospital, Taipei, Taiwan. . Anest Analg 2005 Dec;101(6):1834-7. Ed: Exposing another human being to the addictive risk of a powerful dose of narcotics in order to save 4-5 minutes is wrong.  Fentanyl has no place in epidural anesthesia.  

Epidural: C-Sections: Sufentanil Did Add Significant Pain Relief to Ropivacaine Alone: In a DB study of 60 women undergoing C-sections, 120 mg ropivacaine 1%, or 120 mg ropivacaine plus 10 microg or 20 microg sufentanil was injected with additional epidural ropivacaine if necessary. The onset time for the sensory block was not significantly different among the groups. Also, VAS scores at delivery did not differ significantly between the plain ropivacaine 1% group (18 mm), the 10-microg sufentanil group (1 mm), and the 20-microg sufentanil group (6 mm). The total dose of ropivacaine was slightly higher in the plain ropivacaine 1% group (145 mg) compared to the patients receiving additional 10 microg sufentanil (130 mg, P = 0.02) or 20 microg sufentanil (129  mg, P = 0.01). The incidence of maternal side-effects and neonatal outcome were similar in all groups. Ropivacaine 1% alone provided sufficient analgesia. Sufentanil addition did not significantly improve the quality of epidural anaesthesia with ropivacaine 1.0% for Caesarean section. Epidural ropivacaine 1% with and without sufentanil addition for Caesarean section. Bachmann-Mennenga B, et al. Klinikum Minden, Germany. . Acta Anesthes Scand 2005 Apr;49(4):525-31. Ed: In this study, pain with ropivacaine alone was quite mild.  If rescue medication was needed, it could be easily provided by a non-narcotic medication.

Epidural in Labor: Fentanyl Not Needed; High Dose Harms Newborn, Reduces Successful Breastfeeding: In a DB study of 177 women who previously breast-fed a child and who requested labor epidural analgesia, the children of those in the no fentanyl group did non-significantly better than the intermediate-dose fentanyl group (intent to administer between 1 and 150 mug epidural fentanyl) and significantly better than the high-dose epidural fentanyl group (intent to administer > 150 mug epidural fentanyl). Mothers is the high-dose fentanyl reported more difficulty breast-feeding (21%) than women who were randomly assigned to receive an intermediate fentanyl dose (10%), or no fentanyl (10%)(P = 0.09). Neurobehavior scores were lowest in the infants of women who were randomly assigned to receive more than 150 mug fentanyl (P = 0.03). At 6 weeks postpartum, more high-dose epidural fentanyl women were not breast-feeding (17%) than women who were randomly assigned to receive either an intermediate fentanyl dose (5%) or no fentanyl (2%) (P = 0.005). Effect of Labor Epidural Analgesia with and without Fentanyl on Infant Breast-feeding: A Prospective, Randomized, Double-blind Study. Beilin Y, et al. Anesthesiol 2005 Dec;103(6):1211-1217.

Epidural in Labor: Bupivacaine Equal Pain Relief, Fewer Side-Effect, and Most Satisfaction: In a DB study of 90 mothers with term, uncomplicated pregnancies comparing intermittent bolus epidural analgesia (bupivacaine + fentanyl), patient-controlled epidural analgesia (bupivacaine + fentanyl), or patient-controlled epidural analgesia (bupivacaine), the intermittent bolus epidural analgesia group felt they could influence labor most (p = 0.03), and in the interview they expressed most satisfaction. In this group, the total drug utilization was smallest (bupivacaine: p <0.0001 comparing all groups, fentanyl: p = 0.03 comparing the two fentanyl-receiving groups). No differences in pain occurred. Vomiting (p = 0.04) and pruritus (p <0.0001) were more common or more severe in the groups receiving fentanyl. Patient-controlled epidural analgesia in labor does not always improve maternal satisfaction. Nikkola E, et al. Turku University, Finland. . Acta Obstet Gyn Sand 2006;85(2):188-94. (loss)

Epidural in Labor: Sufentanil Added No Benefit to Bupivacaine: In a DB study of 40 women in labor using a combined spinal-epidural technique, intrathecal sufentanil 10 mcg did no better than 12 ml of 0.25% epidural bupivacaine. Pham LH, et al. Harvard. J Clin Anesth 1996;8:497-501. 

Epidural Thoracic Analgesia: Fentanyl No Better Pain Relief than Added Bupivacaine: In a DB study of 24 patients after major abdominal surgery, adding fentanyl 50 mcg or bupivacaine 50 mg or fentanyl 50 with bupivacaine 25 or 12.5 made no difference with pain relief with bupivacaine being very slightly better. However, mean arterial pressure did decrease more with the bupivacaine. Torda TA, et al. Sydney Australia. Br J Anaesth 1995;74:35-40.

Epidural Thoracic Analgesia: Bupivacaine with Isoflurane did as Well as Conventional Anesthesia with Isoflurane and IV Fentanyl: In a DB study of 30 patients undergoing thoracotomy, there was no significant difference in pain relief, although there was a non-significant trend favoring fentanyl. Aguilar JL, et al. Barcelona. Rev Esp Anest Reanim 1994;41:278-81.

Epidural Thoracic Analgesia: Sufentanil No Better than Bupivacaine with Adrenaline: In a DB study of 30 patients undergoing lateral thoracotomy, there was no difference in pain relief between sufentanil 50 mcg and bupivacaine 0.5% with adrenaline 5 mcg/ml (dose 40 mg) although both were superior to placebo. Supplemental fentanyl was given to 4 of the fentanyl vs. 1 of the bupivacaine patients. Hypotensive episodes occurred in 50% of sufentanyl and 100% of bupivacaine patients. Haak-van der Lely F, et  al. Anesthesia 1994;49:116-8.

Epidural Thoracic Analgesia: Fentanyl No Added Value to Ropivacaine Alone: In a DB study of 30 women undergoing abdominal surgery for gynecologic tumors, ropivacaine 0.375% did as well at suppressing pain as pupivacaine 0.125% with sufentanil. Side-effects were similar. Gottschalk A, et al. Reg Anesth Pain Med 2002;27:367-73. A lower dose of ropivacaine 0.2% did not do as well. Anesth Analg 2002;95:1344-50 and Anesth Analg 2001;93:1587-92, although it was as effective for everything except pain on mobilization in Anasth Intensiv Notfallmed 2001;36:219-23. Tenoxicam can also improve pain relief in TEA with bupivacaine. Anaesth Intensive Care 2002;30:160-6. Epinephrine can as well. Anesth Analg 2002;94:1598-605. TEA with bupivacaine and isoflurane did better than IV anesthesia with propofol and fentanyl. Aesth Analg 2001;92:848-54.

Epidural: Total Gastrectomy: Fentanyl No Better Pain Relief than Ketamine, But More Low Blood Pressure: Beograd. Acto ChirIugosl 1999;46(1-2):47-52  

Epidural: Fentanyl Narcotic Added No Benefit to Bupivacaine Alone in Coronary Bypass Surgery: In a DB study of 60 patients undergoing off-pump coronary artery bypass grafting, thoracic epidural anesthesia with bupivacaine 0.125% alone, did just as well as bupivacaine 0.125% with fentanyl 3 microg/ml or bupivacaine 0.125% with clonidine 0.6 microg/ml. Pain control was very good and was not significantly different between the groups using similar infusion rates after surgery. Paraesthesia in dermatomes T1 or C8 occurred equally in all three groups. There was no neurological complication related to TEA in this study. Comparison of three different epidural solutions in off-pump cardiac surgery: pilot study. Olivier JF, et al. l'Universite de Montreal, Canada. Br J Anaesth 2005 Nov;95(5):685-91.

Head Injury (Severe): Ketamine as Good as Sufentanil Combined with Midazolam in Maintaining Perfusion: In a DB study of patients with severe head injury being mechanically ventilated, sedation with a continuous infusion of ketamine-midazolam was just as effective in maintaining intracranial pressure and cerebral perfusion as a continuous infusion of sufentanil-midazolam. The requirements of neuromuscular blocking agents, propofol, and thiopental were similar. Safety of sedation with ketamine in severe head injury patients: comparison with sufentanil. Bourgoin A, et al. Marseille University Hospital System, France. Crit Care Med 2003 Mar;31(3):711-7.

Hysterectomy (Abdominal): Fentanyl Inferior to Clonidine as Add-on to Bupivacaine: In a DB PC study of 75 women undergoing abdominal hysterectomy, bupivacaine combined with clonidine or fentanyl in patient-controlled epidural analgesia found both drugs superior to placebo, but nausea was lower and satisfaction of patients higher with clonidine (p<0.05). Topcu I, et al. Anasth Intensiv Notfallmed Schmerz 2005;40:521-5.

Induction with Propofol Better with Ketamine than Fentanyl: In a DB PC study of 90 adults undergoing surgery, ketamine 0.5 mg/kg before induction with propofol improved the hemodynamic profile better than fentanyl 1 mcg/kg with less prolonged apnea and had and better laryngeal mask airway insertion conditions than normal saline. Randomized double-blind comparison of ketamine-propofol, fentanyl-propofol and propofol-saline on haemodynamics and laryngeal mask airway insertion conditions. Goh PK, et al. University Malaya Medical Centre, Kuala Lumpur, Malaysia. Anesthes Intensive Care 2005 Apr;33(2):223-8.

Injection Pain of Diazepam: Relieved Much Better by Ketamine Than by Fentanyl: In a DB study of 150 patients undergoing IV diazepam injections as part of surgery, ketamine 10 mg did much better than fentanyl in reducing the pain of diazepam injection (p < 0.001). The effect of ketamine and fentanyl in reducing the pain of diazepam injection. Khosravi MB, et al. Shiraz University, Iran. . Middle East J Anesth 2004 Oct;17(6):1093-8.

Injection Pain of Propofol: Lidocaine Better than Fentanyl or Morphine and as Good as Meperidine with Fewer Side-Effects: In a DB PC study comparing I.V. pretreatment with fentanyl 150 microg, morphine 4 mg, meperidine 40 mg, 2% lidocaine 3 mL or placebo in reducing propofol injection pain in 175 patients, lidocaine and meperidine significantly reduced propofol injection pain more than placebo (P < 0.05), but there were more side effects in the meperidine group. Fentanyl and morphine reduced the intensity of propofol injection pain (P < 0.05) and had some effect in reducing the incidence of propofol injection pain, but the difference did not reach statistical significance. The analgesic effect of fentanyl, morphine, meperidine, and lidocaine in the peripheral veins: a comparative study. Pang WW, et al. Show-Chwan Memorial Hospital, Changhua, Taiwan. Anesth Analg 1998 Feb;86(2):382-6.

Injection Pain of Rocuronium: Lidocaine and Ondonsetron Both More Effective than Fentanyl: In a 250-patient DB PC study trying to minimize the pain of rocuronium injection, lidocaine 30 mg did better than narcotics tramadol 50 mg, and fentanyl 100 mcg with 74% vs. 60% vs. 30% experiencing no pain vs. 20% for placebo and 56% for ondansetron 4 mg. Researchers concluded that lidocaine was the most effective, and fentanyl the least. The prevention of pain from injection of rocuronium by ondansetron, lidocaine, tramadol, and fentanyl. Memis D, et al. Trakya University, Edirne, Turkey. . Anest Analg 2002 Jun;94(6):1517-20

Lithotripsy: Ketorolac Did as Well for Pain with Many Fewer Side-Effects and Much Faster Discharge: In a DB study of 60 patients undergoing extracorporeal shock wave lithotripsy, IV ketorolac 60 mg 30 min before ESWL did as good as relieving pain and with fewer side-effects and earlier discharge time than fentanyl 100 mcg 3 min before ESWL. All patients received 2.5 mg midazolam IV 3 min before ESWL for intraoperative sedation. The incidence of oxygen supplement was much lower in ketorolac group (1/30) compared with that of fentanyl group (20/30), P < 0.01. The frequency of dizziness was much lower in ketorolac group (1/30) than that in fentanyl group (25/30), P < 0.01. Three patients in fentanyl group complained of nausea, but none did in ketorolac group. The discharge time from PAR was much shorter in ketorolac group (15 min) than that in fentanyl group (50 min), P < 0.01. Effects of intravenous ketorolac and fentanyl combined with midazolam on analgesia and side effects during extracorporeal shock wave lithotripsy. Yang, CP, et al. National Defense Medical Center, Taipei, Taiwan, R.O.C., Acta Anest Sin 2002 Mar;40(1):9-12.

Lithotripsy: Tenoxicam Better than Fentanyl or Tramadol with Fewer Side-Effects: In a DB study of 120 patients undergoing, neither IV fentanyl 1 microgram/kg, nor IV tramadol HCl 1.5 mg/kg did as well as tenoxicam 0.3 mg/kg when given before lithotripsy. Nausea or vomiting were significantly higher for fentanyl and tramadol vs. tenoxicam (15.0% and 25.0% vs. 0.0%). Oxygen saturation in fentanyl group was also significantly lower than the other two groups (p < 0.01). Prospective and randomized trial of intravenous tenoxicam versus fentanyl and tramadol for analgesia in outpatient extracorporeal lithotripsy. Chia YY, et al. Taiwan, R.O.C. Acta Anesth Sin 1998 Mar;36(1):17-22.

Spinal Anesthesia Study: Levobupivacaine Alone Did Just as Well; Fentanyl Added No Benefit: Fentanyl has been used as an adjunct to racemic bupivacaine in spinal anaesthesia. In a DB study of 50 patients undergoing urological surgery with spinal anesthesia, 2.6 mL of 0.5% levobupivacaine alone did just as well as 2.3 mL of 0.5% levobupivacaine with fentanyl 15 microg in 0.3 mL. The study solution was injected into the subarachnoid space at the L3-L4 interspace. There were no significant differences between the two groups in the haemodynamic changes, and quality of sensory and motor block. Levobupivacaine and fentanyl for spinal anaesthesia: a randomized trial. Lee YY, et al. Kwong Wah Hospital, Hong Kong SAR. . Eur J Anesthiol 2005 Dec;22(12):899-903.

Surgery: Esmolol Better than Fentanyl for Heart Rate Control: In a DB PC study of 60 patients undergoing elective surgery with laryngoscopy and endotracheal intubation comparing 10 ml saline 30 seconds before anesthesia induciton to fentanyl 2 mg/kg or esmolol 2 mg/kg, fentanyl 2 mg/kg 2 minutes prior to laryngoscopy and intubation failed to protect against elevation of both the heart rate and systolic blood pressure, whereas esmolol at 2 mg/kg provided consistent and reliable protection against the increase of heart rate but not arterial blood pressure. Efficacy of fentanyl and esmolol in the prevention of haemodynamic response to laryngoscopy and endotracheal intubation. Hussain AM, et al. Aga Khan University Hospital, Karachi, Pakistan. . J Coll Physicians Surg Pak 2005 Aug;15(8):454-7.

Surgery: Carpal Tunnel Axillary Plexus Block: No Difference Clonidine vs. Sufentanil vs. Tramadol: In a DB PC study of 80 patients undergoing carpal tunnel release performed under axillary plexus block with ropivacaine 0.75% 20 ml comparing tramadol 100 mg, clonidine 1.5 g/kg, sufentanil 20 g vs. placebo, the onset time of anesthesia was sufenanil 11 min; clonidine 12 and tramadol 14 min vs. placebo 20 min. Similar results were obtained for duration of anesthesia and analgesia with the 3 medications each superior to placebo. Only one placebo patient needed surgical infiltration. Adjuvants in the axillary brachial plexus blockade. Comparison between clonidine, sufentanil and tramadol. Antonucci S. Popoli (Pescara), Italy.

Unethical Research

Thomas Jefferson Medical School Helps Push Narcotics with Placebo Trial: The fentanyl HCl PATS is a needle-free, credit card-sized, preprogrammed system that is applied to the patient's upper outer arm or chest. In a DB PC study of 484 adults in the postanesthesia care unit after major surgery, patients were first titrated with opioids and then randomized to fentanyl HCl PATS 40 microg or placebo for 24 hours. Supplemental IV fentanyl was available to patients upon request in both treatment groups for the first 3 hours. The primary efficacy end-point was the percentage of patients who discontinued participation in the study because of inadequate analgesia. Fewer patients receiving the fentanyl HCl PATS discontinued because of inadequate analgesia compared with placebo (29% versus 60%; P < 0.0001). Mean last pain intensity scores were 3.5 and 5.4 for the fentanyl HCl PATS and placebo groups, respectively. Patients (73.4%, PGA) and investigators (72.1%, IGA) considered the fentanyl HCl PATS a good or excellent method of pain control, but they were comparing it to sugar pills, not real non-narcotic pain relievers. An iontophoretic fentanyl patient-activated analgesic delivery system for postoperative pain: a double-blind, placebo-controlled trial. Viscusi ER, et al. Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. . Ed: This is the study Thomas Jefferson was paid to do for Johnson & Johnson to help them get their FDA approval to push narcotics.  It was unethical in my opinion not to include a non-narcotic comparator, since Thomas Jefferson knew that its study would be used to promote narcotics to physicians and patients and since consumers have a right to know if fentanyl is really as good as the drug salesman claims.  Thomas Jefferson knew or should have known that fentanyl has never been shown to be superior to non-narcotics and that it is immoral to needlessly subject humans to narcotics.  Many non-narcotics have been shown as good or better than highly addictive narcotics for post-op pain.

Unethical Study by University of Pittsburgh Comparing Highly Addictive Narcotic Only to Placebo for Post-Op Pain: In a DB PC study of 205 patients undergoing major abdominal, orthopedic or thoracic surgery, a patient-controlled transdermal system (PCTS) under development consists of a preprogrammed, self-contained drug-delivery system that uses electrotransport technology (E-TRANS, ALZA Corp, Mountain View, CA) delivering 40 micro g of fentanyl HCl over 10 min per on-demand dose for patient-controlled analgesia (PCA) was better than placebo. Only, 25% of patients in the fentanyl HCl PCTS 40 microg group withdrew from the study because of inadequate analgesia in the first 3 hours vs. 40% of the placebo group (P < 0.05). The fentanyl HCl PCTS 40 micro g was associated with lower VAS scores and higher mean patient and investigator global assessment scores compared with placebo. The safety and efficacy of a fentanyl patient-controlled transdermal system for acute postoperative analgesia: a multicenter, placebo-controlled trial. Chelly JE, et al. University of Pittsburgh Medical Center, Pennsylvania. . Anesth Analg 2004 Feb;98(2):427-33. 

   Ed: These researchers must know or should have known that many studies have proven that non-narcotics work as well or better than narcotics for post-op pain.  They gave into the wishes of the ALZA/Johnson & Johnson Corporation to compare this highly addictive narcotic only to placebo, thus depriving future physicians and patients of the absolutely necessary knowledge of how this pain reliever compares to non-narcotics. This is defective and unethical research in my opinion. It helps a narcotic manufacturer push an inferior, highly addictive product and inevitably injury countless future patients through unnecessary addiction.  In the field of law, the use of a placebo would be considered a straw man.  It proves nothing and is easy to beat.  In real life, a doctor isn't faced with the decision of using a placebo or a narcotic.  The decision is whether to use a narcotic or a non-narcotic.  Doing better than placebo proves absolutely nothing of value for treating pain.  Doctors and patients need to know how this dangerous narcotic compares to available and much safer non-narcotics.  I am also investigating whether these patients were even told that effective non-narcotic were available if they chose not to participate in the study.  Not informing them could be considered malpractice.  Informing them should be required by law.

Florida Department of Law Enforcement records showing that abuse of the fentanyl patch resulted in the deaths of 115 people in Florida in 2004.

Thomas E. Radecki, M.D., J.D.

modern-psychiatry.com