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

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

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.

Study Overview

• Status: Unknown
• Conditions: Pain; Supratentorial Brain Tumor
• Intervention / Treatment: Drug: Ketorolac; Drug: Ropivacaine; Drug: Epinephrine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Fang Luo, M.D; Phone Number: +8613611326978; Email: 13611326978@163.com
• Study Contact Backup: Name: Yitong Jia, M.D; Phone Number: +8613811109032; Email: 13811109032@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: The ketorolac group; 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; 30ml of local infiltration solution containing 60mg ropivacaine; Drug: Ropivacaine; 30ml of local infiltration solution containing 6mg ketorolac; Drug: Epinephrine; 30ml of local infiltration solution containing 0.1mg epinephrine
ACTIVE_COMPARATOR: The control group; In the control group, preoperative peri-incisional scalp infiltration will be performed using 30ml of 60 mg ropivacaine and 0.1mg epinephrine.	Drug: Ropivacaine; 30ml of local infiltration solution containing 6mg ketorolac; Drug: Epinephrine; 30ml of local infiltration solution containing 0.1mg epinephrine

What is the study measuring?

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 for"no 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

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Fang Luo, M.D, Beijing Tiantan hospital

Publications and helpful links

General Publications

• Vacas S, Van de Wiele B. Designing a pain management protocol for craniotomy: A narrative review and consideration of promising practices. Surg Neurol Int. 2017 Dec 6;8:291. doi: 10.4103/sni.sni_301_17. eCollection 2017.
• Andersen KV, Nikolajsen L, Haraldsted V, Odgaard A, Soballe K. Local infiltration analgesia for total knee arthroplasty: should ketorolac be added? Br J Anaesth. 2013 Aug;111(2):242-8. doi: 10.1093/bja/aet030. Epub 2013 Mar 20.
• Solovyova O, Lewis CG, Abrams JH, Grady-Benson J, Joyce ME, Schutzer SF, Arumugam S, Caminiti S, Sinha SK. Local infiltration analgesia followed by continuous infusion of local anesthetic solution for total hip arthroplasty: a prospective, randomized, double-blind, placebo-controlled study. J Bone Joint Surg Am. 2013 Nov 6;95(21):1935-41. doi: 10.2106/JBJS.L.00477.
• Song J, Li L, Yu P, Gao T, Liu K. Preemptive scalp infiltration with 0.5% ropivacaine and 1% lidocaine reduces postoperative pain after craniotomy. Acta Neurochir (Wien). 2015 Jun;157(6):993-8. doi: 10.1007/s00701-015-2394-8. Epub 2015 Apr 7.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2021
• Primary Completion (ANTICIPATED): July 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: October 20, 2019
• First Submitted That Met QC Criteria: October 24, 2019
• First Posted (ACTUAL): October 28, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 21, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Adrenergic alpha-Agonists; Adrenergic Agonists; Anesthetics, Local; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Ketorolac; Ropivacaine; Epinephrine
• Other Study ID Numbers: KY-2018-034-02-6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No