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

Sponsor

Beijing Tiantan Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT04034836

Collaborator

(none)

132

Enrollment

Location

Arms

26.6

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative Neurosurgery	Drug: Scalp blocks with ropivacaine plus parecoxib Drug: Scalp blocks with ropivacaine and intravenous parecoxib Drug: Scalp blocks with ropivacaine and intravenous saline	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

132 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Oct 12, 2019

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: The scalp blocks group 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 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.
Active Comparator: The i.v. group 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 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.
Active Comparator: The control group 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 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.

Arm

Intervention/Treatment

Experimental: The scalp blocks group

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

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.

Active Comparator: The i.v. group

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

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.

Active Comparator: The control group

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

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.

Outcome Measures

Primary Outcome Measures

The time to the first rescue analgesic [Within 48 hours after the operation]
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.

Secondary Outcome Measures

Numerical rating scale of pain [At 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, 24 hours, 48 hours after surgery]
Pain will be assessed after surgery by a numerical rating scale (0 indicates no pain, 10 indicates the most severe pain imaginable)
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 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).
The doses of extra sufentanil boluses [During the surgery]
Intraoperative analgesic requirement defined as extra sufentanil boluses required to blunt significant sympathetic response to surgical stimulation will be recorded.
Number of participates using extra sufentanil boluses [During the surgery]
Intraoperative analgesic requirement defined as extra sufentanil boluses required to blunt significant sympathetic response to surgical stimulation will be recorded.
Number of participates with postoperative nausea and vomiting (PONV) [Within 48 hours postoperatively]
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.
Number of participates with bradycardia [Within 48 hours postoperatively]
An above 20% of decrease in heart rate from baseline values will be considered as clinically significant.
Number of participates with hypotension [Within 48 hours postoperatively]
An above 20% of decrease in blood pressure from baseline values will be considered as clinically significant
The time during PACU [Approximately 2 hours after the surgery]
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
Length of stay (LOS) [Approximately 2 weeks after the surgery]
LOS is defined as the number of nights spent in the hospital after surgery
Adverse Events [Approximately 2 weeks after the surgery]
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.
Serious adverse events (SAEs) [Approximately 2 weeks after the surgery]
Serious adverse events (SAEs) will include death, immediately life-threatening conditions, coma, inpatient hospitalization or prolongation of existing hospitalization, et al.
patient satisfaction score (PSS) [At 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, 24 hours, 48 hours after surgery]
Patient satisfaction will be assessed by the patient satisfaction score (PSS) (0 for unsatisfactory and 10 for very satisfactory)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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);