postoperative analgesia: transdermal - anfofo · 2015. 9. 14. · 2 esa congress glasgow 2003:...

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ESA Congress Glasgow 2003: Transdermal Postoperative Analgesia

Postoperative Analgesia:Transdermal

Klaus A. LehmannDepartment of AnaesthesiologyUniversity of Cologne, Germany



Inefficacy of high-dose transdermal fentanyl in a patient with neuropathic pain, a case report.Bleeker et al.; Eur J Pain 5:325 (2001)

Patient, after admittance, with a total of 34 fentanyl TTS patches of 100 g/h located on the anterior and posterior body surface


Transdermal fentanyl for the treatment of pain after major urological operationsLehmann KA et al.; Eur J Clin Pharmacol 41:17 (1991)

50 patients, 75 g/h fentanyl vs. placebo + iv fentanyl PCA:high acceptance in both groups, lower respiratory rates in late hours (8-10) with fentanyl;PCA supplementation obviously necessary.


References (1): Recent Publications

• Gellasch KL et al.: Comparison of transdermal administration of fentanyl versus intramuscular administration of butorphanol for analgesia after onychectomy in cats. J Am Vet Med Assoc 2002; 220:1020

• Wilkinson AC et al.: Evaluation of a transdermal fentanyl system in Yucatan miniature pigs. Contemp Top Lab Anim Sci 2001;40:12

• Glerum LE et al.: Analgesic effect of the transdermal fentanyl patch during and after feline ovariohysterectomy. Vet Surg 2001;30:351


intravenous

transdermal

transmucosal,intranasal

2


0

10

20

30

40

50

60

70

80

90

100

cum

ulat

ive

dose

(mg )

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34time from PCA start (hrs)

PCA Piritramid

Intravenous PCA:individual variability,fast onset of action titration

The PCA-Principle:

WYNIWYGWhat you need is what you get.


Transdermal Fentanyl

0.0

1.0

2.0

3.0

fent

anyl

pla

s ma

conc

entra

tion s

(ng/

ml)

0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72

treatment hours

from Gourlay et al. (1991)

delay, steady state, decay (75 µg/h)

hours

delay time 12,7 (1,2-31,3)

steady state concentrations 12-24

decay time 16,1 (2,3-22,3)

50 g/h 18,975 g/h 16,7


Opioids: Transdermal Application

Passive• Dihydroetorphine• Buprenorphine• Fentanyl• Morphine

(de-epithelialised skin)

Active• Buprenorphine• Fentanyl• Hydromorphone• Nalbuphine• Morphine• Sufentanil


Partial versus full agonists for opioid-mediated analgesia –focus on fentanyl and buprenorphineZuurmond et al; Acta Anaesthesiol Belg 53:193 (2002)

Rat paw withdrawal after low and high thermal stimulation (ED50 in g/kg)

Low intensity

ED50

High intensity

ED50

Ratiohigh / low

ED50

Fentanyl 15 32 2.3Buprenorphine 16 152 24Morphine 360 2200 11.8

F

B


Postop. pain control by transdermal fentanyl. Comparison of two dosages to a fixed-interval i.m. morphine regimen …Cigada et al.; Minerva Anestesiol 58:1323 (1992)

• 21 patients, transdermal fentanyl 70-100 g/h, applied 1 h before orthopaedic surgery, vs. i.m. morphine 150 g/kg every 6 h

• no significant difference in pain intensity

• significantly lower respiratory rates with trans-dermal fentanyl, isolated significant differences in peripheral haemoglobin saturations

No clinically important adverse side effects were found in any of the study groups.


Transdermal fentanyl for postoperative pain management in patients recovering from abdominal gynecologic surgerySevarino et al.; Anesthesiology 77:463 (1992)

93 patients, 25 or 50 g/h transdermal fentanyl vs. placebo + iv morphine PCA: less morphine consumption with TTSF

.. the only benefit noted with this form of analgesic therapy ..

mov

emen

t

3


Continuous administration of fentanyl for postoperative pain: epidural, intravenous and transdermal routes …Van Lersberghe et al.; J Clin Anesth 6:308 (1994)

54 patients, 75 g/h fentanyl by 3 routes at constant rate provided almost equal amount of analgesia, but con-tinuous epidural application im-paired spontaneous respiration.


Transdermal fentanyl after abdominal hysterectomy …Sandler et al.; Anesthesiology 81:1169 (1994)

Transdermal fentanyl 50 or 75 g/h, applied 2 h before surgery to 120 women. Between 5 and 36 h, the TTSF groups had significantly increased abnormal respiratory pattern including apneic episodes.

Although good analgesia is the result of this combination therapy with iv morphine PCA, it is associated with a high incidence of respiratory depression requiring intense monitoring, oxygen supplementation, removal of patches (11%) and naloxone (8%).


Postoperative analgesia and plasma levels after transdermal fentanyl for orthopedic surgery …Van Bastelaere et al.;J Clin Anesth 7:26 (1995)

40 adult patients with transdermal fentanyl 75 g/h or placebo, 72 h observation period. Additional morphine use was significantly lower in the active group. Plasma fentanyl concentrations were in the normal range (1.63 ng/ml).

Fentanyl (20)

Placebo (20)

Hypoventilation 1 0

Decreased oxygen saturation 2 0

Respiratory depression 1 1

Sedation 1 0

Itching 1 0

Nausea 2 0

Urine retention 3 0

Gastroparesis 1 0

Erythema 1 0


Biopharmaceutics of a new transdermal fentanyl deviceFiset et al.; Anesthesiology 83:459 (1995)

Of the 14 male surgical subjects who received postop. transdermal fentanyl (Cygnus device), 3 had clinically significant toxicity, mandating early removal of the device.

The variability in effect of the Cygnus transdermal fentanyl device is appreciably greater than that reported for the currently available Duragesic transdermal device, which is contraindicated for postoperative pain.


Postoperative pain control with a new transdermal fentanyl delivery systemMiguel et al.; Anesthesiology 83:470 (1995)

143 gynecological patients with postop. placebo or fast onset Anaquest transdermal fentanyl 60-80 or 90-100 g/h + M-PCA

Concerns exist regarding the side effects of this new transdermal fentanyl patch.

placebo

60-80

90-100

PCA


Postoperative analgesia with transdermal fentanyl following lower abdominal surgeryBroome et al.; Anaesthesia 50:300 (1995)

81 hysterectomy patients with transdermal fentanyl 25, 50 or 75 g/h vs. placebo. Overall sedation scores were not increased by transdermal fentanyl, but respiratory rates decreased with higher dosage.

TTS fentanyl may be a useful method of providing effective background analgesia in postoperative patients. However, id did not provide sufficient analgesia for use without supplemental iv morphine PCA.

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Respiratory changes during treatment of postoperative pain with high dose transdermal fentanylBülow et al.; Acta Anaesthesiol Scand 39:835 (1995)

Average pulse oximeter readings & mean time with saturation below 90%; ASA I patients undergoing upper abdominal surgery, receiving 100 g/h fentanyl or placebo.

Recruitment was stopped after enrolment of 24 patients, on safety grounds.


Transdermal fentanyl in postoperative painLehmann LJ et al.; Reg Anesth 22:24 (1997)

• 40 ASA I-II patients, 18-69 yr, abdominal surgery

• transdermal fentanyl 50-75 g/h, applied 60 min prior to induction, vs. placebo

• less 36 h postoperative ketorolac or morphine requirements with active treatment

• no clinically relevant respiratory depression reported

• average fentanyl plasma concentrations at 12 and 24 h: 0.98 and 1.22 ng/ml


Transdermal fentanyl system plus im ketorolac for the treatment of postoperative painReinhart et al.; Can J Anaesth 44:377 (1997)

Transdermal fentanyl 70-80 g/h vs. placebo in 92 patients. The active group required less rescue ketorolac, but showed slightly more oxygen desaturation.


Does continuous delivery of transdermal fentanyl affect analgesic efficacy or patient safety ?Sevarino et al.; J Clin Anesth 9:173 (1997)

VAS following TTS Fentanyl in 62 orthopedic patients receiving 50 or 75 g/h or placebo 2 h before induction + morphine PCA

no significant differences


Does continuous delivery of transdermal fentanyl affect analgesic efficacy or patient safety ?Sevarino et al.; J Clin Anesth 9:173 (1997)

Cumulative opioid requirements (TTS fentanyl + PCA morphine equivalents)

no significant advantage to the routine use of continuous transdermal opioid delivery in patients receiving iv PCA


Pharmacokinetics of transdermal fentanyl in the peri-operative period in young childrenPaut et al.; Anaesthesia 55:1202 (2000)

Time course of fentanyl concentrations up to 144 h after application (8 children 18-60 months, single dose 25 g/h for 72 h)

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Perioperative pharmacokinetics of transdermal fentanyl in elderly and young adult patientsThompson et al.; Br J Anaesth 81:152 (1998)

Mean (SEM) plasma fentanyl concentrations in 9 elderly (64-82 yr) and 10 young (25-38 yr) adult patients;TTSF 50 g/h,72 h application

no difference in postop. PCA morphine requirements between groups;2 cases of respiratory depression after 16 and 26 h;transdermal fentanyl not recommended for postoperative use


Active Transdermal Application

• Iontophoresis• Electrophoresis

(Electroosmotic Transport)

• Electroporation(high voltage electric field pulses)

• Phonophoresis, Sonophoresis(Ultrasound)


Iontophoresis

+ -

BH+ A-Cl - Na +


Iontophoresis: an alternative to the use of carriers in cutaneous drug deliverySingh, Maibach; Adv Drug Deliv Rev 18:379 (1996)

Iontophoretic pathways:a) appendageal,b) intercellular


Iontophoresis: Clinical Applicationantibioticsglucocorticoids, antihistaminicspeptides

local anaesthetics• lidocaine, mepivacaine, procaineNSAIDs• diclofenac, ketoprofen, ketorolac, salicylic acid ..opioids• hydromorphone, fentanyl, morphine, sufentanil


Dermal anaesthesia: comparison of EMLA cream with iontophoretic local anaesthesiaIrsfeld et al.; Br J Anaesth 71:375 (1993)

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The iontophoresis of fentanyl citrate in humansAshburn et al.; Anesthesiology 82:1146 (1995)

Mean ± SEM fentanyl concentration vs. time after 120 min iontophoretic fentanyl delivery in different currents (5 adult volunteers)


Fentanyl delivery from an electrotransport system …Gupta et al.; J Clin Pharmacol 38:951 (1998)

E-TRANS: continuous delivery with 100 A for 26 h,additional boluses at t =1 or t = 25 h


Electrically-assisted transdermal delivery of buprenorphineBose et al.; J Control Release 73:197 (2001)

Effect of iontophoresis for 4 h (0.5 mA/cm2) and electroporation (500 V, 10 ms, 20 pulses) followed by passive delivery for 24 h through human epidermis


References (2): Other Drugs

• Hagihara R et al.: A case of effective treatment with clonidineointment for herpetic neuralgia after bone marrow transplantation in a child. Masui 2002;51:777

• Ozaki M et al.: Transdermal ketoprofen mitigates the severity of postoperative sore throat. Can J Anaesth 2001;48:1080

• Azevedo VM et al.: Transdermal ketamine as an adjuvant for postoperative analgesia after abdominal gynecological surgery using lidocaine epidural blockade.Anesth Analg 2000;91:1479

• Owen MD et al: Postoperative analgesia using a low-dose, oral-transdermal clonidine combination: lack of clinical efficacy.J Clin Anesth 1997;9:8


References (3): Nitroglycerine

• Lauretti GR et al.: Double-blind evaluation of transdermal nitroglycerine as adjuvant to oral morphine for cancer pain management. J Clin Anesth 2002;14:83

• Lauretti GR et al.: The effect of transdermal nitroglycerin on spinal S(+)-ketamine antinociception following orthopedic surgery. J Clin Anesth 2001;13:576

• Lauretti GR et al.: Transdermal nitroglycerine enhances spinal neostigmine postoperative analgesia following gynecological surgery. Anesthesiology 2000;93:943

• Lauretti GR et al.: Transdermal nitroglycerine enhances spinal sufentanil postoperative analgesia following orthopedic surgery. Anesthesiology 1999;90:734

• Berrazueta JR et al.: Successful treatment of shoulder pain syndrome due to supraspinatus tendinitis with transdermal nitroglycerin. A double blind study. Pain 1996;66:63


References (4): Mishaps• Frölich MA et al.: Opioid overdose in a patient using a fentanyl

patch during treatment with a warming blanket.Anesth Analg 2001;93:647

• Alsahaf MH, Stockwell M: Respiratory failure due to the combined effects of transdermal fentanyl and epidural bupivacaine/diamorphine following radical nephrectomy.J Pain Symptom Manage 2000;20:210

• Newshan G: Heat-related toxicity with the fentanyl transdermal patch. J Pain Symptom Manage 1998;16:277

• Hardwick WE et al.: Respiratory depression in a child unintentionally exposed to transdermal fentanyl patch.South Med J 1997;90:962

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In vivo iontophoresis of fentanyl and sufentanil in rats …Thysman, Préat; Anesth Analg 77:61 (1993)

• Nevertheless, a major drawback of the transdermal administration, both by iontophoresis or passive diffusion, of a lipophilic compound such as fentanyl or sufentanil is drug accumulation in the skin and its slow release from the cutaneous depot.

• The delivery of the drug could be sustained for several hours after current cutting and/or patch withdrawal.


Transdermal fentanyl citrate … effects on postoperative pulmonary functionMason HH; Am J Crit Care 2:61 (1993)

Current postoperative analgesic therapies that include concomitant use of narcotic agonists and nonsteroidal anti-inflammatory drugs require adjustment of drug dosages to provide adequate pain relief while avoiding drug-induced complications.

postoperative analgesia: transdermal - anfofo · 2015. 9. 14. · 2 esa congress glasgow 2003:...

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