IV Dexmedetomidine in the Duration of Spinal Anesthesia With Hyperbaric Bupivacaine: Double Blind Randomized Trial.

Use of Intravenous Dexmedetomidine as an Adjuvant to Extend the Duration of Spinal Anesthesia With Hyperbaric Bupivacaine in Orthopedic Surgery in Hospital Central "Dr. Ignacio Morones Prieto": Double Blind Randomized Trial.

Introduction: Spinal anesthesia produces sensitive and motor block according to the administered local anesthetic. The total duration of surgical anesthesia depends on the dose, intrinsic properties of the anesthetic, and the use of additional drugs. Dexmedetomidine is an alpha-2 adrenergic agonist that has sedative and analgesic effects. The specific action site in the spinal cord receptors and in the locus coeruleus provide as well hypnotic and sympatholytic characteristics. The combination of spinal anesthesia and intravenous dexmedetomidine is a safe option for hemodynamically stable patients undergoing elective surgery. Material and methods: Double blind randomized trial. The objective is to time and compare the total duration of neuraxial blockade with spinal hyperbaric bupivacaine plus intravenous dexmedetomidine, against hyperbaric bupivacaine by itself. 60 patients shall be included, between the ages of 18 and 65 years, classified by the American Society of Anesthesiologists (ASA) I and II, undergoing lower limb elective orthopedic procedure, with spinal anesthesia plus epidural catheter. 50% of the patients (group A) will receive spinal hyperbaric bupivacaine and IV dexmedetomidine at 0.5 mcg/kg (real weight), and the other 50% (group B) will receive spinal hyperbaric bupivacaine plus IV 0.9% saline solution in equivalent volume.

Study Overview

• Status: Recruiting
• Conditions: Anesthesia; Dexmedetomidine
• Intervention / Treatment: Drug: Dexmedetomidine injection; Drug: Sodium Chloride 0.9% infusion

Detailed Description

Neuraxial blockade is produced by interrupting nervous impulse transmission with the administration of a local anesthetic. When the drug in injected directly into the subarachnoid space, it passes through the pia mater and enters the Virchow-Robin orifices all the way to the nerve ganglion of the deepest dorsal roots. This nerve endings are highly accessible and easily anesthetized, even with a low dose of local anesthetic, in comparison with the extradural nerves. The speed of the spinal blockade depends on the size, surface, and degree of myelination of the fibers exposed to the anesthetic. However, the regression or termination of the desired effect appears because of the decrease in drug concentration within the cerebrospinal fluid, which happens when the blood vessels inside the pia mater absorb the substances into the systemic circulation to be metabolized and excreted. The rate of elimination depends on the distribution of local anesthetic; while the diffusion surface is larger, the drug exposure to the vessels increases, and thus the time of action will be shorter.

Bupivacaine is one of the most used local anesthetics for spinal anesthesia, with high protein binding and a slow onset because of it relatively elevated pKa. The standard doses for clinical practice make it appropriate for surgical procedures that take 2.5 to 3 hours. The administration of complementary drugs such as dexmedetomidine altogether with the local anesthetic allows a reduction in the dosage, as well as in the requirements for analgesics and sedative drugs along the procedure and through the first hours of the postoperative period.

Dexmedetomidine properly carries its mechanism of action in the pre and post synaptic alpha-2 receptors along the dorsal horn of the spinal cord, decreasing the release of neurotransmitters and thus the pulsatile transmission of impulses. On the other hand, when administered as an IV infusion, this alpha agonist has shown the ability to reach light sedation levels, easily reversed by verbal or tactile stimulus. When acting at the locus coeruleus presynaptic spots, the effect of trans and postoperative analgesia can also be consistently observed. Because of these characteristics, the benefits of intravenous dexmedetomidine have been recently tested over the length and quality of spinal anesthesia with local anesthetics, by being administered as bolus and then as maintenance infusion at variable doses per kilogram.

This therapeutic alternative has been applied during several types of infraumbilical surgeries, such as varicocelectomy, hernioplasty, orchiectomy, and lower limb interventions, without the risk of producing nausea, vomiting, headache, or shivering. The use of this adjuvant provides longer lasting nervous blockade, as well higher time for postoperative analgesia, which helps to reduce the consumption of sedative drugs and opioids since the beginning of the intervention until up to the following first 24 hours. Finally, the undesired effects that have been reported in some populations when receiving this drug (hypotension and bradycardia), appear unfrequently and can be easily reversed with the use of common prescription hemodynamic drugs (atropine, ephedrine).

However, it is common to observe differing therapeutic responses following drug administration during daily clinical practice, which can be often attributed to interindividual differences in drug pharmacokinetics, linked to race, ethnicity, and social habits, that can develop enzymatic variations or genetic polymorphisms. Currently, there are many bibliographic references that support the theories that punctually describe these changes in pharmacological responses between ethnic groups, which is why there is a constant need for testing the efficacy and safety of certain drugs, to improve patient safety and clinical outcomes in all the medical fields.

In this case, the objective of our trial is to evaluate the clinical response to the therapeutic scheme based on intravenous dexmedetomidine added to spinal anesthesia. We expect to determine if this drug could and should be considered regularly as an adjuvant to prolong the duration and improve the anesthetic and analgesic conditions of neuraxial blockade with intrathecal bupivacaine in orthopedic lower limb surgery.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Liliana Serrano Ibarrola, MD; Phone Number: +52 3313270064; Email: ibarrola_92@hotmail.com
• Study Contact Backup: Name: Juan Francisco Hernández Sierra, M in C; Phone Number: +52 4443082889; Email: kiko_hdzs@hotmail.com

Study Locations

• Mexico
  • San Luis Potosí, Mexico, 78210
    • Recruiting
    • Hospital Central Dr Ignacio Morones Prieto
    • Contact: Liliana Serrano Ibarrola, MD; Phone Number: +52 3313270064; Email: ibarrola_92@hotmail.com
    • Contact: Juan Francisco Hernández Sierra, M in C; Phone Number: +52 4443082889

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Previously accepted and signed informed consent.
• Age between 18 and 65 years
• Male or female
• ASA classified I or II
• Undergoing elective lower limb orthopedic surgery
• Neuraxial anesthesia with 10 mg of spinal bupivacaine (2ml at 0.5%)
• Inert epidural catheter

Exclusion Criteria

• Basal heart rate lower than 55 beats per minute
• Basal mean arterial pressure (MAP) lower than 65 mmHg
• Non-compensated heart disease
• Sinus bradycardia
• Drug allergy or intolerance

• Contraindication for neuraxial blockade

  • Coagulopathy
  • Lumbar structural pathology and/or vertebral instrumentation
  • Local active infection at punction site
  • Thrombocytopenia (lower than 80 K platelets)
  • Non-controlled psychiatric disease
  • Patients that receive drugs such as NSAIDs, acetaminophen and/or opioids within less than 3 hours prior to the procedure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group A; IV bolus of dexmedetomidine, blindly administered and tittered to 0.5mcg per kilogram (real weight), diluted in 10 ml of 0.9% saline solution during 15 minutes before the spinal block. Once the anesthetic effect is confirmed, the maintenance IV infusion, based on dexmedetomidine 100 mcg diluted in 100 ml of 0.9% saline solution tittered at 0.5 mcg per kilogram per hour (real weight), begins.	Drug: Dexmedetomidine injection; IV initial bolus and trans operative dexmedetomidine infusion.; Other Names: Precedex infusion
PLACEBO_COMPARATOR: Group B; IV 10 ml initial bolus of 0.9% saline solution during the 15 minutes before the spinal block. Once de anesthetic effect is confirmed, the maintenance infusion of IV 0.9% saline solution (100 ml in equivalent dosage per hour) begins.	Drug: Sodium Chloride 0.9% infusion; IV initial bolus and trans operative infusion of 0.9% saline solution.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total time of spinal anesthesia with hyperbaric bupivacaine	Time (minutes) from anesthetic onset, until first sign (sensitive/motor) of blockade regression.	Up to 300 minutes
Presence of post-operative pain	Patient refers pain (Yes or No)	Up to 120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effects Adverse Effects	Hypotension and/or Bradycardia during drug infusion	Through anesthetic period while administering IV drug

Collaborators and Investigators

• Sponsor: Hospital Central "Dr. Ignacio Morones Prieto"
• Investigators: Study Director: Juan Francisco Hernández Sierra, M in C, Universidad Autonoma de San Luis Potosí

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 31, 2022
• Primary Completion (ANTICIPATED): June 10, 2022
• Study Completion (ANTICIPATED): June 15, 2022

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: April 18, 2022
• First Posted (ACTUAL): April 19, 2022

Study Record Updates

• Last Update Posted (ACTUAL): June 13, 2022
• Last Update Submitted That Met QC Criteria: June 9, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 24-CEI-001-20160427

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