Effects of Pre-emptive Scalp Infiltration With Ketorolac and Ropivacaine for Post-craniotomy Pain

Study Overview
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Brief Summary
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The PAINLESS study is a single-center, prospective, randomized, open-label, blinded-endpoint (PROBE) controlled clinical study to compare the efficacy and safety of pre-emptive scalp infiltration with ropivacaine plus ketorolac and ropivacaine alone for postoperative pain relief in adults undergoing elective supratentorial craniotomies.

Detailed Description
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The proposed study will be a single-center, prospective, randomized, open-label, blinded-endpoint clinical trial designed to test the hypothesis that the addition of ketorolac to pre-emptive scalp infiltration analgesia can significantly improve analgesia after craniotomies. One hundred participants will be randomized to the ketorolac group or the control group. Patients in the ketorolac group will receive pre-emptive scalp infiltration with opivacaine,ketorolac and epinephrine while patients in the control group will receive pre-emptive scalp infiltration with ropivacaine and epinephrine.The primary outcome measure will be cumulative doses of patient-controlled analgesia (PCA) butorphanol consumption from 0 to 48 h postoperatively.

Official Title
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Effects of Pre-emptive Scalp Infiltration With Ketorolac and Ropivacaine for Postoperative Pain Relief After Elective Supratentorial Craniotomy (PAINLESS)

Conditions
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Pain, Supratentorial Brain Tumor

Intervention / Treatment
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* Drug: Ketorolac
* Drug: Ropivacaine
* Drug: Epinephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled for elective supratentorial tumour resection; Planned general anaesthesia; American Society of Anesthesiologists (ASA) physical status I - II; Age ranging from 18 to 65 years old; Participates required to fix their head in a head clamp intraoperatively; Participates with an anticipated awake within 2 hours after surgery. Exclusion Criteria: Allergy/intolerance to study drugs including anesthetic drugs, ketorolac and epinephrine; Expected delayed extubation or no plan to extubate; History of neurosurgeries; Long-term use of analgesics and sedatives (more than 2 weeks) Receiving any painkiller within 24 h before the operation; Extreme body mass index (BMI) (less than 15 or more than 35); Patients with impaired cardiopulmonary; Patients with impaired renal function; Patients with impaired hepatic function; History of chronic headache; Patients with cognitive deficit; Patients with intellectual disability; Patients with uncontrolled epilepsy; Patients with psychiatric disorders; Difficulties in using PCA device Difficulties in understanding the use of numeral rating scale (NRS) ; Patients with suspected intracranial hypertension; Pregnant or at breastfeeding; Infection at the incisional site； History of radiation therapy and chemotherapy preoperatively With great likelihood of postoperative radiation therapy and chemotherapy based on preoperative imaging.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The ketorolac group<br>Patients assigned to the ketorolac group will receive pre-emptive scalp infiltration with 30ml of local infiltration solution containing 60 mg ropivacaine, 6 mg ketorolac and 0.1mg epinephrine. | Drug: Ketorolac<br>* 30ml of local infiltration solution containing 60mg ropivacaine<br>Drug: Ropivacaine<br>* 30ml of local infiltration solution containing 6mg ketorolac<br>Drug: Epinephrine<br>* 30ml of local infiltration solution containing 0.1mg epinephrine<br>|
| Active Comparator: The control group<br>In the control group, preoperative peri-incisional scalp infiltration will be performed using 30ml of 60 mg ropivacaine and 0.1mg epinephrine. | Drug: Ropivacaine<br>* 30ml of local infiltration solution containing 6mg ketorolac<br>Drug: Epinephrine<br>* 30ml of local infiltration solution containing 0.1mg epinephrine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cumulative doses of patient-controlled analgesia (PCA) butorphanol consumption from 0 to 48 h postoperatively | The primary outcome measure will be cumulative doses of PCA butorphanol consumption from 0 to 48 h postoperatively | 0 to 48 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time to first request for patient-controlled analgesia butorphanol | The time to first request for patient-controlled analgesia butorphanol | Within 48hours postoperatively | 
| frequency of pressing patient-controlled analgesia pump | frequency of patient-controlled analgesia pump | Within 48hours postoperatively | 
| numeral rating scale (NRS) Score | 0 forno pain and 10 for 'pain as severe as you can imagine | at 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 72 hours, 1 week, 2 weeks, 1 month, 3 months and 6 months postoperatively | 
| Pain control satisfaction score (PCSS) postoperatively | 0 for unsatisfactory and 10 for very satisfactory | at 24 hours, 48 hours, 72 hours, 1 week, 1 month, 3 months and 6 months | 
| Ramsay sedation score (RSS) | 1: Anxious, agitated, restless; Ramsey 2: Cooperative, oriented, tranquil; Ramsey 3: Responsive to commands only If Asleep; Ramsey 4: Brisk response to light glabellar tap or loud auditory stimulus; Ramsey 5: Sluggish response to light glabellar tap or loud auditory stimulus; Ramsey 6: No response to light glabellar tap or loud auditory stimulus. Asleep; Ramsey 4: Brisk response to light glabellar tap or loud auditory stimulus; Ramsey 5: Sluggish response to light glabellar tap or loud auditory stimulus; Ramsey 6: No response to light glabellar tap or loud auditory stimulus. | at 2 hours, 4 hours, 8 hours, 24 hours and 48 hours and 72 hours postoperatively | 
| pulse oxygen saturation(SpO2) | SpO2 | 1 minutes before anesthesia induction, 1 minutes after anesthesia induction, 1 minutes after scalp infiltration, at the beginning of skull drilling, mater cutting and skin closure and at 2hours, 4 hours, 8 hours , 24 hours and 48 hours postoperatively | 
| mean arterial blood pressure(MAP) | MAP | 1 minutes before anesthesia induction, 1 minutes after anesthesia induction, 1 minutes after scalp infiltration, at the beginning of skull drilling, mater cutting and skin closure and at 2hours, 4 hours, 8 hours , 24 hours and 48 hours postoperatively | 
| heart rate(HR) | HR | 1 minutes before anesthesia induction, 1 minutes after anesthesia induction, 1 minutes after scalp infiltration, at the beginning of skull drilling, mater cutting and skin closure and at 2hours, 4 hours, 8 hours , 24 hours and 48 hours postoperatively | 
| respiratory rate(RR) | RR | 1 minutes before anesthesia induction, 1 minutes after anesthesia induction, 1 minutes after scalp infiltration, at the beginning of skull drilling, mater cutting and skin closure and at 2hours, 4 hours, 8 hours , 24 hours and 48 hours postoperatively | 
| Length of hospital stay | Length of hospital stay | Length of hospital stay, an arverage of 2 weeks | 
| Wound healing score | Skin Healing 1: fully healed; 2: ≤3 cm in total not healed; 3: >3 cm not healed; 4: areas of necrosis ≤3 cm; 5: areas of necrosis >3 cm Infection 1: none; 2: ≤0.5-cm margin of redness; 3: more redness or superficial pus; 4: deep infection; not applicable Hair Regrowth 1: even regrowth along wound; 2: ≤3 cm not regrowing; 3: >3-6 cm not regrowing; 4: >6 cm not regrowing; not applicable | at 3 weeks and 6 weeks after surgery | 
| postoperative nausea and vomiting(PONV) | 0, absent; 1, nausea but not requiring treatment; 2, nausea requiring treatment; and 3, vomiting | within 48 hours postoperatively | 
| The presence of respiratory depression | respiratory rate <10 breaths per minute or SpO2 was<90 % | within 48 hours postoperatively | 
| The incidence of haematoma, wound infection or gastric ulcers | side effects | during hospitalization, within 2 weeks postoperatively |