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

January 29, 2018 updated by: Alfonso Fiorelli, University of Campania "Luigi Vanvitelli"

Is The Pre-Emptive Administration Of Ketamine A Significant Adjunction To Intravenous Morphine Analgesia For Controlling Post-Operative Pain? A Randomized, Double Blind, Placebo Controlled Clinical Trial.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

75

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Naples, Italy, 84100
        • Alfonso Fiorelli

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ketamine Group
Five minutes before thoracotomy incision, Ketamine Group received a bolus dose of ketamine 1 mg/kg intravenously
Drug: Ketamine
A bolus dose of ketamine 1 mg/kg intravenously five minutes before surgical incision
Placebo Comparator: Placebo Group
Five minutes before thoracotomy incision, Placebo Group received a bolus dose of normal saline 1 mg/kg intravenously
Drug: Normal Saline
A bolus dose of normal saline 1 mg/kg intravenously five minutes before surgical incision

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Pain Scores on the Visual Analog Scale at 48 hours
Time Frame: 6 hours, 12 hours, 24 hours, 36 hours, and 48 hours after suregry
The primary end-point was to evaluate whether ketamine was able to reduce the postoperative pain at the first 48 post-operative hours, compared to placebo. The pain levels were scored using a Visual Analogue scale (VAS) ranging from 0=absence of pain to 10= maximal level of pain.
6 hours, 12 hours, 24 hours, 36 hours, and 48 hours after suregry

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in c-Reactive Protein (CRP) serum levels at 48 hours
Time Frame: 6 hours, 12 hours, 24 hours, 36 hours, and 48 hours following surgery.
The inflammatory response was represented by the measurements of c-Reactive Protein (CRP) serum levels in both arms
6 hours, 12 hours, 24 hours, 36 hours, and 48 hours following surgery.
Change From Baseline in morphine consumption at 48 hours
Time Frame: 6 hours, 12 hours, 24 hours, 36 hours, and 48 hours of postoperative course.
Cumulative dose of morphine consumption (in mg) was registered in post-operative course
6 hours, 12 hours, 24 hours, 36 hours, and 48 hours of postoperative course.
Indicence of clinical adverse effect in the entire post operative course
Time Frame: entire post-operative course
blurred vision, hallucination, nightmares, vertigo, or nausea and vomiting
entire post-operative course

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Campania "Luigi Vanvitelli"

Investigators

  • Principal Investigator: Alfonso Fiorelli, MD, PhD, University of Campania "Luigi Vanvitelli"

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 5, 2012

Primary Completion (Actual)

December 21, 2014

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

January 15, 2018

First Submitted That Met QC Criteria

January 29, 2018

First Posted (Actual)

January 30, 2018

Study Record Updates

Last Update Posted (Actual)

January 30, 2018

Last Update Submitted That Met QC Criteria

January 29, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 513/12

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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