This double-blind randomised controlled trial was performed at the endoscopy unit of the Radboud University Medical Centre (Nijmegen, The Netherlands).
The study had been approved by the regional ethics committee CMO Arnhem-Nijmegen, The Netherlands (chairperson R. Dekhuijzen) on September 1, 2016 (METC nr 2016–2624), and registered at EudraCT on 19th may 2016 (2016-002210-46), All the procedures were performed in accordance with the Declaration of Helsinki. This manuscript reporting adhered to CONSORT guidelines.
Randomization and blinding
After obtaining written informed consent, patients were randomly assigned to either lidocaine or placebo treatment in a 1:1 ratio by an independent research team. The randomisation process was conducted by drawing sealed envelopes that contained the word alfentanil or saline written on a piece of paper. The first treatment that was drawn was allocated to the first subject, the second treatment drawn was allocated to the second subject and so on. Extra envelops were available in case of patients dropping out of the study before completion. The randomization details were not revealed until the end of the study. The inclusion was stopped at the moment that the 76th patient received either lidocaine or placebo. Study medication was blindly prepared and delivered in identically appearing 50 ml syringes at the endoscopy unit.
Potential participants were assessed for eligibility during the pre-operative anaesthesia assessment. Patients with IBD, ASA 1 or 2, between 18 and 65 years, scheduled for colonoscopy with PSA were eligible for inclusion. Exclusion criteria defined as: pregnancy, emergency colonoscopy, allergies for study medication, previously diagnosed rhythm disturbances i.e. first, second or third degree AV block, Brugada syndrome, cardiomyopathy, BMI < 18 kg m− 2, BMI > 35 kg m− 2, obstructive sleep apnea syndrome and uncontrolled hypertension.
Lidocaine was administered intravenously with a bolus of 1.5 mg kg− 1 followed by a continuous infusion of 2 mg kg− 1 h− 1 ideal body weight. This is a commonly used dosage in abdominal surgery for analgesia.(9, 11) The placebo group received 0.9% saline in equivalent volumes.
All patients were monitored with non-invasive blood pressure, electrocardiography, pulse oximetry and capnography during PSA. Supplemental oxygen (3 l min− 1) was administered by a nasal cannula. Procedural sedation was performed by the same health care provider in all the patients.
We performed PSA according to a standardized protocol. The Ramsey Sedation Scale score was maintained at 4 and 5. (RSS 0–6; 1 = patient is anxious, 6 = patient is unresponsive).(13) Patients received a bolus propofol of 1 mg kg− 1 followed by an infusion of 4.5 mg kg− 1 h− 1 ideal body weight. If needed, an additional 20 mg bolus of propofol was administered. The pain score was measured with the Wong Baker Face Scale (WBFS).(14, 15) An additional alfentanil dose of 0.25 mg was given when a score of ≥ 4 was observed. (WBFS 0 = no hurts, 10 = hurts worst) At the end of the colonoscopy total dose of propofol and alfentanil was registered.
We registered the number of incidents of hypoxia and of hypotension during PSA. Hypoxia was noted when saturation was ≤ 92% and an intervention was needed,(16) like: vigorous tactile stimulation, airway repositioning, suctioning, increased oxygen delivery, oral or nasal airway placement, application of positive pressure or ventilation with bag mask. Hypotension was noted when mean arterial pressure (MAP) < 60 mmHg and 5 mg ephedrine was administered.(17)
After colonoscopy, patients remained at the recovery room until the Aldrete score was ≥ 9 for at least 30 minutes (maximum total score is 10; a score of ≥ 9 is required for discharge).(18) Pain was assessed according to a Numeric Rating Scale (NRS 0–10; 0 = no pain, 10 = worst pain imaginable) when they were fully awake.(15)
Additionally, patients were asked if there was any unpleasant recall of the procedure and potential adverse effects of lidocaine were registered like tinnitus, metal taste, blurred vision or double vision.
The primary endpoint was the difference between alfentanil dosage in patients with and without lidocaine during the colonoscopy. Additionally we evaluated the difference in propofol dosage, the number of cardiorespiratory adverse events and postprocedural NRS between groups.
A dose of 10 µg kg− 1 alfentanil is commonly used for PSA, according to this the following sample size was calculated.(19) An alfentanil dose of 0.625 mg in the placebo group, and 0.25 mg in patients receiving lidocaine, with a standard deviation of 0.58 mg was expected. This leaves us with a n of 38 per group, to achieve a 80% chance for the difference of 0.375 mg to be statistically significant with an α of 0.05.
Descriptive statistics are presented as mean ± SD [minimum - maximum], unless stated otherwise.
A t-test was used to compare the difference between the two groups. The frequencies of cardiorespiratory incidents and postprocedural NRS were reported and compared between groups using te Fisher Exact test. Statistical analysis was performed using IBM SPSS Statistics V25.0. P < 0.05 was considered statistically significant.