Clinical trial NCT00313378: Effects of Perioperative Systemic Ketamine on Development of Long-term Neuropathic Pain After Thoracotomy
Official title: Effects of Perioperative Systemic Ketamine on Development of Long-term Neuropathic Pain After Thoracotomy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Partial Pneumonectomy Under Lateral or Posterolateral Thoracotomy.
Keywords: Thoracotomy
Neuropathic pain
Nerve trauma
Ketamine
NMDA receptors
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2006-04-12
Enrollment: 78
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Lung surgery under thoracotomy is known to induce long-term pain which can be considered as neuropathic in many patients concerned \[1,2\]. The suspected origin of neuropathy is a direct traumatism of intercostal nerve(s) \[3\]. Among the possible preventive treatments that can be administered during the initial aggression, ketamine \[4,5\] appears as the easiest to use, as it is already commonly administered intra and postoperatively for improvement of analgesia \[6\].

Detailed description: Lung surgery under thoracotomy is known to induce long-term pain which can be considered as neuropathic in many patients concerned \[1,2\]. The suspected origin of neuropathy is a direct traumatism of intercostal nerve(s) \[3\]. Among the possible preventive treatments that can be administered during the initial aggression, ketamine \[4,5\] appears as the easiest to use, as it is already commonly administered intra and postoperatively for improvement of analgesia \[6\]. This study compares two groups of patients undergoing thoracotomy for partial pneumonectomy, one receiving intravenous ketamine since the beginning of procedure and then during 48 hours, the other receiving inactive normal saline (placebo). The study is prospective, randomized, and double-blinded. The primary endpoint is to reduce chronic pain (on visual analogue scale) at the 4th month after surgery with ketamine. The objective is to obtain a mean value under 20/100 in the ketamine group, considering that the expected mean value for the control group is 38/100 (based on personal observations). The secondary endpoints are lower scores of neuropathic pain in the ketamine group, assessed by the NPSI questionnaire \[7\]. The impact of treatment on quality of life, assessed by a questionnaire (SF-36), is also studied. The data collected by clinical and psychophysical examination performed on all patients at the 4th month after surgery will be also considered for analysis, in order to understand better the features of post-thoracotomy neuropathic pain.

Eligibility criteria: Inclusion Criteria:

* elective partial pneumonectomy under lateral or posterolateral thoracotomy, performed under standardized general anesthesia.

Exclusion Criteria:

* Patient's refusal
* Bad health status
* Previous neuropathic pain or treatment acting on neuropathic pain
* Major postoperative complication
* Intolerance to ketamine
* Epidural anesthesia

Primary outcomes:
measure: Reduction of chronic pain
Secondary outcomes:
measure: Reduction of signs of neuropathic pain.
measure: Improvement of quality of life.
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Clermont-Ferrand University Hospital
state: Auvergne
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Christian Duale, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Perttunen K, Tasmuth T, Kalso E. Chronic pain after thoracic surgery: a follow-up study. Acta Anaesthesiol Scand. 1999 May;43(5):563-7. doi: 10.1034/j.1399-6576.1999.430513.x.
citation: Gotoda Y, Kambara N, Sakai T, Kishi Y, Kodama K, Koyama T. The morbidity, time course and predictive factors for persistent post-thoracotomy pain. Eur J Pain. 2001;5(1):89-96. doi: 10.1053/eujp.2001.0225.
citation: Rogers ML, Henderson L, Mahajan RP, Duffy JP. Preliminary findings in the neurophysiological assessment of intercostal nerve injury during thoracotomy. Eur J Cardiothorac Surg. 2002 Feb;21(2):298-301. doi: 10.1016/s1010-7940(01)01104-6.
citation: Felsby S, Nielsen J, Arendt-Nielsen L, Jensen TS. NMDA receptor blockade in chronic neuropathic pain: a comparison of ketamine and magnesium chloride. Pain. 1996 Feb;64(2):283-291. doi: 10.1016/0304-3959(95)00113-1.
citation: 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.
citation: De Kock M, Lavand'homme P, Waterloos H. 'Balanced analgesia' in the perioperative period: is there a place for ketamine? Pain. 2001 Jun;92(3):373-380. doi: 10.1016/S0304-3959(01)00278-0.
citation: Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, Rostaing S, Lanteri-Minet M, Collin E, Grisart J, Boureau F. Development and validation of the Neuropathic Pain Symptom Inventory. Pain. 2004 Apr;108(3):248-257. doi: 10.1016/j.pain.2003.12.024.
citation: Duale C, Sibaud F, Guastella V, Vallet L, Gimbert YA, Taheri H, Filaire M, Schoeffler P, Dubray C. Perioperative ketamine does not prevent chronic pain after thoracotomy. Eur J Pain. 2009 May;13(5):497-505. doi: 10.1016/j.ejpain.2008.06.013. Epub 2008 Sep 9.