Parecoxib as an Adjuvant to Scalp Nerve Blocks for Relief of Post-craniotomy Pain

NCT04034836 | Unknown Phase 4 DMC

• 1 other identifier: KY 2018-034-02-2
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

Pain is common for the first 2 days after major craniotomy. Inadequate analgesia induced sympathetically mediated hypertension may lead to an increased risk for post-operative complications, such as arterial hypertension, intracranial hemorrhage, prolonged hospital stay, and mortality.Pain after craniotomy derives from the scalp and pericranial muscles.Scalp block with local anesthesia seems to provide effective and safe anesthetic management.Scalp block can be performed by directly blocking the six different nerves that provide the sensory innervation of the scalp in neurological surgery.Even if adrenaline as an additive agent, scalp block using 0.5% or 0.75% bupivacaine with adrenaline could only improve postoperative analgesic for up to six hours after craniotomy.However, pain is common for the first 2 days after major elective intracranial surgery, and the relatively short analgesic time of scalp nerve blocks does not seem to meet the requirements of craniotomy. Therefore, how to improve the quality and duration of scalp nerve blocks with local anesthetics is of great significance.Parecoxib is a NSAIDs that specifically inhibits the enzyme COX-2.Liu et al firstly applied parecoxib as an adjuvant to local anesthetics on peripheral nerve blocks and reported 20 mg parecoxib added to ropivacaine injected locally on the brachial plexus nerve prolonged the motor and sensory block times of the nerve blockade and ameliorated postoperative pain intensity for patients receiving forearm orthopaedic surgery. However, there has not been reported about local application of parecoxib on scalp nerve blocks. The investigators postulate that parecoxib may be also ideal for scalp nerve blocks for relief of post-craniotomy pain, and further research is needed. The APONIA trial aims to establish whether scalp blocks with a mixture of ropivacaine plus parecoxib is able to relieve patients' postoperative pain compared with local anesthetics alone, thereby potentially changing medical practice.

Conditions

Pain, Postoperative; Neurosurgery

Keywords

Pain, Postoperative; Parecoxib; Ropivacaine; Scalp nerve blocks; Craniotomy

Outcome Measures

Primary Outcomes (1)

• The time to the first rescue analgesic

  Postoperatively, when the patient reports an NRS score of 4 or more or at the request of the patient, patients will be treated with morphine 2 mg intravenously as first rescue analgesic. Morphine 5 mg intravenously will be used as a second rescue analgesic if the NRS remained at 4 despite the use of morphine 2 mg.

  Within 48 hours after the operation

Secondary Outcomes (12)

• Numerical rating scale of pain

  At 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, 24 hours, 48 hours after surgery

• Glasgow Coma Scale (GCS) score

  At 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, 24 hours, 48 hours after surgery

• The doses of extra sufentanil boluses

  During the surgery

• Number of participates using extra sufentanil boluses

  During the surgery

• Number of participates with postoperative nausea and vomiting (PONV)

  Within 48 hours postoperatively

Study Arms (3)

The scalp blocks group

EXPERIMENTAL

The scalp blocks group will receive scalp blocks with ropivacaine, 20ml, plus 10 mg parecoxib (diluted in 2 mL NS) with epinephrine (5 ug/mL) and i.v. saline 2ml;

Drug: Scalp blocks with ropivacaine plus parecoxib

The i.v. group

ACTIVE COMPARATOR

The i.v. group will receive scalp blocks with ropivacaine 20ml, plus saline 2ml with epinephrine (5 ug/mL) together with 10 mg parecoxib (diluted in 2 mL NS) intravenously.

Drug: Scalp blocks with ropivacaine and intravenous parecoxib

The control group

ACTIVE COMPARATOR

The control group will receive scalp blocks with ropivacaine, 20ml, plus saline 2ml with epinephrine (5 ug/mL) and i.v. saline 2ml;

Drug: Scalp blocks with ropivacaine and intravenous saline

Interventions

Scalp blocks with ropivacaine plus parecoxib DRUG

Scalp blocks with ropivacaine 0.75% wt/vol, 20ml, plus 10 mg parecoxib (diluted in 2 mL NS) with epinephrine at 1:200,000 (5 ug/mL) and i.v. saline 2ml;An independent researcher will prepare the study solution in a separate operating room. The study solutions with syringes (50-ml) for the scalp blocks and syringes (5-ml) for intravenous injection are prepared and numbered with a 23-gauge needle by an independent researcher, after opening the envelope containing the allocation of treatment. After induction, the assigned solutions will be injected subcutaneously or intravenously separately by the anesthesiologist. The scalp blocks will be performed along the lines of the technique previously described by Pinosky et al. The following nerves were blocked bilaterally: the supraorbital and supratrochlear nerves; the zygomatico-temporal nerves; the auriculotemporal nerves; the postauricular branches of the greater auricular nerves; the greater, lesser, and third occipital nerves.

The scalp blocks group

Scalp blocks with ropivacaine and intravenous parecoxib DRUG

Scalp blocks with ropivacaine 0.75% wt/vol, 20ml, plus saline 2ml with epinephrine at 1:200,000 (5 ug/mL) together with 10 mg parecoxib (diluted in 2 mL NS) intravenously. An independent researcher will prepare the study solution in a separate operating room. The study solutions with syringes (50-ml) for the scalp blocks and syringes (5-ml) for intravenous injection are prepared and numbered with a 23-gauge needle, after opening the envelope containing the allocation of treatment. After induction, the assigned solutions will be injected subcutaneously or intravenously separately by the anesthesiologist. The scalp blocks will be performed along the lines of the technique previously described by Pinosky et al. The following nerves were blocked bilaterally: the supraorbital and supratrochlear nerves; the zygomatico-temporal nerves; the auriculotemporal nerves; the postauricular branches of the greater auricular nerves; the greater, lesser, and third occipital nerves.

The i.v. group

Scalp blocks with ropivacaine and intravenous saline DRUG

Scalp blocks with ropivacaine 0.75% wt/vol, 20ml, plus saline 2ml with epinephrine at 1:200,000 (5 ug/mL) and i.v. saline 2ml. An independent researcher will prepare the study solution in a separate operating room. The study solutions with syringes (50-ml) for the scalp blocks and syringes (5-ml) for intravenous injection are prepared and numbered with a 23-gauge needle by an independent researcher, after opening the envelope containing the allocation of treatment. After induction, the assigned solutions will be injected subcutaneously or intravenously separately by the anesthesiologist. The scalp blocks will be performed along the lines of the technique previously described by Pinosky et al. The following nerves were blocked bilaterally: the supraorbital and supratrochlear nerves; the zygomatico-temporal nerves; the auriculotemporal nerves; the postauricular branches of the greater auricular nerves; the greater, lesser, and third occipital nerves.

The control group

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients aged 18 to 64 years
• American Society of Anesthesiologists (ASA) physical status of I, II and III
• Preoperative Glasgow Coma Scale (GCS) score of 15/15
• Scheduled for elective craniotomy under general anesthesia

You may not qualify if:

• Patients with chronic headache or chronic pain syndrome for any reason
• Patients with psychiatric disorders, uncontrolled epilepsy, coagulopathy, infection around puncture point
• Inability to understand and incapacity to use the pain scales before surgery
• Pregnancy or at breastfeeding;
• Participation in another intervention trial that interferes with the intervention or outcome of this trial
• History of allergies to any of the study drugs
• Refusal to participate or unable to acquire informed consent provided by the patients and/or legal guardian
• Having their first craniotomy surgery with an occipital bone defect
• Excessive alcohol or drug abuse, chronic opioid use (more than 2 weeks or 3 days per week for more than 1 month), use of drugs with confirmed or suspected sedative or analgesic effects, use of any painkiller within 24 hours before surgery
• Extreme body mass index (BMI) (\< 15 or \> 35);

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100070, China

RECRUITING

Related Publications (14)

• Gottschalk A, Berkow LC, Stevens RD, Mirski M, Thompson RE, White ED, Weingart JD, Long DM, Yaster M. Prospective evaluation of pain and analgesic use following major elective intracranial surgery. J Neurosurg. 2007 Feb;106(2):210-6. doi: 10.3171/jns.2007.106.2.210.

  PMID: 17410701 BACKGROUND

• Basali A, Mascha EJ, Kalfas I, Schubert A. Relation between perioperative hypertension and intracranial hemorrhage after craniotomy. Anesthesiology. 2000 Jul;93(1):48-54. doi: 10.1097/00000542-200007000-00012.

  PMID: 10861145 BACKGROUND

• Flexman AM, Ng JL, Gelb AW. Acute and chronic pain following craniotomy. Curr Opin Anaesthesiol. 2010 Oct;23(5):551-7. doi: 10.1097/ACO.0b013e32833e15b9.

  PMID: 20717011 BACKGROUND

• Dunn LK, Naik BI, Nemergut EC, Durieux ME. Post-Craniotomy Pain Management: Beyond Opioids. Curr Neurol Neurosci Rep. 2016 Oct;16(10):93. doi: 10.1007/s11910-016-0693-y.

  PMID: 27604271 BACKGROUND

• Chaki T, Sugino S, Janicki PK, Ishioka Y, Hatakeyama Y, Hayase T, Kaneuchi-Yamashita M, Kohri N, Yamakage M. Efficacy and Safety of a Lidocaine and Ropivacaine Mixture for Scalp Nerve Block and Local Infiltration Anesthesia in Patients Undergoing Awake Craniotomy. J Neurosurg Anesthesiol. 2016 Jan;28(1):1-5. doi: 10.1097/ANA.0000000000000149.

  PMID: 25493926 BACKGROUND

• Lee EJ, Lee MY, Shyr MH, Cheng JT, Toung TJ, Mirski MA, Chen TY. Adjuvant bupivacaine scalp block facilitates stabilization of hemodynamics in patients undergoing craniotomy with general anesthesia: a preliminary report. J Clin Anesth. 2006 Nov;18(7):490-4. doi: 10.1016/j.jclinane.2006.02.014.

  PMID: 17126775 BACKGROUND

• Nguyen A, Girard F, Boudreault D, Fugere F, Ruel M, Moumdjian R, Bouthilier A, Caron JL, Bojanowski MW, Girard DC. Scalp nerve blocks decrease the severity of pain after craniotomy. Anesth Analg. 2001 Nov;93(5):1272-6. doi: 10.1097/00000539-200111000-00048.

  PMID: 11682413 BACKGROUND

• Bala I, Gupta B, Bhardwaj N, Ghai B, Khosla VK. Effect of scalp block on postoperative pain relief in craniotomy patients. Anaesth Intensive Care. 2006 Apr;34(2):224-7. doi: 10.1177/0310057X0603400203.

  PMID: 16617645 BACKGROUND

• Romsing J, Moiniche S. A systematic review of COX-2 inhibitors compared with traditional NSAIDs, or different COX-2 inhibitors for post-operative pain. Acta Anaesthesiol Scand. 2004 May;48(5):525-46. doi: 10.1111/j.0001-5172.2004.00379.x.

  PMID: 15101847 BACKGROUND

• Romsing J, Moiniche S, Ostergaard D, Dahl JB. Local infiltration with NSAIDs for postoperative analgesia: evidence for a peripheral analgesic action. Acta Anaesthesiol Scand. 2000 Jul;44(6):672-83. doi: 10.1034/j.1399-6576.2000.440607.x.

  PMID: 10903014 BACKGROUND

• Koppert W, Wehrfritz A, Korber N, Sittl R, Albrecht S, Schuttler J, Schmelz M. The cyclooxygenase isozyme inhibitors parecoxib and paracetamol reduce central hyperalgesia in humans. Pain. 2004 Mar;108(1-2):148-53. doi: 10.1016/j.pain.2003.12.017.

  PMID: 15109518 BACKGROUND

• Williams DL, Pemberton E, Leslie K. Effect of intravenous parecoxib on post-craniotomy pain. Br J Anaesth. 2011 Sep;107(3):398-403. doi: 10.1093/bja/aer223.

  PMID: 21841050 BACKGROUND

• Liu X, Zhao X, Lou J, Wang Y, Shen X. Parecoxib added to ropivacaine prolongs duration of axillary brachial plexus blockade and relieves postoperative pain. Clin Orthop Relat Res. 2013 Feb;471(2):562-8. doi: 10.1007/s11999-012-2691-y. Epub 2012 Nov 21.

  PMID: 23179117 BACKGROUND

• Krauss P, Marahori NA, Oertel MF, Barth F, Stieglitz LH. Better Hemodynamics and Less Antihypertensive Medication: Comparison of Scalp Block and Local Infiltration Anesthesia for Skull-Pin Placement in Awake Deep Brain Stimulation Surgery. World Neurosurg. 2018 Dec;120:e991-e999. doi: 10.1016/j.wneu.2018.08.210. Epub 2018 Sep 7.

  PMID: 30196173 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Ropivacaine; parecoxib

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Fang Luo, M.D.

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fang Luo, M.D.

CONTACT

+86 13611326978; 13611326978@163.com

Chunmei Zhao, M.D.

CONTACT

+86 15510286930; zhaochunmei1206@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Pain Management

Study Record Dates

• First Submitted: July 21, 2019
• First Posted: July 26, 2019
• Study Start: October 12, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: June 16, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)