Prevention of Persistent Postsurgical Pain After Thoracotomy

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Hospital Clinic of Barcelona.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier:
NCT01243801
First received: November 15, 2010
Last updated: June 22, 2011
Last verified: June 2011

November 15, 2010
June 22, 2011
September 2008
October 2011   (final data collection date for primary outcome measure)
  • Change from subjective pain scales: Visual Analogical Scale, Neuropathic Pain Symptoms Inventory, Catastrophism Scale [ Time Frame: -1day, 3 days, 7 days, 3 months, 6 months ] [ Designated as safety issue: No ]
    Pain measured with these subjective scales are assessed preoperatively (-1 day) and 3, 7 days, 3 and 6 months after surgery
  • Change from hyperalgesia periincisional area [ Time Frame: -1day, 3day,7day,3 months, 6 months ] [ Designated as safety issue: No ]
    Hyperalgesia is measured with von Frey monofilaments, electronic von frey and electric brush around the surgical incision and in a separate area (thigh)
Same as current
Complete list of historical versions of study NCT01243801 on ClinicalTrials.gov Archive Site
Adverse effects [ Time Frame: any time until 6 months ] [ Designated as safety issue: Yes ]
Any adverse effects related to the use of ketamine (cognitive effects, visual effects, haemodynamic effects or sedation effects)
Same as current
Not Provided
Not Provided
 
Prevention of Persistent Postsurgical Pain After Thoracotomy
Phase 4 Study of Prevention of Persistent Postsurgical Pain After Thoracotomy Using Ketamine

Postthoracotomy acute pain is followed by persistent postsurgical pain in 20-30% of the patients, defined as pain that lasts more than 3-6 months after surgery. Acute pain and hyperalgesia around the surgical wound are some of the risk factors associated to the development of chronic pain. Ketamine, as a NMDA antagonist mainly at spinal level, might reduce periincisional hyperalgesia and persistent postsurgical pain after thoracotomy. Therefore, the investigators hypothesized that continuous ketamine infusion at subanesthetic dose would potentiate epidural ropivacaine and fentanyl-induced analgesia after thoracotomy, reduce periincisional hyperalgesia and long-term postoperative pain. To test these hypothesis, the investigators administered a low dose of intravenous ketamine or epidural ketamine or placebo to patients who received an epidural infusion of ropivacaine and fentanyl for postthoracotomy pain.

Chronic pain is a frequent complication after common surgical procedures such as amputation, mastectomy or thoracotomy. A rate between 20 and 60% of patients undergoing thoracotomy are reported to develop long-lasting pain.

The causes of chronic pain after surgery are not fully known but several risk factors have been identified including pre and postoperative pain, nerve injury during surgery and physicological and genetic factors. The observed symptoms of allodynia and hyperalgesia in the periincisional area and evidence of intercostal nerve injury due to rib retraction during surgery suggest a neuropathic aetiology.

Excitatory neurotransmitters, acting through N-metil-aspartate receptor, have been recently postulated to play an important role in the development and maintenance of pathologic pain states. In experimental pain research, NMDA receptor antagonists reduced wind-up and central sensitization. Ketamine is one of the few NMDA antagonists available in clinical practice that, administered at subanesthetic doses, would inhibit the spinal processing of nociceptive input.

It has been proposed that analgesic drugs might more adequately prevent central sensitization when administered during the entire period of high-intensity noxious stimulation.

Therefore, the investigators hypothesized that continuous ketamine infusion would potentiate epidural ropivacaine and fentanyl-induced analgesia after posterolateral thoracotomy or minithoracotomy, reduce periincisional hyperalgesia and long-term postoperative pain. To test these hypothesis, the investigators administered a low dose of intravenous or epidural ketamine or placebo to patients who received an epidural infusion of ropivacaine and fentanyl for postthoracotomy pain.

The Institutional Review Board of the hospital approved this study, and each patient gave written informed consent. The investigators planned to enroll 90 patients who were scheduled to undergo posterolateral thoracotomy or minithoracotomy in this double-blind, controlled, randomized study. Patients who met the inclusion and exclusion criteria would be included and assigned to one of the three groups by a computer-generated schedule. Patients, nurses in charge of postoperative care, and staff members, who inform the patient performed analgesia, and collected data are blinded to the group.

The day before surgery patients are instructed on the use of Patient Controlled Analgesia pump, Visual Analogue Scale (VAS) and the Quantitative Sensory Testing. Subjective tests (VAS, neuropathic pain symptom inventory, pain catastrophizing scale) and QST are also performed the day before surgery.

Anesthetic management is standardized to all study patients. Premedication with sublingual diazepam (5-10 mg) is administered 2 hours before surgery. A thoracic epidural catheter is placed before induction through the T7-8 interspace. General anesthesia is induced by fentanyl (3 mcg/kg), propofol (2mg/kg) and cisatracurium (0.15 mg/kg). A double-lumen endobronchial tube is placed to perform differential one-lung ventilation. The left radial arteria is secured for arterial pressure monitoring and arterial blood sampling. Monitoring included electrocardiography, haemoglobin oxygen saturation, end-tidal carbon dioxide tension and invasive arterial pressure. A bolus of ketamine or placebo, intravenous or epidurally, according to the group of study is administered before skin incision. The study drug is prepared and placed by a nurse who does not participate in the anesthesia or evaluation of postoperative pain. Anesthesia is maintained by sevoflurane 1.5-2%, fentanyl and cisatracurium titrated according to the patients´needs. At the end of the skin closure, 5-7 ml of ropivacaine 0.2% is administered epidurally followed by epidural infusion of ropivacaine 0.15% and fentanyl 2mcg/ml and epidural or intravenous infusion of ketamine or placebo according to the group. Patients are extubated in the operating room and transferred to the postanesthesia care unit.

Epidural infusion is maintained for 48 hours at a rate of 3-6ml/h, boluses of 2-3 ml are allowed every 20 minutes.The protocol for rescue analgesia consisted of the first administration of iv metamizol 2g per 8 hours. The second rescue analgesia line consisted of the adjunction of subcutaneous methadone 3-6 mg per 8 hours. Patients remained in the postanesthesia care unit for 24 hours. Pain at rest and on coughing is assessed with VAS at 1-4-8-12-24-72 hours. Side effects including cognitive effects such as nightmares or hallucinations, blurred vision, sedation (not arousable except by persisting verbal or tactile stimulation), or haemodynamic effects (hypertension over 20% their basal values). Subjective test and QST are performed at 72h, 7 day, 3 and 6 months after surgery.

The investigators considered 30 patients per group in order to obtain 3 points of difference of the ratio between the hyperalgesia area and the incision length, considering a SD of differences of 3.5, type I error of 0.05 and statistical power of 0.9.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Persistent Pain
  • Postoperative Hyperalgesia
Drug: Ketamine
Intravenous ketamine 0.5mg/kg(induction of anesthesia)and 0.25 mg/kg/h for 48h Epidural Ketamine 0.5 mg/kg(induction of anesthesia)and 0.25 mg/kg/h for 48h
  • Active Comparator: Epidural ketamine
    • Bolus of epidural ketamine during the induction of anesthesia
    • Epidural infusion of ketamine during the first 48 h after surgery

    Postoperative analgesia: Epidural "Patient Controlled Analgesia" with ropivacaine and fentanyl

    Intervention: Drug: Ketamine
  • Active Comparator: Intravenous ketamine
    • Bolus of intravenous ketamine administered during the induction of anesthesia
    • Intravenous infusion during the first 48 hours after surgery

    Postoperative analgesia: Epidural "Patient Controlled Analgesia" with ropivacaine plus fentanyl

    Intervention: Drug: Ketamine
  • Placebo Comparator: Placebo
    Postoperative analgesia: Epidural "Patient Controlled Analgesia" with ropivacaine and fentanyl
    Intervention: Drug: Ketamine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
90
December 2011
October 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients over 18 years old submitted to thoracotomy or minithoracotomy expected to be extubated in the operating room

Exclusion Criteria:

  • Allergy or intolerance to ketamine, local anesthetics or opioids
  • Chronic preoperative pain
  • Chronic opioid treatment
  • Drug addiction
  • Polyneuropathy
  • Ischemic cardiopathy
  • Psychiatric disease
Both
18 Years and older
No
Spain
 
NCT01243801
BTB-10
No
Beatriz Tena, Anesthesiology Department. Hospital Clinic Barcelona
Hospital Clinic of Barcelona
Not Provided
Principal Investigator: Beatriz Tena, MD Hospital Clinic of Barcelona
Study Director: Carmen Gomar, PhD Hospital Clinic of Barcelona
Study Chair: Irene Rovira, PhD Hospital Clinic of Barcelona
Study Chair: Maria J Jimenez, PhD Hospital Clinic of Barcelona
Study Chair: Guillermina Fita, PhD Hospital Clinic of Barcelona
Study Chair: Samuel Garcia, MD Hospital Clinic of Barcelona
Study Chair: Jordi Perez, PhD Hospital Clinic of Barcelona
Study Chair: Daniel Poggio, MD Hospital Clinic of Barcelona
Study Chair: Jose Rios Hospital Clinic of Barcelona
Hospital Clinic of Barcelona
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP