Diclofenac Administered Before Skull Operations Reduces the Severity of Headache After the Intervention
Condition: Postcraniotomy Headache; Intraoperative Analgesic Use; Postoperative Analgesic Use; Postoperative Complications
MeSH terms: Headache; Postoperative Complications
Study type: Interventional
Phase: Phase 4

Summary: 
      Purpose:

      According to the proposal of the International Headache Society acute postcraniotomy headache
      (PCH) is defined as a headache of variable intensity, being most serious at the site of
      surgical intervention and developing within 7 days after craniotomy. Typically, pain resolves
      within 3 months after surgery. According to the literature the incidence of acute PCH during
      the postoperative period is 60% among patients undergoing elective craniotomies. No
      standardized international guidelines are available on the treatment of PCH to the present
      day. Treatment methods can be different based on the country and institution where they are
      used, or even physicians individually can have distinct medication regime, which sometimes
      happens to be habitual and lacks clinical evidences.

      The Department of Anesthesiology and Intensive Care Medicine at the University of Debrecen
      has been giving 100 mg diclofenac with analgesic purpose, as part of the premedication to
      neurosurgical patients for several years. It was observed that the postoperative headache
      following craniotomy was milder comparing to data published in the international literature.
      A pilot study was carried out with similar settings which found the that incidence of PCH was
      lower and less analgesics were required without any further unwanted side-effects among
      patients who received 100 mg diclofenac as part of the premedication.

      Hypothesis:

      100 mg preoperatively given diclofenac significantly reduces the incidence and severity of
      postcraniotomy headache.
    

Detailed description: 
      Before surgery, every patient's previous history was taken routinely and along with this,
      special attention was paid to a history of preoperative headache, its severity and any
      analgesics used regularly prior to surgery. In this study 200 cooperative adults (over 18
      years) undergoing elective craniotomy were randomly assigned into two groups with: 100
      patients received 7.5 mg midazolam and 100 mg diclofenac as premedication, while the other
      100 members of the control group received only 7.5 mg midazolam one hour prior to surgery.
      Envelop randomization was used to schedule patients to diclofenac or to placebo groups.
      Neither the anesthetists, nor the physician obtaining the postoperative VAS scores were aware
      of the actual patient's grouping (diclofenac or placebo) during the entire study. For
      induction of anesthesia, we used propofol (1-2,5 mg/kgBW), whereas for maintenance of
      anesthesia we used the combination of fentanyl, rocuronium, and sevoflurane. Craniotomy and
      opening the dura occurred always after the tissue saturation of sevoflurane and low-flow
      anesthetic technique was applied at a sevoflurane concentration ranging from 1.2 to 2.1 V% as
      required for maintenance of adequate anesthesia. Fentanyl was administered as an initial
      bolus of 100-150 µg followed by a maintenance dose of 2 µg/kgBW/h. The total dose of fentanyl
      was calculated offline after the procedure in all cases. The surgical site was infiltrated by
      a combination of 2% lidocaine and epinephrine in all cases. All patients were admitted to the
      neurosurgical ICU for postoperative observation. A stepwise analgesic regimen was decided
      prior the study. Severity of pain was assessed regularly by the ICU nurses and additional
      analgesics were used if the patient complained a headache severity of VAS >3. In these cases
      additional paracetamol (1-2 g given intravenously) was administered. If this was not
      effective, an additional dose of 100 mg diclofenac was given to the patients. In case of
      further ineffectivity, tramadol was administered in a dose of 100 mg per os or iv. At the end
      of the study the cumulative dose of analgesics that was administered to the patients was
      calculated. For sake of clarity we transformed analgesic doses to equianalgetic doses of
      intramuscular morphine according to the table of the Oxford Pain Site and these values were
      used for further comparisons of analgesic requirements.

      Pain assessment occurred at bedrest state by using a 0-10 scaled visual analogue scale (VAS).
      Assessment of actual VAS scores was regularly performed by the nurses of the neurosurgical
      ICU during days 1-5 and rescue analgesics were given according to the actual needs of the
      patients. An independent physician (who was unaware of randomization) performed an additional
      check of VAS scores by asking the patient, what was her/his worse pain during the day. As the
      patient's satisfaction was considered to be dependent on the worse pain, only these VAS
      scores were used for further analysis.

      The investigators intended to answer the following study questions:

        -  Our research intended to examine whether 100 mg preoperatively give diclofenac reduces
           the incidence and severity of PCH on the first and fifth postoperative days.

        -  Is there a difference in the incidence and severity of PCH between patients who
           underwent infra- or supratentorial interventions?

        -  Does 100 mg preoperatively give diclofenac reduce intraoperative and postoperative
           analgesic needs?

        -  Does 100 mg preoperatively give diclofenac increase the incidence of postoperative
           hemorrhagic events?

      Grouping of the patients:

      The anesthesiologist on duty assigned the participants randomly to the control or to the
      diclofenac group by using envelope randomization technique the day before the surgery.

      Members of the control group received 7.5 mg midazolam, while members of the diclofenac group
      received 7.5 mg midazolam and 100 mg diclofenac for premedication.

      Gathering data:

      Since no objective method exist to measure pain patients were asked to rate their headache
      subjectively with the help of a visual analog scale, where 0 stands for no pain and 10 for
      intolerable pain. In order to make the interpretation of data easier the scale was divided
      into three parts: between 1 and 3 the headache is mild, from 4 to 6 it is moderate, while 7
      or a greater value represents a particularly strong pain.

      The sites of the surgical intervention, intra- and postoperative analgesic needs,
      postoperative complications were recorded individually onto a personal data sheet.

      Each data mentioned above was registered by a third pre-trained, independent (blind) member
      of the study team, who was unaware of the premedication and grouping of patients.

      Statistical methods:

      Statistical analysis was performed using Statistica for Windows (Statsoft, Tulsa, USA)
      statistical program. A normality test revealed that data of VAS scores and analgesic
      requirements show non-normal distribution, therefore a non-parametric Mann-Whitney test was
      used for further comparisons. A p-value of <0.05 was accepted as statistically significant
      during analysis.
    

Intervention name(s): Diclofenac; Midazolam
Intervention type(s): Drug; Drug
Other intervention name(s): DICLOFENAC-ratiopharm; Voltaren; DICLOFENAC-STADA; Dormicum
Intervention MeSH terms: Diclofenac; Midazolam
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: premedication; diclofenac; postoperative headache; Visual Analog Scale