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

Study Overview
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Brief Summary
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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.

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

Conditions
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Pain, Postoperative, Neurosurgery

Intervention / Treatment
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* Drug: Scalp blocks with ropivacaine plus parecoxib
* Drug: Scalp blocks with ropivacaine and intravenous parecoxib
* Drug: Scalp blocks with ropivacaine and intravenous saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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);

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The scalp blocks group<br>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<br>* 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.<br>|
| Active Comparator: The i.v. group<br>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<br>* 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.<br>|
| Active Comparator: The control group<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical rating scale of pain | Pain will be assessed after surgery by a numerical rating scale (0 indicates no pain, 10 indicates the most severe pain imaginable) | At 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, 24 hours, 48 hours after surgery | 
| Glasgow Coma Scale (GCS) score | The scale is composed of three tests: eye, verbal and motor responses. The three values separately as well as their sum are considered. The lowest possible GCS (graded 1 in each element) is 3 (deep coma or death), while the highest is 15 (fully awake person). | 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 | Intraoperative analgesic requirement defined as extra sufentanil boluses required to blunt significant sympathetic response to surgical stimulation will be recorded. | During the surgery | 
| Number of participates using extra sufentanil boluses | Intraoperative analgesic requirement defined as extra sufentanil boluses required to blunt significant sympathetic response to surgical stimulation will be recorded. | During the surgery | 
| Number of participates with postoperative nausea and vomiting (PONV) | Vomiting will be defined as the forceful expulsion of gastric contents, and nausea will be defined as an unpleasant sensation associated with the urge to vomit. | Within 48 hours postoperatively | 
| Number of participates with bradycardia | An above 20% of decrease in heart rate from baseline values will be considered as clinically significant. | Within 48 hours postoperatively | 
| Number of participates with hypotension | An above 20% of decrease in blood pressure from baseline values will be considered as clinically significant | Within 48 hours postoperatively | 
| The time during PACU | Patients will be transferred to the postoperative care unit (PACU) after extubation. A modified Aldrete score > 9 will be required for discharge from the PACU to a ward. The time during PACU is defined as the duration in the PACU after surgery | Approximately 2 hours after the surgery | 
| Length of stay (LOS) | LOS is defined as the number of nights spent in the hospital after surgery | Approximately 2 weeks after the surgery | 
| Adverse Events | An AE will be defined as any untoward medical occurrence, such as local hematoma, nerve injury, intra-arterial injection, allergic or toxic reaction, deriving facial nerve paralysis from scalp block. | Approximately 2 weeks after the surgery | 
| Serious adverse events (SAEs) | Serious adverse events (SAEs) will include death, immediately life-threatening conditions, coma, inpatient hospitalization or prolongation of existing hospitalization, et al. | Approximately 2 weeks after the surgery | 
| patient satisfaction score (PSS) | Patient satisfaction will be assessed by the patient satisfaction score (PSS) (0 for unsatisfactory and 10 for very satisfactory) | At 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, 24 hours, 48 hours after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Postoperative, Parecoxib, Ropivacaine, Scalp nerve blocks, Craniotomy