Evaluation of Periop Biochemical Stress Factors in Craniotomy Neurosurgical Procedure With Respect to Preop Hypertension
Condition: Perioperative Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 4

Summary: 
      Perioperative hypertension is commonly associated with surgical craniotomy. As the
      sympathetic nervous system and the renin-angiotensin-aldosterone system play a key role in
      the development of this hypertension, preoperative single dose therapy with a -adrenergic
      receptor blocker or an angiotensin converting enzyme (ACE) inhibitor may be useful in
      preventing this. To assess this as well as to study potential markers of these two systems,
      the investigators will perform a randomized, double blind, placebo controlled study to
      compare the single dose effect of preoperative administration of a -receptor blocking drug
      (atenolol) and an ACE inhibitor (lisinopril) with a control group receiving a placebo tablet
      (glucose) on perioperative hypertension in craniotomy patients.
    

Detailed description: 
      All patients included in the study will be visited 12 hours preoperatively for determination
      of base-line (preoperative) blood pressure and heart rate, at which time a blood sample will
      be taken and the patients will be randomized. The next day, sixty minutes prior to surgery,
      all patients will receive oral diazepam (10mg) and the blinded study medication. This
      medication was previously prepared by an independent pharmacist, and dispensed in appropriate
      packaging. Thus, Group C, the control group, will receive a glucose tablet (10mg), Group A,
      will receive oral atenolol (50mg) and Group L will receive oral lisinopril (5mg). An
      intravenous cannula will be placed and normal saline will be infused at the rate of 60 - 70
      ml/hr. Haemodynamics (blood pressure and heart rate) will be monitored using a multichannel
      monitor (and the patient's radial artery (non-dominant arm) will be cannulated for further
      blood sampling and blood pressure monitoring (Agilent Technologies, MA, USA). Anaesthesia
      will beinduced with thiopental (4-5 mg.kg-1) and fentanyl, (1-2μg.kg-1). Vecuronium,
      (0.06-0.1 mgkg-1) will be administered to facilitate tracheal intubation and to maintain
      neuromuscular blockade. Isoflurane (0.7 - 1.2 MAC) will be administered to maintain the
      Bispectral Index (BIS) (Aspect Medical System Inc, MA, USA), within the range of 35 - 45. End
      tidal CO2 partial pressure will be maintained between 4-4.6 kPa (IntelliVue Anesthetic Gas
      Modules-G1, Redmond, WA, USA). During the surgery, intravenous fentanyl and vecuronium will
      be administered at the discretion of the anaesthetist for pain control and muscle relaxation
      respectively. An increase in mean arterial pressure (MAP) in excess of 20% of the
      pre-operative value will be treated either by increasing the inspired isoflurane
      concentration or by administering metoprolol. Additionally, a decrease in MAP exceeding 20%
      will be treated by reducing the isoflurane inspired concentration or by the administration of
      ephedrine in small doses (2.5-4mg). Ondansetron (4mg) will be administered 45 minutes before
      the expected conclusion of surgery and neuromuscular agents will be reversed using 2.5 mg of
      neostigmine and 0.4 mg of glycopyrrolate at the end of skin suturing. Isoflurane will be
      discontinued at the last suture, and patients will be extubated when they respond to verbal
      stimulation or coughed. The total amount and type of fluids administered during the procedure
      will be recorded.

      The MAP, HR, end-tidal isoflurane, and end tidal CO2 will be recorded every 10 min following
      induction until extubation, and MAP and HR only, every 30 min after admission to the
      neuro-intensive care unit for 12 hrs. These data will be collected from the monitors using
      printouts after each case and the anesthesia record will also be photocopied. Postoperative
      pain will be treated with paracetamol (1gm) administered rectally every 6 hrs and morphine
      injection (2.5mg) intravenously as required.

      Hypertension is defined as any mean arterial blood pressure (MAP) more than 20% of the
      preoperative value (determined 12hrs before the surgery, vide supra).

      Blood samples (3 ml) will be collected from each patient pre operatively from venapuncture
      (12hrs before the surgery), and intra-operatively at the time of dural opening, and
      immediately after extubation, via the arterial line. Collected blood samples will immediately
      be centrifuged and stored at -70°C for analysis of plasma renin, aldosterone, norepinephrine,
      and serum sodium concentrations.
    

Intervention name(s): atenolol; lisinopril; glucose
Intervention type(s): Drug; Drug; Other
Intervention description(s): administered 60 minutes pre procedure; administered 60 minutes pre procedure; administered 60 minutes pre procedure
Intervention MeSH terms: Atenolol; Lisinopril
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: β-blocker; ACE inhibitor; Stress; Craniotomy; Postop hypertension; neurosurgical patients