We followed the recommended process described in the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement .
After approval by the Lausanne University Hospital Ethics Committee (Commission d’Ethique Romande, protocol number CHUV 317/15, Chairperson Prof. André Pannatier) on 26th October 2015, this study was prospectively registered on clinicaltrials.gov (NCT02565342). All patients aged 18 to 70 years, American Society of Anesthesiologists score (ASA) I-II, scheduled for middle or lateral clavicle fracture ORIF at the Lausanne University Hospital were eligible to participate in this study. Exclusion criteria included existing neurological deficit in the upper limb, history of neck surgery or radiotherapy, moderate to severe pulmonary disease, contraindications to peripheral nerve block (e.g., allergy to local anaesthetics, coagulopathy, infection in the area), pre-existing opioid treatment, any distracting pain (i.e. polytraumatized patients), pregnancy and cognitive or psychiatric condition that might affect patient assessment. All surgeries were performed electively. Written informed consent was obtained prior to the day of surgery.
Ultrasound-guided interscalene brachial plexus block
All US-ISB were performed prior to surgery in a dedicated block procedure room, following an extrafascial approach without nerve stimulation [8,9,10]. These blocks were administered or directly supervised by one of the authors (EA) who had no further involvement in the study protocol. Patients were positioned supine with the head turned 45 degrees to the non-operative side. Electrocardiogram, pulse oximetry, and blood pressure monitors were routinely applied, and supplemental oxygen was provided. Peripheral intravenous (i.v.) access was established and midazolam 1 to 4 mg i.v. was administered for anxiolysis and sedation as needed. The needle insertion site was sterilized with a solution of chlorhexidine 2% in isopropyl alcohol 70%. Under sterile conditions, a high-frequency linear array transducer (18–6 MHz, HF Linear Array 8870, BK Ultrasound, Peabody, Massachusetts) was placed over the interscalene region to visualize the carotid artery and brachial plexus in the short axis view. The C5, C6, and C7 roots were identified as described by Martinoli and colleagues . After skin infiltration with 1 to 3 mL of lidocaine 1%, a 22-gauge 50-mm insulated block needle (SonoPlex Stim cannula, Pajunk®, Geisingen, Germany) was inserted in-plane with the US beam on the lateral side of the transducer. The needle was then advanced under direct US guidance through the middle scalene muscle and toward the lateral border of the brachial plexus sheath. The brachial plexus sheath was identified as the linear hyperechoic layer surrounding the roots of the brachial plexus. The final needle tip was positioned extrafascially, about 3 to 5 mm laterally to the brachial plexus sheath, at a depth equidistant between C5 and C6 roots. All patients received 20 mL of bupivacaine 0.5% with epinephrine 1:200,000 through the block needle without repositioning, except in cases of reported paraesthesia.
Intraoperative and postoperative procedure
After application of routine monitors in the operating theatre, patients received a standard general anaesthetic. Anaesthesia was induced using Sufentanil 0.1 to 0.2 μg kg− 1 i.v. and Propofol 2 to 4 mg kg− 1 i.v. with endotracheal intubation facilitated by rocuronium 0.6 mg kg− 1 i.v. Maintenance of anaesthesia was via inhaled sevoflurane 1.6 to 2.4% in a 40:60 mixture of oxygen and air. Positive pressure ventilation was initiated with tidal volume and rate adjusted to maintain an end-tidal PCO2 of 35 to 40 mmHg. Sufentanil 2.5–5.0 μg i.v. was administered as needed to treat increases in blood pressure or heart rate of more than 15% above pre-induction baseline values. Muscle relaxation was antagonized with neostigmine 50 μg kg− 1 and glycopyrrolate 5 to 10 μg kg− 1 at the end of surgery. In the Post-Anesthesia Care Unit (PACU), pain (numeric rating scale [NRS] ≥ 4 or patient request for analgesia) was treated with i.v. morphine 1–2 mg every 10 min as needed for 2 h following our institutional procedure. Once oral intake was initiated, patients received oral acetaminophen 1000 mg every 6 h and oxycodone 5 mg every 4 h as needed. Antiemetic medications on the ward included ondansetron 4 mg i.v. and metoclopramide 10 mg i.v. as needed.
Block assessment and definition of successful block
Assessment of sensory and motor blocks was performed by a research assistant every 5 min after local anaesthetic injection, for a total duration of 30 min. Sensory block was tested in the C5 and C6 dermatomes using a blunt tip needle pin-prick test (0, no perception; 1, decreased sensation; 2, normal sensation). Motor block was tested using arm abduction (C5), and forearm flexion (C6) (inability to overcome gravity, 0; reduced force compared to contralateral arm, 1; no loss of force, 2). A successful block was defined as complete sensory (score, 0) and motor (score, 0) block in the distribution of the C5 and C6 nerve roots within 30 min of performing the US-ISB block.
The primary outcome was total i.v. morphine consumption at 2 postoperative hours upon departure from the PACU. Secondary outcomes were intraoperative Sufentanil administration; i.v. morphine equivalent consumption at 24 postoperative hours; pain scores at rest (NRS 0–10) at 2 and 24 postoperative hours; and rate of postoperative nausea and vomiting (PONV) within 24 postoperative hours. Opioids were converted into equianalgesic doses of i.v. morphine for analysis (i.v. morphine 10 mg = oral oxycodone 20 mg) [3, 12].
Control cohort selection
All patients aged 18 to 70 years old, ASA score I-II, who had undergone middle or lateral clavicle fracture ORIF under general anaesthesia only, between September 2012 and August 2015 at the same institution as this study was conducted, were included in the historical control cohort. Exclusion criteria included pre-existing opioid tolerance, any distracting pain (i.e. polytraumatized patients), pregnancy and cognitive or psychiatric condition that might affect patient pain assessment. All surgeries were performed electively. The data was collected using the surgical calendar software in use at our institution.
Statistical analysis and matching procedure
Categorical variables are presented as frequencies and continuous variables are summarized as mean values with 95% confidence intervals (95% CI). In the preliminary analysis, ISB-treated and Non-ISB-treated patients were compared using the Student’s t test or Mann–Whitney U test for continuous variables, and the Fisher’s exact test or Pearson Chi-square test for categorical variables, as appropriate. To assess the impact of the US-ISB procedure on the outcomes, we matched each ISB-treated patient with a Non-ISB-treated patient and computed the difference in means. The matching procedure was 1-to-1 nearest-neighbour matching using the Mahalanobis metric . Therefore, for each exposed (ISB) individual, one unexposed (Non-ISB) individual, having the smallest possible Mahalanobis distance between the two vectors of covariates, (patients’ and intervention characteristics), was selected, and reversely for each non-exposed individual. Patients characteristics considered for the matching procedure were the gender, the age, the body mass index, the ASA score, the fracture location, the total dose of Propofol at induction and the duration of surgery. The standardized mean differences were computed for each variable before and after matching to assess the performance of the matching procedure (i.e. balance checking). We also used a logistic regression approach to assess whether some variables (gender, age, body mass index, ASA score, fracture location) were associated with the allocation of US-ISB. Significance was considered at P < 0.05 based on a two-tailed probability. Statistical analyses were performed using the Stata 15 statistical package (Stata Corporation, College Station, Texas, U.S.A.).