Clinical trial NCT02058485: Dexmedetomidine Premedication in Hypertensive Patients
Official title: Does the Use of Dexmedetomidine for Premedication Provide Hemodynamic Stability in Hypertensive Patients?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Keywords: hypertension
dexmedetomidine
midazolam
premedication
Lead sponsor: Duzce University
Sponsor class: OTHER
First posted: 2014-02-10
Enrollment: 162
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: Hypertensive patients' often severe hypotensive response after induction of anesthesia and excessive increase in blood pressure to stresses such as laryngoscopy, intubation, surgical incision and extubation. There are many publications in the literature of preoperative evaluation of patients with hypertension and perioperative treatment of hypertension but is not sufficient about anesthetic management of these patients. Purpose of our study, was to investigate the haemodynamic effects of dexmedetomidine and midazolam used for premedication in hypertensive patients relative to each other and according to the normotensive patients.

Detailed description: A total of 140 female patients, aged 40-60, normotensive or stage 1-2 hypertensive, scheduled for myomectomy or hysterectomy were randomly enrolled to 4 groups: Group ND (normotensive-dexmedetomidine); Group HD (hypertensive-dexmedetomidine); group NM (normotensive-midazolam); Group HM (hypertensive- midazolam). Twenty-one patients were excluded. The study drugs were administered 15 min before induction of anesthesia via intravenous infusion. Group ND (N= 29) received dexmedetomidine 0.5 µg.kg-1 in normotensive patient; Group HD (N= 30) received dexmedetomidine 0.5 µg.kg-1 in hypertensive patient; group NM (N= 30) received midazolam 0.025 mg. kg-1 in normotensive patient; Group HM (N= 30) received midazolam 0.025 mg. kg-1 in hypertensive patient. The study drugs was prepared by the anesthetist not included in the study in unlabeled syringes that determined by computer according to the group. The investigators and attending anesthesiologists were blinded to the randomization. Monitoring devices included noninvasive arterial blood pressure, electrocardiography, capnography, pulse oximetry and bispectral index.

For induction of anesthesia with fentanyl 1 µg. kg-1 IV and propofol infusion was in the presence of BIS monitoring. Propofol infusion was stopped when BIS value was 60. Endotracheal intubation was performed after rocuronium 0.6 mg. kg-1 iv administered, Anesthesia was maintained with sevoflurane in air/oxygen 50:50 mixture, titrated to achieve a BIS value between 40 and 60. If the MBP value was increased \> 25% of the baseline value on two consecutive readings within 2-3 min, antihypertensive therapy was administered (nitroglycerine 5 µg.min-1 iv infusion) after excluded possible cause ( inadequate anesthesia, hypoxia, hypercapnia etc). Bradycardia ( HR\< 45 beat/min) persisting for \> 2 min was treated with atropine 0.5 mg IV, boluses. At the end of the surgery sevoflurane turned off, and 100% oxygen was administered. Tramadol 1 mg.kg-1 IV was administered for postoperative pain control. Neuromuscular block was antagonized with neostigmine (0.04 mg.kg-1 IV) and atropine (0.01 mg.kg-1 IV). Tracheal extubation was performed when obeying simple commands (open eye, squeeze hand etc) Systolic blood pressure (SBP), diastolic blood pressure ( DBP), mean blood pressure ( MBP) and heart rate ( HR) were recorded at several times as follows: baseline (T0 ), 5 minutes after administration of study drugs (T1), 10 minutes after administration of study drugs (T2), immediately after induction (T3), 1 minute after intubation (T4), 5 minute after intubation (T5), at surgical incision (T6), 15 minutes after surgical incision (T7), 30 minutes after surgical incision (T8), 1 minute after extubation (T9), 5 minute after extubation (T10). Propofol amount for induction, time between induction and initial surgery, demand of antihypertensive therapy, rescue atropine were recorded. Side effects (bradycardia, dryness of the mouth, respiratory depression) were evaluated.

The group sizes (N= 30) were calculated to detect a 25% changes in MBP value with a power of 80% and a significance level of 0.05. Quantitative clinical and demographic characteristics were compared using One Way ANOVA. Chi-square tests (Likelihood ratio or Pearson) were used to examine the relationships between categorical demographic data and groups. Baseline measurements of hemodynamic parameters showed significant differences between groups for the initial values of the measurement period values have been adjusted by subtracting the beginning. The values obtained after the correction in respect of groups were compared using one-way analysis of variance. In addition, perioperative use of antihypertensive drugs that affect the measurements were evaluated by analysis of co-variance, but there is not significant effect was removed from the model. Additionally periodic variations were examined by One way Repeated Measures Analysis of Variance for groups separately, and a significance level of 0.05.

Eligibility criteria: Inclusion Criteria:

* Normotensive
* Hypertension with stage 1 or 2
* Scheduled for myomectomy or hysterectomy operation
* Aged 40-60
* ASA I or II
* BMI is under 30 kg/m2

Exclusion Criteria:

* Untreated hypertension
* Users of ACE inhibitors as antihypertensive therapy
* History of severe cardiovascular disease, renal disease, diabetes mellitus, cerebrovascular disease
* An allergy to study drugs
* Difficult airway
* If the time more than fifteen minutes between the start of surgery and the induction
* If necessary blood transfusion was required

Primary outcomes:
measure: peroperative hemodynamic changes
timeFrame: 2 hours
Secondary outcomes:
measure: antihypertensive requirements
timeFrame: 2 hours
Other outcomes:
measure: Propofol amount
timeFrame: 2 hours
measure: rescue atropine
timeFrame: 2 hours
measure: Side effects
timeFrame: 2 hours
Locations:
city: Duzce
country: Turkey
facility: Duzce University Medicine School, Anesthesiology and Reanimation Department
Study officials:
affiliation: Duzce University
name: Gulbin Sezen
role: STUDY_DIRECTOR
affiliation: Duzce University
name: Yavuz Demiraran
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kunisawa T, Nagata O, Nagashima M, Mitamura S, Ueno M, Suzuki A, Takahata O, Iwasaki H. Dexmedetomidine suppresses the decrease in blood pressure during anesthetic induction and blunts the cardiovascular response to tracheal intubation. J Clin Anesth. 2009 May;21(3):194-9. doi: 10.1016/j.jclinane.2008.08.015.
citation: Menda F, Koner O, Sayin M, Ture H, Imer P, Aykac B. Dexmedetomidine as an adjunct to anesthetic induction to attenuate hemodynamic response to endotracheal intubation in patients undergoing fast-track CABG. Ann Card Anaesth. 2010 Jan-Apr;13(1):16-21. doi: 10.4103/0971-9784.58829.
citation: Basar H, Akpinar S, Doganci N, Buyukkocak U, Kaymak C, Sert O, Apan A. The effects of preanesthetic, single-dose dexmedetomidine on induction, hemodynamic, and cardiovascular parameters. J Clin Anesth. 2008 Sep;20(6):431-6. doi: 10.1016/j.jclinane.2008.04.007.
citation: Sezen G, Demiraran Y, Seker IS, Karagoz I, Iskender A, Ankarali H, Ersoy O, Ozlu O. Does premedication with dexmedetomidine provide perioperative hemodynamic stability in hypertensive patients? BMC Anesthesiol. 2014 Dec 10;14:113. doi: 10.1186/1471-2253-14-113. eCollection 2014.