1. Multimodal Pain Management
Tong Joo (TJ) Gan, MD, FRCA, FFARCS(I)
 Professor of Anesthesiology
Vice Chairman Clinical Research
Duke University Medical Center
Durham, North Carolina

2. Faculty Disclosure
It is the policy of The France Foundation to ensure balance, independence, objectivity, and scientific rigor in all its sponsored educational activities. All faculty, activity planners, content reviewers, and staff participating in this activity will disclose to the participants any significant financial interest or other relationship with manufacturer(s) of any commercial product(s)/device(s) and/or provider(s) of commercial services included in this educational activity. The intent of this disclosure is not to prevent a person with a relevant financial or other relationship from participating in the activity, but rather to provide participants with information on which they can base their own judgments. The France Foundation has identified and resolved any and all conflicts of interest prior to the release of this activity.
Dr. Gan has received grants/research support from Acacia, Baxter, Durect, Eisai, and NICOM. He has received honoraria from Baxter, Eisai, Fresenius, Hospira, and Xanodyne.

3. Educational Learning Objectives
Describe the importance of improving time to gastrointestinal recovery that occurs postsurgery and consider how this affects length of hospital stay and overall quality of patient care
Evaluate the evidence for therapeutic options that may improve gastrointestinal recovery postsurgery and integrate these efforts toward supporting overall surgical quality measures
Describe how interprofessional collaboration surrounding gastrointestinal surgery can result in better alignment with current surgical quality measures and formulate strategies to integrate this into current practice

4. Patient Case
65-year-old man, 95 kg, with a history of biopsy positive cancer of the rectum
Scheduled for a left hemicolectomy
Past medical history
Non-insulin dependent diabetes
Hypertension
Chronic back pain

5. Patient Case – Medical History
Previous surgery
Appendectomy
Knee arthroscopy
ACL repair
Social history
Occasional drinker
Nonsmoker

6. Patient Case – Medical History
Medication history
Vicodin® 1 tab TID
Ibuprofen PRN
Atenolol 50 mg OD
Multivitamin daily
Gliclazide 30 mg

7. Patient Case – Anesthetic Plan
Patient scheduled for partial colectomy
Anesthetic
General anesthesia
Fentanyl 100 mcg and midazolam 3 mg as premedication
Induction with propofol, anesthetic maintained with sevoflurane, air and oxygen
Rocuronium as the neuromuscular blocker
Ondansetron as prophylactic antiemetic

8. Patient Case – Postoperative Pain Management
Surgery duration 3.5 hrs
Patient extubated and transferred to PACU
Postoperative pain management
Patient-controlled analgesia (PCA) with morphine, with 2 mg bolus, 8 min lockout and 30 mg 4 hr maximum dose
In the PACU, complained of pain 9/10 on a verbal rating scores (VRS) of 0-10

9. Opioids and Postoperative Ileus
Does the use of systemic opioids contribute to postoperative ileus?

10. Opioid-based Analgesia and Bowel Function
40 colectomy patients
Correlation between morphine PCA dose and first bowel sounds (P = 0.001), flatulence, (P = 0.003), and first bowel movement (shown, P = 0.002)
No correlation between incision length and morphine dose
ICD-9-CM coded POI correlates with systemic morphine (OR = 12.1;
95% CI, )
Total Morphine (mg)
350.0
300.0
250.0
200.0
150.0
100.0
50.0
R = 0.48 P = 0.002
Hours to First Bowel Movement
Cali RL, et al. Dis Colon Rectum. 2000;43:
Goettsch WG, et al. Pharmacoepidemiol Drug Saf. 2007;16:

11. Postoperative Analgesia and
Postoperative Ileus
While opioids are often the analgesic of choice following abdominal surgery, they decrease gastric motility, inhibit small and large intestinal propulsion, and have other GI effects that contribute to the abdominal discomfort associated with POI

12. Postoperative Pain Management
What would you do? A. Change to a different opioid in the PCA B. Add ketorolac C. Insert an epidural D. Boluses of morphine

13. Postoperative Pain Management
There are a number of possible options.
The following slides provide some evidence to support the use of nonsteroidal anti-inflammatory drugs and epidurals as opioid-sparing approaches.

14. Opioid-sparing Effects of Ketorolac – Postoperative Bowel Function in Colorectal Surgery Patients
M: IV patient-controlled analgesia morphine
M+K: IV patient-controlled analgesia morphine plus ketorolac
Chen JY, et al. Clin J Pain. 2009;25:

15. Epidural Analgesia and Duration of Postoperative Ileus
Study
Surgery
Earlier Gas
Earlier Stool
*P-value
Hjortso et al, 1985
Major abdominal No NS
Wallin et al, 1986
Scheinin et al, 1987
Colonic
---
Yes
< 0.05
Ahn et al, 1988
Colorectal
< 0.001
Bredtmann et al, 1990
Jayr et al, 1993
Morimoto et al, 1995
Proctocolectomy/IPAA
< 0.01
Liu et al, 1995
< 0.005
Scott et al, 1996
Bradshaw et al, 1998
Welch et al, 1998
Gastrointestinal
Neudecker et al, 1999
Laparoscopic sigmoidectomy
Carli et al, 2001
Carli et al, 2002
Steinberg et al, 2002
< 0.002
*Compared with systemic analgesic regimens;
IPAA: ileal pouch anal anastomosis
Adapted from Person B, Wexner S. Curr Probl Surg. 2006;43:12-65.

16. Meta-analysis of Epidural Analgesia (EA) vs Opioid Parenteral Analgesia after Colorectal Surgery
16 randomized, controlled trials ( ) compared postoperative epidural analgesia (local anesthetic) with parenteral opioid analgesia in patients following colorectal surgery
Length of hospital stay: no statistically significant difference between the groups
Pain intensity: Lower visual analog scale pain scores at 24 and 48 hours with EA (P < 0.001)
Duration of postoperative ileus: reduced by 36 hr with EA (P < 0.001)
Anastomotic leak and cardiopulmonary complications: no significant difference between groups
Hypotension, pruritus, and urinary retention were more common in the EA group
Marret E, et al. Br J Surgery. 2007;94:

17. Postoperative Pain Management – Opioid-sparing Strategies
The use of epidural analgesia and nonsteroidal anti-inflammatory drugs (NSAIDs) for postoperative pain management both help to minimize postoperative opioid consumption. Along with providing pain relief, these strategies help to minimize opioid-related GI dysfunction. Both approaches are associated with a reduction in the duration of postoperative ileus compared with parenteral opioids

18. Patient Case – Postoperative Pain Management
Treatment
Added ketorolac 15 mg
Gave bolus dose of morphine 6 mg (in 2 mg aliquots)
Increased PCA dose of morphine to 3 mg per push

19. Patient Case – Postoperative Day 1
Patient’s pain score is 7/10
Complaint of persistent nausea and 2 episodes of retching
Itching of the front of chest and back
Treatment
Promethazine 12.5 mg
Meperidine 25 mg

20. Patient Case – Postoperative Day 3
Day 3 after surgery, pain range between 4/10 to 8/10. Still on PCA morphine, not helping too much
5 doses of ketorolac, maximum doses given
Still complains of nausea
Used 70 mg morphine on first 24 hrs and 80 mg over the next 24 hrs

21. Patient Case – Postoperative Day 4
No bowel sounds, no flatus, no bowel movement
Abdomen slightly distended
Nasogastric tube drained yellowish fluid
Persistent nausea
Drowsiness and slight confusion

22. Postoperative Pain Management
What would you do?
Additional boluses of morphine
Start a morphine infusion via the PCA
Change to a different opioid
Insert an epidural

23. Postoperative Pain Management
Since the patient had not responded well to fairly large doses of morphine, starting an infusion or further boluses of morphine would not be helpful. Some patients may respond better to a different opioid with a lower incidence of side effects. Hence this could be a viable option. Insertion of an epidural at this stage may also be considered if there are no other contraindications.

24. Patient Case – Postoperative Pain Management
Pain team consulted
Change to hydromorphone PCA
Started celecoxib 200 mg BID

25. Patient Case – Postoperative Course
Postoperative Day 7: presence of flatus and bowel sounds
Advanced diet to semi-solid
Continue to make progress
Day 10: full bowel function established
Day 11: patient discharged

26. Patient Case – Continued
Suspicious looking left kidney found during surgery
Renal mass confirmed on MRI
6 weeks later, patient admitted for left partial nephrectomy

27. What Would Be Your Anesthetic and Pain Management Plan?
Preoperative epidural
Preoperative celecoxib
Preoperative gabapentin
Intraoperative small dose ketamine infusion
All the above

28. Gabapentin and Postoperative Pain–Systematic Review
Ho KY, et al. Pain. 2006;126:

29. Gabapentin and Postoperative Pain
Pain Scores
Morphine Consumption
Ho KY, et al. Pain. 2006;126:

30. Perioperative Gabapentin 1200 mg Adverse Events
Odds Ratio
P value
Nausea
0.72 ( )
0.06
Vomiting
0.58 ( )
0.007
Pruritus
0.27 ( )
0.01
Sedation
3.86 ( )
Respiratory Depression
1.07 ( )
0.93
Odds ratio < 1 favors gabapentin over control (reduced risk for opioid-related side effects)
Ho KY, et al. Pain. 2006;126:

31. Celecoxib 400 mg/day in Laparoscopic Surgery
* P < 0.05 vs Control (actual P values listed)
White P, et al. Can J Anaesth 2007;54:

32. Intravenous Ketamine and Postoperative Pain Systematic Review
Visual Analogue Scale (VAS)
of pain intensity
Elia N, Tramèr M. Pain. 2005;113:61-70.
WMD: weighted mean difference

33. Multimodal Perioperative Pain Management
Preoperative gabapentin, short-term use of celecoxib, and intraoperative ketamine infusion are additional evidence-based strategies for improving perioperative analgesia, reducing opioid requirements, and minimizing opioid-related side effects.

34. Patient Case – Anesthetic and Postoperative Pain Management Plan
T9/T10 thoracic epidural placement preoperatively for postoperative pain control
Preoperative celecoxib 400 mg followed by celecoxib 200 mg BID
Preoperative single dose of gabapentin 1200 mg
Intraoperative ketamine bolus 0.5 mg/kg followed by an infusion of 10 kg mcg/kg/min

35. Patient Case – Postoperative Pain Management
Surgery uneventful
Lasted for 3 hrs
Postoperative epidural infusion with bupivacaine % with hydromorphone 10 mcg/mL infused at 8 mL/h
Continued with celecoxib 200 mg BID
Pain score 2-3/10

36. Patient Case – Postoperative Course
Postoperative Day 2: epidural discontinued
Patient tolerated a full meal the day after surgery with no nausea and vomiting
Urine through catheter started to be clear
Normal renal function established
Continued on celecoxib 200 mg BID
Pain score 2-3/10

37. Patient Case – Postoperative Course
Day 3: patient discharged
Patient was satisfied with the pain management during his second surgery
Use of multimodal strategy greatly enhanced pain control with reduction in side effects

38. Summary This case illustrates
Opioid use can result in many adverse effects including nausea and vomiting and delayed bowel recovery after surgery
Pain involves complex mechanisms
Opioid adjuncts improve pain control
A multimodal pain management strategy improves analgesia and lowers the incidence and severity of side effects