• Sjoerd de Hoogd, Abraham J Valkenburg, van Dongen Eric P A EPA, Edgar J Daeter, Joost van Rosmalen, Albert Dahan, Dick Tibboel, and Knibbe Catherijne A J CAJ.
• From the Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein (SdH, CAJK), Intensive Care and Department of Paediatric Surgery, Erasmus MC - Sophia Children's Hospital, Rotterdam (AJV, DT, CAJK), Department of Anaesthesiology and Intensive Care (EPAvD), Department of Cardiothoracic Surgery, St. Antonius Hospital, Nieuwegein (EJD), Department of Biostatistics, Erasmus MC, Rotterdam (JvR), Department of Anaesthesiology, Leiden University Medical Centre (AD) and Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands (CAJK).
• Eur J Anaesthesiol. 2019 Jan 1; 36 (1): 32-39.

BackgroundThe clinical relevance of the suggested hyperalgesic effects of remifentanil is still unclear, especially in the long term.ObjectiveThe current study evaluated the impact of remifentanil on thermal thresholds 3 days and 12 months after surgery, measured with Quantitative Sensory Testing.DesignA single-blind, randomised controlled trial.SettingA tertiary care teaching hospital in The Netherlands, from 2014 to 2016.PatientsA total of 126 patients aged between 18 and 85 years, undergoing cardiothoracic surgery via sternotomy (coronary artery bypass grafts and/or valve replacement) were included. Exclusion criteria were BMI above 35 kg m, history of cardiac surgery, chronic pain conditions, neurological conditions, allergy to opioids or paracetamol, language barrier and pregnancy.InterventionsPatients were allocated randomly to receive intra-operatively either a continuous remifentanil infusion or intermittent intra-operative fentanyl as needed in addition to standardised anaesthesia with propofol and intermittent intravenous fentanyl at predetermined time points.Main Outcome MeasuresWarm and cold detection and pain thresholds 3 days and 12 months after surgery. In addition the use of remifentanil, presence of postoperative chronic pain, age, opioid consumption and pre-operative quality of life were tested as a predictor for altered pain sensitivity 12 months after surgery.ResultsBoth warm and cold detection, and pain thresholds, were not significantly different between the remifentanil and fentanyl groups 3 days and 12 months after surgery (P > 0.05). No significant predictors for altered pain sensitivity were identified.ConclusionEarlier reports of increased pain sensitivity 1 year after the use of remifentanil could not be confirmed in this randomised study using Quantitative Sensory Testing. This indicates that remifentanil plays a minor role in the development of chronic thoracic pain. Still, the relatively high incidence of chronic thoracic pain and its accompanying impact on quality of life remain challenging problems.Trial RegistrationThe study was registered at EudraCT (ref: 2013-000201-23) and ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02031016).

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