Abstract
We have performed a systematic literature review and a meta-analysis investigating the effect of beta-adrenergic antagonist on perioperative pain in randomized clinical trials (RCTs). The search included the CENTRAL, CINAHL, EMBASE, and MEDLINE databases (from inception to 10 February 2015). From the retrieved full texts, we hand-searched the references and PubMed related citations. A total of 11 RCTs consisting data of 701 adult patients were eligible for this systematic review. Esmolol was evaluated in ten trials and propranolol in one. Esmolol decreased the need for rescue analgesics by 32–50 %; p < 0.05 (n = 7) and the proportion of patients needing rescue analgesia from 100 to 65 %; p < 0.005 (n = 1), and propranolol decreased the need for rescue analgesics by 72 %; p < 0.001 (n = 1). The time to the first rescue analgesics was longer (p < 0.05) and pain ratings were lower (p < 0.05) in patients with beta-adrenergic antagonists. However, in two opioid-controlled studies, one in knee arthroscopy and another in tubal ligation patients, the proportion of patients needing rescue analgesia was two-times higher in esmolol-treated patients: 52–57 vs. 23–34 %, p < 0.05. Adverse effects were rarely reported, and as reported were mostly cardiovascular alterations. In conclusion, intra-operative beta-adrenergic antagonists’ administration may decrease postoperative pain and analgesic consumption when given as an adjuvant to general anesthesia.
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References
Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006;367:1618–25.
Drdla-Schutting R, Benrath J, Wunderbaldinger G, Sandkühler J. Erasure of a spinal memory trace of pain by a brief, high-dose opioid administration. Science. 2012;335:235–8.
Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC. A new adrenergic betareceptor antagonist. Lancet. 1964;1:1080–1.
Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E, Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1337–45.
Chia YY, Chan MH, Ko NH, Liu K. Role of beta-blockade in anaesthesia and postoperative pain management after hysterectomy. Br J Anaesth. 2004;93:799–805.
Collard V, Mistraletti G, Taqi A, Asenjo JF, Feldman LS, Fried GM, Carli F. Intraoperative esmolol infusion in the absence of opioids spares postoperative fentanyl in patients undergoing ambulatory laparoscopic cholecystectomy. Anesth Analg. 2007;105:1255–62.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.
Celebi N, Cizmeci EA, Canbay O. Intraoperative esmolol infusion reduces postoperative analgesic consumption and anaesthetic use during septorhinoplasty: a randomized trial. Rev Bras Anestesiol. 2014;64:343–9.
Hwang WJ, Moon YE, Cho SJ, Lee J. The effect of a continuous infusion of low-dose esmolol on the requirement for remifentanil during laparoscopic gynecologic surgery. J Clin Anesth. 2013;25:36–41.
Ozturk T, Kaya H, Aran G, Aksun M, Savaci S. Postoperative beneficial effects of esmolol in treated hypertensive patients undergoing laparoscopic cholecystectomy. Br J Anaesth. 2008;100:211–4.
Teimoori B, Khoshfetrat M, Beyrami F, Sakhavar N, Dehbashi Z, Narouie B, Davarian A. Propranolol decreases the post-operative pain and analgesic administration following abdominal hysterectomy. Life Sci J. 2012;9:1216–20.
Coloma M, Chiu JW, White PF, Armbruster SC. The use of esmolol as an alternative to remifentanil during desflurane anesthesia for fast-track outpatient gynecologic laparoscopic surgery. Anesth Analg. 2001;92:352–7.
Kavak Akelma F, Ergıl J, Özkan D, Akinci M, Özmen M, Gümüş H. A comparison of the effects of intraoperative esmolol and lidocaine infusions on postoperative analgesia. Anestezi Dergisi. 2014;22:25–31.
López-Álvarez S, Mayo-Moldes M, Zaballos M, Iglesias BG, Blanco-Dávila R. Esmolol versus ketamine-remifentanil combination for early postoperative analgesia after laparoscopic cholecystectomy: a randomized controlled trial. Can J Anaesth. 2012;59:442–8.
Said-Ahmed HAF. The effect of intra-operative esmolol infusion on post-operative opioid consumption and incidence of shivering in patients undergoing ambulatory laparoscopic inguinal hernia repair. Acta Anaesth Italica. 2009;60:31–44.
Smith I, Van Hemelrijck J, White PF. Efficacy of esmolol versus alfentanil as a supplement to propofol-nitrous oxide anesthesia. Anesth Analg. 1991;73:540–6.
Lee MH, Chung MH, Han CS, Lee JH, Choi YR, Choi EM, Lim HK, Cha YD. Comparison of effects of intraoperative esmolol and ketamine infusion on acute postoperative pain after remifentanil-based anesthesia in patients undergoing laparoscopic cholecystectomy. Korean J Anesthesiol. 2014;66:222–9.
Pertovaara A. The noradrenergic pain regulation system: a potential target for pain therapy. Eur J Pharmacol. 2013;15(716):2–7.
Hagelüken A, Grünbaum L, Nürnberg B, Harhammer R, Schunack W, Seifert R. Lipophilic beta-adrenoceptor antagonists and local anesthetics are effective direct activators of G-proteins. Biochem Pharmacol. 1994;47:1789–95.
Avram J, Krejcie TC, Hetnhorn TK, Niemann CU. Beta-adrenergic blockade affects initial drug distribution due to decreased cardiac output and altered blood flow distribution. J Pharmacol Exp Ther. 2004;311:617–24.
Liang DY, Shi X, Li X, Li J, Clark JD. The β2-adrenergic receptor regulated morphine tolerance and physical dependence. Behav Brain Res. 2007;181:118–26.
Chu LF, Cun T, Ngai LK, Kim JE, Zamora AK, Young CA, Angst MS, Clark DJ. Modulation of remifentanil-induced postinfusion hyperalgesia by the beta-blocker propranolol in humans. Pain. 2012;153:974–81.
Barresi M, Grasso C, Licata F, Li Volsi G. Noradrenergic modulation of neuronal responses to N-methyl-d-aspartate in the vestibular nuclei: an electrophysiological and immunohistochemical study. Neuroscience. 2014;265:172–83.
Bronzino JD, Kehoe P, Mallinson K, Fortin DA. Increased extracellular release of hippocampal NE is associated with tetanization of the medial perforant pathway in the freely moving adult male rat. Hippocampus. 2001;11:423–9.
Buffalari DM, Grace AA. Noradrenergic modulation of basolateral amygdala neuronal activity: opposing influences of alpha-2 and beta receptor activation. J Neurosci. 2007;27:12358–66.
Sarabdjitsingh RA, Kofink D, Karst H, de Kloet ER, Joëls M. Stress-induced enhancement of mouse amygdalar synaptic plasticity depends on glucocorticoid and β-adrenergic activity. PLoS One. 2012;7:e42143.
Stanton PK, Sarvey JM. Blockade of norepinephrine-induced long-lasting potentiation in the hippocampal dentate gyrus by an inhibitor of protein synthesis. Brain Res. 1985;361:276–83.
Vanhoose AM, Winder DG. NMDA and beta1-adrenergic receptors differentially signal phosphorylation of glutamate receptor type 1 in area CA1 of hippocampus. J Neurosci. 2003;23:5827–34.
Chen YW, Chu CC, Chen YC, Hung CH, Wang JJ. Propranolol elicits cutaneous analgesia against skin nociceptive stimuli in rats. Neurosci Lett. 2012;524:129–32.
Chen YW, Chu CC, Chen YC, Hung CH, Wang JJ. Intrathecal propranolol displays long-acting spinal anesthesia with a more sensory-selective action over motorblockade in rats. Eur J Pharmacol. 2011;667:208–14.
Yasui Y, Masaki E, Kato F. Esmolol modulates inhibitory neurotransmission in the substantia gelatinosa of the spinal trigeminal nucleus of the rat. BMC Anesthesiol. 2011;11:15.
Holinstat M, Voss B, Bilodeau ML, Hamm HE. Protease-activated receptors differentially regulate human platelet activation through a phosphatidic acid-dependent pathway. Mol Pharmacol. 2007;71:686–94.
Roberts R, Sciorra VA, Morris AJ. Human type 2 phosphatidic acid phosphohydrolases. Substrate specifity of the type 2a, 2b, 2c enzymes and cell surface activity of the 2a isoform. J Biol Chem. 1998;273:22059–67.
Ye X, Hama K, Contos JJ, Anliker B, Inoue A, Skinner MK, Suzuki H, Amano T, Kennedy G, Arai H, Aoki J, Chun J. LPA3-mediated lysophospatidic acid signalling in embryo implantation and spacing. Nature. 2005;435:104–8.
Hermans EJ, van Marle HJ, Ossewaarde L, Henckens MJ, Qin S, van Kesteren MT, Schoots VC, Cousijn H, Rijpkema M, Oostenveld R, Fernández G. Stress-related noradrenergic activity prompts large-scale neural network reconfiguration. Science. 2011;334:1151–3.
Szabadi E. Functional neuroanatomy of the central noradrenergic system. J Psychopharmacol. 2013;27:659–93.
Kokki H. Ketoprofen pharmacokinetics, efficacy, and tolerability in pediatric patients. Paediatr Drugs. 2010;12:313–29.
Kim Y, Hwang W, Cho ML, Her YM, Ahn S, Lee J. The effects of intraoperative esmolol administration on perioperative inflammatory responses in patients undergoing laparoscopic gastrectomy: a dose-response study. Surg Innov. 2014;. doi:10.1177/1553350614532534.
Kim YS, Kang SH, Song KY, Cho ML, Her YM, Huh JW, Lee J. The immunomodulatory role of esmolol in patients undergoing laparoscopic gastrectomy due to gastric cancer. Anaesthesia. 2013;68:924–30.
Cadirci E, Suleyman H, Hacimuftuoglu A, Halici Z, Akcay F. Indirect role of beta2-adrenergic receptors in the mechanism of analgesic action of nonsteroidal antiinflammatory drugs. Crit Care Med. 2010;38:1860–7.
Powell ND, Sloan EK, Bailey MT, Arevalo JM, Miller GE, Chen E, Kobor MS, Reader BF, Sheridan JF, Cole SW. Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis. Proc Natl Acad Sci USA. 2013;110:16574–9.
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Härkänen, L., Halonen, J., Selander, T. et al. Beta-adrenergic antagonists during general anesthesia reduced postoperative pain: a systematic review and a meta-analysis of randomized controlled trials. J Anesth 29, 934–943 (2015). https://doi.org/10.1007/s00540-015-2041-9
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DOI: https://doi.org/10.1007/s00540-015-2041-9