The Use of Ketamine as Rescue Analgesia in the Recovery Room Following Opioid Administration. A Double-Blind Randomised Trial in Postoperative Patients - Full Text View

Sponsored by:	Bayside Health
Information provided by:	Bayside Health
ClinicalTrials.gov Identifier:	NCT00163969

Purpose

This clinical trial will determine if postoperative patients who have postoperative pain, which has been refractory to morphine administration, will have improved pain relief following a bolus administration of ketamine as compared with an ongoing morphine dosing regimen

Condition	Intervention	Phase
Post Operative Pain	Drug: ketamine	Phase IV

Drug Information available for: Ketamine Ketamine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	The Use of Ketamine as Rescue Analgesia in the Recovery Room Following Opioid Administration. A Double-Blind Randomised Trial in Postoperative Patients.

Further study details as provided by Bayside Health:

Primary Outcome Measures:

Pain scores at rest in recovery and at four hours postoperatively

Secondary Outcome Measures:

Morphine protocol consumption.
Sedation scores – Recovery Room and four hours.
PONV scores – Recovery Room and four hours.
Frequency of antiemetic administration – Recovery Room and up to four hours.
Quality of recovery score preoperatively and at four hours.
Adverse events (vivid dreams, nausea, hallucinations, respiratory depression, pruritus) – Recovery Room and at four hours.
Time to discharge from the recovery room.

Estimated Enrollment:	40
Study Start Date:	April 2002
Estimated Study Completion Date:	September 2004

Detailed Description:

Some patients require large doses of opioids to control postoperative pain, which can result in a prolonged period of poor pain control, and potentially increased side effects associated with large morphine doses. This may be due to insufficient morphine dose to that individual or acute tolerance ( 1 ). Ketamine is not just an anaesthetic agent but at lower doses is known to provide efficacious analgesia ( 2, 3 ). Ketamine has been shown to have a marked analgesic effect on high intensity nociceptive stimuli ( 4 ) as exhibited in postoperative pain. When given for opioid analgesia resistant cancer pain in bolus doses at two different concentrations it has been shown to be effective and have a morphine-sparing effect, without undue complications ( 5 ).

Ketamine has been suggested to work pre-emptively and also by many other routes other than intravenously ( 6 - 9 ) .

Previous studies have compared morphine with morphine and ketamine administered as PCA or intramuscularly ( 10 - 12 ) in postoperative patients with varying effects. Javery et al. ( 11 ) showed that pain scores were lower in patients who received ketamine but Reeves et al. in a later but similar study showed no significant difference ( 13 ).

The authors have noted that in the postoperative situation with morphine resistant pain, a bolus dose of ketamine not only leads to a marked decline in pain but it also remains efficacious for several hours. This prolonged effect was also noted in opioid resistant cancer pain ( 5 ). This indeed may have relevance to the prevention of onset of chronic post surgical pain ( 14 ) and earlier discharge from the Post Anaesthetic Care Unit.

Morphine and ketamine are not without side effects. Respiratory depression, nausea, vomiting and vivid dreams, being well documented will hence be a secondary endpoint. A quality of recovery score will also be measured ( 15 ) and four hours postoperatively.

This study is designed to compare a morphine regimen in the form of a standard Post Anaesthetic Care Unit pain protocol with a bolus dose of ketamine to be implemented if the pain protocol has been inadequate. Any patient in pain, despite two doses of morphine will be included. Thereafter the patients will be randomised to receive either a further solution of ketamine or continuation of the morphine protocol. This randomised, double-blinded, trial will be based in the Post Anaesthetic Care Unit under close anaesthetic and nursing staff supervision.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Those patients requiring the routine pain protocol to be implemented as used in the Post Anaesthetic Care Unit who need more than two doses of morphine (and having received intraoperative morphine).

Exclusion Criteria:

Exclusion Criteria
1. Known allergy to morphine or ketamine.
2. Past history of major psychiatric disturbance or currently taking psychiatric medication/s.
3. Chronic morphine usage.
4. Chronic pain syndrome or chronic painful medical condition.
5. Unable to obtain a reliable pain score in recovery due to language barriers or residual anaesthesia.
6. Known pregnancy.
7. Cases where primary anaesthetist prefers alternate therapy.
8. Aged less than 18 years.
9. Weight less than 50 kilograms or greater than 100 kilograms.
10. Use of ketamine intraoperatively.
11. Use of major regional block.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00163969

Locations

Australia, Victoria
The Alfred Commercial Rd Prahran
Melbourne, Victoria, Australia, 3181

Sponsors and Collaborators

Bayside Health

Investigators

Principal Investigator:

David E Lindholm, MBBS FANZCA

The Alfred

More Information

Publications:

1. Mercadante S, Portnenory R K Opioid poorly responsive cancer pain. Part 2. Basic Mechanisms That Could Shift Dose response for Analgesia. Journal of Pain and Symptom Management Vol 21 No. 3 March 2001, 255 – 264. 2. Clements J A, Nimmo W S Pharmokinetics and analgesic effect of ketamine in man British Journal of Anaesthesia 1981, 53, 27. 27 – 30. 3. Owen H, Reekie R M, Clemets J A , et al. Analgesia from morphine and ketamine Anaesthesia 1987, 42 1051 – 1056. 4. Arendt-Neilsen L, Petersen-Felix S, Fischer M, Bak P, Bjerring P, Zbinden AM The effect of n-methyl-D-aspartate antagonist (ketamine) on single and repeated nociceptive stimuli: a placebo-controlled experimental human study. Anesthesia and Analgesia. 81 (1) 63 – 8, 1995 July 5. Mercandate S, Arcun E, Tinelli W and Casuccio C Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: A randomised, controlled, double-blind assessor, double-dose study. Journal of Pain and Symptom Management , Vol 20 No 4, October 2 P 246 – 6. Stubhaug A, Brevik H, Eide P K, Krunen M, Foss A Mapping of punctuale hyperalgesia around a surgical incision demonstrated that ketamine is a powerful suppressor of central sensitisation to pain following surgery. Acta Anaesthesidosiga Scandinavia 41 (9) 1997, 1124 – 32 7. Aida S, Yamakura T, Baba H Pre-emptive analgesia by intravenous low-dose ketamine and epidural morphine in gastrectomy: a randomised double-blind study. Anesthesiology 92 (6) 1624 – 30 June 2000 8. Azevedo V M, Lauretti G R, Pereisa N L, Reis M P Transdermal ketamine as an adjuvant for postoperative analgesia after abdominal gynaecological surgery using lidocaine epidural blockade. Anesthesia and Analgesia 91 (6) 1479 – 82 Dec 2000. 9. Schmid R L, Sandler A N, Katz J Use and Efficacy of Low Dose Ketamine in the Management of Acute Postoperative Pain: a review of current techniques and outcomes Pain 82 1999 111-125 10. Adriaenssens G, Vermeyer K M, et al. Postoperative analgesia with I/V patient controlled morphine: effect of adding ketamine. British Journal of Anaesthesia 83 (3) Sept 1999 393 – 396 11. Javery K B, Ussery T W, Steger H G, Colcough G W Comparison of morphine and morphine with ketamine for postoperative analgesia Can J Anaesth 1996 43 (3) 212 – 215 12. Marcus R J, Victoria B A, Rushman S C, Thompson J P Comparison of ketamine and morphine for analgesia after tonsillectomy in children. British Journal of Anaesthesia 84 (6) 739 – 742 June 2000 13. Reeves M, et al. Adding ketamine to morphine for patient controlled analgesia after major abdominal surgery. A double-blinded, randomised controlled trial. Anaesthesia and Analgesia 93 2001 116 – 120 14. Macrae W A, Davies H T O Chronic post surgical pain Epidemiology of Pain edited by Crombie I K. IASP Press. Seattle 1999. 125 - 142 15. Myles P S, Hunt J O, Nightingale C E, Fletcher H, Beh T, Tanil D, Nagy A, Rubinstein A, Ponsford J Development and psychometer testing of a quality of recovery score after general anaesthesia and surgery in adults. Anaesthesia and Analgesia 1999 January: 88 (1): 83 - 90

Study ID Numbers:	161/01
Study First Received:	September 12, 2005
Last Updated:	October 10, 2006
ClinicalTrials.gov Identifier:	NCT00163969
Health Authority:	Australia: National Health and Medical Research Council

Keywords provided by Bayside Health:

Pain
Wind-up
opioid
ketamine
pre-emptive

Study placed in the following topic categories:

Excitatory Amino Acids
Signs and Symptoms
Postoperative Complications

Ketamine
Pain
Pain, Postoperative

Additional relevant MeSH terms:

Anesthetics, Intravenous
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Agents
Anesthetics, Dissociative
Pharmacologic Actions

Pathologic Processes
Sensory System Agents
Anesthetics, General
Therapeutic Uses
Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents
Excitatory Amino Acid Antagonists

ClinicalTrials.gov processed this record on January 15, 2009