Pre-emptive Scalp Infiltration With Dexamethasone Plus Ropivacaine for Post-Craniotomy Pain in Children

At present, pediatric postoperative analgesia has not been fully understood and controlled, particularly craniotomy surgery. On the one hand, professional evaluation of postoperative pain for young children is difficult; on the other hand, the particularity of craniotomy adds (such as consciousness obstacle, sleepiness, et al) disturbance to the pain assessment in children. Although opioids administration is regarded as the first-line analgesic for post-craniotomy pain management, it may be associated with delayed awakening, respiratory depression, hypercarbia and it may interfere with the neurologic examination. For the avoidance of side-effects of systemic opioids, local anesthetics administered around the incision have been performed clinically. However, some studies revealed that the analgesic effect of local anesthetics was unsatisfactory due to its short pain relief duration, steroid as adjuvant can enhance postoperative analgesia and prolong postoperative analgesia time. As is reported that postoperative pain of craniotomy is mainly caused by skin incision and reflection of muscles, preventing the liberation of inflammatory mediators around the incision seems to be more effective than simply blocking nerve conduction. Researchers have clarified that the addition of dexamethasone to local infiltration of analgesia could provide significant analgesic effects and significantly prolong the duration of analgesic effects without obvious complications for various types of surgeries. To date, no studies have evaluated the addition of dexamethasone to local infiltration for patients receiving craniotomy. Thus, investigators suppose that pre-emptive scalp infiltration with steroid (Dexamethasone) plus local anesthetic (ropivacaine) could relieve postoperative pain after craniotomy in children.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative; Children
• Intervention / Treatment: Drug: The dexamethasone plus ropivacaine; Drug: The ropivacaine

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing TianTan Hospital
    • Beijing, Beijing, China
      • Beijing Children's hospital affiliated to capital medical university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 12 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• An elective craniotomy under general anesthesia;
• American Society of Anesthesiologists (ASA) physical status of I or II;
• Participates with an anticipated fully recovery within 2 hours postoperatively;
• Informed consent by parent(s) and/or legal guardian.

Exclusion Criteria:

• History of allergies to any of the study drugs;
• Drugs with confirmed or suspected sedative or analgesic effects; receiving any painkiller within 24 h before surgery; children who received steroids;
• Psychiatric disorders;
• Uncontrolled epilepsy;
• Chronic headache;
• Peri-incisional infection;
• Body mass index exceeded the 99th percentile for age;
• Children who must use a patient-controlled analgesia (PCA) device;
• Children who cannot understand an instruction of pain scales before surgery.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: The dexamethasone plus ropivacaine group; Patients in the dexamethasone plus ropivacaine group will receive a peri-incisional scalp infiltration with 0.025% dexamethasone and 0.2% ropivacaine and normal saline miscible liquids.	Drug: The dexamethasone plus ropivacaine; The local infiltration solution containing 0.25mg Dexamethasone and 2mg ropivacaine per milliliter. The total volume is 20 ml. The assigned solution will be injected subcutaneously by surgeons along the incision and throughout the entire thickness of the scalp before skin incision. The volume of local infiltration solution will be decided by surgeons according to the cut length, and the capacity of the solution will be recorded by investigators.
ACTIVE_COMPARATOR: The ropivacaine group; Patients in the ropivacaine group will receive a peri-incisional scalp infiltration with 0.2% ropivacaine and normal saline miscible liquids.	Drug: The ropivacaine; The local infiltration solution containing 2mg ropivacaine per milliliter. The total volume is 20 ml. The assigned solution will be injected subcutaneously by surgeons along the incision and throughout the entire thickness of the scalp before skin incision. The volume of local infiltration solution will be decided by surgeons according to the cut length, and the capacity of the solution will be recorded by investigators.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS)	Postoperative pain will be estimated by using the modified Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS). 0 indicates no pain, 10 indicates the most severe pain imaginable.	At 24 hours after the operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 1 month after surgery
Heart rate		During the operation and at 2 hours, 4 hours, 8 hours, 24 hours after surgery
Mean arterial pressure		During the operation and at 2 hours, 4 hours, 8 hours, 24 hours after surgery
The total consumption of opioids during the operation		During procedure
The total consumption of anaesthetic during the operation		During procedure
modified Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS)	Postoperative pain will be estimated by using the modified Children's Hospital of Eastern Ontario Pain Scale (mCHEOPS). 0 indicates no pain, 10 indicates the most severe pain imaginable.	At 2 hours, 4 hours, 8 hours, 48 hours, 72 hours, 1 week, 2 weeks after surgery
The time to the first rescue analgesic	Rescue analgesics will be administered if the patient exhibits signs of sympathetic stimulation in the form of undue tachycardia, a rise in mean arterial pressure (rise of >20% from the baseline), and mCHEOPS score above 5 (range 1 to 10) or if the children are in obvious pain and distress at any time point during a subjective assessment by the intensivist or parents.	Within 48 hours after the operation
Patient satisfactory scale (PSS)	0 for unsatisfactory, and 10 for very satisfied	At 2 hours, 4 hours, 8 hours, 48 hours, 72 hours, 1 week, 2 weeks after surgery
length of stay (LOS)	LOS will be recorded as the number of nights spent in hospital after surgery.	Approximately 2 weeks after the operation
The occurrence of postoperative nausea and vomiting (PONV)	PONV will be rated by participants as: 0, absent; 1, nausea not requiring treatment; 2, nausea requiring treatment; and 3, vomiting.	At 2 hours, 4 hours, 8 hours, 24 hours after surgery
Ramsay Sedation Scale (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.	At 2 hours, 4 hours, 8 hours, 24 hours after surgery
The occurrence of respiratory depression	Respiratory depression is defined as persistent (more than 1 minutes) oxygen desaturation 90 percent or respiratory rate less than 8 breaths per minute, or oxygen desaturation less than 94 percent along with respiratory rate less than 10 breaths per minute requiring supplemental oxygen to maintain oxygen saturation more than 94 percent in the absence of clinically obvious upper airway obstruction.	Within 48 hours after the operation
Incisional related adverse events	Incisional related adverse events Including delayed incisional healing, incisional infection, intracranial infection, scar healing.	Approximately 2 weeks after the operation
The occurrence of the Adverse events (AEs) and serious adverse events (SAEs)	An AE was defined as any untoward medical occurrence. An SAE included death, immediately life-threatening conditions, coma, in-patient hospitalisation or prolongation of existing hospitalisation.	Within 2 weeks after the operation

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Collaborators: Beijing Children's Hospital
• Investigators: Principal Investigator: Ming Ge, M.D., Beijing Children' Hospital, Capital Medical University

Publications and helpful links

General Publications

• 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.
• Bronco A, Pietrini D, Lamperti M, Somaini M, Tosi F, del Lungo LM, Zeimantz E, Tumolo M, Lampugnani E, Astuto M, Perna F, Zadra N, Meneghini L, Benucci V, Bussolin L, Scolari A, Savioli A, Locatelli BG, Prussiani V, Cazzaniga M, Mazzoleni F, Giussani C, Rota M, Ferland CE, Ingelmo PM. Incidence of pain after craniotomy in children. Paediatr Anaesth. 2014 Jul;24(7):781-7. doi: 10.1111/pan.12351. Epub 2014 Jan 28.
• Law-Koune JD, Szekely B, Fermanian C, Peuch C, Liu N, Fischler M. Scalp infiltration with bupivacaine plus epinephrine or plain ropivacaine reduces postoperative pain after supratentorial craniotomy. J Neurosurg Anesthesiol. 2005 Jul;17(3):139-43. doi: 10.1097/01.ana.0000171730.41008.da.
• Ikeuchi M, Kamimoto Y, Izumi M, Fukunaga K, Aso K, Sugimura N, Yokoyama M, Tani T. Effects of dexamethasone on local infiltration analgesia in total knee arthroplasty: a randomized controlled trial. Knee Surg Sports Traumatol Arthrosc. 2014 Jul;22(7):1638-43. doi: 10.1007/s00167-013-2367-5. Epub 2013 Jan 11.
• Ju NY, Cui GX, Gao W. Ropivacaine plus dexamethasone infiltration reduces postoperative pain after tonsillectomy and adenoidectomy. Int J Pediatr Otorhinolaryngol. 2013 Nov;77(11):1881-5. doi: 10.1016/j.ijporl.2013.08.037. Epub 2013 Sep 8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 2, 2019
• Primary Completion (ACTUAL): June 5, 2020
• Study Completion (ACTUAL): July 5, 2020

Study Registration Dates

• First Submitted: August 8, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (ACTUAL): August 9, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 21, 2020
• Last Update Submitted That Met QC Criteria: July 19, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anesthetics, Local; Dexamethasone; Ropivacaine
• Other Study ID Numbers: KY 2018-066-02-2

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