Ethical statement and registration
The study (registered at ClinicalTrials.gov Identifier: NCT03793816) was approved by the local Ethics Committee (EK No. 1399/2018) and conducted according to the guidelines of the Declaration of Helsinki on Biomedical Research Involving Human Subjects. All subjects provided written informed consent.
Study design and participants
This study was a single-centre, randomized, self-controlled trial (RCT). The Consolidated Standards of Reporting Trials reporting guideline was followed. Each patient served as his/her own control . Patients aged 14 years or older, with chronically recurrent tonsillitis and a planned tonsillectomy were eligible. Exclusion criteria: a history of abscesses in the tonsillar region (i.e., quinsy), a coagulation disorder, suspicion of an untreated malignancy, and planned removal of only one tonsil. Figure 1 depicts the study flow diagram.
Procedures, randomization, and blinding
For electrosurgical removal of one randomised tonsil, we used the BiZact™ Open Sealer/Divider (Medtronic/Covidien IIc, Mansfield, MA, USA), a single-use device (here, referred to as “device”), connected to a Valleylab™ FT10 Energy Platform. It creates a seal by applying radiofrequency energy to tissue interposed between the jaws. A cutting blade is then surgeon-activated. We performed an incision of the palatal arch, located the cranial pole of the tonsil, dissected along the tonsil capsule, and detached the tonsil.
The contralateral tonsil was removed with a cold-steel technique (i.e., scissors and/or Freer raspatories), with localized bipolar forceps for cauterization, and compression with cotton balls (here, referred to as the “CSB” or the control side). The analgesic regime included non-steroidal anti-inflammatory drugs, and occasionally, tramadol.
Block randomization (block size of 12) was applied to determine the side to begin with (first side, left/right) and the technique to begin with (the device or the CSB). Patients were blinded to the sidedness, and un-blinding was planned with a follow-up phone call (see below).
The main outcome measurement was the time from the first incision to tonsil placement on the instrument table. Surgeon handedness was recorded, and experience was classified, based on the number of tonsillectomies performed prior to trial participation (less than 10 times, between 10 and 20 times, between 20 and 30 times, and more than 30 times).
Secondary intraoperative outcomes were the time required to stop bleeding, and blood loss, measured as the suction fluid volume including flush water and the number and weight of cotton balls used (scale, KERN & SOHN GmbH, Balingen, Germany).
Postoperative outcomes were paper–pencil ratings of pain on a visual analogue scale (VAS) of 100 mm for each side. Pain was evaluated once after awakening from surgery (day 0) and 5 times per day (at waking up, during breakfast, before lunch, during dinner, and before falling asleep) on days 1, 3, 5, 7, and 10. Patients re-visited the clinic once to return pain scales, discuss histological findings, and undergo a wound healing assessment. Wound healing was rated on a VAS of 100 mm for the right and left tonsillar fossae (from 0 mm =“no coatings/inflammation”, to 100 mm =“massive coating/inflammation”).
Bleeding events were categorized as follows: type I: no intervention required; type II: bleeding controlled with local measures; type III: bleeding controlled in the operating room; i.e., a return-to-theatre (RTT) event; IV: external carotid artery ligation required; and V: death .
Approximately 2 months later, a follow-up phone call was planned. Patients were interviewed with yes/no questions on residual pain and side differences.
The sample size calculation was based on previous experience with the device and the average time for performing a CSB. A sample size of 42 was calculated to have 80% power for detecting a difference of 2 min between mean times, assuming a standard deviation of 4.5 min, when evaluated with a paired t test and a 0.05 two-sided significance level. To provide for potential dropouts, 48 patients were included in this study.
To assess the primary objective, we performed a linear mixed model regression with the surgical time as a dependent variable, the surgical device (device vs. CSB) and sequence (first or second tonsil) as fixed effects, a random intercept for each patient and each surgeon. Also, the effects of other variables on the surgical time were evaluated. In all cases, we used the same mixed model, but we added each variable of interest as a further fixed effect to the model. For the secondary objectives, the dependent variable was the time to stop bleeding.
In regard to pain difference, for each time point, the mean difference in pain between the control and device sides was computed, with the 95% confidence interval (95% CI).
p values < 0.05 were considered statistically significant. These p values and corresponding 95% CIs were for descriptive purposes only; hence, no multiplicity corrections were applied. All analyses and data visualizations were performed with R version 3.6.3 (R Foundation for Statistical Computing, Vienna, Austria).