Safety and Efficacy of Addition of Hyaluronidase to Lidocaine and Bupivacaine in Scalp Nerves Block in Elective Craniotomy Operations, Comparative Study
Condition: Addition of Hyalase to Local Anesthetic in Scalp Block
Study type: Interventional
Phase: Early Phase 1

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
    

Intervention name(s): Hyaluronidase; Lidocaine; Bupivacaine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Scalp nerves block will be done using lidocaine (2%) in a maximum dose of 300 mg and bupivacaine (0.5%) with maximum allowed dose 175 mg in group A, Hyaluronidase will be added in group H in a dose of 1500 IU (The minimum and maximum effective doses of hyaluronidase are not known. The doses used range from0.75 IU/ml to 300 IU/ml; lidocaine (2%) in a maximum dose of 300 mg and bupivacaine (0.5%); bupivacaine (0.5%)
Other intervention name(s): Hyaluronidase with lidocaine and bupivacaine; Lidocaine alone; Bupivacaine alone
Intervention MeSH terms: Lidocaine; Bupivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
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.
Masking: Double (Participant, Investigator)
Primary purpose: Supportive Care