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Does the β-receptor antagonist esmolol have analgesic effects?: A randomised placebo-controlled cross-over study on healthy volunteers undergoing the cold pressor test
Örebro University, School of Medical Sciences. Department of Anaesthesia and Intensive Care, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.ORCID iD: 0000-0002-3066-9544
(Clinical Epidemiology and Biostatistics)
Department of Anaesthesia and Intensive Care, School of Medical Sciences, Örebro University, Örebro, Sweden.
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Anaesthesia and Intensive Care, Örebro University Hospital, Örebro, Sweden.
2018 (English)In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 35, no 3, p. 165-172Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Esmolol may attenuate the sympathetic response to pain and reduce postoperative opioid consumption. It is not clear whether esmolol has an analgesic effect per se.

OBJECTIVES: The aim of this study was to evaluate the analgesic effect of esmolol in the absence of anaesthetics and opioids. We tested the hypothesis that esmolol would reduce the maximum pain intensity perceived during the cold pressor test (CPT) by 2 points on a 0 to 10 numeric pain rating scale (NRS) compared to placebo.

DESIGN: Randomised, placebo-controlled cross-over study.

SETTING: Postoperative recovery area, Örebro University Hospital. Study period, November 2013 to February 2014.

PARTICIPANTS: Fourteen healthy volunteers. Exclusion criteria included ongoing medication, pregnancy and breastfeeding and participation in other medical trials.

INTERVENTIONS: At separate study sessions, participants received interventions: esmolol (0.7 mg kg bolus over 1 min followed by infusion at 10 μg kg min); 0.9% normal saline bolus then remifentanil infusion at 0.2 μg kg min and 0.9% normal saline bolus and infusion according to a random sequence. All infusions were administered over 30 min.

MAIN OUTCOME MEASURES: Perceived maximum pain intensity score, pain tolerance and haemodynamic changes during CPT, and occurrence of side-effects to interventions compared to placebo, respectively.

RESULTS: Esmolol did not reduce perceived pain intensity or pain tolerance during the CPT. The NRS-max score was similar for esmolol, 8.5 (±1.4) and placebo, 8.4 (±1.3). The mean difference was 0.1 [95% confidence interval (-1.2 to 1.4)], P value equal to 0.83. Remifentanil significantly reduced NRS-max scores, 5.4 (±2.1) compared to placebo, [mean difference -3.1 (95% confidence interval (-4.4 to -1.8)), P < 0.001]. Side-effects were seen with remifentanil but not with esmolol.

CONCLUSION: No direct analgesic effect of esmolol could be demonstrated in the present study. The postoperative opioid-sparing effect demonstrated in previous studies, could therefore be secondary to other factors such as avoidance of opioid-induced hyperalgesia, synergy with coadministered opioids or altered pharmacokinetics of those drugs.

TRIAL REGISTRATION: European clinical trials database, https://eudract.ema.europa.eu/, EudraCT no. 2011-005780-24.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018. Vol. 35, no 3, p. 165-172
National Category
Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:oru:diva-62086DOI: 10.1097/EJA.0000000000000711ISI: 000430786800003PubMedID: 28922338Scopus ID: 2-s2.0-85042412590OAI: oai:DiVA.org:oru-62086DiVA, id: diva2:1154196
Note

Funding Agency:

Medical Research Fund, Örebro County Council, Örebro, Sweden

Available from: 2017-11-01 Created: 2017-11-01 Last updated: 2018-08-16Bibliographically approved
In thesis
1. Perioperative complications in obese patients: A thesis on risk reducing strategies
Open this publication in new window or tab >>Perioperative complications in obese patients: A thesis on risk reducing strategies
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Aspiration of gastric content and delayed or failed intubation are the leading causes of anesthesia-related mortality and morbidity. In the recovery period, airway obstruction with subsequent hypoxia is a relatively common cause of morbidity, and is highly associated to the amount of opioids administered, especially in obese patients.

The overall aim of this thesis was to study these risk factors for airway complications and postoperative hypoxia in obese patients, and to evaluate possible strategies for their prevention.

In Study I, intubation times and incidence of failed intubation in obese patients were compared between direct laryngoscopy and videolaryngoscopy with the Stortz® C-MAC™. In Studies II and III, the effect of esmolol vs. remifentanil on the esophageal junction, and the possible analgesic properties of low-dose esmolol vs. placebo were evaluated using high-resolution manometry and the cold pressor test, respectively. Finally, in Study IV, the possible opioid-sparing effect of esmolol after laparoscopic gastric bypass surgery was evaluated.

The use of videlaryngoscopy did not shorten intubation times, however appeared to reduce the incidence of failed intubation. Our results also show that esmolol has a favorable profile, compared to remifentanil, with regard to the protection against passive regurgitation and aspiration of gastric content. No analgesic effect of low-dose esmolol was however demonstrated. The intraoperative administration of esmolol instead of remifentanil also did not reduce the requirement of morphine for treatment of post-operative pain.

The use of Stortz® C-MAC™ may be recommended for intubation of obese patients. Further studies are however required to clarify the possible role of esmolol in anesthesia.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2017. p. 74
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 167
Keywords
Intubation time, videolaryngoscopy, obesity, esophagogastric junction, remifentanil, esmolol, high-resolution manometry, pulmonary aspiration, postoperative pain, postoperative opioid-sparing
National Category
Surgery
Identifiers
urn:nbn:se:oru:diva-59411 (URN)978-91-7529-215-1 (ISBN)
Public defence
2017-11-24, Örebro universitet Campus USÖ, hörsal C2, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2017-08-29 Created: 2017-08-29 Last updated: 2017-11-06Bibliographically approved

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Ander, Fredrikde Leon, AlexAhlstrand, Rebecca

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