Are Opioids the Worse Pain Killers?

Xavier Capdevila M.D.,Ph.D.Head of Department

Department of Anesthesiology and Critical Care MedicineLapeyronie University Hospital and Montpellier School of Medicine

Montpellier , France

Conflicts of interest: •Pajunk•B Braun•GE Healthcare•Baxter•Janssen•Abbott

Nineteen articles; 603 patients

Ilfeld et al Anesthesiology 2008

Patients given 4 days of perineural ropivacaine attained the 3 discharge criteria in a median (25th-75th centiles) of 25 ( 21-47)h compared with 71 (46-89)h in the selected center. Decrease in time until discharge readiness of 46h

Ilfeld et al Pain 2010

Patients given 4 days of perineural ropivacaine attained the 3 discharge criteria in a median (25th-75th centiles) of 47 ( 29-69)h compared with 62 (45-79)h in that multicentric trial. Decrease in time until discharge readiness of 15h

A Comprehensive Anesthesia Protocol that Emphasizes Peripheral Nerve Blockade for Total Knee and Total Hip Arthroplasty

JAMES R. HEBL, SANDRA L. KOPP, MIR H. ALI, TERESE T. HORLOCKER, JOHN A. DILGER, MD, ROBERT L. LENNON, BRENT A. WILLIAMS, ARLEN D. HANSSEN AND MARK W. PAGNANO

THE JOURNAL OF BONE & JOINT SURGERY ·VOLUME 87-A · SUPPLEMENT 2 · 2005

Cumulative 24 h consumption of i.v. morphine (in milligrams) for break-through pain after operation

Pain intensity (0–10-point scale, ranging from 0, no pain, to 10, maximum pain) at rest at 2, 4, 12, and 24 h after operation

All surgeries

« Respiratory depression remains a major safety concern »

Postoperative sedationNausea and vomiting

0minutes

5

D+15

0 4hours

D+7D0

Naloxone

0

100

200

300

400

500

600

Pain inflammation

Carrageenan

Time (days)

Paw

pre

ssur

e (g

)

Inflammation + Fentanyl

orFentanyl

NaCl

Naive rats

*

*

Angst M.S, Koppert W., Pain 2003

//

2 4 8 160.5 240

20

40

60

80

100

//

*

*

1

Desflurane

Remifentanil

Post - extubation time (h)

Guignard et al. Anesthesiology 2000

Visual Analog Scale

(mm)

Remifentanil vs. desflurane Remifentanil vs. desflurane based anesthesiabased anesthesia

Guignard et al. Anesthesiology 2000

0

20

40

60

0.5 10 4 12 20

/

2

///

//

Morphine (mg)

Post - extubation time (h)

Desflurane

Remifentanil P < 0.05 vs. desflurane

OpiatesStress Surgery

SurgeryOpiatesHypnotics

opioids

opioids

opioids

CAM: cellular adhesivity moleculCMH: histocompatibility major complexKIR: killer inhibitor-receptor

μ3

Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats. Dose and timing study. Shavit Y, Ben-Eliyahu S, Zeidel A, Beilin B. Neuroimmunomodulation. 2004;11(4):255-60

Fentanyl suppresses NKCC and increases the risk of tumor metastasis. Suppression of NK cells at a time when surgery may induce tumor dissemination can be critical for metastases. Acute administration of a moderate dose of opiates during surgery should be applied cautiously in cancer patients

Forty patients were included : half were assigned to each protocol of anesthesia.

In each anesthetic group, half the patients were undergoing surgery for malignant diseases.

Blood samples were collected during the perioperative period.

Morphine in clinically relevant doses promotes tumor neovascularization in a human breast tumor xenograft model in mice leading to increased tumor progression.

24

British Journal of Cancer (2007) 97, 1523 – 1531

Morphine during two weeksAssociation M+C: better analgesia , better survival

25

Anesth Analg 2010;110:1630–5

319 Patients

Fifty patients had surgery with paravertebral anesthesia and analgesia combined with general anesthesia, and 79 patients had general anesthesia combined with postoperative morphine analgesia.

Nowadays , opioids are useful in the perioperative period as first line

analgesics in very painfull surgeries, however regional techniques should be often preferred in order to limit adverse

events and immunomodullary dysfunctions.

Anesthesia and Analgesia June 2010 • Volume 110 • Number 6

« Even though the evidence is inconclusive and at times conflicting, we ignore the possibility that anesthesia may contribute to the recurrence of cancer, months or even years after cancer surgery.

So what should we do? An obvious choice is to use regional anesthesia whenfeasible, alone or in combination with general anesthesia, to minimize the amount of opioid administered, and to consider using NSAIDs, especially specific COX-2 inhibitors. Of course, what we really need are good prospective, randomized,and controlled clinical trials ».