The Impact of Esmolol Administration on Postoperative Recovery (esmolol)

The Effect of Intraoperative Esmolol Administration on Postoperative Recovery and Chronic Pain

The aim of this study will be to investigate the effect of a continuous infusion of low dose esmolol on intraoperative and postoperative opioid consumption, as well as on postoperative recovery and chronic pain

Study Overview

• Status: Recruiting
• Conditions: Pain, Postoperative; Analgesia; Pain, Acute; Nociceptive Pain; Inguinal Hernia Repair; Pain, Chronic Post-Surgical; Esmolol
• Intervention / Treatment: Drug: Esmolol Hydrochloride; Drug: normal saline

Detailed Description

Contemporary anaesthesiology requires the quest of ways to restrict the use of opioids, which aim at the alleviation of severe postoperative and chronic pain. This is not only due to the side effects involved but also to the epidemic dimensions their use entails. Esmolol, an extremely short-acting cardioselective antagonist of β1 adrenergic receptors, is effectively used in order to attenuate the stress response and minimize undesirable perioperative hemodynamic changes. More specifically, esmolol has been used effectively to reduce pain during induction of anesthesia with propofol and treat tachycardia and hypertension during laryngoscopy. However, recent studies also highlight a possible antinociceptive and/or analgesic effect of esmolol. Therefore, The aim of this study will be to investigate the effect of a continuous infusion of low dose esmolol on intraoperative and postoperative opioid consumption, as well as on postoperative recovery and chronic pain

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vasiliki Samartzi; Email: v.samartzi2@gmail.com

Study Locations

• Greece
  • Athens, Greece, 10676
    • Recruiting
    • Evangelismos General Hospital
    • Contact: Vasiliki Samartzi; Email: v.samartzi2@gmail.com
    • Contact: Kassiani Theodoraki, DESA; Phone Number: 6974634162; Email: ktheodoraki@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients
• American Society of Anesthesiologists (ASA) classification I-II
• elective inguinal hernia repair

Exclusion Criteria:

• body mass index (BMI) >35 kg/m2
• β-blocker administration preoperatively
• systematic use of analgesic agents preoperatively
• chronic pain syndromes preoperatively
• neurological or psychiatric disease on treatment
• pregnancy
• severe hepatic or renal disease
• history of cardiovascular diseases/ arrhythmias/ conduction abnormalities
• hemodynamic instability
• drug or alcohol abuse
• language or communication barriers
• lack of informed consent
• bilateral inguinal hernia repair

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: esmolol group; loading dose of esmolol 0.05 mL/kg and maintenance dose of esmolol 0.3 mL/kg/h	Drug: Esmolol Hydrochloride; In the esmolol group, patients will receive a bolus dose of esmolol followed by a continuous infusion of esmolol intraoperatively
Placebo Comparator: placebo group; loading dose of 0.9% sodium chloride 0.05 mL/kg and maintenance dose of 0.9% sodium chloride 0.3 mL/kg/h	Drug: normal saline; In the placebo group, patients will receive a bolus dose of normal saline followed by a continuous infusion of normal saline intraoperatively

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pain score 3 hours postoperatively	pain score by the use of Numeric Rating Scale (NRS) 3 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	3 hours postoperatively
pain score 6 hours postoperatively	pain score by the use of Numeric Rating Scale (NRS) 6 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	6 hours postoperatively
pain score 24 hours postoperatively	pain score by the use of Numeric Rating Scale (NRS) 24 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	24 hours postoperatively

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from baseline in Quality of Recovery (QoR)-15 score after surgery	The QoR-15 is a quality of recovery scale that consists of 15 questions (items),including questions regarding pain (2 items), physical comfort (5 items), self-care ability (2 items), psychological support (2 items) and emotional state (4 items). Every item is scored on a scale of 10, with the lowest total score of 0 and the highest score of 150. The higher the score, the better the recovery quality of the patient	24 hours postoperatively
pain score on arrival to Post-Anesthesia Care Unit (PACU)	pain score by the use of Numeric Rating Scale (NRS) on arrival to PACU, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	immediately postoperatively
Post Anesthesia Care Unit (PACU) duration of stay	duration of patient stay at PACU	immediately postoperatively
sedation on arrival to Post-Anesthesia Care Unit	sedation will be assessed with a 5-point sedation scale, where: 1, patient perfectly conscious; 2, patient feels a little drowsy; 3, patient seems to be sleeping but immediately reacts to verbal stimulation; 4, patient seems to be sleeping but slowly reacts to verbal stimulation and 5, patient seems to be sleeping and does not react to verbal stimulation but does react to a stimulus such as shaking or pain	immediately postoperatively
morphine consumption in Post-Anesthesia Care Unit (PACU)	mg of morphine requested during patient PACU stay	immediately postoperatively
sleep quality	subjective evaluation of sleep quality by patients, based on a sleep questionnaire (evaluation of sleep duration, number of nocturnal awakenings and marking of sleep quality)	24 hours postoperatively
first mobilization after surgery	patients will be questioned regarding the time at which they mobilized after surgery	24 hours postoperatively
fentanyl requirement during surgery	dose of required fentanyl intraoperatively to maintain systolic arterial blood pressure and heart rate within the 20% of baseline value	intraoperatively
incidence of chronic pain 1 month after surgery	occurrence of chronic pain at the site of the operation 1 month after surgery, with the use of the Numeric Rating Scale (NRS), at rest and during movement	1 month after surgery
incidence of chronic pain 3 months after surgery	occurrence of chronic pain at the site of the operation 3 months after surgery, with the use of the Numeric Rating Scale (NRS), at rest and during movement	3 months after surgery
sedation at discharge from Post-Anesthesia Care (PACU) Unit	sedation will be assessed with a 5-point sedation scale, where: 1, patient perfectly conscious; 2, patient feels a little drowsy; 3, patient seems to be sleeping but immediately reacts to verbal stimulation; 4, patient seems to be sleeping but slowly reacts to verbal stimulation and 5, patient seems to be sleeping and does not react to verbal stimulation but does react to a stimulus such as shaking or pain	at discharge from Post Anesthesia Care Unit (PACU), approximately 1 hour postoperatively
sevoflurane consumption during general anesthesia	the sevoflurane vaporizer will be weighed before anesthetic induction and at the end of anesthesia and consequently sevoflurane consumption during anesthesia will be determined	change of sevoflurane vaporizer weight from before induction to end of anesthesia, an average period of 1-2 hours
time to first request for analgesia	the time for the first patient request for analgesia will be noted	during stay in Post-Anesthesia Care Unit (PACU), approximately 1 hour postoperatively
tramadol consumption in the first 24 hours	patients will be followed for cumulative tramadol consumption for 24 hours postoperatively	24 hours postoperatively
gastrointestinal recovery after surgery	patients will be questioned regarding the time they first felt enteral sounds and the time they had their first flatus after surgery	24 hours postoperatively
first fluid intake	patients will be questioned regarding the time they had their first fluid intake	24 hours postoperatively
first solid intake	patients will be questioned regarding the time they had their first solid intake	24 hours postoperatively
hospitalization time	duration of hospital stay after surgery in hours	96 hours postoperatively
side effects postoperatively	patients will be monitored for side-effects of the administered agents postoperatively	48 hours postoperatively
duration of nociception level<25 intraoperatively	nociception level (NOL) is a device that measures the status of analgesia intraoperatively. Levels<25 suggest adequate intraoperatively analgesia	intraoperatively
pain score at discharge from Post-Anesthesia Care Unit (PACU)	pain score by the use of Numeric Rating Scale (NRS) at discharge from PACU, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	at discharge from Post Anesthesia Care Unit (PACU), approximately 1 hour postoperatively]
time to emergence	time from sevoflurane discontinuation to first patient response (eye opening)	up to 2 hours after start of surgery
time to extubation	time from sevoflurane discontinuation to tracheal extubation	up to 2 hours after start of surgery
satisfaction from analgesia	satisfaction from postoperative analgesia on a four-point Likert scale with 1 marked as minimal satisfaction and 4 as maximal satisfaction	at discharge from Post Anesthesia Care Unit, approximately 1 hour postoperatively
change from baseline in cortisol levels after surgery	blood samples will be collected to measure the variation in cortisol levels from the induction of anesthesia till the arrival of the patient to the Post Anesthesia CAre Unit	during patient stay in the Post Anesthesia Care Unit, approximately 2 hours postoperatively
change from baseline in prolactin levels after surgery	blood samples will be collected to measure the variation in prolactin levels from the induction of anesthesia till the arrival of the patient to the Post Anesthesia CAre Unit	during patient stay in the Post Anesthesia Care Unit, approximately 2 hours postoperatively
change from baseline in lactate levels after surgery	blood samples will be collected to measure the variation in lactate levels from the induction of anesthesia till the arrival of the patient to the Post Anesthesia CAre Unit	during patient stay in the Post Anesthesia Care Unit, approximately 2 hours postoperatively

Collaborators and Investigators

• Sponsor: Aretaieion University Hospital

Publications and helpful links

General Publications

• Andresen K, Rosenberg J. Management of chronic pain after hernia repair. J Pain Res. 2018 Apr 5;11:675-681. doi: 10.2147/JPR.S127820. eCollection 2018.
• Egan TD. Are opioids indispensable for general anaesthesia? Br J Anaesth. 2019 Jun;122(6):e127-e135. doi: 10.1016/j.bja.2019.02.018. Epub 2019 Mar 28.
• Salome A, Harkouk H, Fletcher D, Martinez V. Opioid-Free Anesthesia Benefit-Risk Balance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Clin Med. 2021 May 12;10(10):2069. doi: 10.3390/jcm10102069.
• Bahr MP, Williams BA. Esmolol, Antinociception, and Its Potential Opioid-Sparing Role in Routine Anesthesia Care. Reg Anesth Pain Med. 2018 Nov;43(8):815-818. doi: 10.1097/AAP.0000000000000873.
• Gelineau AM, King MR, Ladha KS, Burns SM, Houle T, Anderson TA. Intraoperative Esmolol as an Adjunct for Perioperative Opioid and Postoperative Pain Reduction: A Systematic Review, Meta-analysis, and Meta-regression. Anesth Analg. 2018 Mar;126(3):1035-1049. doi: 10.1213/ANE.0000000000002469.
• Watts R, Thiruvenkatarajan V, Calvert M, Newcombe G, van Wijk RM. The effect of perioperative esmolol on early postoperative pain: A systematic review and meta-analysis. J Anaesthesiol Clin Pharmacol. 2017 Jan-Mar;33(1):28-39. doi: 10.4103/0970-9185.202182.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: October 1, 2022
• First Submitted That Met QC Criteria: October 1, 2022
• First Posted (Actual): October 5, 2022

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pathological Conditions, Anatomical; Hernia, Abdominal; Hernia; Pain, Postoperative; Hernia, Inguinal; Chronic Pain; Acute Pain; Nociceptive Pain; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic beta-1 Receptor Antagonists; Esmolol
• Other Study ID Numbers: 89/24-03-2022

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