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Opioid-free anaesthesia for anterior total hip replacement under general anaesthesia: the Observational Prospective Study of Opiate-free Anesthesia for Anterior Total Hip Replacement trial

2021; Elsevier BV; Volume: 126; Issue: 4 Linguagem: Inglês

10.1016/j.bja.2021.01.001

ISSN

1471-6771

Autores

Brendan Urvoy, Christophe Aveline, N. Belot, C. Catier, Hélène Beloeil,

Tópico(s)

Cardiac, Anesthesia and Surgical Outcomes

Resumo

Editor—Intraoperative nociception is the consequence of the interactions of multiple noxious stimuli that promote peripheral and central sensitisation. Opioid-based anaesthesia increases postoperative complications and alters the immunomodulatory signalling pathways.1Sacerdote P. Franchi S. Panerai A.E. Non-analgesic effects of opioids: mechanisms and potential clinical relevance of opioid-induced immunodepression.Curr Pharm Des. 2012; 18: 6034-6042Crossref PubMed Scopus (59) Google Scholar Dexmedetomidine (Dex), a selective α2-adrenergic receptor agonist, has sedative and analgesic properties, improves glial functions, and reduces postoperative oxidative stress and neuronal apoptosis.2Wang K. Wu M. Xu J. et al.Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis.Br J Anaesth. 2019; 126: 777-794Abstract Full Text Full Text PDF Scopus (54) Google Scholar To our knowledge, there is no information about the use of opioid-free anaesthesia (OFA) with Dex during total hip arthroplasty (THA) under general anaesthesia (GA). After ethical approval (Comité de Protection des Personnes Est 1; No. SI 19.02.05.66548, ID RCB 2018-A03393-52; September 4, 2019), registration (NCT04112277; registered on September 30, 2019), and written informed consent, 100 patients aged 18–85 yr scheduled for primary unilateral THA using an anterior approach under GA were included from October 2019 to January 2020. The control group was retrieved from the electronic medical record and the anaesthesia information management system (DIANE; Bow Medical, Amiens, France) after consecutive analysis of all patients operated on during the 6 months preceding the start of the Observational Prospective Study of Opiate-free Anesthesia for Anterior Total Hip Replacement (ASOPHA) trial and meeting the criteria for inclusion, exclusion, and perioperative rehabilitation identical to those used in the ASOPHA trial, inclusion being discontinued after 100 patients were identified. This processing was authorised by the Ethics Committee and the Commission Nationale de l'Informatique et des Libertés (No. 2210577v0; December 19, 2018). With the exception of the use of sufentanil, the same perioperative multimodal analgesia and rehabilitation programme for THA was used in the two groups. Premedication included paracetamol 1 g, ketoprofen 100 mg, and pregabalin 150 mg, all p. o. Patients received tranexamic acid 15 mg kg−1, nefopam 20 mg, ketamine 0.5 mg kg−1, droperidol 1.25 mg, dexamethasone 8 mg (all i.v.), and a peri-articular infiltration (levobupivacaine 0.5%). In the PACU, morphine i.v. was titrated (3 and 2 mg [5 min]−1 in patients 50 kg) in case of NRS score >3. Postoperative nausea and vomiting (PONV) were treated by ondansetron 4 mg. Oxygen was administered for Spo2 ≤94%. Patients were mobilised from the fourth postoperative hour. Home-discharge criteria were NRS score <3 at rest, ability to dress, ability to climb at least one stair, normal voiding, and absence of PONV and surgical complications. These criteria, determined for more than 4 yr in the orthopaedic rehabilitation process, were the same in the two groups. General anaesthesia was induced with propofol 2 mg kg−1 and cisatracurium 0.2 mg kg−1, and maintained with sevoflurane (air:O2 50:50). In the OFA group, Dex (diluted to 4 μg ml−1 in sodium 0.9%) 0.7 μg kg−1 was infused over 20 min before induction using a standard syringe pump (Alaris® TIVA; CareFusion, Voisins le Bretonneux, France), continued at 1.5 μg kg−1 h−1 until the incision, gradually reduced by 0.5 μg kg−1 h−1 every 10–15 min, and interrupted at the time of acetabular component impaction, usually about 30 min before skin closure. In the control group, sufentanil was administered during the induction at the discretion of the anaesthetist, and afterwards based on cardiovascular responsiveness. Systolic arterial pressure (SAP) was maintained within 30% of baseline values by adjusting the sevoflurane concentration and, if necessary, boluses of urapidil 25 mg, ephedrine 6 mg, phenylephrine 50–100 μg, or atropine 0.5 mg i.v. Dexmedetomidine was interrupted when SAP ≤60 mm Hg or an HR <40 beats min−1 for 3 min. The primary outcome was the 24 h morphine equivalent consumption (excluding sufentanil). Secondary endpoints included NRS scores, vasoactive drugs, time between surgical closure to tracheal extubation, PONV, episodes of Spo2 ≤94%, and hospital length of stay (LOS). Ninety-one patients per group were required to detect a 30% reduction in the primary outcome (α 0.05, power; β 0.9; reference: 24 h opioid requirement 16 [10] mg from the first 50 patients receiving sufentanil). Data were compared with two-tailed parametric or non-parametric tests as required. A multivariate analysis was performed to identify risk factors associated with 24 h opioid use. Patient characteristics were comparable between groups (Supplementary Table 1). The mean dose of sufentanil administered intraoperatively in the control group was 0.41 (0.18) μg kg−1. Opioid-free anaesthesia reduced the morphine equivalent consumption (0 [0–10] mg vs 10 [0–28] mg; P=0.002), the risk ratio (RR) of 24 h opioid requirement (RR: 0.69; 95% confidence interval [CI]: 0.52–0.91; P=0.009), and morphine titration (Table 1). In multivariate analysis (Supplementary Table 2), OFA was associated with lower odds of 24 h opioid consumption (odds ratio [OR]: 0.38; 95% CI: 0.16–0.90; P=0.028), whilst NRS score ≥4 in PACU was associated with higher risk (OR: 2.48; 95% CI: 1.97–3.12; P<0.001). Numeric rating scale scores were significantly improved by OFA (Supplementary Fig 1). Opioid-free anaesthesia increased ephedrine consumption (mean difference: 3.0 mg; 95% CI: 0.3–5.8 mg; P=0.035) without differences in vasopressor or atropine use. Opioid-free anaesthesia prolonged the extubation time (mean difference: 7.0 min; 95% CI: 3.6–10.5 min; P<0.001) without impact on PACU discharge (Table 1). Opioid-free anaesthesia reduced O2 requirement in PACU (RR: 0.68; 95% CI: 0.53–0.88; P=0.003) and at 24 h (RR: 0.41; 95% CI: 0.18–0.95; P=0.04). Patients were discharged earlier in the OFA group (mean difference: –1.3 days; 95% CI: –2.1 to –0.6 days; P<0.001).Table 1Postoperative opioid use and opioid side-effects. There were 100 patients each in the control and OFA groups unless otherwise indicated. There were 100 patients analysed in each group during the first 24 h, which decreased after according to their discharge from the ward. Time to extubation: time from skin closure to extubation. OFA, opioid-free anaesthesia; PONV, postoperative nausea and vomiting; SAP, systolic arterial pressure; Spo2, oxygen saturation. Data are expressed as mean (standard deviation), median [inter-quartile range], or number (%).OFAControlP-valuePatients who requested opioid during the first 24 h42 (42)61 (61)0.007Morphine in PACU (mg)0 [0–3]3 [0–6]0.008Time to first morphine requirement in PACU (min)57 (30)38 (23)0.002Patients who did not require morphine titration66 (66)50 (50)0.02Time to extubation (min)19 (15)12 (9)<0.001Time to PACU discharge (min)103 (36)106 (35)0.45Intraoperative maximal SAP (mm Hg)123 (19)137 (20)<0.001Intraoperative minimal SAP (mm Hg)79 (17)80 (16)0.55Intraoperative maximal HR (beats min−1)75 (11)72 (13)0.09Intraoperative minimal HR (beats min−1)58 (9)57 (9)0.28Intraoperative atropine5 (5)9 (9)0.23Oxycodone consumption (mg) 24–48 h0 [0–10] (n = 91)0 [0–15] (n = 99)0.10 48–72 h0 [0–10] (n = 63)6 [0–20] (n = 88)0.08 72–96 h0 [0–10] (n = 20)6 [0–20] (n = 60)0.26Walking ability from the fourth hour96 (96)75 (75)<0.001PONV PACU05 (5)0.024 PACU-24 h7 (1)3 (1)0.19 24–48 h4 (4.4) (n = 91)2 (2.0) (n = 99)0.35Spo2 ≤94% PACU45 (45)66 (66)0.003 2–24 h7 (7)17 (17)0.029 24–48 h1 (1.0) (n = 91)6 (6.1) (n = 99)0.07 Open table in a new tab Our data provide relevant information of an OFA strategy, including Dex for use in THA, and complement data from studies in non-articular surgery.3Turgut N. Turkmen A. Gökkaya S. Altan A. Hatiboglu M.A. Dexmedetomidine-based versus fentanyl-based total intravenous anesthesia for lumbar laminectomy.Minerva Anestesiol. 2008; 74: 469-474PubMed Google Scholar, 4Hwang W. Lee J. Park J. Joo J. Dexmedetomidine versus remifentanil in postoperative pain control after spinal surgery: a randomized controlled study.BMC Anesthesiol. 2015; 15: 21Crossref PubMed Scopus (52) Google Scholar, 5Tufanogullari B. White P.F. Peixoto M.P. et al.Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables.Anesth Analg. 2008; 106: 1741-1748Crossref PubMed Scopus (219) Google Scholar Low-dose systemic Dex potentiates descending noradrenergic inhibitory controls originating from the thalamus and the locus coeruleus, reduces descending facilitation nociceptive processes and the spinal function of N-methyl-D-aspartate receptors, and attenuates microglia activation, giving Dex anti-hyperalgesic effects.2Wang K. Wu M. Xu J. et al.Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis.Br J Anaesth. 2019; 126: 777-794Abstract Full Text Full Text PDF Scopus (54) Google Scholar,6Trang T. Beggs S. Wan X. Salter M.W. P2X4-receptor-mediated synthesis and release of brain-derived neurotrophic factor in microglia is dependent on calcium and p38-mitogen-activated protein kinase activation.J Neurosci. 2009; 29: 3518-3528Crossref PubMed Scopus (347) Google Scholar,7Funai Y. Pickering A.E. Uta D. et al.Systemic dexmedetomidine augments inhibitory synaptic transmission in the superficial dorsal horn through activation of descending noradrenergic control: an in vivo patch-clamp analysis of analgesic mechanisms.Pain. 2014; 155: 617-628Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar The lower opioid use in the OFA group could explain the decrease in O2 requirement. Dexmedetomidine preserved the hypercapnic ventilatory response and exhibited hypercapnic arousal similar to that observed during natural sleep.8Hsu Y.W. Cortinez L.I. Robertson K.M. et al.Dexmedetomidine pharmacodynamics: part I: crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers.Anesthesiology. 2004; 101: 1066-1076Crossref PubMed Scopus (282) Google Scholar The delayed time to extubation, probably related to the sedative and analgesic effects of Dex, did not influence rehabilitation. The 3 mg difference in ephedrine requirement in the OFA group must be interpreted with caution, as vasopressor use was left to the discretion of the anaesthetist. The inhomogeneous definition of hypotension/bradycardia and the different Dex infusion modalities are possible explanations for the heterogeneity of results amongst studies.2Wang K. Wu M. Xu J. et al.Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis.Br J Anaesth. 2019; 126: 777-794Abstract Full Text Full Text PDF Scopus (54) Google Scholar, 3Turgut N. Turkmen A. Gökkaya S. Altan A. Hatiboglu M.A. Dexmedetomidine-based versus fentanyl-based total intravenous anesthesia for lumbar laminectomy.Minerva Anestesiol. 2008; 74: 469-474PubMed Google Scholar, 4Hwang W. Lee J. Park J. Joo J. Dexmedetomidine versus remifentanil in postoperative pain control after spinal surgery: a randomized controlled study.BMC Anesthesiol. 2015; 15: 21Crossref PubMed Scopus (52) Google Scholar, 5Tufanogullari B. White P.F. Peixoto M.P. et al.Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables.Anesth Analg. 2008; 106: 1741-1748Crossref PubMed Scopus (219) Google Scholar, 6Trang T. Beggs S. Wan X. Salter M.W. P2X4-receptor-mediated synthesis and release of brain-derived neurotrophic factor in microglia is dependent on calcium and p38-mitogen-activated protein kinase activation.J Neurosci. 2009; 29: 3518-3528Crossref PubMed Scopus (347) Google Scholar Dexmedetomidine reduces transiently cardiac output by lowering HR without significant impairment in systolic or diastolic left and right cardiac function.9Lee S.H. Choi Y.S. Hong G.R. Oh Y.J. Echocardiographic evaluation of the effects of dexmedetomidine on cardiac function during total intravenous anaesthesia.Anaesthesia. 2015; 70: 1052-1059Crossref PubMed Scopus (20) Google Scholar The change in HR during Dex infusion mimics that observed in natural sleep.10Kang D. Lim C. Shim D.J. et al.The correlation of heart rate between natural sleep and dexmedetomidine sedation.Korean J Anesthesiol. 2019; 72: 164-168Crossref PubMed Scopus (8) Google Scholar This study is limited by its observational nature from a single centre. However, groups were similar and the study was adequately powered for the main outcome (0.48 effect size). The use of propensity scores could have been helpful to increase the similarity between groups, but this model may still be subject to bias and imbalance between groups by unmeasured confounding variables. Except for the use of Dex instead of sufentanil, perioperative measures were conducted similarly. In conclusion, during total hip arthroplasty performed under general anaesthesia, opioid-free anaesthesia can reduce postoperative opioid consumption, pain scores, and hospital length of stay, and can mitigate opioid side-effects when compared with an opioid-based strategy. Side-effects were limited without clinical complications. The authors declare that they have no conflicts of interest. The following is the Supplementary data to this article: Download .docx (.03 MB) Help with docx files Multimedia component 1

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