Safety and Efficacy of Dexmedetomidine in Controlling Hemodynamics During Resection of Active Thyroid Secreting Tumors

Safety and Efficacy of Dexmedetomidine in Controlling Hemodynamics During Resection of Active Thyroid Secreting Tumors, A Randomized Multicentric Controlled Clinical Trial

Experienced anesthesiologists often attempt to anticipate and blunt the hypertensive responses seen in varying degrees at critical moments of surgical stimulation. Additionally, it may take a long time to treat acute intraoperative hypertension using anesthetics, and there may be a subsequent period of hypotension due to over-compensation. Most practicing anesthesiologists rely on antihypertensive drugs for the rapid control of elevated arterial blood pressure, when volatile anesthetics and narcotics need to be discontinued for awakening. Relatively high doses of antihypertensive drugs, such as labetalol, nicardipine, or esmolol, are commonly used, regardless of the anesthetic technique.One of the main methods to control arterial blood pressure intraoperatively, was to use a typical antihypertensive regimen on an as-needed basis as well as common methods; adjustments in the concentration of volatile anesthetic.

Study Overview

• Status: Active, not recruiting
• Conditions: Thyroid Neoplasms
• Intervention / Treatment: Drug: Dexmedetomidine Injection [Precedex]

Detailed Description

Thyroidectomy is the commonest endocrine surgical procedure being carried out throughout the globe. It is performed for thyroid cancer, solitary thyroid nodules, and autoimmune thyroid disease. The challenging scenarios can be encountered at any stage during thyroidectomy, be it preoperative, intraop or postoperative period .

Anesthesia for thyroid surgery may be complicated by difficult airways due to an enlarged thyroid mass and hemodynamic fluctuations due to thyroid hormone secretion . Cardiac complications are equally challenging as also the presence of various co-morbidities which make the task of anesthesiologist extremely difficult. Thyroid storm can occur during intra-op and post-op period in inadequately prepared surgical patients. The complexity of surgical intervention also adds to these existing challenges. Moreover, there always exists a potential risk of uncontrolled hemorrhage from a vascular injury.

Airway management is important during thyroid surgery. The time from induction of anesthesia and subsequent loss of consciousness to endotracheal intubation is one of the most important stages of anesthesia because of acute and dramatic changes occur in the cardiovascular and respiratory system. Direct laryngoscopy and tracheal intubation potentially increase sympathetic response. Significant increases in plasma adrenaline and noradrenaline levels have been reported within the first five minutes after intubation, which then return to preinduction values.

As a result, tachycardia, hypertension and cardiac arrhythmias may frequently, and hypotension and bradycardia may rarely be encountered. The main reason for the sympathoadrenal response to endotracheal intubation is the stimulation of the supraglottic region. Hemo-dynamic changes begin with laryngoscopy, reach a maximum level within 1-2 minutes, and return to pre-laryngoscopy values after approximately five minutes. While these transient hemodynamic responses do not cause significant problems in healthy individuals, they may have negative consequences in risky cases.

So, a greater focus is required for hemodynamic instability induced by thyroid hormone-secreting tumors or hyperthyroidism. This patient experienced intraoperative hemodynamic instability while manipulating the thyroid mass, which is not typically associated with thyroidectomy except in cases of thyroid storm, which is an acute, severe hypermetabolic state caused by excessive thyroid hormone release or increased adrenal activity. Because of the huge size of the thyroid mass, these abrupt hemodynamic changes during thyroid manipulation can be attributed to carotid baroreceptor baroreflex.

Also, Special attention should be paid to thyroid storms by anesthesiologists. These can occur in patients with uncontrolled hyperthyroidism by a trigger such as surgery. patients show features of tachycardia, hypertension, palpitation, and hyperthermia. In particular, an acute thyroid crisis at the time of anesthetic induction may be mistakenly diagnosed as malignant hyperthermia. In both cases, an increase in blood pressure is the main phenomenon, but in this case, the intraoperative blood pressure suddenly dropped with no response to inotropic (ephedrine) or vasoactive (phenylephrine) agents. There was no evidence to indicate an endocrine surge because the patient was in a euthyroid state, and there was no evidence of a tumor that secreted catecholamines histologically.

There is other several possible causes of intraoperative hemodynamic instability; the first is supposedly baroreflex-mediated hemodynamic instability caused by surgical manipulation during thyroidectomy. In such cases, the mass was too large, and the carotid sinus was depressed and stimulated when the surgeon touched the superior pole of the thyroid gland. The second cause is supposedly acute heart failure or thromboembolism. In thyrotoxicosis, catastrophic events such as dysrhythmia, thromboembolism, and heart failure can occur. However, these events rarely occur in a euthyroid state.

The baroreflex is a short-term mechanism to maintain adequate blood pressure by regulating the sympathetic vasomotor tone. It controls the heart rate, contractility, and peripheral resistance in response to nerve impulses entering the baroreceptors . Baroreceptors are mechano-receptor sensory neurons located in the aortic arch and carotid sinus . They sense a stretch in the arterial wall when the pressure changes . The signals from the baroreceptors will eventually reach the vasomotor center in the brain. The vasomotor center will modulate blood pressure by suppressing sympathetic excitement and increasing the vagal tone on the sinoatrial node of the heart .

The baroreflex is known to adapt to chronic changes in vascular properties by changing its sensitivity and operating set-point. Surgical decompression of the carotid artery led to an acute rebound ipsilateral baroreceptor dysfunction, and haemodynamic instability. Similar phenomena have been observed during experimental evaluation of the baroreflex.

In some cases, the ipsilateral carotid sinus is selectively blocked to prevent transmission of aberrant afferent signals to the CNS. Such nerve blocks do not form part of thyroid surgery. The experience of this case, however, gives us cause to consider whether a unilateral carotid sinus block prior to thyroid mobilization could reduce the incidence and severity of hemodynamic instability in selected cases. This could be performed under direct vision, but should never be undertaken bilaterally.

Experienced anesthesiologists often attempt to anticipate and blunt the hypertensive responses seen in varying degrees at critical moments of surgical stimulation. Additionally, it may take a long time to treat acute intraoperative hypertension using anesthetics, and there may be a subsequent period of hypotension due to over-compensation. Most practicing anesthesiologists rely on antihypertensive drugs for the rapid control of elevated arterial blood pressure, when volatile anesthetics and narcotics need to be discontinued for awakening. Relatively high doses of antihypertensive drugs, such as labetalol, nicardipine, or esmolol, are commonly used, regardless of the anesthetic technique.

In anesthesia practice, to suppress hemodynamic responses to laryngoscopy and tracheal intubation; in addition to pharmacological approach, glossopharyngeal and superior laryngeal nerve blocks can be applied with various drugs. Bolus and infusion applications of dexmedetomidine suppress sympathetic activation in endotracheal intubation and extubation. Dexmedetomidine has found widespread use in many areas of daily anesthesia practice because of its inhibition of sympathetic activity, and reduction in hemodynamic response with its effects on sympathetic nerve endings, induction of sedation, anxiolysis and analgesia with its anesthetic and opioid protective effect without any impact on spontaneous breathing. Tissue perfusion decreases due to decrease in cardiac output and blood pressure secondary to sympatholytic activation of central and peripheral pathways following infusion of its loading dose with resultant prolongation of recovery from neuromuscular block, decrease in the requirement for Musculo relaxant drugs and decrease opioid use, making it attractive for use as an adjunct to general anesthesia.

Dexmedetomidine (Precedex), a potent and highly selective α-2 adrenoceptor agonist, has been described as a unique sedative with analgesic, sympatholytic, and respiratory-preserving properties. It has been approved by the U.S. Food and Drug Administration for short-term sedation (< 24 h) of initially intubated and mechanically ventilated adult patients in the intensive care unit (ICU) and for sedation of non-intubated patients during surgical and other procedures. It's clinical applications have been greatly expanded in recent decades due to many favorable physiological effects. Dexmedetomidine is currently being used off-label intraoperatively in the dose range of 0.2 - 0.7 μg/kg/hr to reduce opioid and anesthetic requirements, which may shorten recovery time.

While it has been suggested that alpha2-agonists decrease the adrenergic response to the trauma of surgery and improve perioperative hemodynamic stability, the most frequently reported adverse reactions to dexmedetomidine use in a Phase III study of 401 patients were hypotension, nausea, and bradycardia. A meta-analysis of several randomized controlled trials of dexmedetomidine in noncardiac surgery found a trend towards improved cardiac outcomes, but the incidence of perioperative hypotension and bradycardia was significantly increased.

One of the main methods to control arterial blood pressure intraoperatively, was to use a typical antihypertensive regimen on an as-needed basis as well as common methods; adjustments in the concentration of volatile anesthetic. The investigator, therefore, designed a study to determine whether the addition of dexmedetomidine would provide a greater perioperative hemodynamic stability in patients undergoing thyroidectomy of active thyroid secreting tumors with less side effects or non.

Aim of the study to Investigate whether adding dexmedetomidine infusion would improve perioperative hemodynamic stability in patients undergoing thyroidectomy for active thyroid secreting tumors with fewer side effects.

After obtaining approval from south Egypt cancer institute's ethics committee, 80 cancer thyroid patients undergoing thyroid resection surgeries will be enrolled in the study. Written informed consent will be taken from each patient.Consented patients were allocated into one of two anesthetic groups: labetalol group or Dexmedetomidine group after being assessed for inclusion and exclusion criteria.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Asyut, Egypt, 171516
    • South Egypt Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients subjected to thyroid resection surgeries for active thyroid tumors.
• The enrolled age will be from 20 years to 65 years
• ASA, I-III and NYHA, I-II.

Exclusion Criteria:

• ASA physical status >III and NYHA >II,
• body mass index >40 kg/m2,
• pregnant women,
• preoperative opioid consumption,
• Allergy to dexmedetomidine
• Contraindications as hypotension or cardiovascular compromise
• Unwilling to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: labetalol Group (Control group); where patients will receive an initial bolus dose of labetalol 20 mg by slow IV injection over a 2-minute period before surgical incision to achieve target hemodynamics. Additional injections of 40 to 80 mg can be given on demand at 10-minute intervals until a desired supine blood pressure is achieved or a total of 300 mg has been used then continuous infusion of diluted labetalol solution will be administered at a rate of 2 mL/min to deliver 2 mg/min to control BP swings intraoperatively.	Drug: Dexmedetomidine Injection [Precedex]; The study medications as dexmedetomidine and labetalol was prepared by an anesthesia assistant not involved in the study. A 50 ml syringe was filled with 50 μg dexmedetomidine diluted in normal saline solution in Dexmedetomidine group, while, 1 ml labetalol (50 mg) diluted in N.S solution in a 50 ml syringe for infusion in labetalol group was prepared.; Other Names: precedex infusion group
Active Comparator: Dexmedetomidine group (Active Group); where patients will receive an iv-bolus dose of 0.5-1 μg/kg of dexmedetomidine over 10 min before surgical incision followed by IV infusion of 0.2 - 0.7 μg/kg/h to control BP intraoperatively.	Drug: Dexmedetomidine Injection [Precedex]; The study medications as dexmedetomidine and labetalol was prepared by an anesthesia assistant not involved in the study. A 50 ml syringe was filled with 50 μg dexmedetomidine diluted in normal saline solution in Dexmedetomidine group, while, 1 ml labetalol (50 mg) diluted in N.S solution in a 50 ml syringe for infusion in labetalol group was prepared.; Other Names: precedex infusion group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative hemodynamics	mean blood pressure values	5 hours intraoperatively
Intraoperative hemodynamics	heart rate values	5 hours intraoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensity of pain	Intensity of pain at rest measured by 11 point NRS Scale ( 0= no pain, 10= worst imaginable pain)	24 hours postoperatively
Sedation:	Sedation: assessed by 6 point Ramsay sedation score (RSS).(1=anxious, 6=no response)	24 hours postoperatively

Collaborators and Investigators

• Sponsor: South Egypt Cancer Institute
• Investigators: Principal Investigator: mohammed fa abd el hamed, lecturer, lecturer of anaesthesia

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 7, 2024
• First Submitted That Met QC Criteria: February 22, 2026
• First Posted (Actual): February 25, 2026

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 22, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Dexmedetomidine
• Other Study ID Numbers: 18- 2024-685

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No