The key to a successful Acute Pain Service is not so much the use of sophisticated drugs and high technology equipment, but an excellent organisational structure and well trained medical and nursing personnel.

3. Fentanyl forFentanyl for
perioperative painperioperative pain
managementmanagement
Dr Alex Yeo Sow Nam

4. The key to a successful Acute Pain
Service is not so much the use of
sophisticated drugs and high
technology equipment, but an excellent
organisational structure and well
trained medical and nursing personnel.

5. Acute Pain Services
“Postoperative Rehabilitation Service”
(H. Kehlet 1995)
Multidisciplinary care of postoperative patients
with utilisation of optimal pain therapy to achieve
reduction of postoperative morbidity, mortality and
hospital stay:
• multimodal pain therapy
• early aggressive mobilisation
• early enteral feeding
• early and organised discharge from hospital

6. Acute Pain Services
“Comprehensive Pain Service”(Cousins1996)
Treatment of in-patients with pain of any
origin in close cooperation with a
multidisciplinary pain clinic:
• postoperative pain
• posttraumatic pain
• subacute pain
• chronic pain
• cancer pain

7. ParacetamolParacetamol
 neglected analgesic
 minimal side effects
 more useful if given regularly
 daily 90 mg/kg (6 g/day – 1 g/4hrs)
 careful in
 Malnourished patients
 Alcoholics
 Hepatic impairment
Standard Operating Procedures, APS, RPH

8. NSAIDsNSAIDs
 Not a routine prescription!
 Extreme care in
 Elderly
 Renal problems
 Expected hypovolaemia/hypotension
 Combination with other renal toxic agents
 Patients in whom bone repair is essential
 If Nil By Mouth: parecoxib 40 mg/BD
 Then naproxen 250-500 mg BD
 If contraindications, celecoxib 100-200 mg BD
 Prescribe time limit for regular intake!
Standard Operating Procedures, APS, RPH

9. Parenteral OpioidsParenteral Opioids
 PCA preferred route of administration
 Intravenous infusion if patient
 Unable to use PCA
– Comprehension
– Mechanics
– Psychology
 Bolus doses better SC than IM
 Discourage IM use!!!!!

10. ’’10 mg morphine10 mg morphine IMIM PRN 4hrly’PRN 4hrly’
Delayed onset of action
Unpredictable absorption
 Site of injection
 Muscle perfusion
Potential for nerve damage
Potential for infection
Discomfort for patient

12. Why then ‘IM” ?Why then ‘IM” ?
Nursing tradition: No IV injections
 Risk of adverse effects?????
Belief: Parenteral is better than oral!
 Why?

13. ’’10 mg morphine10 mg morphine IMIM PRN 4hrly’PRN 4hrly’
Standard dose fits all!
 Too low for many!
 Too strong for others!
Contradicts data on analgesic
requirements!

15. 6 8 10 12 14
Theoretical Relation Between AnalgesicTheoretical Relation Between Analgesic
Drug Level, Dosing Interval, and ClinicalDrug Level, Dosing Interval, and Clinical
ResponseResponse
Pain
Analgesia
Sedation
Ferrante FM, et al. Anesth Analg. 1988;67:457-61.
Analgesicdrug
concentration
Time (hours)
Dose Dose Dose
Dose
Minimum
analgesic
concentration
IM
PCA
IM=intramuscular; PCA=patient controlled analgesia

16. Patient Controlled AnalgesiaPatient Controlled Analgesia
Principles
– Small IV bolus!
– Lockout interval appropriate to route
of administration!
– Patient titrates amount needed against
pain experienced!

17. Principle Concept of TitrationPrinciple Concept of Titration
P a t ie n t e x p e r ie n c e s e ffe c t o f d r u g
D r u g w o r k s
P a t ie n t a d m in is t e r s d r u g
P a t ie n t e x p e r ie n c e s p a in
Good pain relief?
Wait!
Yes No

18. Opioids via PCAOpioids via PCA
 Routinely no background infusion
 Exceptions:
– Previous long-term opioid use
– Established high usage
 No 4 hr dose limit
 5 min lockout time in most cases
Standard Operating Procedures, APS, RPH

19. Pethidine PharmacologyPethidine Pharmacology
Pethidine also has structural similarities to
atropine and other tropane alkaloids and may
have some of their effects and side effects.
Unlike morphine, a potent mu opioid receptor
agonist, pethidine exerts its analgesic effects
by acting as an agonist at the
kappa opioid receptor, primarily.
In addition to its anticholinergic effects, it has
local anesthetic activity related to its
interactions with sodium ion channels
"The cocaine-like behavioral effects of meperidine are mediated by activity at the
dopamine transporter". . Izenwasser, Sari et. Al. European Journal of Pharmacology
(January/February 1996). 297 (1-2): 9–17

20. Pethidine PharmacologyPethidine Pharmacology
 It has also been associated with cases of
serotonin syndrome, suggesting some interaction with
serotonergic neurons,
 It is more lipid-soluble than morphine, resulting in a
faster onset of action.
 Its duration of clinical effect is 120–150 minutes
although it is typically administered in 4-6 hour
intervals. Pethidine has been shown to be less
effective than morphine, diamorphine or
hydromorphone at easing severe pain,
"Meperidine: A Critical Review". Latta, Kenneth S.; Brian Ginsberg, Robert
L. Barkin American Journal of Therapeutics (Lippincott Williams &
Wilkins) January/February 2002). 9 (1): 53–68.

21. Pethidine's apparent in vitro efficacy as an "
antispasmodic" is due to its local anesthetic
effects. It does not, contrary to popular
belief, have antispasmodic effects in vivo.
"Meperidine and Lidocaine Block of Recombinant Voltage-
Dependent Na+
Channels: Evidence that Meperidine is a Local
Anesthetic". Anesthesiology 91 (5): 1481–1490. Wagner, Larry E.,
II; Michael Eaton, Salas S. Sabnis, Kevin J. Gingrich (November
1999)

22. Pethidine is no more effective than morphine
at treating biliary or renal pain, and its low
potency, short duration of action, and unique
toxicity (i.e., seizures, delirium, other
neuropsychological effects) relative to other
available opioid analgesics have seen it fall out
of favor in recent years for all but a very few,
very specific indications.
"Subjective, Psychomotor, and Physiological Effects of Cumulative Doses of Opioid
µ Agonists in Healthy Volunteers". The Journal of Pharmacology and Experimental
Therapeutics (American Society for Pharmacology and Experimental Therapeutics)
Walker, Diana J.;et al (June 1999). 289 (3): 1454–1464

23. Australia, has put strict limits on its use.
Nevertheless, some physicians continue to use it
as a first line strong opioid.
Use of pethidine for pain management in the emergency department:
a position statement of the NSW Therapeutic Advisory Group"
New South Wales Therapeutic Advisory Group.. Retrieved 2007-
01-17

24. Adverse effectsAdverse effects
 opioids as a class: nausea, vomiting, sedation,
dizziness, diaphoresis, urinary retention and
constipation. Unlike other opioids, it does not cause
miosis. Overdosage can cause muscle flaccidity,
respiratory depression, obtundedness, cold and
clammy skin, hypotension and coma. A narcotic
antagonist such as naloxone is indicated to reverse
respiratory depression.
 Serotonin syndrome has occurred in patients
receiving concurrent antidepressant therapy with
selective serotonin reuptake inhibitors or monoamine
oxidase inhibitors.

25. Adverse effectsAdverse effects
Convulsive seizures sometimes observed in
patients receiving parenteral pethidine on a
chronic basis have been attributed to
accumumulation in plasma of the metabolite
norpethidine (normeperidine).
Fatalities have occurred following either
oral or intravenous pethidine overdosage.
"A reassessment of trends in the medical use and abuse of opioid
analgesics and implications for diversion control: 1997-2002". J
Pain Symptom Manage 2004, 28 (2): 176–188. Gilson AM, Ryan
KM, Joranson DE, Dahl JL

26. Meperidine is alive and well in the new millennium: evaluation
of meperidine usage patterns and frequency of adverse drug
reactions. Pharmacotherapy. 2004 Jun;24(6):776-83..Seifert CF,
Kennedy S.
Twenty-five percent of patients who received meperidine had some
degree of renal insufficiency. The average daily dose of meperidine was
230 mg; cumulative doses ranged from 10-7200 mg.
Adverse drug reactions documented in 20 (14%) of 141 patients were
confusion, anxiety, nervousness, hallucinations, twitching, and seizure.
Sixteen of the 20 patients received meperidine by PCA pump or a
combination of PCA and intravenous administration. Patients with ADRs
to meperidine were older (58.5 vs 46.4 yrs, p = 0.004), received more
concomitant benzodiazepines (65.0% vs 4.1%, p < 0.0001), and had a
longer hospital stay (median 9.5 vs 4.6 days, p < 0.001) than those who
did not experience an ADR.

27. FentanylFentanyl
Induction
cardiostable
Postoperation pain relief
Continuous/ PCA
Fast onset/ Short acting/ Potent
Lower chance of overdose
Short context sensitive half time
S/E: Pruritus; nausea

28. Opioid Ideal untuk BalancedOpioid Ideal untuk Balanced
AnesthesiaAnesthesia– Mengurangi nyeri & rasa cemas selama operasi
– Mengurangi respon somatis dan otonom karena
adanya gangguan jalan nafas
– Meningkatkan stabilisasi hemodinamik yang
disebabkan oleh rangsang nyeri (intra-operative
analgesia);
– Mengurangi kebutuhan inhalasi anesthesia
(mengurangi biaya)
– Menghasilkan efek analgesia pasca bedah dengan ES
minimal

29. Drug By Anesthesiologist By Patient
Sufentanil 100% 100%
Fentanyl 100% 94%
Morfin 90% 90%
Petidine 56%* 100%
Flacke J, et al. Comparison of Morphine, Meperidine, Fentanyl, and Sufentanil in Balanced Anesthesia: A Double-Blind Study. Anesth
Analg. 1985;64:897-910
Rendahnya tingkat kepuasan dokter anesthesi pada petidine
disebabkan oleh tingginya angka kejadian ES takikardi
(31%)
100% Dokter Anesthesi menyatakan puas terhadap
kinerja Fentanyl & Sufenta saat melakukan induksi

30. Fentanyl secara signifikan lebih berhasil mencegah respon yang
tidak diinginkan terhadap rangsang nyeri dari luka bedah
dibandingkan morfin
**p<0.01
PCEF (Patient Controlled Epidural Fentanyl)
PCIM (Patient Controlled Intravenous Morphine)
Cooper DW, et al. Patient controlled analgesia: epidural fentanyl and i.v.
morphine compared after caesarean section. British Journal of
Anersthesia. 1999, 82(3):388-370.
Fentanyl : mencegah respon yang tidak diinginkan
terhadap rangsang nyeri dari luka bedah

31. *P<0.05, ***P<0.001
PCEF (Patient Controlled Epidural Fentanyl)
PCIM (Patient Controlled Intravenous Morphine)
Cooper DW, et al. Patient controlled analgesia: epidural fentanyl and
i.v. morphine compared after caesarean section. British Journal of
Anersthesia. 1999, 82(3):388-370.
Fentanyl secara signifikan lebih berhasil mencegah respon yang
tidak diinginkan terhadap rangsang nyeri dari luka bedah
dibandingkan morfin
2.2. Efikasi Fentanyl pada Balanced Anesthesia
dibandingkan dengan Opioid lainFentanyl lebih baik memberikan efek analgesik paska
bedah dibandingkan morfin

32. 0309/PK-Fent/NF
Fentanyl lebih aman untuk pasien dengan gangguan
fungsi hati dibandingkan opioid yang lain

33. Systemic Opioids –Systemic Opioids –
Patient Controlled Analgesia andPatient Controlled Analgesia and
Respiratory DepressionRespiratory Depression
0.16%12,600Schug 2000
0.23%4,000Looi-Lyons 1996
0.78%510Whitley 1991
0.03%3,299Oswalt 1990
0.37%747McIntyre 1990
Incidence# of PatientsAuthor

34. Systemic Opioid
Administration
Reported Problems with PCA Use:
• Operator Error
• prescription
• drug
• programming
• equipment choice
• Patient-Related Errors
• relatives (‘Parent Controlled Analgesia’!)
• deliberate overuse
• Equipment Failure
• electronic malfunction
• mechanical malfunction (‘syphoning’)

35. 15 Cases of Severe Respiratory Depression15 Cases of Severe Respiratory Depression
in 12,000 PCA Patientsin 12,000 PCA Patients
– incorrect prescription: 3 cases
– relative using button: 3 cases
– obstructive sleep apnea: 2 cases
– low level of consciousness: 2 cases
– patient after discharge PACU: 1 case
– technical problem with pump: 2 cases
– young males high use: 2 cases
Audit Data, Acute Pain Service, Auckland Hospital

36. Systemic Opioid
Administration
Conclusions:
• PCA alone is the safest way to administer
systemic opioids.
• Addition of background infusion decreases
safety, but does not increase benefit.
• Human error is the most common cause for
disaster.
• Patient only is permitted to push button.

37. The Chance for Anaesthesiology
“The Departments of Anaesthesiology now
have a golden opportunity to expand their
services into a field where we easily can get
many satisfied customers, something very
different from the operating room or the
intensive care unit, where our patients are
asleep or too sick to appreciate our efforts.”
(Breivik. Pain Digest 1993;3:27)