Fentanyl for perioperative Fentanyl for perioperative pain managementpain management

Dr Alex Yeo Sow Nam

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.

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

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

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

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

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 mg morphine10 mg morphine IMIM PRN 4hrly’PRN 4hrly’

Delayed onset of actionUnpredictable absorption

Site of injection Muscle perfusion

Potential for nerve damagePotential for infectionDiscomfort for patient

Why then ‘IM” ?Why then ‘IM” ?

Nursing tradition: No IV injections Risk of adverse effects?????

Belief: Parenteral is better than oral! Why?

’’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!

6 8 10 12 14

Theoretical Relation Between Analgesic Theoretical Relation Between Analgesic Drug Level, Dosing Interval, and Clinical Drug Level, Dosing Interval, and Clinical

ResponseResponse

Pain

Analgesia

Sedation

Ferrante FM, et al. Anesth Analg. 1988;67:457-61.

Ana

lges

ic d

rug

conc

entra

tion

Time (hours)

Dose Dose Dose

Dose

Minimum analgesic concentration

IMPCA

IM=intramuscular; PCA=patient controlled analgesia

Patient Controlled AnalgesiaPatient Controlled Analgesia

Principles– Small IV bolus!– Lockout interval appropriate to route

of administration!– Patient titrates amount needed against

pain experienced!

Principle Concept of TitrationPrinciple Concept of Titration

P atien t exp erien ces e ffec t o f d ru g

D ru g works

P atien t ad m in is te rs d ru g

P atien t exp erien ces p a in

Good pain relief?

Wait!

Yes No

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

Pethidine PharmacologyPethidine PharmacologyPethidine 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

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.

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)

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

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

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.

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

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.

FentanylFentanyl

InductioncardiostablePostoperation pain reliefContinuous/ PCAFast onset/ Short acting/ PotentLower chance of overdose Short context sensitive half timeS/E: Pruritus; nausea

Opioid Ideal untuk Balanced Opioid 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

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

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

*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 lain

Fentanyl lebih baik memberikan efek analgesik paska bedah dibandingkan morfin

0309/PK-Fent/NF

Fentanyl lebih aman untuk pasien dengan gangguan fungsi hati dibandingkan opioid yang lain

Systemic Opioids – Systemic Opioids – Patient Controlled Analgesia and Patient 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

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’)

15 Cases of Severe Respiratory Depression 15 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

Systemic Opioid AdministrationConclusions:

• 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.

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)