The Pre-Emptive Administration Of Ketamine for Controlling Post-thoracotomy Pain

NCT ID: NCT03415191

Last Updated: 2018-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-05
• Study Completion Date: 2015-02-01

Brief Summary

The goal of this paper is to evaluate whether the pre-emptive administration of Ketamine would potentiate the effect of intravenous morphine analgesia in management of post thoracotomy pain. This was a single center, double-blind, placebo controlled, parallel-group, prospective study. Patients were randomly assigned to receive 1 mg/kg ketamine (Ketamine Group) or an equivalent dose of normal saline (Placebo Group) before thoracotomy in 1:1 ratio. All patients received postoperatively intravenous morphine administration as additional analgesic regimen Primary end-point was pain relief measured with Visual Analogue Scale at rest. The secondary end-points were the reduction of inflammatory response expressed by plasma c-reactive protein levels, the morphine consumption, and the rate of side effects. The measurements were carried out 6; 12; 24; 36; and 48 post operative hours.

Detailed Description

Thoracotomy is one of the most painful surgical incision. Inadequate control of pain can have several detrimental effects, including increased postoperative morbidity and delayed recovery as well as occurrence of post thoracotomy syndrome. Therefore, choosing an effectiveness analgesic regimen for thoracic surgery is critical. Many strategies including intercostal nerve block, intra pleural analgesia, lumbar or thoracic epidural, paravertebral block, intra venous narcotics, intrathecal or epidural narcotics or trans-cutaneous nerve stimulation have been used with varied success. However, the ideal strategy remains an open issue. Different factors including trauma of chest wall, thoracic viscera, diaphragm, and intercostal nerves concur to thoracotomy pain development. Thus, due to multifactorial genesis of pain following thoracotomy a multimodal analgesic approach rather than a single method seems to be more effective because it blocks noxious input at different targets and levels of pain pathways.

Ketamine is an antagonist of N-methyl-D-aspartate (NMDA) receptor that not only abolishes peripheral afferent noxious stimulation, but it may also prevent central sensitization of nociceptors as shown in animal studies. In thoracic surgery, there are contradictory results on the efficacy of ketamine for controlling pain due to different dose, type of surgery/patient, and postoperative analgesic regimen used in the various studies. Mathew et al. in a recent review concluded that adding low-dose ketamine to intravenous morphine analgesia following thoracotomy was safe and could provide a significant better pain relief and reduction of morphine consumption compared to placebo. D'Alonzo et al. found that the administration of a single dose of ketamine prior to chest incision failed to significantly reduce the pain scores and inflammation in the first 24 post-operative hours. Similarly, Yazigi et al. reported that pre-emptive intravenous low-dose ketamine followed by continuous administration during surgery did not decrease acute pain scores and supplemental morphine consumption. Other studies reported that the epidural infusion of Ketamine before thoracotomy or during thoracic surgery provides better postoperative analgesia compared to placebo group or epidural ropivacaine group In the present study, the investigators supposed that the pre-emptive administration of Ketamine would potentiate the effect of intravenous opioid analgesia with reduction of pain scores, inflammatory response and morphine consumption without increasing morbidity in patients undergoing thoracotomy.

This was a single center, double-blind, placebo controlled, parallel-group, prospective study. Patients were randomly assigned to receive 1 mg/kg ketamine (Ketamine Group) or an equivalent dose of normal saline (Placebo Group) before thoracotomy in 1:1 ratio. All patients received postoperatively intravenous morphine administration as additional analgesic regimen Primary end-point was pain relief measured with Visual Analogue Scale at rest. The secondary end-points were the reduction of inflammatory response expressed by plasma c-reactive protein levels, the morphine consumption, and the rate of side effects. The measurements were carried out 6; 12; 24; 36; and 48 post operative hours.

Conditions

Post Thoracotomy Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ketamine Group

Five minutes before thoracotomy incision, Ketamine Group received a bolus dose of ketamine 1 mg/kg intravenously

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

A bolus dose of ketamine 1 mg/kg intravenously five minutes before surgical incision

Placebo Group

Five minutes before thoracotomy incision, Placebo Group received a bolus dose of normal saline 1 mg/kg intravenously

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: DRUG

A bolus dose of normal saline 1 mg/kg intravenously five minutes before surgical incision

Interventions

Ketamine

A bolus dose of ketamine 1 mg/kg intravenously five minutes before surgical incision

Intervention Type: DRUG

Normal Saline

A bolus dose of normal saline 1 mg/kg intravenously five minutes before surgical incision

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• aged more than 18 years old,
• planned for an elective partial pneumonectomy (partial or total lobectomy involving one or more lobes, except total pneumonectomy)
• standard lateral thoracotomy for management of non small cell lung cancer (NSCLC)

Exclusion Criteria

• allergy to Ketamine
• ASA score more than 3
• previous thoracic surgical procedures or lung resection
• mental disease
• participation to other studies
• lack of written informed consent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Campania Luigi Vanvitelli

OTHER

Sponsor Role: lead

Responsible Party

Alfonso Fiorelli

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alfonso Fiorelli, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Campania Luigi Vanvitelli

Locations

Alfonso Fiorelli

Naples, , Italy

Countries

Italy

References

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Reference Type: BACKGROUND

PMID: 24216528 (View on PubMed)

Fiorelli A, Vicidomini G, Laperuta P, Busiello L, Perrone A, Napolitano F, Messina G, Santini M. Pre-emptive local analgesia in video-assisted thoracic surgery sympathectomy. Eur J Cardiothorac Surg. 2010 Mar;37(3):588-93. doi: 10.1016/j.ejcts.2009.07.040. Epub 2009 Sep 12.

Reference Type: BACKGROUND

PMID: 19748277 (View on PubMed)

Burton AW, Lee DH, Saab C, Chung JM. Preemptive intrathecal ketamine injection produces a long-lasting decrease in neuropathic pain behaviors in a rat model. Reg Anesth Pain Med. 1999 May-Jun;24(3):208-13. doi: 10.1016/s1098-7339(99)90129-3.

Reference Type: BACKGROUND

PMID: 10338169 (View on PubMed)

Lee IO, Lee IH. Systemic, but not intrathecal, ketamine produces preemptive analgesia in the rat formalin model. Acta Anaesthesiol Sin. 2001 Sep;39(3):123-7.

Reference Type: BACKGROUND

PMID: 11688102 (View on PubMed)

Mathews TJ, Churchhouse AM, Housden T, Dunning J. Does adding ketamine to morphine patient-controlled analgesia safely improve post-thoracotomy pain? Interact Cardiovasc Thorac Surg. 2012 Feb;14(2):194-9. doi: 10.1093/icvts/ivr081. Epub 2011 Nov 28.

Reference Type: BACKGROUND

PMID: 22159259 (View on PubMed)

Joseph C, Gaillat F, Duponq R, Lieven R, Baumstarck K, Thomas P, Penot-Ragon C, Kerbaul F. Is there any benefit to adding intravenous ketamine to patient-controlled epidural analgesia after thoracic surgery? A randomized double-blind study. Eur J Cardiothorac Surg. 2012 Oct;42(4):e58-65. doi: 10.1093/ejcts/ezs398. Epub 2012 Jul 12.

Reference Type: BACKGROUND

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Tena B, Gomar C, Rios J. Perioperative epidural or intravenous ketamine does not improve the effectiveness of thoracic epidural analgesia for acute and chronic pain after thoracotomy. Clin J Pain. 2014 Jun;30(6):490-500. doi: 10.1097/AJP.0000000000000005.

Reference Type: BACKGROUND

PMID: 24281290 (View on PubMed)

D'Alonzo RC, Bennett-Guerrero E, Podgoreanu M, D'Amico TA, Harpole DH, Shaw AD. A randomized, double blind, placebo controlled clinical trial of the preoperative use of ketamine for reducing inflammation and pain after thoracic surgery. J Anesth. 2011 Oct;25(5):672-8. doi: 10.1007/s00540-011-1206-4. Epub 2011 Aug 2.

Reference Type: BACKGROUND

PMID: 21809148 (View on PubMed)

Yazigi A, Abou-Zeid H, Srouji T, Madi-Jebara S, Haddad F, Jabbour K. The effect of low-dose intravenous ketamine on continuous intercostal analgesia following thoracotomy. Ann Card Anaesth. 2012 Jan-Mar;15(1):32-8. doi: 10.4103/0971-9784.91479.

Reference Type: BACKGROUND

PMID: 22234019 (View on PubMed)

Suzuki M, Haraguti S, Sugimoto K, Kikutani T, Shimada Y, Sakamoto A. Low-dose intravenous ketamine potentiates epidural analgesia after thoracotomy. Anesthesiology. 2006 Jul;105(1):111-9. doi: 10.1097/00000542-200607000-00020.

Reference Type: BACKGROUND

PMID: 16810002 (View on PubMed)

Feltracco P, Barbieri S, Rizzi S, Ori C, Groppa F, De Rosa G, Frigo AC, Padrini R. Brief report: perioperative analgesic efficacy and plasma concentrations of S+ -ketamine in continuous epidural infusion during thoracic surgery. Anesth Analg. 2013 Jun;116(6):1371-5. doi: 10.1213/ANE.0b013e31828cbaf0. Epub 2013 Apr 4.

Reference Type: BACKGROUND

PMID: 23558843 (View on PubMed)

Other Identifiers

513/12

Identifier Type: -

Identifier Source: org_study_id