Working… Menu

Evaluation of Periop Biochemical Stress Factors in Craniotomy Neurosurgical Procedure With Respect to Preop Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02441842
Recruitment Status : Completed
First Posted : May 12, 2015
Last Update Posted : February 8, 2017
Information provided by (Responsible Party):
Sanjib Adhikary, Milton S. Hershey Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Perioperative Hypertension Drug: atenolol Drug: lisinopril Other: glucose Phase 4

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 and fentanyl, (1-2μ 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Evaluation of Perioperative Biochemical Stress Factors in Craniotomy Neurosurgical Procedure With Respect to Preoperative Hypertension
Study Start Date : March 2006
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Group A : Atenolol
oral atenolol (50mg)
Drug: atenolol
administered 60 minutes pre procedure

Placebo Comparator: Group C: Placebo
glucose tablet (10mg)
Other: glucose
administered 60 minutes pre procedure

Active Comparator: Group L: Lisinopril
oral lisinopril (5mg)
Drug: lisinopril
administered 60 minutes pre procedure

Primary Outcome Measures :
  1. MAP changes [ Time Frame: time of incision, extubation and 12 hours postop ]
    MAP changes associated with preoperative single dosage treatment with atenolol or lisinopril, at the time of dural incision and at extubation, as well as 12 hours postoperatively compared to the control group

  2. HR changes [ Time Frame: time of incision, extubation and 12 hours postop ]
    HR changes associated with preoperative single dosage treatment

Secondary Outcome Measures :
  1. plasma concentrations of vasoactive markers [ Time Frame: 12 hours before procedure, during time of dural opening and immediately following extubation ]
    blood sample taken

  2. plasma concentrations of serum sodium levels [ Time Frame: 12 hours before procedure, during time of dural opening and immediately following extubation ]
    blood sample taken

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Scheduled to undergo craniotomy for a supratentorial brain tumor resection
  • Weight between the limits of 70 - 100 kgs

Exclusion Criteria:

  • Weight less than 70 kgs or more thank 100 kgs
  • Meds for hypertension
  • Evidence of raised intracranial pressure, hypertension, cardiovascular, endocrine or renal disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02441842

Sponsors and Collaborators
Milton S. Hershey Medical Center
Layout table for investigator information
Principal Investigator: K.V. Parthiban, PhD Christian Medical College, Dept of Neurological Sciences

Layout table for additonal information
Responsible Party: Sanjib Adhikary, Assist Prof; Dir. Acute Pain, Regional Anesthesia/ Orthopedics, Milton S. Hershey Medical Center Identifier: NCT02441842     History of Changes
Other Study ID Numbers: 5820 / 2006
First Posted: May 12, 2015    Key Record Dates
Last Update Posted: February 8, 2017
Last Verified: February 2017
Keywords provided by Sanjib Adhikary, Milton S. Hershey Medical Center:
ACE inhibitor
Postop hypertension
neurosurgical patients
Additional relevant MeSH terms:
Layout table for MeSH terms
Vascular Diseases
Cardiovascular Diseases
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents