Does a Single Intravenous Dose of Ketamine Reduce the Need for Supplemental Opioids in Post-Cesarean Section Patients?

NCT00486902 | Completed Results

• 1 other identifier: 0524-030
• Study Type: interventional
• Target: 188
• Locations: 1 country
• Sites: 1

Brief Summary

Pain control after cesarean delivery is associated with improved breastfeeding and infant rooming-in times. In addition, inadequate analgesia leads to elevated plasma catecholamine concentrations, which negatively affect every organ system. There is growing evidence that ketamine, N-methyl-D-aspartate receptor antagonist, is efficacious when used as an adjuvant in postoperative pain control. A 2006 Cochrane Collaboration systemic review and meta-analysis concluded, "Ketamine in subanesthetic doses….is effective in reducing morphine requirements in the first 24 hours after surgery." Ketamine's prolonged analgesic effect, despite its short half-life and its use in low doses, is theorized to be due to blockade of spinal cord central sensitization. Central sensitization is a phenomenon whereby repeated painful stimulus leads to more severe pain perception over time despite no change in the intensity of the painful stimulus.Ketamine may also prevent the development of acute opioid tolerance. Ketamine's analgesic effects have also demonstrated in the obstetric population. Post-cesarean delivery morphine requirements in women who received ketamine as part of a general anesthesia technique were decreased. Similary, low-dose ketamine in conjunction with bupivacaine-only spinal anesthesia reduced postoperative analgesic requirements compared to bupivacaine-only spinal anesthesia and bupivacaine-fentanyl spinal anesthesia. In the United States, healthy women scheduled for elective cesarean delivery commonly receive spinal anesthesia with bupivacaine-fentanyl-morphine. To our knowledge, IV ketamine has not been studied as an adjuvant to this regimen in the analgesic management in post-cesarean delivery patients. Multimodal therapy for postoperative pain control is widely practiced due to the advantage it provides in blocking multiple pain pathways while minimizing side effects of each individual pain medication. We hypothesize that low dose intravenous ketamine will improve multi-modal post-cesarean analgesia compared to placebo. The purpose of this study is to evaluate this hypothesis and study the possible side effects of this regimen in combination with bupivacaine-fentanyl-morphine spinal anesthesia.

Conditions

Ketamine Adverse Reaction; Effects of; Anesthesia, Spinal and Epidural, in Pregnancy; Complication of Labor and/or Delivery

Keywords

Ketamine; Spinal Anesthesia; C-section

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Requiring Supplemental Analgesia in the First 24 Hours Following Cesarean Delivery

  Request for oral hydrocodone/acetaminophen for pain not controlled by around the clock non-steroidal antiflammatory drugs in the first 24 hours following cesarean delivery.

  24 hours

Secondary Outcomes (6)

• Verbal Pain Scores (0 to 10) at First Analgesia Request

  24 hours

• Cumulative Hydrocodone/Acetaminophen for Supplemental Analgesia to Treat Breakthrough Pain

  72 hours

• Postoperative Nausea

  24 hours

• Postoperative Vomiting

  24 hours

• Postperative Pruritus

  24 hours

Study Arms (2)

Ketamine

EXPERIMENTAL

Subjects receive IV ketamine 10 mg 5 minutes after infant delivery.

Drug: Ketamine

Placebo

PLACEBO COMPARATOR

Subjects receive IV Saline 20 mL 5 minutes after infant delivery

Drug: Placebo

Interventions

Ketamine DRUG

Ketamine 10 mg diluted to 20 mL delivered over 10 minutes via an infusion pump set at 2ml/minute

Also known as: N-methyl-D-aspartate (NMDA)

Ketamine

Placebo DRUG

Saline 20 mL IV infusion delivered over 10 minutes via an infusion pump set at 2ml/minute

Also known as: 0.9% Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Eligible women are at term (≥37 week gestation),
• Healthy,
• ASA class 1-2,
• Scheduled for elective cesarean section whose anesthetic plan is for spinal anesthesia with intrathecal morphine and intravenous ketorolac analgesia for post operative analgesia

You may not qualify if:

• Women with American Society of Anesthesiologists physical status \>2,
• Body mass index ≥40 kg/m2,
• Known allergy to any of the study medications,
• Contraindication to the spinal anesthesia,
• History of substance abuse,
• History of hallucinations,
• Chronic opioid therapy,
• Chronic pain.

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (23)

• Yost NP, Bloom SL, Sibley MK, Lo JY, McIntire DD, Leveno KJ. A hospital-sponsored quality improvement study of pain management after cesarean delivery. Am J Obstet Gynecol. 2004 May;190(5):1341-6. doi: 10.1016/j.ajog.2003.10.707.

  PMID: 15167840 BACKGROUND

• Subramaniam K, Subramaniam B, Steinbrook RA. Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review. Anesth Analg. 2004 Aug;99(2):482-95, table of contents. doi: 10.1213/01.ANE.0000118109.12855.07.

  PMID: 15271729 BACKGROUND

• Bell RF, Dahl JB, Moore RA, Kalso E. Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004603. doi: 10.1002/14651858.CD004603.pub2.

  PMID: 16437490 BACKGROUND

• Menigaux C, Fletcher D, Dupont X, Guignard B, Guirimand F, Chauvin M. The benefits of intraoperative small-dose ketamine on postoperative pain after anterior cruciate ligament repair. Anesth Analg. 2000 Jan;90(1):129-35. doi: 10.1097/00000539-200001000-00029.

  PMID: 10624993 BACKGROUND

• Menigaux C, Guignard B, Fletcher D, Sessler DI, Dupont X, Chauvin M. Intraoperative small-dose ketamine enhances analgesia after outpatient knee arthroscopy. Anesth Analg. 2001 Sep;93(3):606-12. doi: 10.1097/00000539-200109000-00016.

  PMID: 11524327 BACKGROUND

• Kwok RFK, Lim J, Chan MTV, Gin T, Chiu WKY. Preoperative ketamine improves postoperative analgesia after gynecologic laparoscopic surgery. Anesth Analg. 2004 Apr;98(4):1044-1049. doi: 10.1213/01.ANE.0000105911.66089.59.

  PMID: 15041596 BACKGROUND

• Argiriadou H, Himmelseher S, Papagiannopoulou P, Georgiou M, Kanakoudis F, Giala M, Kochs E. Improvement of pain treatment after major abdominal surgery by intravenous S+-ketamine. Anesth Analg. 2004 May;98(5):1413-8, table of contents. doi: 10.1213/01.ane.0000111204.31815.2d.

  PMID: 15105223 BACKGROUND

• Guillou N, Tanguy M, Seguin P, Branger B, Campion JP, Malledant Y. The effects of small-dose ketamine on morphine consumption in surgical intensive care unit patients after major abdominal surgery. Anesth Analg. 2003 Sep;97(3):843-847. doi: 10.1213/01.ANE.0000075837.67275.36.

  PMID: 12933413 BACKGROUND

• Guignard B, Coste C, Costes H, Sessler DI, Lebrault C, Morris W, Simonnet G, Chauvin M. Supplementing desflurane-remifentanil anesthesia with small-dose ketamine reduces perioperative opioid analgesic requirements. Anesth Analg. 2002 Jul;95(1):103-8, table of contents. doi: 10.1097/00000539-200207000-00018.

  PMID: 12088951 BACKGROUND

• Xie H, Wang X, Liu G, Wang G. Analgesic effects and pharmacokinetics of a low dose of ketamine preoperatively administered epidurally or intravenously. Clin J Pain. 2003 Sep-Oct;19(5):317-22. doi: 10.1097/00002508-200309000-00006.

  PMID: 12966258 BACKGROUND

• Suzuki M, Tsueda K, Lansing PS, Tolan MM, Fuhrman TM, Ignacio CI, Sheppard RA. Small-dose ketamine enhances morphine-induced analgesia after outpatient surgery. Anesth Analg. 1999 Jul;89(1):98-103. doi: 10.1097/00000539-199907000-00017.

  PMID: 10389785 BACKGROUND

• Aida S, Yamakura T, Baba H, Taga K, Fukuda S, Shimoji K. Preemptive analgesia by intravenous low-dose ketamine and epidural morphine in gastrectomy: a randomized double-blind study. Anesthesiology. 2000 Jun;92(6):1624-30. doi: 10.1097/00000542-200006000-00020.

  PMID: 10839912 BACKGROUND

• Kararmaz A, Kaya S, Karaman H, Turhanoglu S, Ozyilmaz MA. Intraoperative intravenous ketamine in combination with epidural analgesia: postoperative analgesia after renal surgery. Anesth Analg. 2003 Oct;97(4):1092-1096. doi: 10.1213/01.ANE.0000080205.24285.36.

  PMID: 14500163 BACKGROUND

• Ilkjaer S, Nikolajsen L, Hansen TM, Wernberg M, Brennum J, Dahl JB. Effect of i.v. ketamine in combination with epidural bupivacaine or epidural morphine on postoperative pain and wound tenderness after renal surgery. Br J Anaesth. 1998 Nov;81(5):707-12. doi: 10.1093/bja/81.5.707.

  PMID: 10193280 BACKGROUND

• Woolf CJ, Chong MS. Preemptive analgesia--treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg. 1993 Aug;77(2):362-79. doi: 10.1213/00000539-199377020-00026. No abstract available.

  PMID: 8346839 BACKGROUND

• Mao J, Price DD, Mayer DJ. Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions. Pain. 1995 Sep;62(3):259-274. doi: 10.1016/0304-3959(95)00073-2.

  PMID: 8657426 BACKGROUND

• Ngan Kee WD, Khaw KS, Ma ML, Mainland PA, Gin T. Postoperative analgesic requirement after cesarean section: a comparison of anesthetic induction with ketamine or thiopental. Anesth Analg. 1997 Dec;85(6):1294-8. doi: 10.1097/00000539-199712000-00021.

  PMID: 9390597 BACKGROUND

• Kashefi P. The benefits of intraoperative small-dose ketamine on postoperative pain after cesarean section. Anesthesiology 2006;104, Supp 1.

  BACKGROUND

• Sen S, Ozmert G, Aydin ON, Baran N, Caliskan E. The persisting analgesic effect of low-dose intravenous ketamine after spinal anaesthesia for caesarean section. Eur J Anaesthesiol. 2005 Jul;22(7):518-23. doi: 10.1017/s026502150500089x.

  PMID: 16045141 BACKGROUND

• Downing JW, Mahomedy MC, Jeal DE, Allen PJ. Anaesthesia for Caesarean section with ketamine. Anaesthesia. 1976 Sep;31(7):883-92. doi: 10.1111/j.1365-2044.1976.tb11899.x.

  PMID: 9839 BACKGROUND

• Dich-Nielsen J, Holasek J. Ketamine as induction agent for caesarean section. Acta Anaesthesiol Scand. 1982 Apr;26(2):139-42. doi: 10.1111/j.1399-6576.1982.tb01741.x.

  PMID: 7102236 BACKGROUND

• Maduska AL, Hajghassemali M. Arterial blood gases in mothers and infants during ketamine anesthesia for vaginal delivery. Anesth Analg. 1978 Jan-Feb;57(1):121-3. doi: 10.1213/00000539-197801000-00026. No abstract available.

  PMID: 24371 BACKGROUND

• Bar-Oz B, Bulkowstein M, Benyamini L, Greenberg R, Soriano I, Zimmerman D, Bortnik O, Berkovitch M. Use of antibiotic and analgesic drugs during lactation. Drug Saf. 2003;26(13):925-35. doi: 10.2165/00002018-200326130-00002.

  PMID: 14583068 BACKGROUND

MeSH Terms

Interventions

Ketamine; N-Methylaspartate; Saline Solution

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aspartic Acid; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Robert J. McCarthy
• Organization: Northwestern University Feinberg School of Medicine

r-mccarthy@northwestern.edu

312-926-9015

Study Officials

• Cynthia A Wong, M.D.

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesiology

Study Record Dates

• First Submitted: June 13, 2007
• First Posted: June 15, 2007
• Study Start: July 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: April 14, 2014
• Results First Posted: May 6, 2011

Record last verified: 2014-03

Locations

US (1)