Clinical trial NCT03411330: Safety and Efficacy of Addition of Hyaluronidase to Lidocaine and Bupivacaine in Scalp Nerves Block in Elective Craniotomy Operations, Comparative Study
Official title: Safety and Efficacy of Addition of Hyaluronidase to Lidocaine and Bupivacaine in Scalp Nerves Block in Elective Craniotomy Operations, Comparative Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Addition of Hyalase to Local Anesthetic in Scalp Block
Lead sponsor: Cairo University
Sponsor class: OTHER
Collaborators: name: Mohamed, Ahmed A., M.D.
name: Tarek Ahmed Radwan
name: Mohamed Mahmoud Mohamed
name: Hatem Abdellatif Mohamed
name: Badawy Mohammed Al-Kholy
First posted: 2018-01-26
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The investigators hypothesize that, the addition of hyaluronidase may affect the quality of the block by enhancing the spread of the local anaesthetics through the facial planes and thus, reaching the target nerves more easily, rapid and effective that may provide better effective block in short duration and lasting for longer duration. This effect will be measured in terms of "stress response" and " analgesic quality" Total sample size of 64 patients randomly allocated into two equal groups. According to study "Hyaluronidase in sub-Tenon's anesthesia for phacoemulsification" that was done and published in International Journal of Ophthalmology (2012) to detect difference in post-operative pain between those patients receiving Lidocaine only versus Lidocaine and hyaluronidase, sample size of 29 patients per group is needed with confidence level 95% power of the study 80% \& type I error 0.05. Sample size calculation was done using Medcalc Software version 15.4.
Primary purpose: SUPPORTIVE_CARE

Brief summary: Safety and efficacy of addition of hyaluronidase to lidocaine and bupivacaine in scalp nerves block in elective craniotomy operations,Comparative study

Detailed description: Patients undergoing craniotomy operations are susceptible to many injurious stimuli such as skin incision, insertion of cranial pins, dural incision, dural and skin closure. They cause different levels of nociception and these stimuli can result in sudden increases in blood pressure and heart rate due to triggering stress response.

Strategies to blunt these noxious stimuli and attenuate this stress response include administration of systemic opioids, deepening the level of anaesthesia. Scalp nerves block by local anaesthetics also can be used.

However, most systemically administered medications studied for post-craniotomy pain usually associated with side effects such as sedation, nausea, and vomiting and depressed ventilation such events are particularly important for post-craniotomy patients.

Using regional aesthetic techniques in addition to general anaesthesia have been conducted as multimodality managements for post-craniotomy pain and to decrease systemic administration of analgesics and hence decrease their systemic complications.

The stress response is the hormonal and metabolic changes that follow injury or trauma. This includes wide range of endocrinological and immunological effects. The stress response to surgery is characterized by increased secretion of pituitary hormones and activation of the sympathetic nervous system. Hypothalamic activation of the sympathetic autonomic nervous system results in increased secretion of catecholamines from the adrenal medulla and release of norepinephrine from presynaptic nerve terminals. IL-6 is produced in substantial quantities at the site of a surgical wound.IL-6 enters the circulation, and its concentration correlates with the severity of surgery and thus with the magnitude of the tissue injury. At 24 to 36 h after surgery, the levels of IL-6 in the plasma reach preoperative values, because its production is attenuated. Postoperative pain behaves like wound on plasma IL-6: intense postoperative pain correlates with the magnitude of tissue injury and subsides days after. Pain in the first 24 hours after brain surgery is a significant problem, with 60% to 80% of patients experiencing moderate to severe pain.

Blockade of scalp innervation which anesthetises both the superficial and deep layers of the scalp, was used as a means of decreasing hemodynamic reactions during and after craniotomy operations. Various protocols to control postoperative pain were suggested, including infiltration of the scalp with local anaesthetics. These include the use of 0.5% bupivacaine combined with additional lidocaine 2 %.

Hyaluronidase is a naturally produced enzyme, it's produced by various types of bacteria, and primary helps bacteria to dissolve hyaluronic acid that constitutes major component of the connective tissue substance thus helping spread of other bacterial products. On December 2005, the FDA approved a synthetic (recombinant or rDNA) human hyaluronidase. The addition of hyaluronidase to local anaesthetics has been shown to enhance safely and effectively the diffusion of the drug, thereby increasing the analgesic efficacy especially in the first minutes after injection

Eligibility criteria: Inclusion Criteria:

1. ASA Ι and II.
2. Both males and females, age (18-60) years.
3. Supine position.
4. Glasco coma scale more than 12.
5. Elective craniotomy operations.

Exclusion Criteria:

1. ASA ΙII or IV
2. History of allergy to the study drugs.
3. Surgery to remove pituitary tumours or affecting pituitary hormones.
4. Glasco coma scale less than 12.
5. The need for postoperative ventilation.

Primary outcomes:
measure: Post-operative pain evaluation
timeFrame: up to 24 hours postoperatively
Secondary outcomes:
measure: Haemodynamic Measures
timeFrame: Every 5 minutes during operation In first 24 hours postoperatively
measure: Interleukin 6 measurement
timeFrame: Interleukin 6 level will be measured before surgery (9:00 A.M),30 minutes after scalp nerves block, 60 minutes after skin incision and after 6 hours post-operative.
measure: Intraoperative rescue dose of opioid
timeFrame: 6 hours postoperative then every 2 hours for 24 hours.
measure: Time of first analgesic request
timeFrame: Intraoperative
measure: Haemodynamic effects
timeFrame: up to 24 hours postoperatively
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ahmed Abdalla Mohamed
Study officials:
References:
citation: Mohamed AA, Radwan TA, Mohamed MM, Mohamed HA, Mohamed Elemady MF, Osman SH, Safan TF, Khair TM, Ali NA, Fahmy RS, Belita MI, Abdalla SR, Seleem AA, Atta EM, Zaid OI, Ragab AS, Salem AE, AlKholy BM. Safety and efficacy of addition of hyaluronidase to a mixture of lidocaine and bupivacaine in scalp nerves block in elective craniotomy operations; comparative study. BMC Anesthesiol. 2018 Sep 15;18(1):129. doi: 10.1186/s12871-018-0590-9.