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CO2 laser or dissection tonsillectomy: A systematic review and meta-analysis of clinical outcomes

      Abstract

      Objective

      Recent evidence has suggested that performing a tonsillectomy with CO2 laser results in favorable intraoperative and postoperative outcomes. This study aimed to compare the clinical outcomes of CO2 and dissection tonsillectomy.

      Methods

      We conducted a systematic search in PubMed, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL), until the 1st of September 2021 for completed studies comparing intraoperative and postoperative outcomes of CO2 laser and dissection tonsillectomy. Primary outcomes were operative time, intraoperative blood loss, and postoperative pain. Secondary outcomes included postoperative hemorrhage and tonsillar fossa healing. A random-effects pairwise meta-analysis of both randomized and non-randomized trials was performed. A subgroup analysis considering the randomization of trials was carried out, and sensitivity analyses linked to the quality of included papers or the age of patients were executed. Quality assessment was appraised with the Cochrane risk of bias and ROBINS-I tools for randomized and non-randomized trials, respectively.

      Results

      Eight trials with 632 cases contributed data to this review. For operative time, a significant difference in favor of CO2 laser tonsillectomy was documented (SMD = -1.32; 95% CI = -2.24 to -0.40; p < 0.005). This was also the case for intraoperative blood loss (SMD = -3.94; 95% CI = -5.62 to -2.26; p < 0.00001). For postoperative pain, no significant differences were detected on day one and seven between the intervention groups (SMD = -0.24; 95% CI = -1.11 to 0.63; p = 0.59 and SMD = 1.31; 95% CI = -0.14 to 2.75; p = 0.08, respectively). CO2 laser tonsillectomy was not superior to conventional dissection tonsillectomy regarding postoperative bleeding rates (OR = 0.50; 95% CI = 0.10 to 2.53; p = 0.40).

      Conclusion

      This study demonstrates that CO2 laser tonsillectomy is more likely to result in a clinically meaningful decrease in operative time and blood loss compared to the conventional dissection technique in both pediatric and adult patients. We found no significant difference in postoperative pain and bleeding. Performing further level-1 trials on this topic with a standardized and validated outcome measurement method will enable more robust conclusions to be drawn.

      Keywords

      1. Introduction

      Tonsillectomy is one of the most commonly performed surgical procedures worldwide [
      • Lowe D.
      • Van Der Meulen J.
      • Cromwell D.
      • Lewsey J.
      • Copley L.
      • Browne J.
      • et al.
      Key messages from the national prospective tonsillectomy audit.
      ] and the second most frequent ambulatory surgical intervention in children [
      • Hall M.J.
      • Schwartzman A.
      • Zhang J.
      • Liu X.
      Ambulatory surgery data from hospitals and ambulatory surgery centers: United States, 2010.
      ]. Since the original description of tonsillar tissue removal by Cornelius Celsus in the first century AD, various tonsillectomy techniques have been utilized to decrease complications and postoperative morbidity [
      • Feldmann H.
      Hais-nasen-ohren- BDG Der.
      ]. Ideally, a tonsillectomy should be as atraumatic as possible, with minimal intraoperative blood loss, reduced operative time and postoperative pain, and decreased risk of postoperative hemorrhage [
      • Johnson L.B.
      • Elluru R.G.M.C.
      Complications of adenotonsillectomy.
      ]. However, despite the development of various techniques, intraoperative and postoperative bleeding and postoperative pain, remain significant complications of tonsillectomy. Especially in children, bleeding could be potentially risky given their limited blood volume as opposed to that of adults [
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      ,
      • Mitchell R.B.
      • Archer S.M.
      • Ishman S.L.
      • Rosenfeld R.M.
      • Coles S.
      • Finestone S.A.
      • et al.
      Clinical practice guideline: tonsillectomy in children (Update)–executive summary.
      ]. Postoperative pain is also an important issue not only because it causes discomfort to the patient but also because it hampers oral intake, thus resulting in an increased risk of dehydration, infection, and postoperative bleeding [
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      ,
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      ].
      Conventional (i.e., traditional or “cold”) technique was deemed the ‘gold standard’ tonsillectomy technique before the introduction of newer methods [
      • O-Lee T.J.
      • Rowe M.
      Electrocautery versus cold knife technique adenotonsillectomy: a cost analysis.
      ]. This technique involves the use of cold instruments for the removal of the palatine tonsil along with its capsule from the tonsillar fossa, while hemostasis is achieved using ligatures, sutures, or monopolar/bipolar diathermy [
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      ]. It is considered a safe method and is still preferred by many surgeons given the low risk of postoperative hemorrhage [
      • Lowe D.
      • Van Der Meulen J.
      • Cromwell D.
      • Lewsey J.
      • Copley L.
      • Browne J.
      • et al.
      Key messages from the national prospective tonsillectomy audit.
      ]. However, there has been increasing pressure to further reduce surgical time and minimize complications following tonsillectomy. Towards this aim, with the advances in technology, new dissection methods have become available. These novel methods are also known as ‘hot’ techniques and include monopolar and bipolar diathermy tonsillectomy, radiofrequency tonsil ablation, coblation tonsillectomy, tonsillectomy using a harmonic scalpel and laser tonsillectomy [

      Hossain A.T., Bhuyan M.A.H., Afroza S., Kabir S., Huq AZ.CO2 laser tonsillectomy: a comparison with conventional technique. Bangladesh J Otorhinolaryngol. 15(1):6–9.

      ]. The evidence as to whether these surgical methods are associated with different postoperative bleeding rates appears to be conflicting, although “hot” tonsillectomy techniques are associated with fewer intraoperative bleeding [
      • Mitchell R.B.
      • Archer S.M.
      • Ishman S.L.
      • Rosenfeld R.M.
      • Coles S.
      • Finestone S.A.
      • et al.
      Clinical practice guideline: tonsillectomy in children (Update)–executive summary.
      ].
      Laser-assisted surgery, in particular, was first introduced in Otorhinolaryngology in the early 1980s, and ever since, various modifications have been implemented for tonsillectomy. Laser tonsillectomy is associated with reduced operative time, postoperative pain, and less intraoperative blood loss [
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      ]. Argon plasma coagulation (APC) laser, potassium titanyl phosphate (KTP) laser, neodymium-doped yttrium aluminum garnet (Nd: Yag) laser and carbon dioxide (CO2) laser have all been utilized for tonsillectomy for many years [
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      ]. Laser's energy absorption causes tissue heating, which results in tissue cutting and simultaneous hemostasis photothermally [
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      ,
      • Ali Alharbi F.
      Postoperative pain after tonsillectomy; comparison between CO2 laser versus conventional dissection tonsillectomy.
      ]. It allows precise cutting and rapid tissue vaporization by focusing the laser beam on a small area and producing extreme heat at thousands of degrees rate [

      Hossain A.T., Bhuyan M.A.H., Afroza S., Kabir S., Huq AZ.CO2 laser tonsillectomy: a comparison with conventional technique. Bangladesh J Otorhinolaryngol. 15(1):6–9.

      ]. In this way, there is minimal adjacent tissue damage by scattered energy and thus less edema and scarring than conventional techniques [
      • Alberti P.W.
      The complications of CO2 laser surgery in otolaryngology.
      ,
      • Jäckel M.C.
      • Petzold S.
      • Dimmer V.
      • Mall G.
      • Reck R.
      Die mikrochirurgische tonsillektomie mit dem CO2-laser: eine analyse klinischer und morphologischer daten.
      ]. Amongst the available laser techniques, CO2 laser tonsillectomy is the most frequently performed, as it presents excellent soft-tissue ablation and hemorrhage control [
      • Unkel C.
      • Lehnerdt G.
      • Schmitz K.J.
      • Jahnke K.
      Laser-tonsillotomy for treatment of obstructive tonsillar hyperplasia in early childhood: a retrospective review.
      ].
      The current systematic review and meta-analysis compared the intraoperative and postoperative outcomes of CO2 laser technique and conventional tonsillectomy in both adult and pediatric patients. The primary endpoints were operative time, intraoperative blood loss, and postoperative pain. The secondary outcomes were tonsillar fossa healing and postoperative hemorrhage.

      2. Methods

      This systematic review with meta-analysis was registered with PROSPERO (CRD42021271684). In addition, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed [
      • Liberati A.
      • Altman D.G.
      • Tetzlaff J.
      • Mulrow C.
      • Gøtzsche P.C.
      • Ioannidis J.P.A.
      • et al.
      The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.
      ].

      2.1 Eligibility criteria

      Original trials comparing CO2 laser with conventional dissection tonsillectomy were synthesized concerning surgical time, postoperative pain, intraoperative hemorrhage, tonsillar fossa healing, and postoperative hemorrhage. Only articles comparing CO2 laser tonsillectomy with cold-steel tonsillectomy were included. No age restrictions were applied. We excluded trials that examined the effects of CO2 laser on various surgical procedures, which analyzed tonsillectomies executed with different laser systems, or did not present quantifiable data. Lastly, both randomized and non-randomized studies were considered for both the qualitative and the quantitative synthesis. Only trials investigating outcomes of bilateral tonsillectomy qualified for the quantitative synthesis.

      2.2 Literature search

      Two reviewers (A.T. and A.F.) conducted a comprehensive electronic database and manual literature search in a blinded fashion to identify published and unpublished studies comparing CO2 laser with conventional cold-steel tonsillectomy. In particular, we searched the databases of PubMed, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) up to the 1st of September 2021. The registries of ClinicalTrials.gov, International Standard Randomized Controlled Trial Number (ISRCTN), and Australian New Zealand Clinical Trials Registry (ANZCTR) were also searched for completed but unpublished studies up to the same date. Additionally, online databases, registries of clinical trials, and reference lists of relevant studies were used. This search was executed in accordance with PRISMA guidelines and the following search terms were used for PubMed “laser, CO2 laser and tonsillectomy” and was adjusted to each included online database (Supplemental file 1). Of note, no specific filters were applied.

      2.3 Selection of studies

      Two researchers (A.T. and A.F.) independently identified potentially relevant records. Following deduplication, the remainder of the articles were assessed for eligibility with title and abstract screening according to the predetermined criteria. Full texts were obtained for the remaining articles. Any arising disagreement was resolved through consensus.

      2.4 Extraction of data

      Two investigators (A.T. and A.F.) extracted data pertaining to the year of publication, the period of patients’ recruitment, the country in which the trials were conducted, patients’ number and demographics, the intervention groups, the eligibility criteria, follow-up time, and outcome data (primary and secondary measurements).

      2.5 Outcome assessment

      The primary endpoints were operative time, intraoperative blood loss, and postoperative pain on the first and seventh days. Postoperative tonsillar fossa healing and postoperative hemorrhage (reactionary or secondary) were considered secondary outcomes.

      2.6 Quality assessment

      Two independent reviewers (A.T. and F.D.) assessed the risk of bias within and across randomized and non-randomized controlled trials utilizing the Cochrane Collaboration's ‘risk of bias’ tool [
      • Higgins J.P.
      • Altman DG.
      Chapter 8: assessing risk of bias in included studies.
      ] and ROBINS-I tool [
      • Sterne J.A.
      • Hernán M.A.
      • Reeves B.C.
      • Savović J.
      • Berkman N.D.
      • Viswanathan M.
      • et al.
      ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions.
      ], respectively.

      2.7 Statistical analysis

      A pair-wise meta-analysis utilizing the Review Manager (RevMan) Software (Version 5.3) [

      Review Manager. Cochrane Collab 2011. (5.1. Copenhagen: the nordic cochrane centre).

      ] was carried out. We conducted a random-effects quantitative synthesis implementing the effect size of standardized mean difference (SMD) and calculated 95% confidence intervals (CIs) [
      • Deeks J.J.
      • Higgins J.P.
      • Altman D.G.
      Analysing data and undertaking meta-analyses.
      ]. The effect measure of odds ratio (OR) effect measure was implemented for ordinal data [
      • Deeks J.J.
      • Higgins J.P.
      • Altman D.G.
      Analysing data and undertaking meta-analyses.
      ]. A p-value of less than 0.05 indicated statistical significance.
      Of note, for those trials that failed to provide standard deviations (SDs) of the described continuous outcome measures, SDs were borrowed from other studies included in the current meta-analysis [
      • Furukawa T.A.
      • Barbui C.
      • Cipriani A.
      • Brambilla P.
      • Watanabe N.
      Imputing missing standard deviations in meta-analyses can provide accurate results.
      ].
      The statistical heterogeneity of the extracted data from eligible for inclusion studies was quantified using the I-squared measure. On that occasion, a p-value of less than 0.05 indicated statistical significance [
      • Fletcher J.
      What is heterogeneity and is it important?.
      ].
      The following classification of statistical heterogeneity was considered [
      • Higgins J.P.
      • Thompson S.G.
      Quantifying heterogeneity in a meta-analysis.
      ]:
      • − I2 = 0–40%: not important heterogeneity;
      • − I2 = 30–60%: moderate heterogeneity;
      • − I2 = 50–90%: substantial heterogeneity;
      • − I2 = 75–100%: considerable heterogeneity.
      The implementation of a funnel plot for publication bias detection was avoided due to the limited number of included studies [

      Jonathan A.C. Sterne Matthias egger David Moher. Addressing reporting biases. Cochrane handbook for systematic reviews of interventions.

      ].

      2.8 Synthesis of the results

      This meta-analysis analyzed quantitatively operative time, intraoperative bleeding, postoperative pain, and postoperative hemorrhage rates. Tonsillar fossa healing was assessed in a qualitative way. Both randomized and non-randomized studies were considered.

      2.9 Subgroup and sensitivity analysis

      Subgroup analysis linked to randomization of the included studies was conducted. Due to the inherent limitations of non-randomized studies, it was deemed inappropriate to synthesize randomized and non-randomized data in the same plot [
      • Reeves B.C.
      • Deeks J.J.
      • Higgins J.P.T.W.G.
      including non-randomized studies.
      ]. Instead, subgroup analysis was implemented to analyze information separately [
      • Reeves B.C.
      • Deeks J.J.
      • Higgins J.P.T.W.G.
      Including non-randomized studies.
      ]. Additionally, a preplanned sensitivity analysis was conducted, keeping only those trials at low risk of bias [
      • Higgins J.P.
      • Altman DG.
      Chapter 8: assessing risk of bias in included studies.
      ]. Of additional note, trials of unclear and moderate risk of bias were excluded. Lastly, sensitivity analysis was executed to comparatively evaluate the impact of CO2 laser and dissection tonsillectomy on the pediatric population, including exclusively studies with patients younger than eighteen years old.

      2.10 Clinical interpretation of the results

      For continuous data, Cohen's rule of thumb was followed for the interpretation of effect sizes and the classification was as follows [
      • Cohen J.
      Statistical power analysis for the behavioral sciences.
      ]:
      • − SMD < 0.4: small effect;
      • − 0.4 ≤ SMD < 0.7: moderate effect;
      • − 0.7 ≤ SMD: large effect.

      3. Results

      3.1 Literature search

      The literature search yielded a total number of 711 potentially relevant studies. Following deduplication, the remaining 535 studies’ eligibility was assessed according to the data delivered by their title and abstract. Sixteen articles were deemed to be relevant to the topic and were further assessed with full-text screening. Eight studies were judged to be eligible for inclusion in the qualitative synthesis. Ultimately, the results from five randomized and two non-randomized controlled trials were pooled together (Fig. 1).

      3.2 Study characteristics

      Five randomized [
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      ,
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      ,
      • Ali Alharbi F.
      Postoperative pain after tonsillectomy; comparison between CO2 laser versus conventional dissection tonsillectomy.
      ,
      • Thangavel S.
      • Saxena S.K.
      • Alexander A.
      Comparison of intraoperative and postoperative morbidity between carbondioxide laser tonsillectomy and dissection tonsillectomy-A randomized clinical trial.
      ,
      • Bhankhodia B.P.
      • Aiyer R.G.
      • Raval J.B.
      Comparative study of CO2 laser assisted and electrocautery assisted tonsillectomy with conventional tonsillectomy.
      ] and three non-randomized [

      Hossain A.T., Bhuyan M.A.H., Afroza S., Kabir S., Huq AZ.CO2 laser tonsillectomy: a comparison with conventional technique. Bangladesh J Otorhinolaryngol. 15(1):6–9.

      ,
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      ,
      • Gandhi G.
      • Bhat P.S.
      • Pradheep K.
      A comparative study of CO2 laser tonsillectomy versus conventional tonsillectomy in our experience.
      ] trials qualified for systematic reviewing. Of these, seven papers published between 2004 and 2021 with a total of 532 patients were included in the quantitative synthesis. Four trials were carried out in India [
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      ,
      • Thangavel S.
      • Saxena S.K.
      • Alexander A.
      Comparison of intraoperative and postoperative morbidity between carbondioxide laser tonsillectomy and dissection tonsillectomy-A randomized clinical trial.
      ,
      • Bhankhodia B.P.
      • Aiyer R.G.
      • Raval J.B.
      Comparative study of CO2 laser assisted and electrocautery assisted tonsillectomy with conventional tonsillectomy.
      ,
      • Gandhi G.
      • Bhat P.S.
      • Pradheep K.
      A comparative study of CO2 laser tonsillectomy versus conventional tonsillectomy in our experience.
      ], one in Bangladesh [

      Hossain A.T., Bhuyan M.A.H., Afroza S., Kabir S., Huq AZ.CO2 laser tonsillectomy: a comparison with conventional technique. Bangladesh J Otorhinolaryngol. 15(1):6–9.

      ], one in Iran [
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      ], one in Saudi Arabia [
      • Ali Alharbi F.
      Postoperative pain after tonsillectomy; comparison between CO2 laser versus conventional dissection tonsillectomy.
      ], and one in Malaysia [
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      ]. Of note, the age of participants ranged between 4 and 45 years (Tables 1 and 2).
      Table 1Study characteristics.
      Lead author (year)Study DesignCountryNumber of enrolled patientsRecruitment time periodAge (years) [range]Males / Females
      Ishlah (2004)
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      RCTMalaysia60January 2001–May 20026–49CO2 laser tonsillectomy 18:12 / Dissection tonsillectomy 17:13
      Mohammadi (2007)
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      Interventional prospective controlled studyIran100February 2002–September 20045–1550:50
      Hossain (2009)

      Hossain A.T., Bhuyan M.A.H., Afroza S., Kabir S., Huq AZ.CO2 laser tonsillectomy: a comparison with conventional technique. Bangladesh J Otorhinolaryngol. 15(1):6–9.

      Interventional retrospective controlled studyBangladesh52October 2007–May 200815–35N/A
      Alharbi (2015)
      • Ali Alharbi F.
      Postoperative pain after tonsillectomy; comparison between CO2 laser versus conventional dissection tonsillectomy.
      RCTSaudi Arabia126May 2011–August 201416–45N/A
      Thangavel (2018)
      • Thangavel S.
      • Saxena S.K.
      • Alexander A.
      Comparison of intraoperative and postoperative morbidity between carbondioxide laser tonsillectomy and dissection tonsillectomy-A randomized clinical trial.
      RCTIndia126August 2014–August 20167–18CO2 laser tonsillectomy 26:37 / Dissection tonsillectomy 30:33
      Gandhi (2019)
      • Gandhi G.
      • Bhat P.S.
      • Pradheep K.
      A comparative study of CO2 laser tonsillectomy versus conventional tonsillectomy in our experience.
      Interventional prospective controlled studyIndia40June 2017–May 20185–35CO2 laser tonsillectomy 9:11 / Dissection tonsillectomy 8:12
      Kumar (2020)
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      RCTIndia68N/A4–15CO2 laser tonsillectomy 18:16 / Dissection tonsillectomy 19:15
      Bhankhodia (2021)
      • Bhankhodia B.P.
      • Aiyer R.G.
      • Raval J.B.
      Comparative study of CO2 laser assisted and electrocautery assisted tonsillectomy with conventional tonsillectomy.
      RCTIndia60April 2014–December 20164–28N/A
      (RCT= Randomized Controlled Trial, CO2 = Carbon Dioxide, N/A = Not Applicable)
      Table 2Intervention characteristics.
      Lead author (year)Inclusion criteriaIntervention groups (patients)OutcomesMeasurement of surgical timeMeasurement of blood lossPostoperative pain assessment
      Ishlah (2004)
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      Chronic or recurrent tonsillitis30 conventional tonsillectomy / 30 CO2 laser tonsillectomy
      • (1)
        Intraoperative time
      • (2)
        Intraoperative blood loss
      • (3)
        Postoperative pain
      • (4)
        Postoperative hemorrhage
      From insertion of Boyle-Davis mouth gag until removal of tonsil tissue
      • (1)
        Weight of tonsil swabs before and after tonsillectomy
      • (2)
        Volume of suctioned blood
      VAS
      Mohammadi (2007)
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      N/A100 CO2 laser tonsillectomy on one side and ipsilateral conventional on the other side
      • (1)
        Intraoperative time
      • (2)
        Intraoperative blood loss
      • (3)
        Postoperative pain
      • (4)
        Postoperative hemorrhage
      • (5)
        Tonsillar fossa healing
      N/A
      • (1)
        Number of soaked gauzes
      • (2)
        Volume of suctioned blood
      Question on the most painful side 24 hours and 7 days postoperatively
      Hossain (2009)

      Hossain A.T., Bhuyan M.A.H., Afroza S., Kabir S., Huq AZ.CO2 laser tonsillectomy: a comparison with conventional technique. Bangladesh J Otorhinolaryngol. 15(1):6–9.

      Age > 10 years40 conventional tonsillectomy / 12 CO2 laser tonsillectomy
      • (1)
        Intraoperative time
      • (2)
        Intraoperative blood loss
      • (3)
        Postoperative pain
      • (4)
        Postoperative hemorrhage
      • (5)
        Tonsillar fossa healing
      N/A
      • (1)
        Number of soaked gauzes
      • (2)
        Volume of suctioned blood
      Question on the level of pain 24 hours and 7 days postoperatively
      Alharbi (2015)
      • Ali Alharbi F.
      Postoperative pain after tonsillectomy; comparison between CO2 laser versus conventional dissection tonsillectomy.
      (1) Recurrent tonsillitis or (2) Obstructive tonsillar hypertrophy with sleep apnea (3) No general contraindications for tonsillectomy63 conventional tonsillectomy / 63 CO2 laser tonsillectomy
      • (1)
        Intraoperative time
      • (2)
        Intraoperative blood loss
      • (3)
        Postoperative pain
      • (4)
        Postoperative hemorrhage
      N/AN/AVAS
      Thangavel (2018)
      • Thangavel S.
      • Saxena S.K.
      • Alexander A.
      Comparison of intraoperative and postoperative morbidity between carbondioxide laser tonsillectomy and dissection tonsillectomy-A randomized clinical trial.
      (1) Chronic tonsillitis, fulfilling Scottish Intercollegiate Guidelines Network criteria (2) Age between 7-18 years (3) No suspected malignancy (4) No bleeding disorders63 conventional tonsillectomy / 63 CO2 laser tonsillectomy
      • (1)
        Intraoperative time
      • (2)
        Intraoperative blood loss
      • (3)
        Postoperative pain
      From insertion of Boyle-Davis mouth gag until removal of the gag after removal of tonsil tissue
      • (1)
        Weight of tonsil swabs before and after tonsillectomy
      • (2)
        Volume of suctioned blood
      VAS
      Gandhi (2019)
      • Gandhi G.
      • Bhat P.S.
      • Pradheep K.
      A comparative study of CO2 laser tonsillectomy versus conventional tonsillectomy in our experience.
      (1) Recurrent tonsillitis (2) Age between 5 - 35 years (3) No bleeding disorder (4) No anemia (5) No acute tonsillar infection20 conventional tonsillectomy / 20 CO2 laser tonsillectomy (with or without adenoid hypertrophy removal)
      • (1)
        Intraoperative blood loss
      • (2)
        Intraoperative time
      N/ANumber of soaked cotton ballsN/A
      Kumar (2020)
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      (1) Chronic adenotonsillitis or (2) Obstructive Sleep Apnea Syndrome and (3) Patients aged from 3 years to 15 years34 conventional tonsillectomy / 34 CO2 laser tonsillectomy
      • (1)
        Intraoperative time
      • (2)
        Intraoperative blood loss
      • (3)
        Post-operative pain
      • (4)
        Occurrence of secondary complications
      From mucosal incision to complete hemostasis, excluding the time for adenoidectomy
      • (1)
        Weight of tonsil swabs before and after tonsillectomy
      • (2)
        Volume of suctioned blood. Separate suction bottle and swabs for adenoidectomy.
      Wong-Baker FACES pain scale
      Bhankhodia (2021)
      • Bhankhodia B.P.
      • Aiyer R.G.
      • Raval J.B.
      Comparative study of CO2 laser assisted and electrocautery assisted tonsillectomy with conventional tonsillectomy.
      N/A30 conventional tonsillectomy / 30 CO2 laser tonsillectomy
      • (1)
        Intraoperative blood loss
      • (2)
        Intraoperative time
      • (3)
        Postoperative pain
      • (4)
        Tonsillar fossa healing
      From mucosal incision to removal of tonsil and hemostasis
      • (1)
        Amount of in suction bottle
      • (2)
        Number of soaked cotton balls
      Wong-Baker FACES pain scale
      (CO2 = Carbon Dioxide, VAS = Visual Scale Analogue, N/A = Not Available)

      3.3 Quality assessment

      Overall, four of the randomized trials were deemed to be at low risk of bias [
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      ,
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      ,
      • Ali Alharbi F.
      Postoperative pain after tonsillectomy; comparison between CO2 laser versus conventional dissection tonsillectomy.
      ,
      • Thangavel S.
      • Saxena S.K.
      • Alexander A.
      Comparison of intraoperative and postoperative morbidity between carbondioxide laser tonsillectomy and dissection tonsillectomy-A randomized clinical trial.
      ] and one of them at unclear risk of bias [
      • Bhankhodia B.P.
      • Aiyer R.G.
      • Raval J.B.
      Comparative study of CO2 laser assisted and electrocautery assisted tonsillectomy with conventional tonsillectomy.
      ] (Table 3). The three non-randomized controlled trials included in the present systematic review were evaluated with the ROBINS-I scale and were judged to be at moderate risk of bias [

      Hossain A.T., Bhuyan M.A.H., Afroza S., Kabir S., Huq AZ.CO2 laser tonsillectomy: a comparison with conventional technique. Bangladesh J Otorhinolaryngol. 15(1):6–9.

      ,
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      ,
      • Gandhi G.
      • Bhat P.S.
      • Pradheep K.
      A comparative study of CO2 laser tonsillectomy versus conventional tonsillectomy in our experience.
      ] (Table 4).
      Table 3Quality assessment of randomized controlled studies (Cochrane Collaboration's tool).
      Lead author (year)Bias in randomizationBias in allocation concealmentBias in blinding of participantsBias in blinding of personnelBias due to incomplete outcome dataBias due to selective outcome reportingOther bias
      Ishlah (2005)
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      Low RiskUnclear RiskLow RiskUnclear RiskLow RiskLow RiskLow Risk
      Thangavel (2018)
      • Thangavel S.
      • Saxena S.K.
      • Alexander A.
      Comparison of intraoperative and postoperative morbidity between carbondioxide laser tonsillectomy and dissection tonsillectomy-A randomized clinical trial.
      Low RiskLow RiskLow RiskUnclear RIskLow RiskLow RiskLow Risk
      Alharbi (2015)
      • Ali Alharbi F.
      Postoperative pain after tonsillectomy; comparison between CO2 laser versus conventional dissection tonsillectomy.
      Low RiskLow RiskLow RiskUnclear RIskLow RiskLow RiskUnclear Risk
      Bhankhodia (2021)
      • Bhankhodia B.P.
      • Aiyer R.G.
      • Raval J.B.
      Comparative study of CO2 laser assisted and electrocautery assisted tonsillectomy with conventional tonsillectomy.
      Low RiskLow RiskUnclear RiskUnclear RiskUnclear RiskLow RiskUnclear Risk
      Kumar (2020)
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      Low RiskLow RiskUnclear RiskUnclear RiskLow RiskLow RiskLow Risk
      Table 4Quality assessment of non-randomized studies (ROBINS-I tool).
      Lead author (year)Bias due to confounding factorsBias in selection of participants into the studyBias in classification of interventionsBias due to deviations from intended interventionsBias due to missing outcome dataBias in measurement of outcomesBias in selection of the reported resultsOverall bias
      Mohammadi

      (2007)
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      Low RiskLow RiskLow RiskLow RiskLow RiskModerate RiskLow RiskModerate Risk
      Hossain (2009)

      Hossain A.T., Bhuyan M.A.H., Afroza S., Kabir S., Huq AZ.CO2 laser tonsillectomy: a comparison with conventional technique. Bangladesh J Otorhinolaryngol. 15(1):6–9.

      Low RiskLow RiskLow RiskLow RiskLow RiskModerate RiskLow RiskModerate Risk
      Gandhi (2019)
      • Gandhi G.
      • Bhat P.S.
      • Pradheep K.
      A comparative study of CO2 laser tonsillectomy versus conventional tonsillectomy in our experience.
      Low RiskLow RiskLow RiskLow RiskLow RiskModerate RiskLow RiskModerate Risk

      4. Synthesis of the results

      4.1 Intraoperative Blood Loss

      We assessed the intraoperative blood loss by data extracted from five randomized and two non-randomized trials. CO2 laser technique was found to be significantly superior to dissection in terms of intraoperative blood loss (SMD = -3.94; 95% CI = -5.62 to -2.26; p < 0.00001; Fig. 2). We found substantial interstudy heterogeneity in this outcome (I2 = 97%; p < 0.00001). The study of Mohammadi et al. [
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      ], which was not included in the quantitative synthesis, also reported the superiority of CO2 laser.
      Fig 2
      Fig. 2Forest plot of standardized mean differences for the assessment of intraoperative blood loss. Two different subgroups are considered. The vertical line demonstrates no difference between the two comparison groups. SMD = standardized mean difference, IV= inverse variance, SD = standard deviation, CI = confidence interval.

      4.2 Operative time

      Five randomized and three non-randomized trials reported data on intraoperative time. Operative time was significantly lower in patients that underwent CO2 laser tonsillectomy (SMD = -1.32; 95% CI = -2.24 to -0.40; p < 0.005; Fig. 3). Substantial interstudy heterogeneity was found regarding this outcome (I2 = 95%; p < 0.00001). Mohammadi et al. also reported a significant difference in the duration of operating time in favor of the CO2 group.
      Fig 3
      Fig. 3Forest plot of standardized mean differences for the assessment of intraoperative time. Two different subgroups are considered. The vertical line demonstrates no difference between the two comparison groups. SMD = standardized mean difference, IV= inverse variance, SD = standard deviation, CI = confidence interval.

      4.3 Postoperative pain

      Five randomized and two non-randomized trials contributed data to analyzing postoperative pain. The pooled results demonstrated no significant difference in the pain levels described on the first postoperative day among the patients who underwent CO2 laser or conventional tonsillectomy (SMD = -0.24; CI = -1.11 to 0.63; p = 0.59; Fig. 4). Furthermore, pain intensity on the seventh postoperative day was lower in the patients subjected to dissection tonsillectomy compared to those that underwent CO2 laser tonsillectomy (SMD = 1.31; 95% CI = -0.14 to 2.75; p < 0.08; Fig. 5). However, no significant difference was identified between the two groups. Regarding these outcomes, a considerable interstudy heterogeneity was found on the first and seventh postoperative day (I2 = 94%; p < 0.00001 and I2 = 97%; p < 0.00001, respectively). Two studies not included in the quantitative synthesis [
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      ,
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      ] found postoperative pain to be equivocal between the two compared techniques, with no significant difference in pain scores during the follow-up, verifying the present meta-analysis results. On the contrary, Hossain et al. [

      Hossain A.T., Bhuyan M.A.H., Afroza S., Kabir S., Huq AZ.CO2 laser tonsillectomy: a comparison with conventional technique. Bangladesh J Otorhinolaryngol. 15(1):6–9.

      ] associated CO2 laser tonsillectomy with less postoperative pain.
      Fig 4
      Fig. 4Forest plot of standardized mean differences for the assessment of postoperative pain on the first postoperative day. Two different subgroups are considered. The vertical line demonstrates no difference between the two comparison groups. SMD = standardized mean difference, IV= inverse variance, SD = standard deviation, CI = confidence interval.
      Fig 5
      Fig. 5Forest plot of standardized mean differences for the assessment of postoperative pain on the seventh postoperative day. Two different subgroups are considered. The vertical line demonstrates no difference between the two comparison groups. SMD = standardized mean difference, IV= inverse variance, SD = standard deviation, CI = confidence interval.

      4.4 Postoperative hemorrhage

      Post-tonsillectomy hemorrhage rates, either reactionary or secondary, were assessed using available data from seven studies. It appeared that 2.76% of the dissection patients bled postoperatively, whereas the rate was 0.53% for the CO2 laser patients. However, CO2 laser tonsillectomy was not significantly superior over dissection tonsillectomy in terms of postoperative bleeding rates (OR = 0.50; 95% CI = 0.10 to 2.53; p = 0.40; Fig. 6). No significant heterogeneity was spotted (I2 = 0%; p = 0.64). More specifically, Hossain et al. [

      Hossain A.T., Bhuyan M.A.H., Afroza S., Kabir S., Huq AZ.CO2 laser tonsillectomy: a comparison with conventional technique. Bangladesh J Otorhinolaryngol. 15(1):6–9.

      ] reported one out of the forty patients who underwent conventional tonsillectomy to be re-admitted with postoperative reactionary hemorrhage and two patients with secondary hemorrhage. In addition, out of the twelve patients subjected to laser tonsillectomy, one patient was re-admitted due to secondary hemorrhage. Furthermore, Alharbi et al. [
      • Ali Alharbi F.
      Postoperative pain after tonsillectomy; comparison between CO2 laser versus conventional dissection tonsillectomy.
      ] noticed that two out of the sixty-three patients who underwent dissection tonsillectomy presented reactionary hemorrhage, whereas no reactionary or secondary hemorrhage occurred among the sixty-three patients subjected to laser-assisted tonsillectomy. Similarly, Kumar et al. [
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      ] reported secondary bleeding in one patient out of the thirty-four patients subjected to conventional dissection tonsillectomy and no postoperative bleeding events among thirty-four patients from the CO2 laser group. From the remaining studies, Mohammadi et al. detected no statistical significance in the immediate and late postoperative hemorrhage incidence between the two techniques [
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      ]. The rest of the trials did not report any incidence of postoperative hemorrhage [
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      ,
      • Bhankhodia B.P.
      • Aiyer R.G.
      • Raval J.B.
      Comparative study of CO2 laser assisted and electrocautery assisted tonsillectomy with conventional tonsillectomy.
      ,
      • Gandhi G.
      • Bhat P.S.
      • Pradheep K.
      A comparative study of CO2 laser tonsillectomy versus conventional tonsillectomy in our experience.
      ].
      Fig 6
      Fig. 6Forest plot of odds ratios for the assessment of postoperative hemorrhage. Two different subgroups are considered. M-H= Mantel-Haenszel, CI= Confidence Interval.

      4.5 Tonsillar fossa healing

      Tonsillar fossa healing was assessed by qualitatively synthesizing data from three studies. Hossain et al. [

      Hossain A.T., Bhuyan M.A.H., Afroza S., Kabir S., Huq AZ.CO2 laser tonsillectomy: a comparison with conventional technique. Bangladesh J Otorhinolaryngol. 15(1):6–9.

      ] described earlier leukocytic membrane formation in patients subjected to laser tonsillectomy (5-7 days) compared to cold-steel tonsillectomy (7-14 days). On the contrary, in the study of Bhankhodia et al. [
      • Bhankhodia B.P.
      • Aiyer R.G.
      • Raval J.B.
      Comparative study of CO2 laser assisted and electrocautery assisted tonsillectomy with conventional tonsillectomy.
      ] for the dissection group, tonsillar fossa healing was rapid and occurred within one week, whereas in the CO2 laser group, it occurred after one more week. Finally, Mohammadi et al. [
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      ] reported identical effects on leukocytic membrane formation and final cicatrization for both methods of tonsillectomy.

      4.6 Subgroup analysis

      Operative time was assessed based on the results of randomized (SMD = -1.02; CI = -2.15 to 0.11; p = 0.08; Fig. 3) and non-randomized trials (SMD = -2.11; CI = -3.28 to -0.94; p = 0.0004; Fig. 3). Statistically significant difference in favor of CO2 laser tonsillectomy in terms of operative time was detected only in the subgroup of non-randomized trials. Heterogeneity was considerable in both randomized and non-randomized subgroup analyses (I2 = 96%; p < 0.00001 and I2 =76%; p = 0.04, respectively).
      Intraoperative blood loss was also evaluated based on the results of both randomized (SMD = -4.75; CI = -7.03 to -2.46; p < 0.0001; Fig. 2) and non-randomized trials (SMD = -2.19; CI = -4.07 to -0.31; p = 0.002; Fig. 2). Patients presented statistically significantly less intraoperative blood loss during CO2 laser in comparison with dissection tonsillectomy. Heterogeneity was considerable for both the randomized and non-randomized subgroup analyses (I2 = 98%; p < 0.00001 and I2 = 90%; p = 0.002, accordingly).
      Post-tonsillectomy hemorrhage rates were assessed based on the results of randomized (OR = 25; 95% CI = 0.03 to 2.28; p = 0.22; Fig. 6) and non-randomized trials (OR = 1.12; 95% CI = 0.11 to 11.89; p = 0.92; Fig. 6). Heterogeneity was not statistically significant for the randomized subgroup analysis (I2 = 0%; p = 0.22).

      4.7 Sensitivity analyses

      A pre-specified sensitivity analysis was conducted, in which we excluded trials of unclear and moderate risk of bias. One randomized [
      • Bhankhodia B.P.
      • Aiyer R.G.
      • Raval J.B.
      Comparative study of CO2 laser assisted and electrocautery assisted tonsillectomy with conventional tonsillectomy.
      ] and two non-randomized controlled trials [

      Hossain A.T., Bhuyan M.A.H., Afroza S., Kabir S., Huq AZ.CO2 laser tonsillectomy: a comparison with conventional technique. Bangladesh J Otorhinolaryngol. 15(1):6–9.

      ,
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      ,
      • Gandhi G.
      • Bhat P.S.
      • Pradheep K.
      A comparative study of CO2 laser tonsillectomy versus conventional tonsillectomy in our experience.
      ] did not qualify for the sensitivity analysis.
      Pain intensity levels on the first postoperative day were significantly higher in the dissection group than the CO2 laser group (SMD = 0.33; 95% CI = 0.09 to 0.57; p = 0.007; Fig. 9). Heterogeneity was not statistically significant (I2 = 12%; p = 0.32). On day seven, the difference between CO2 laser and conventional tonsillectomy regarding the postoperative pain was found not to be statistically significant (SMD = 0.76; 95% CI = -0.68 to 2.11; p = 0.30; Fig. 10). Heterogeneity was considerable (I2 = 97%; p < 0.00001).
      Operative time was shorter (SMD = -1.50; 95% CI = -2.23 to -0.67; p = 0.0004; Ι2 = 92%; Fig. 8) and intraoperative blood loss was less in CO2 laser tonsillectomies (SMD = -3.01; 95% CI = -5.09 to -0.92; p = 0.005; Ι2 = 98%; Fig. 7). In both comparisons, statistically significant differences were identified between the two groups. For the operative time and blood loss, the levels of heterogeneity were considerable (I2 = 92%; p < 0.00001 and I2 = 98%; p < 0.00001, respectively).
      Fig 7
      Fig. 7Forest plot of standardized mean differences for the assessment of intraoperative blood loss (sensitivity analysis). Two different subgroups are considered. The vertical line demonstrates no difference between the two comparison groups. SMD = standardized mean difference, IV= inverse variance, SD = standard deviation, CI = confidence interval.
      Fig 8
      Fig. 8Forest plot of standardized mean differences for the assessment of intraoperative time (sensitivity analysis). Two different subgroups are considered. The vertical line demonstrates no difference between the two comparison groups. SMD = standardized mean difference, IV= inverse variance, SD = standard deviation, CI = confidence interval.
      Fig 9
      Fig. 9Forest plot of standardized mean differences for assessing postoperative pain on the first postoperative day (sensitivity analysis). Two different subgroups are considered. The vertical line demonstrates no difference between the two comparison groups. SMD = standardized mean difference, IV= inverse variance, SD = standard deviation, CI = confidence interval.
      Fig 10
      Fig. 10Forest plot of standardized mean differences for assessing postoperative pain on the seventh postoperative day (sensitivity analysis). Two different subgroups are considered. The vertical line demonstrates no difference between the two comparison groups. SMD = standardized mean difference, IV= inverse variance, SD = standard deviation, CI = confidence interval.
      Finally, post-tonsillectomy hemorrhage rate was lower after CO2 laser tonsillectomy (OR = 0.25; 95% CI = 0.03 to 2.28; p = 0.22; Fig. 11). However, the result was not statistically significant. Heterogeneity was also insignificant (I2 = 0%; p = 0.82).
      Fig 11
      Fig. 11Forest plot of odds ratios for assessing postoperative hemorrhage (sensitivity analysis). Two different subgroups are considered. M-H= Mantel-Haenszel, CI= Confidence Interval.
      Additionally, a sensitivity analysis of trials comparing the effects of CO2 laser and dissection exclusively on pediatric patients was executed. Two randomized [
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      ,
      • Thangavel S.
      • Saxena S.K.
      • Alexander A.
      Comparison of intraoperative and postoperative morbidity between carbondioxide laser tonsillectomy and dissection tonsillectomy-A randomized clinical trial.
      ] and one non-randomized controlled trial [
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      ] qualified for this sub-analysis.
      Operative time was shorter (SMD = -1.75; 95% CI = -2.76 to -0.74; p = 0.0007; Ι2 = 88%; Fig. 12) and intraoperative blood loss was less in CO2 laser tonsillectomies (SMD = -2.19; 95% CI = -3.16 to -1.23; p < 0.00001; Ι2 = 85%; Fig. 13). In both comparisons, a significant difference was identified between the two groups. For both intraoperative time and blood loss, the levels of heterogeneity were considerable (I2 = 88%; p= 0.0007 and I2 = 85%; p < 0.00001, respectively). Mohammadi et al. [
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      ] detected significantly higher intraoperative blood loss and intraoperative time in pediatric patients after dissection tonsillectomy compared to CO2 laser tonsillectomy.
      Fig 12
      Fig. 12Forest plot of standardized mean differences for the assessment of intraoperative time in pediatric patients (sensitivity analysis). SMD = standardized mean difference, IV= inverse variance, SD = standard deviation, CI = confidence interval.
      Fig 13
      Fig. 13Forest plot of standardized mean differences for the assessment of intraoperative blood loss in pediatric patients (sensitivity analysis). SMD = standardized mean difference, IV= inverse variance, SD = standard deviation, CI = confidence interval.
      Pain on the first postoperative day was not significantly more intense in the dissection group compared to the CO2 laser group (SMD = 0.31; 95% CI = - 0.13 to 0.76; p = 0.16; Fig. 14). Heterogeneity was found to be moderate (I2 = 55%; p = 0.13). On the seventh postoperative day, the difference in pain levels between the CO2 laser and conventional tonsillectomy was found to be significantly more intense in the dissection group (SMD = 1.46; 95% CI = 0.31 to 2.61; p = 0.01; Fig. 15). Heterogeneity was considerable (I2 = 91%; p = 0.001). No significant difference was detected in pain scores in pediatric patients between the two compared techniques in the study of Mohammadi et al. [
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      ]. For the pediatric population, the incidence of postoperative hemorrhage was not significantly different between the CO2 laser and dissection tonsillectomy (p > 0.05) in the studies evaluating pediatric patients [
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      ,
      • Mohammadi G.
      • Moghaddam Y.
      • Radfar R.
      CO2 laser tonsillectomy : a comparison with conventional technique.
      ].
      Fig 14
      Fig. 14Forest plot of standardized mean differences for assessing postoperative pain on the first postoperative day in pediatric patients (sensitivity analysis). SMD = standardized mean difference, IV= inverse variance, SD = standard deviation, CI = confidence interval.
      Fig 15
      Fig. 15Forest plot of standardized mean differences for assessing postoperative pain on the seventh postoperative day in pediatric patients (sensitivity analysis). SMD = standardized mean difference, IV= inverse variance, SD = standard deviation, CI = confidence interval.

      5. Discussion

      It should be noted that no consensus on the optimal tonsillectomy method has been reached yet, although with the advent of technology new methods of tonsil removal became available. Various studies in the literature compare standard blunt dissection to “hot” tonsillectomy techniques. Among them, tonsillectomy by laser microsurgery shows great potential as it enhances the precision of tonsillar excision and consequently provides maximal protection to peritonsillar tissue [
      • Alberti P.W.
      The complications of CO2 laser surgery in otolaryngology.
      ]. Several studies on CO2 laser tonsillectomy have shown a clinical advantage of laser excision over the conventional technique as measured by operative time and intraoperative blood loss without causing any additional morbidity [
      • Magdy E.A.
      • Elwany S.
      • El-Daly A.S.
      • Abdel-Hadi M.
      • Morshedy M.A.
      Coblation tonsillectomy: a prospective, double-blind, randomised, clinical and histopathological comparison with dissection-ligation, monopolar electrocautery and laser tonsillectomies.
      ,
      • Grossenbacher R.
      Experiences with CO2-laser-surgery in otorhinolaryngology.
      ]. The present systematic review was designed to compare the intraoperative and postoperative morbidities of CO2 laser and dissection tonsillectomy in light of the above.
      Postoperative pain is a substantial subjective symptom following tonsillectomy. Minimal postoperative pain is the key for an uncomplicated recovery because it causes patient discomfort and hinders swallowing with a risk of dehydration, infection, and secondary hemorrhage [
      • Tugrul S.
      • Degirmenci N.
      • Eren S.B.
      • Dogan R.
      • Veyseller B.
      • Ozturan O.
      Analgesic effect of magnesium in post-tonsillectomy patients: a prospective randomised clinical trial.
      ]. Even though laser tonsillectomy consistently causes more intense postoperative pain than conventional tonsillectomy [
      • Leach J.
      • Manning S.
      • Schaefer S.
      Comparison of two methods of tonsillectomy.
      ], pain levels on the first and seventh days among the patients subjected to both methods presented no significant clinical differences in this analysis.
      Another variable of major clinical importance which was analyzed in the present systematic review was the operative time. To illustrate, it is widely accepted that reduced operative time limits the exposure to anesthetic agents and thus improves patients’ recovery [
      • Evans C.
      • Richardson P.H.
      Improved recovery and reduced postoperative stay after therapeutic suggestions during general anaesthesia.
      ]. Moreover, a reasonable surgical time enables a larger number of operations to be performed in the operating room [
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      ]. Generally, for surgical procedures performed in a relatively narrow surgical field such as tonsillectomy, better hemostasis is associated with reduced operative time. In laser-assisted tonsillectomy, in particular, simultaneous cutting and coagulation of small size vessels by tissue heating [
      • Sajjadian A.
      • Isaacson G.
      Electrosurgery in the head and neck.
      ] provides a nearly bloodless field to the surgeon during the entire procedure [
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      ]. On the contrary, in cold-steel tonsillectomy, the trauma caused to soft tissue is more severe and leaves an open wound, which requires meticulous hemostasis, either by ligatures or diathermy, a time-consuming procedure. Indeed, the current study results proved that CO2 laser tonsillectomy was statistically significantly superior over dissection tonsillectomy regarding the surgical time, and this is considered one of the major assets of this tonsillectomy technique.
      What is more, intra-operative blood loss was analyzed, and a significant difference in favor of CO2 laser tonsillectomy was detected. In laser tonsillectomy, cutting and coagulation occur simultaneously, and as a result, intraoperative blood loss is minimal, leading to a nearly bloodless surgical field. On the other hand, with the traditional tonsillectomy technique, the tonsil is first dissected and then hemostasis is achieved, resulting in more blood loss.
      Furthermore, it is underlined that CO2 laser tonsillectomy is a hot technique, and it is highlighted that concerns have been raised on potential postoperative bleeding [
      • Mitchell R.B.
      • Archer S.M.
      • Ishman S.L.
      • Rosenfeld R.M.
      • Coles S.
      • Finestone S.A.
      • et al.
      Clinical practice guideline: tonsillectomy in children (Update)–executive summary.
      ], which is the most important complication in tonsillectomy and potentially life-threatening. This is particularly important in the pediatric population, as they bear a lower blood volume than adults [
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      ]. A large prospective audit from the UK and Northern Ireland that presented data from 33,921 patients reported lower postoperative bleeding rates in cold steel tonsillectomy than in hot tonsillectomy techniques [
      • Lowe D.
      • Van Der Meulen J.
      • Cromwell D.
      • Lewsey J.
      • Copley L.
      • Browne J.
      • et al.
      Key messages from the national prospective tonsillectomy audit.
      ]. On the contrary, a systematic review of prospective studies conducted by Leinbach et al. [
      • Leinbach R.F.
      • Markwell S.J.
      • Colliver J.A.
      • Lin S.Y.
      Hot versus cold tonsillectomy: a systematic review of the literature.
      ] and a Cochrane review by Pinder et al. [
      • Pinder D.K.
      • Wilson H.
      • Hilton M.P.
      Dissection versus diathermy for tonsillectomy.
      ] did not find a significant difference in postoperative bleeding rates between hot and cold techniques for tonsillectomy. In this analysis, there was no significant difference in post-tonsillectomy bleeding rates, even though a trend in favor of the laser group (0.53% compared to 2.76%) was found. Given the small number of events (i.e., 1 in the laser group out of 189 patients and 6 in the dissection group out of 217 patients) no robust conclusions could be drawn regarding the preferred method for this variable. With an estimated percentage of post-tonsillectomy bleeding being approximately 3%, we note that in this meta-analysis both techniques performed well below that level [
      • Mitchell R.B.
      • Archer S.M.
      • Ishman S.L.
      • Rosenfeld R.M.
      • Coles S.
      • Finestone S.A.
      • et al.
      Clinical practice guideline: tonsillectomy in children (Update)–executive summary.
      ].
      Moreover, hot tonsillectomy techniques are frequently included in the same category, although their effect on tonsillar tissue is probably not the same. For CO2 laser in particular, since it is a relatively new technique for tonsillectomy, there is a lack of data on its effects on tonsillar fossa healing. This analysis couldn't reach safe conclusions either. One study showed that tonsillar fossa heals faster with cold steel tonsillectomy, one with CO2 laser, and a third one showed no difference between the two methods. The methods used to judge tonsillar fossa healing in these studies were assessing erythema and leucocytic membrane formation during clinical examination, which is highly susceptible to bias. Tonsillar fossa healing is an indicator of recovery from surgery and, therefore, it could be used to compare tonsillectomy techniques, although a more objective way of measurement should be used.
      Overall, CO2 laser tonsillectomy performed better than conventional tonsillectomy in this analysis, in surgical time and intraoperative blood loss, but no significant statistical differences were noted in postoperative pain and bleeding. Evidence comparing CO2 laser tonsillectomy to other commonly performed tonsillectomy techniques is scarce. Magdy et al. [
      • Magdy E.A.
      • Elwany S.
      • El-Daly A.S.
      • Abdel-Hadi M.
      • Morshedy M.A.
      Coblation tonsillectomy: a prospective, double-blind, randomised, clinical and histopathological comparison with dissection-ligation, monopolar electrocautery and laser tonsillectomies.
      ] compared CO2 laser to coblation tonsillectomy in 20 patients and showed significantly lower operative time, intraoperative blood loss, and postoperative pain in the coblation side.
      CO2 lasers have also been used in the treatment of snoring and obstructive sleep apnea in laser-assisted uvulopalatoplasty (LAUP). The most common complications are postoperative pain, dryness of the pharynx, and globus sensation. Postoperative bleeding has a reported rate of 2,6%, which is comparable to tonsillectomy [
      • Wischhusen J.
      • Qureshi U.
      • Camacho M.
      Laser-assisted uvulopalatoplasty (LAUP) complications and side effects: a systematic review.
      ]. Of note, in a prospective study by Pavelec and Bohmanova, CO2 laser performed worse than other laser modalities. More specifically, patients required a median of 9 days of narcotic analgesics and 8 days before return to normal diet [
      • Pavelec V.
      • Bohmanova J.
      A comparison of postoperative recovery from laser-assisted uvulopalatoplasty using different laser systems.
      ].
      Regarding the impact of confounding factors on the results of our meta-analyses, it should be noted that a sensitivity analysis was also executed to investigate the impact of CO2 laser and dissection tonsillectomy on the pediatric population. Except for postoperative pain on day seven, the findings of our primary analysis remained robust after controlling for the inclusion of the pediatric population in the meta-analysis.
      In terms of quality appraisal in the current systematic review, it is worthy of note that five randomized controlled trials were included in the current systematic review. Except for one study, which was found to be at unclear risk of bias, the rest of the randomized trials were associated with a low risk of bias. Three non-randomized controlled studies contributed data to the qualitative synthesis, and two of them also qualified for the quantitative synthesis. Although all of them were deemed at moderate risk of bias, the inherent limitations associated with non-randomized evidence rendered those trials incomparable with well-performed randomized studies.
      For the minimization of bias in our results, a sensitivity analysis that excluded randomized trials of unclear risk of bias and non-randomized controlled trials of medium risk of bias was conducted. The primary and sensitivity analysis demonstrated no significant clinical differences when we accounted for the intraoperative time, and intraoperative blood loss and heterogeneity remained considerable. Lower heterogeneity in the sensitivity analysis was detected only for the comparison of pain on the first postoperative. The pain was statistically lower in the cold dissection group than the CO2 laser group on that day. On the contrary, for the pain on seventh postoperative pain, the levels of heterogeneity remained considerable, and no significant difference was spotted from the comparison of the two groups for this outcome.
      In an attempt to further investigate bias in the study, a subgroup analysis was also executed taking into consideration differences in randomization among the included trials. Overall, the sensitivity and subgroups analysis results indicated that the inclusion of either non-randomized trials or of trials with unclear or medium risk of bias in the quantitative synthesis did not considerably affect the overall results and, as a consequence, did not increase significantly bias in the present study.

      5.1 Strengths and limitations

      This is the first systematic review and meta-analysis comparing CO2 laser with cold-steel dissection tonsillectomy. However, we recognize that the present systematic review has a few limitations. A major drawback of this review is the unsolved high heterogeneity that we failed to eliminate by sensitivity and subgroup analysis. The main source of heterogeneity in the current review may derive from limitations regarding data collection across the studies. More specifically:

      6. Limitations regarding postoperative pain

      Postoperative pain is a vague symptom to evaluate. The significant interpatient pain threshold variability leads to a subjective assessment of pain among the patients. Furthermore, aside from the surgical instrument and surgical method applied, the surgeon's skills determine to a great extent the level of postoperative pain. Another limitation of this review was the utilization of different pain scales across the studies even though the Visual Analogue Scale (VAS) was found to have a uniformly increasing relationship with the Wong-Baker FACES Scale (WBS) and both of them to have an excellent correlation with acute pain [
      • Garra G.
      • Singer A.J.
      • Taira B.R.
      • Chohan J.
      • Cardoz H.
      • Chisena E.
      • et al.
      Validation of the wong-baker FACES pain rating scale in pediatric emergency department patients.
      ]. Thus, the heterogeneity spotted in the current meta-analysis regarding postoperative pain is outmost justified.

      7. Limitations regarding hemostasis

      Even though the CO2 laser method reduced operation time and bleeding because of the simultaneous cutting and coagulation by CO2 laser, Kumar et al. [
      • Kumar A.
      • Kumar S.
      • Krishnan A.
      • Verma M.
      • Garg U.
      • Sharma N.
      A comparative analysis of outcomes of conventional cold dissection versus laser tonsillectomy in pediatric cases in a tertiary care hospital in Haryana.
      ] and Ishlah et al. [
      • Ishlah L.W.
      • Fahmi A.M.
      • Srinovianti N.
      Laser versus dissection technique of tonsillectomy.
      ] used additionally suture ligation or diathermy to secure hemostasis. Therefore, this should be considered another potential limitation of this meta-analysis and a source of heterogeneity.

      8. Limitations regarding intraoperative bleeding

      There was inconsistency regarding the methodology for collecting data regarding intraoperative bleeding. Generally, a fully soaked cotton ball or gauze was considered to be equivalent to around 5 ml of blood. However, there was no consensus regarding the method applied in each study. Of note, some trials only measured the number of soaked tonsillar gauzes, cotton balls, or swabs used during the procedure, while others also considered the amount of blood in the suction bottle. Last but not least, it is worth mentioning that some studies did not present the measurement method of intraoperative blood loss at all.

      9. Limitations regarding operative time

      What is more, surgical time was calculated either from the placement of the Boyle-Davis mouth gag or after the first mucosal incision. To elaborate further, completing the operation was defined either as the achievement of hemostasis in the excised tonsillar bed or the removal of tonsil tissue from the oral cavity. The variation in the starting and finishing times of the surgical procedures compounded the problem of clinical diversity, thus justifying the unresolved statistical heterogeneity. On top of that, some studies did not provide information on measuring surgical time.

      9.1 Implications for future research

      First of all, it is advisable that more high-quality trials be conducted in the future to delineate the comparative efficacy of CO2 laser and cold-steel dissection tonsillectomy. To be more exact, concrete steps are to be taken to minimize interstudy heterogeneity. Towards this direction, the utilization of a common pain assessment tool for recording postoperative pain and a standardization regarding the measurement of surgical time and intraoperative blood loss would be necessary to draw more robust conclusions. Furthermore, more attention should be drawn to post-tonsillectomy bleeding, as the small number of events hamper sufficient data collection. Retrospective case series could be of help, bearing in mind that their results should be interpreted with caution though. Moreover, given laser tonsillectomy is a more expensive technique compared to traditional tonsillectomy, a cost-effectiveness analysis could help understand whether it is a reasonable alternative to the other techniques. From a clinical standpoint, an important question to be answered is whether CO2 laser is superior to other commonly performed “hot” techniques such as coblation and bipolar diathermy tonsillectomy. Our pair-wise meta-analysis study design did not allow us to compare multiple treatments simultaneously. A future network meta-analysis in this field might conclude the relative efficacy of the above interventions.

      10. Conclusion

      This systematic review and meta-analysis evaluated all the existing evidence on the comparative efficacy of CO2 laser over cold-steel dissection tonsillectomy. Regarding intraoperative outcomes, available evidence favored CO2 laser over conventional tonsillectomy since statistically significant lower levels of intraoperative blood loss and shorter operation time were detected in pediatric and adult patients. The findings were inconclusive for postoperative pain and bleeding because no statistically significant difference between those two methods was proven. However, it is suggested that the results of the present study be interpreted with caution since significant statistical heterogeneity levels may have impacted on the quality of evidence provided by the present review. Further high-quality randomized trials with pre-determined registration protocols detailing how outcome measurements will be recorded are warranted to corroborate the results of the current meta-analysis.

      Funding sources

      The authors declare that no funding was received to assist with the preparation of this manuscript.

      Authors’ contributions

      A.T. was the primary author. A.F. assisted the primary author with data extraction, study selection, literature research and the final revision of the manuscript, whereas F.D. was involved in quality assessment. I.T. and P.K. reviewed the final version of the manuscript. K.T., K.G and A.F contributed to the major revision of the manuscript. S.T. and K.T. provided methodological advice and critically reviewed and revised the manuscript. Finally, C.S. and S.T. supervised the study and provided guidance on specific scientific issues. All authors read and approved the final manuscript.

      Availability of data and material

      Not applicable

      Code availability

      Not applicable

      Declaration of Competing Interest

      The authors declare that they have no relevant financial or non-financial interests to disclose.

      Appendix. Supplementary materials

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