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

Not Applicable
Completed
Conditions
Post Thoracotomy Pain
Interventions
Drug: Normal Saline
Registration Number
NCT03415191
Lead Sponsor
University of Campania "Luigi Vanvitelli"
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
75
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Ketamine GroupKetamineFive minutes before thoracotomy incision, Ketamine Group received a bolus dose of ketamine 1 mg/kg intravenously
Placebo GroupNormal SalineFive minutes before thoracotomy incision, Placebo Group received a bolus dose of normal saline 1 mg/kg intravenously
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Pain Scores on the Visual Analog Scale at 48 hours6 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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in c-Reactive Protein (CRP) serum levels at 48 hours6 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

Change From Baseline in morphine consumption at 48 hours6 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

Indicence of clinical adverse effect in the entire post operative courseentire post-operative course

blurred vision, hallucination, nightmares, vertigo, or nausea and vomiting

Trial Locations

Locations (1)

Alfonso Fiorelli

🇮🇹

Naples, Italy

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