World Journal of Otorhinolaryngology - Head and Neck Surgery

REVIEW ARTICLE

Open Access

A scoping review of randomized clinical trials for pain management in pediatric tonsillectomy and adenotonsillectomy

Corresponding Author

Michael C. Shih

[email protected]

Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA

Baylor College of Medicine, Houston, Texas, USA

Correspondence Michael C. Shih, Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Ave., MSC550, Charleston, SC 29425, USA.

Email: [email protected]

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Barry D. Long,

Barry D. Long

Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA

Department of Otolaryngology—Head and Neck Surgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA

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Phayvanh P. Pecha,

Phayvanh P. Pecha

Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA

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David R. White,

David R. White

Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA

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Yi-Chun C. Liu,

Yi-Chun C. Liu

Department of Otolaryngology—Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, USA

Department of Surgery - Division of Pediatric Otolaryngology, Texas Children's Hospital, Houston, Texas, USA

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Emily Brennan,

Emily Brennan

Department of Research and Education Services, Medical University of South Carolina Library, Charleston, South Carolina, USA

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Mariam I. Nguyen,

Mariam I. Nguyen

Charleston County School of the Arts, North Charleston, South Carolina, USA

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Clarice S. Clemmens,

Clarice S. Clemmens

Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA

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Michael C. Shih,

Corresponding Author

Michael C. Shih

[email protected]

Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA

Baylor College of Medicine, Houston, Texas, USA

Correspondence Michael C. Shih, Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Ave., MSC550, Charleston, SC 29425, USA.

Email: [email protected]

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Barry D. Long,

Barry D. Long

Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA

Department of Otolaryngology—Head and Neck Surgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA

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Phayvanh P. Pecha,

Phayvanh P. Pecha

Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA

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David R. White,

David R. White

Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA

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Yi-Chun C. Liu,

Yi-Chun C. Liu

Department of Otolaryngology—Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, USA

Department of Surgery - Division of Pediatric Otolaryngology, Texas Children's Hospital, Houston, Texas, USA

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Emily Brennan,

Emily Brennan

Department of Research and Education Services, Medical University of South Carolina Library, Charleston, South Carolina, USA

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Mariam I. Nguyen,

Mariam I. Nguyen

Charleston County School of the Arts, North Charleston, South Carolina, USA

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Clarice S. Clemmens,

Clarice S. Clemmens

Department of Otolaryngology—Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA

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First published: 18 April 2022

https://doi.org/10.1002/wjo2.54

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Abstract

Objectives

To examine the volume, topics, and reporting trends in the published literature of randomized clinical trials for pharmacologic pain management of pediatric tonsillectomy and adenotonsillectomy and to identify areas requiring further research.

Data Sources

PubMed (National Library of Medicine and National Institutes of Health), Scopus (Elsevier), CINAHL (EBSCO), and Cochrane Library (Wiley).

Methods

A systematic search of four databases was conducted. Only randomized controlled or comparison trials examining pain improvement with a pharmacologic intervention in pediatric tonsillectomy or adenotonsillectomy were included. Data collected included demographics, pain-related outcomes, sedation scores, nausea/vomiting, postoperative bleeding, types of drug comparisons, modes of administration, timing of administration, and identities of the investigated drugs.

Results

One hundred and eighty-nine studies were included for analysis. Most studies included validated pain scales, with the majority using visual-assisted scales (49.21%). Fewer studies examined pain beyond 24 h postoperation (24.87%), and few studies included a validated sedation scale (12.17%). Studies have compared several different dimensions of pharmacologic treatment, including different drugs, timing of administration, modes of administration, and dosages. Only 23 (12.17%) studies examined medications administered postoperatively, and only 29 (15.34%) studies examined oral medications. Acetaminophen only had four self-comparisons.

Conclusion

Our work provides the first scoping review of pain and pediatric tonsillectomy. With drug safety profiles considered, the literature does not have enough data to determine which treatment regimen provides superior pain control in pediatric tonsillectomy. Even common drugs like acetaminophen and ibuprofen require further research for optimizing the treatment of posttonsillectomy pain. The heterogeneity in study design and comparisons weakens the conclusions of potential systematic reviews and meta-analyses. Future directions include more noninferiority studies of unique comparisons and more studies examining oral medications given postoperatively.

Key points

This novel scoping review highlights the heterogeneity of research in pediatric posttonsillectomy pain management.
Even common drugs like acetaminophen and ibuprofen require further research for optimizing the treatment of pediatric posttonsillectomy pain.

INTRODUCTION

Tonsillectomy is a common pediatric ambulatory surgical procedure, second in incidence only to myringotomy with tube insertion in the United States.¹ In 2010, 289,000 ambulatory tonsillectomy procedures were performed in children younger than 15 years of age.² Over the past 35 years, the incidence rates of tonsillectomy have increased significantly, with obstructive sleep-disordered breathing and recurrent throat infections cited as the most common indications for surgery.^3-5

The management of posttonsillectomy pain is oftentimes inadequate and studies have identified tonsillectomies as surgical procedures that induce high levels of pain.^6-8 Although too little pain medication may result in significant patient discomfort and suffering, too much pain medication may result in serious adverse events. Postoperative hemorrhage is a well-described risk for tonsillectomy.⁹ Nonsteroidal anti-inflammatory drugs (NSAIDs) have the theoretical potential to further increase the risk for postoperative bleeding.¹⁰ While opioid analgesics do not increase hemorrhage risk, the risks for respiratory depression and death have been well documented with the use of opioids, as emphasized by the 2013 and 2017 US Food and Drug Administration black box warning and contraindication statements.^{11, 12}

In 2019, The American Academy of Otolaryngology (AAO) released an updated Clinical Practice Guideline for pediatric tonsillectomy. The authors strongly recommended the use of intraoperative intravenous (iv) steroids and postoperative ibuprofen and acetaminophen for pain. Furthermore, the authors strongly recommended against the use of postoperative codeine.¹³ Otherwise, there is no clear consensus or standardization for pediatric tonsillectomy pain regimens. The Clinical Practice Guidelines also highlighted the need for increased research comparing pharmacologic postoperative pain medications, as well as a standardized set of outcomes.¹³

There exists a large amount of published high-level evidence for pharmacologic pain management in pediatric tonsillectomy/adenotonsillectomy. The clinical applicability of these studies varies significantly due to the extensive heterogeneity in pain treatment regimens, such as differences in the timing of administration, dosing, and modes of administration. These differences create difficulties in conducting high-quality systematic reviews and meta-analyses of randomized-controlled trials, which summarize the best available research on a specific question. In contrast, a scoping review, which aims to broadly examine what has been published rather than answer a clinical question, would provide the needed mapping of the overwhelming amount of literature.¹⁴ Furthermore, a scoping review would provide guidance for a clinical trial design that may allow for future high-level systematic reviews and meta-analyses. The purpose of this scoping review is to examine the volume, topics, and reporting trends in the published literature of randomized controlled trials for pain management of pediatric tonsillectomy and adenotonsillectomy and to identify areas requiring further research.

METHODS

Systematic literature search

This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines.¹⁵ A research librarian (E. B.) with expertise in conducting systematic reviews developed detailed search strategies in the following four databases: PubMed (National Library of Medicine, National Institutes of Health), Scopus (Elsevier), CINAHL (EBSCO), and Cochrane Library (Wiley). The search strategies used a combination of subject headings (e.g., Medical Subject Headings [MeSH] in PubMed) and keywords for the following three concepts: tonsillectomy/adenotonsillectomy, pain, and pediatrics. The PubMed search strategy was modified for the other three databases, replacing MeSH terms with appropriate subject headings, when available, and maintaining similar keywords. The search strategies for each database are detailed in Supporting Information Appendix 1. The databases were searched from inception through May 7, 2021, and results were limited to the English language only. To identify additional articles, the reference lists of relevant articles were hand searched, as well as citing articles. References were uploaded to Covidence systematic review software (Veritas Health Innovation) and screened for relevance.

Selection criteria

Only randomized controlled trials with the primary or secondary objective of examining pain improvement with specific pharmacologic intervention in pediatric tonsillectomy patients were included. Abstracts were first independently reviewed by two reviewers (M. S. and B. D. L.) to first identify all randomized controlled studies pertaining to the treatment of tonsillectomies in patients aged 0–18 years. Non-English studies, nonhuman studies, and nonjournal articles were excluded. Studies were considered for inclusion in the final analyses if they were: (1) randomized controlled or comparison trials, (2) involving only patients aged 0–18 years, (3) examining patients that underwent tonsillectomy, tonsillotomy, or adenotonsillectomy, and (4) examining the effects of pharmacologic interventions on postsurgical pain. Quality improvement studies or studies that involved nonpharmacologic interventions (e.g., hot and cold meals, acupressure, or glossopharyngeal block) were excluded. Additionally, studies that included patients that underwent other concomitant procedures (e.g., myringotomy with tympanostomy tube placement) were excluded.

Data collection and analysis

Measures that are relevant to the health care providers and the general public were extracted by two reviewers (M. S. and B. D. L.) and included in the analysis and discussion. Disagreements were resolved by way of discussion. Collected measures included demographics (age, weight, body mass index [BMI], sex, American Society of Anesthesiologists [ASA] physical status, and country where the study was conducted), pain-related outcomes (pain scale used, time points examined, and postoperative analgesic requirements), sedation scores, nausea/vomiting, postoperative bleeding, type of drug comparisons, mode of administration, and timing of administration. These measures were all reported as counts and percentages of publications mentioning the item. Drug comparisons, irrespective of mode and timing of administration, were also counted. In instances of incomplete data, an attempt was made to contact the primary author via email for clarification or sharing of primary data.

The results of this scoping review are presented according to the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).¹⁶ All graphs and tables were performed with Microsoft Excel version 2008 (Microsoft), Prism version 8.0.0 (GraphPad Software), and Cochrane Review Manager (RevMan) version 5.4 (Nordic Cochrane Center, Cochrane Collaboration, 2011). Pooled analysis was performed with each measure was weighted according to the number of publications and were summarized by frequency (N) and percentage (%).

Quality of evidence assessment

The level of evidence for each selected article was evaluated by the Oxford Center for Evidence-Based Medicine.¹⁷ The risk of bias was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions version 6.2, 2021. Two authors (M. S. and B. D. L.) performed a pilot assessment on three studies to check for consistency of assessment. Both then performed independent risk assessments on the remaining studies. All disagreements were resolved by way of discussion. The risk of bias items included the following: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. The risk of bias for each aspect was graded as low, unclear, or high.

RESULTS

A total of 189 randomized controlled and comparison trials met the inclusion criteria for analysis.^18-206 A PRISMA diagram outlining the literature search is shown in Figure 1, and the risk of bias graph is shown in Figure 2. Risk of bias was “unclear” for 16.78% of items, and 4.01% were “high risk.” All studies met Level 2 criteria for the Oxford level of evidence. The included studies were published between 1985 and 2021 (188 articles in total, Turkey 48, US 32, Iran 30, others 78).

Details are in the caption following the image — **Figure 1**
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Preferred reporting items for systematic reviews and meta-analyses diagram

The demographics examined by the literature are shown in Table 1. No studies included only children under 12 years of age (maximum age, 11 years); therefore, we examined studies that included only children under 13 years of age. Most studies focused on children with a maximum age of 7–12 (58.20%), but several studies included patients up to 13–18 years (38.62%) without age subgroup analysis. Most studies reported body weight (71.43%), whereas only 10 (5.29%) studies reported BMI. Most studies indicated ASA 1 (65.61%) and 2 (60.32%) as inclusion criteria.

Table 1. Number of publications that report specific demographics

Variable	Number of publications	Publications (%)
Maximum patient age
7–12	110	58.20
13–18	73	38.62
Unclear	6	3.17
Weight	135	71.43
Body mass index	10	5.29
Sex	158	83.60
American Society of Anesthesiologists (ASA) status
ASA 1	124	65.61
ASA 2	114	60.32
ASA 3	7	3.70
No info	65	34.39

The reported pain-related outcomes are shown in Table 2. Only two studies (1.06%) did not include a pain scale, and nearly half of the studies used a visual-assisted scale (49.21%). Sixteen studies used multiple pain scales. Approximately one in four studies examined time points at and beyond 24 h, whereas a greater majority (84.66%) included time points in the immediate postoperative period. Postoperative analgesic requirements were reported in 76.19% of studies, whereas only approximately 23.28% of studies reported sedation scores.

Table 2. Outcomes examined in the literature

Variable	Number of publications	Publications (%)
Pain scale	186	98.41
Observational scales	69	36.51
CHEOPS	44	23.28
FLACC	14	7.41
Hanallah	7	3.70
TPPPS/PPPM	2	1.06
CHIPPS	1	0.53
CPSC	1	0.53
Visual-assisted scales	93	49.21
VAS	45	23.81
Faces (unspecified)	19	10.05
Wong-Baker	10	5.29
McGrath	9	4.76
Oucher	9	4.76
Maunuksela	1	0.53
Numeric pain scale
Numeric rating scale	3	1.59
Objective pain score	19	10.05
Unvalidated	15	7.29
No pain scale used	2	1.06
Time points (h) examined
≤24	160	84.66
≥24	47	24.87
Postoperative analgesia requirements	144	76.19
Number of patients	76	40.21
Time to first request	51	26.98
Doses (frequency, amount, or number)	81	42.86
Sedation scores	44	23.28
Aldrete	2	1.06
MOAA/S	1	0.53
Ramsay	12	6.35
Riker SAS	1	0.53
Vancouver	1	0.53
Wilson	6	3.17
Unvalidated	21	11.11
Nausea and vomiting	140	74.07
Postoperative bleeding	90	47.62

Abbreviations: CHEOPS, Children's Hospital of Eastern Ontario Pain Scale; CHIPPS, Children and Infants Postoperative Pain Scale; CPSC, Conscious Presence and Self Control Scale; FLACC, Face, Legs, Activity, Cry, Consolability Scale; MOAA/S, Modified Observer's Assessment of Alertness/Sedation Scale; PPPM, Parents' Postoperative Pain Measure; PPPS, Toddler-Preschool Postoperative Pain Scale; Riker SAS, Riker Sedation-Agitation Scale; VAS, Visual Analog Scale.

Table 3 shows the types of comparisons made in the literature. The majority of papers included a placebo or control comparison (62.43%). Most papers aimed to compare different drugs (47.09%), whereas fewer studies sought to compare the timing of administration (3.17%), different modes of administration for the same (9.52%) or different drugs (5.82%), and dose differences (7.41%) (Tables 4 and 5). Across all studies that examined the effects of acetaminophen, nine unique doses between 10 mg/kg (postoperatively every 4 h as needed) and 100 mg/kg (perioperative single dose) were used. Figure 3 exhibits all drug comparisons. Figures 4-6 show drug comparisons split by year of publication. There were fewer comparisons involving opioids after 2015 compared to prior years, whereas studies on local anesthetics and ketamine persisted through all years of publication.

Table 3. Types of comparisons

Variable	Number of publications	Publications (%)
Drug to placebo/control comparison	118	62.43
Only examines placebo/control comparison	55	29.10
Same drug, different dose	14	7.41
Different drugs, not combined	89	47.09
Drug a compared to drug A + drug B	22	11.64
Same drug, different modes of administration	18	9.52
Different drugs, different modes of administration	11	5.82
Timing of administration	6	3.17
Different drugs, different modes of administration, and different timing of administration	2	1.06

Note: The included studies examined 12 different modes of administration (Table 4). The most common were intravenous injection and peritonsillar injection. Regarding the timing of administration (Table 5), most studies compared presurgical or intrasurgical pharmacologic interventions. In contrast, only 23 (12.17%) studies examined postsurgical drug administrations. The frequency of comparisons made for oral drugs given postoperatively is shown in Figure 7.

Table 4. Modes of administration

Mode of administration	Number of publications	Publications (%)
Intramuscular injection	12	6.35
Intranasal spray	2	1.06
Inhalation	3	1.59
Intravenous injection	75	39.68
Intravenous—patient-controlled administration	2	1.06
Mouthwash, oral rinse, or oral spray	6	3.17
Oral	29	15.34
Peritonsillar infiltration	56	29.63
Rectal	15	7.94
Subcutaneous injection	1	0.53
Sublingual	1	0.53
Topical to operation site	18	9.52
Unclear	3	1.59

Table 5. Timing of administration

Timing of administration	Number of publications	Publications (%)
Before surgery	22	11.64
Night before surgery	1	0.53
Within 2 h of surgery	21	11.11
At induction	15	7.94
After induction, before the end of surgery	102	53.97
After intubation	3	1.59
Preincision	77	40.74
During operation	4	2.12
After tonsils removed	10	5.29
At end of surgery	14	7.41
Postoperation	23	12.17
Mixed	13	6.88
Unclear	2	1.06

DISCUSSION

Our work provides the first scoping review of pain and pediatric tonsillectomy. All randomized controlled and comparison trials regarding pharmacologic interventions for pain management in pediatric tonsillectomy and adenotonsillectomy were evaluated. This study provides future researchers guidance by showing which areas require additional randomized controlled trials.

Although this study contains elements similar to a systematic review (i.e., inclusion of a PRISMA diagram, focuses only on randomized controlled trials, assessing the risk of bias), the aim of the study fits within the category of scoping reviews. Specifically examining randomized controlled trials was warranted because pediatric tonsillectomy is a common procedure with high accessibility for randomized controlled trials. Furthermore, the large number of published randomized controlled trials creates expectations for the ability to conduct powerful systematic reviews and meta-analyses. However, our study highlights the heterogeneity in methodology and pain treatment comparisons in the existing literature, thereby elucidating the difficulties in conducting high-level systematic reviews and meta-analyses of randomized controlled trials.

Quality of included studies

The moderate amounts of unclear bias (16.78%) highlight the need for clear reporting of methodology regarding randomization and blinding. In particular, for surgeries like tonsillectomies, the ideal protocol would minimize the number of different operating surgeons and surgical methods involved in these clinical trials. Nonetheless, the overall critical appraisal of studies indicated an acceptably low risk of bias for most studies.

Demographics and patient characteristics

Specific to children, developmental changes in physiology (e.g., puberty) may affect the efficacy, toxicity, and dosing regimens for various medications.²⁰⁷ In our study, we sought to investigate pre- and postpubescent time points. Due to factors of geography, culture, and genetics, the onset of puberty and adolescence varies for each individual, and determining a universally accepted age cutoff becomes challenging. There were many studies that included patients up to 13–18 years of age (39.15%) and these studies did not provide relevant subgroup analyses. In such cases, assigning accurate conclusions to children at different stages of development becomes difficult. It is preferable that future studies develop inclusion criteria for patient age that reflect subgroups of interest. If multiple subgroups are of interest, then subgroup analyses sharpen the ability to develop recommendations specific to an individual patient.

Studies often reported weight but very seldom reported BMI. This may be due to the fact that the definitions of obesity differ between children and adults. For children, obesity is defined as BMI at or above the 95th percentile when compared to children of the same age and sex.²⁰⁸ Weight varies significantly across pediatric patients; the utility of comparing the weight between a 5-year-old child and a 17-year-old adolescent is questionable. Even with height reported alongside weight as lumped means and standard deviations, the pertinent pharmacologic characteristics of individual patients still become lost. Overweight and obese patients generally have larger volumes of distribution of lipophilic medications. For children of different age groups and body sizes, lean body mass, blood volume, and changes in the percentage of total body water influence the volume of distribution for hydrophilic medications.²⁰⁹ Although BMI alone does not convey all the bodily characteristics of a patient, the metric is much more informative than weight alone when examining groups of patients. Future studies should consider reporting the number of pediatric patients who meet the criteria for overweightness (85th–95th percentile for BMI) and obesity (95th percentile or greater).²⁰⁸

ASA status was focused on those related to healthy patients (ASA 1) and mild to moderate systemic disease that is well-controlled (ASA 2). This is appropriate for examining drug effects as a patient will have fewer confounders related to pain and reporting of pain. Furthermore, most studies properly characterized the number of male and female patients per group.

Outcomes

Pain scales were used in 98.41% of studies, with the majority preferring visual-assisted scales over observational scales. Because pain is subjective in nature and pain perception varies across cultures and individuals, there is no clear preferred method of collecting and reporting pain data. However, the usage of both an objective and observational scale in addition to a subjective visual-assisted scale may improve the generalizability and validity of findings. Furthermore, the person who obtains the data (i.e., study staff vs. patient vs. parent) must be described and consistent across the study. Analgesia requirements in the immediate postoperative period may acceptably act as surrogates for pain perception; however, the requirements for administering rescue analgesia must be well-delineated, including the pain scale used. After a patient is discharged from the hospital, confounders for analgesia requirements increase, and specific guidance should be given to caretakers to improve the accuracy and validity of data.

Reports on sedation were of interest as both a complication of medications as well as a confounder for pain. Patients that received pre- and intraoperative interventions may have pain ratings affected by increased or decreased sedation related to the intervention. Furthermore, opioids have been noted to increase the risk for excessive sedation, respiratory depression, and death in children.^210-213 Twenty-three studies utilized six different validated sedation scores. This finding highlights the need to encourage the use of sedation scores and also to standardize methods for quantifying and reporting sedation.

Approximately half of the studies reported postoperative bleeding rates. This complication is specifically relevant to tonsillectomy due to the increased morbidity and mortality associated with hemorrhage.⁹ The risk for postoperative hemorrhage is theoretically increased further by the use of NSAIDs.¹⁰ Previous studies have indicated no increased bleeding risk with the use of ibuprofen, but recent studies suggest the possibility of increased bleeding severity with ibuprofen.^214-217 Furthermore, studies have reported increased bleeding risk with ketorolac, but a meta-analysis suggested that ketorolac may not truly increase the risk for postoperative hemorrhage in pediatric tonsillectomy.²¹⁸ However, our current work has shown that ketorolac only has five comparisons for pain published in the literature. Even if ketorolac does not induce a risk of bleeding, the intervention should first be determined to be a suitable analgesic for this patient population. More clinical trials on ketorolac and ibuprofen, specifically compared with acetaminophen and placebo/controls should, therefore, be conducted.

Areas requiring further investigation

Despite a large number of studies and drug comparisons for pediatric tonsillectomy, there is still no clear consensus on a superior pain treatment regimen. A large barrier is the heterogeneity of comparisons across different dimensions, which include different drugs, modes of administration, timing of administration, duration of treatment, and dosages. A study should ideally examine differences in only one dimension.

Initial efforts should focus on fully understanding drugs with clear safety profiles, which currently include ibuprofen and acetaminophen.¹³ Acetaminophen/paracetamol/propacetamol, medications strongly recommended for pediatric tonsillectomy, has only six self-comparisons published in the literature for pediatric tonsillectomies. These studies compared oral versus rectal, oral versus intramuscular injection, intravenously before induction versus after surgery, oral perioperative 40 versus 100 mg/kg (single dose), acetaminophen versus acetaminophen with ibuprofen, and oral versus rectal acetaminophen with codeine.^{31, 87, 92, 126, 133, 146} Even for this common drug, the literature has not adequately determined the best mode of administration (i.e., intravenous vs. rectal vs. oral), timing of administration, dosages, or duration of treatment postoperatively. These issues become magnified for other less used and less investigated drugs. Furthermore, the wide variation in dosing for acetaminophen highlights the need to determine a standardized dose for comparison studies. After fully characterizing common and relatively safe drugs, researchers can better conduct noninferiority trials for other medications of interest.

The most recent Pediatric Tonsillectomy Clinical Practice Guidelines had expressed the need for increased research comparing oral pharmacologic postoperative pain medications.¹³ Our findings show that only approximately one in four studies examined time points beyond 24 h after surgery, demonstrating the referenced paucity in the literature for home pain control regimens. Further emphasizing this point, only 29 (15.34%) studies examined oral medications. As exhibited in Figure 7, even the most common postsurgical oral pain medications have not been adequately investigated. For such a common and long-established procedure, this finding likely stems from the difficulties in obtaining data from patients after discharge. Without clear standards for follow-up and with follow-ups oftentimes conducted by phone calls, obtaining reliable survey data can be challenging for researchers. In contrast, measures in the immediate postoperative period are more readily accessible.

Only 22 comparisons could be made for add-on regimens (i.e., drug A compared to drug A with drug B). These add-on studies emphasize the ongoing support for multimodal regimens.²¹⁹ However, because the efficacy of individual drugs has not yet been determined, it would be premature to target multimodal regimens.

Limitations

This study is limited by the scope of the project. Because the authors decided to only include patients in randomized controlled and comparison trials, data from retrospective and observational prospective studies are not considered. Also, the nature of pain deriving from tonsillectomy and adenoidectomy are likely different, and therefore the authors excluded any articles only examining adenoidectomy. However, most publications used tonsillectomy with or without adenoidectomy as inclusion criteria. Ideally, our work would have examined only adenoidectomy, tonsillectomy, or adenotonsillectomy, rather than a combination of the latter two surgeries. There are additional factors that may influence post-tonsillectomy pain, such as surgical instrumentation and technique.²²⁰ However, these separate factors should be directly compared in randomized-controlled trials, rather than analyzed through studies aiming to compare pharmacologic interventions. Furthermore, our work does not examine differences across time of publication. Because we included articles from 1985 to 2021, changes in reporting patterns may have already occurred that are not visible from our summative information. Finally, scoping reviews are not designed to assess the quality of the empirical evidence. More targeted systematic reviews would inform the field of the quality of relevant research in these areas.

CONCLUSIONS

Our work elucidates the reporting trends and areas requiring further research for pharmacologic pain management in pediatric tonsillectomy and adenotonsillectomy. Researchers should analyze outcomes for age groups with consideration for varying stages of development, and more studies should provide BMI information in addition to descriptive statistics of weight. Studies should utilize and report validated sedation scores, and complications such as postoperative hemorrhage and nausea/vomiting should be addressed.

With drug safety profiles considered, the literature does not have enough data to determine which treatment regimen provides superior pain control in pediatric tonsillectomy. There is currently inadequate data on oral medications given postoperatively, including acetaminophen and ibuprofen. Timing of drug administration, modes of administration, and duration of treatment require more research. Furthermore, the strength of any systematic reviews and meta-analyses would be diminished by the significant heterogeneity in reporting trends and comparisons made in the existing literature. Future studies should first focus on understanding drugs with adequate safety profiles, which currently include ibuprofen and acetaminophen. Thereafter, noninferiority trials with other drugs of interest should be considered. We hope this scoping review provides a compelling framework for the future reporting and conduct of randomized clinical trials for posttonsillectomy pain management.

AUTHOR CONTRIBUTIONS

Michael Shih, Barry D. Long, and Clarice S. Clemmens: design, conduct, analysis, and manuscript conception. Phayvanh P. Pecha, David R. White, and Yi-Chun Carol Liu: design, analysis, and manuscript conception. Emily Brennan: design, conduct, and manuscript conception. Mariam I. Nguyen: conduct, analysis, and manuscript conception.

ACKNOWLEDGMENTS

We are indebted to Steven Yen, BBA, for his assistance in producing Figures 3-7.

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

Open Research

DATA AVAILABILITY STATEMENT

This review contains only data derived from published articles. No new data was generated.

ETHICS STATEMENT

This study was a review and thus no ethics statement or IRB approval was needed.

Supporting Information

REFERENCES

1Cullen KA, Hall MJ, Golosinskiy A. Ambulatory surgery in the United States, 2006. Natl Health Stat Report. 2009; 11: 1-25.
Google Scholar
2Hall MJ, Schwartzman A, Zhang J, Liu X. Ambulatory surgery data from hospitals and ambulatory surgery centers: United States, 2010. Natl Health Stat Report. 2017; 102: 1-15.
Google Scholar
3Parker NP, Walner DL. Trends in the indications for pediatric tonsillectomy or adenotonsillectomy. Int J Pediatr Otorhinolaryngol. 2011; 75(2): 282-285. doi:10.1016/j.ijporl.2010.11.019
Google Scholar
4Patel HH, Straight CE, Lehman EB, Tanner M, Carr MM. Indications for tonsillectomy: a 10 year retrospective review. Int J Pediatr Otorhinolaryngol. 2014; 78(12): 2151-2155. doi:10.1016/j.ijporl.2014.09.030
Google Scholar
5Erickson BK, Larson DR, St Sauver JL, Meverden RA, Orvidas LJ. Changes in incidence and indications of tonsillectomy and adenotonsillectomy, 1970-2005. Otolaryngol Head Neck Surg. 2009; 140(6): 894-901. doi:10.1016/j.otohns.2009.01.044
Google Scholar
6Gerbershagen HJ, Aduckathil S, van Wijck AJ, Peelen LM, Kalkman CJ, Meissner W. Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology. 2013; 118(4): 934-944. doi:10.1097/ALN.0b013e31828866b3
Google Scholar
7Maier C, Nestler N, Richter H, et al. The quality of pain management in German hospitals. Dtsch Arztebl Int. 2010; 107(36): 607-614. doi:10.3238/arztebl.2010.0607
Google Scholar
8Persino PR, Saleh L, Walner DL. Pain control following tonsillectomy in children: a survey of patients. Int J Pediatr Otorhinolaryngol. 2017; 103: 76-79. doi:10.1016/j.ijporl.2017.10.016
Google Scholar
9Handler SD, Miller L, Richmond KH, Baranak CC. Post-tonsillectomy hemorrhage: incidence, prevention and management. Laryngoscope. 1986; 96(11): 1243-1247. doi:10.1002/lary.1986.96.11.1243
Google Scholar
10Rainsford KD. Profile and mechanisms of gastrointestinal and other side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Am J Med. 1999; 107(6A): 27S-35S, discussion 35S-36S. doi:10.1016/s0002-9343(99)00365-4
Google Scholar
11 US Food and Drug Administration. FDA drug safety communication: FDA requires labeling changes for prescription opioid cough and cold medicines to limit their use to adults 18 years and older. January 11, 2018. Accessed June 13, 2021. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-restricts-use-prescription-codeine-pain-and-cough-medicines-and.Published2018
Google Scholar
12 US Food and Drug Administration. Safety review update of codeine use in children; new Boxed Warning and Contraindication on use after tonsillectomy and/or adenoidectomy. February 20, 2013. Accessed June 13, 2021. https://wayback.archive-it.org/7993/20170722185707/; https://www.fda.gov/Drugs/DrugSafety/ucm339112.htm
Google Scholar
13Mitchell RB, Archer SM, Ishman SL, et al. Clinical practice guideline: tonsillectomy in children (update)—executive summary. Otolaryngol Head Neck Surg. 2019; 160(2): 187-205. doi:10.1177/0194599818807917
Google Scholar
14Pham MT, Rajić A, Greig JD, Sargeant JM, Papadopoulos A, McEwen SA. A scoping review of scoping reviews: advancing the approach and enhancing the consistency. Res Synth Methods. 2014; 5(4): 371-385. doi:10.1002/jrsm.1123
Google Scholar
15Tricco AC, Lillie E, Zarin W, et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018; 169(7): 467-473. doi:10.7326/M18-0850
Google Scholar
16Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015; 4(1):1. doi:10.1186/2046-4053-4-1
Google Scholar
17 OCEBM Levels of Evidence Working Group. The Oxford levels of evidence 2. Oxford Centre for Evidence-Based Medicine. 2016. Accessed June 13, 2021. https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-levels-of-evidence
Google Scholar
18Abdel-Ghaffar HS, Abdel-Haleem AK. Efficacy and safety of intraoperative dexmedetomidine in pediatric posttonsillectomy pain: peritonsillar versus intravenous administration. Egypt J Anaesth. 2011; 27(4): 219-225.
Google Scholar
19Abdel-Ghaffar HS, Sayed JA, Fathy MA, Abdel-Azeem HG, Salem MAM. Preincisional peritonsillar vs. intravenous lornoxicam for posttonsillectomy analgesia: a clinical and platelet aggregometry comparative study. Egypt J Anaesth. 2012; 28(2): 107-115.
Google Scholar
20Abdullah B, Lazim NM, Salim R. The effectiveness of Tualang honey in reducing post-tonsillectomy pain. Kulak Burun Bogaz Ihtis Derg. 2015; 25(3): 137-143. doi:10.5606/kbbihtisas.2015.00008
Google Scholar
21Abu-Shahwan I. Ketamine does not reduce postoperative morphine consumption after tonsillectomy in children. Clin J Pain. 2008; 24(5): 395-398. doi:10.1097/AJP.0b013e3181668aad
Google Scholar
22Akbay BK, Yildizbas S, Guclu E, Yilmaz S, Iskender A, Ozturk O. Analgesic efficacy of topical tramadol in the control of postoperative pain in children after tonsillectomy. J Anesth. 2010; 24(5): 705-708. doi:10.1007/s00540-010-0978-2
Google Scholar
23RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021; 384(8): 693-704. doi:10.1056/NEJMoa2021436
Google Scholar
24Akkaya T, Bedirli N, Ceylan T, et al. Comparison of intravenous and peritonsillar infiltration of tramadol for postoperative pain relief in children following adenotonsillectomy. Eur J Anaesthesiol. 2009; 26(4): 333-337. doi:10.1097/EJA.0b013e32831c8988
Google Scholar
25Akoglu E, Akkurt BC, Inanoglu K, Okuyucu S, Dagli S. Ropivacaine compared to bupivacaine for post-tonsillectomy pain relief in children: a randomized controlled study. Int J Pediatr Otorhinolaryngol. 2006; 70(7): 1169-1173. doi:10.1016/j.ijporl.2005.12.001
Google Scholar
26Alhashemi JA, Daghistani MF. Effects of intraoperative i.v. acetaminophen vs i.m. meperidine on post-tonsillectomy pain in children. Br J Anaesth. 2006; 96(6): 790-795. doi:10.1093/bja/ael084
Google Scholar
27Ali SM, Shahrbano S, Ulhaq TS. Tramadol for pain relief in children undergoing adenotonsillectomy: a comparison with dextromethorphan. Laryngoscope. 2008; 118(9): 1547-1549. doi:10.1097/MLG.0b013e318178272e
Google Scholar
28Amani S, Kheiri S, Ahmadi A. Honey versus diphenhydramine for post-tonsillectomy pain relief in pediatric cases: a randomized clinical trial. J Clin Diagn Res. 9(3), 2015: SC01-SC04. doi:10.7860/JCDR/2015/9784.5635
Google Scholar
29Amin SM, Amr YM. Comparison between preemptive gabapentin and paracetamol for pain control after adenotonsillectomy in children. Anesth Essays Res. 2011; 5(2): 167-170. doi:10.4103/0259-1162.94758
Google Scholar
30Anderson B, Kanagasundarum S, Woollard G. Analgesic efficacy of paracetamol in children using tonsillectomy as a pain model. Anaesth Intensive Care. 1996; 24(6): 669-673. doi:10.1177/0310057X9602400606
Google Scholar
31Anderson BJ, Woollard GA, Holford NH. Acetaminophen analgesia in children: placebo effect and pain resolution after tonsillectomy. Eur J Clin Pharmacol. 2001; 57(8): 559-569. doi:10.1007/s002280100367
Google Scholar
32Antila H, Manner T, Kuurila K, Salanterä S, Kujala R, Aantaa R. Ketoprofen and tramadol for analgesia during early recovery after tonsillectomy in children. Paediatr Anaesth. 2006; 16(5): 548-553. doi:10.1111/j.1460-9592.2005.01819.x
Google Scholar
33April MM, Callan ND, Nowak DM, Hausdorff MA. The effect of intravenous dexamethasone in pediatric adenotonsillectomy. Arch Otolaryngol Head Neck Surg. 1996; 122(2): 117-120. doi:10.1001/archotol.1996.01890140007003
Google Scholar
34Kimiaei Asadi H, Nikooseresht M, Noori L, Behnoud F. The effect of administration of ketamine and paracetamol versus paracetamol singly on postoperative pain, nausea and vomiting after pediatric adenotonsillectomy. Anesth Pain Med. 2016; 6(1):e31210. doi:10.5812/aapm.31210
Google Scholar
35Aspinall RL, Mayor A. A prospective randomized controlled study of the efficacy of ketamine for postoperative pain relief in children after adenotonsillectomy. Paediatr Anaesth. 2001; 11(3): 333-336. doi:10.1046/j.1460-9592.2001.00676.x
Google Scholar
36Atef A, Fawaz AA. Peritonsillar infiltration with tramadol improves pediatric tonsillectomy pain. Eur Arch Otorhinolaryngol. 2008; 265(5): 571-574. doi:10.1007/s00405-007-0479-6
Google Scholar
37Ayatollahi V, Behdad S, Hatami M, Moshtaghiun H, Baghianimoghadam B. Comparison of peritonsillar infiltration effects of ketamine and tramadol on post tonsillectomy pain: a double-blinded randomized placebo-controlled clinical trial. Croat Med J. 2012; 53(2): 155-161. doi:10.3325/cmj.2012.53.155
Google Scholar
38Basuni AS, Ezz HA, Albirmawy OA. Preoperative peritonsillar infiltration of dexamethasone and levobupivacaine reduces pediatric post-tonsillectomy pain: a double-blind prospective randomized clinical trial. J Anesth. 2013; 27(6): 844-849. doi:10.1007/s00540-013-1638-0
Google Scholar
39Bean-Lijewski JD, Kruitbosch SH, Hutchinson L, Browne B. Post-tonsillectomy pain management in children: can we do better. Otolaryngol Head Neck Surg. 2007; 137(4): 545-551. doi:10.1016/j.otohns.2007.06.731
Google Scholar
40Benzon HA, Shah RD, Hansen J, et al. The effect of systemic magnesium on postsurgical pain in children undergoing tonsillectomies: a double-blinded, randomized, placebo-controlled trial. Anesth Analg. 2015; 121(6): 1627-1631. doi:10.1213/ANE.0000000000001028
Google Scholar
41Bergendahl HT, Lönnqvist PA, Eksborg S, et al. Clonidine vs. midazolam as premedication in children undergoing adeno-tonsillectomy: a prospective, randomized, controlled clinical trial. Acta Anaesthesiol Scand. 2004; 48(10): 1292-1300. doi:10.1111/j.1399-6576.2004.00525.x
Google Scholar
42Bhattacharya D, Mondol MC, Dasgupta S, Chakraborty R. A comparison of rectal diclofenac with intravenous pethidine for pain relief following tonsillectomy and adenoidectomy in children. J Anaesthesiol Clin Pharmacol. 2005; 21(2): 143-146.
Google Scholar
43Bone ME, Fell D. A comparison of rectal diclofenac with intramuscular papaveretum or placebo for pain relief following tonsillectomy. Anaesthesia. 1988; 43(4): 277-280. doi:10.1111/j.1365-2044.1988.tb08972.x
Google Scholar
44Boroumand P, Zamani MM, Saeedi M, Rouhbakhshfar O, Hosseini Motlagh SR, Aarabi Moghaddam F. Post tonsillectomy pain: can honey reduce the analgesic requirements. Anesth Pain Med. 2013; 3(1): 198-202. doi:10.5812/aapm.9246
Google Scholar
45Caixeta J, Sampaio J, da Costa P, Avelino M. Analgesia for adenotonsillectomy in children: a comparison between peritonsillar infiltration of tramadol, ketamine, and placebo. Eur Arch Otorhinolaryngol. 2020. 2020; 277(6): 1815-1822. doi:10.1007/s00405-020-05878-z
Google Scholar
46Cakar Turhan KS, Salviz EA, Beton S, Timuroglu ST, Catav S, Ozatamer O. Peritonsillar infiltration with levobupivacaine for posttonsillectomy pain relief: does concentration have any effect? A double-blind randomized controlled clinical study. Eur Rev Med Pharmacol Sci. 2015; 19(7): 1276-1284.
Google Scholar
47Canbay O, Celebi N, Uzun S, Sahin A, Celiker V, Aypar U. Topical ketamine and morphine for post-tonsillectomy pain. Eur J Anaesthesiol. 2008; 25(4): 287-292. doi:10.1017/S026502150700316X
Google Scholar
48Cao JL, Pei YP, Wei JQ, Zhang YY. Effects of intraoperative dexmedetomidine with intravenous anesthesia on postoperative emergence agitation/delirium in pediatric patients undergoing tonsillectomy with or without adenoidectomy: a CONSORT-prospective, randomized, controlled clinical trial. Medicine (Baltimore). 2016; 95(49):e5566. doi:10.1097/MD.0000000000005566
Google Scholar
49Celebi S, Tepe C, Yelken K, Celik O. Efficacy of dexpanthenol for pediatric post-tonsillectomy pain and wound healing. Ann Otol Rhinol Laryngol. 2013; 122(7): 464-467. doi:10.1177/000348941312200710
Google Scholar
50Chen F, Wang CY, Zhang J, et al. Comparison of postoperative analgesic effects between nalbuphine and fentanyl in children undergoing adenotonsillectomy: a prospective, randomized, double-blind, multicenter study. Front Pharmacol. 2020; 11:597550. doi:10.3389/fphar.2020.597550
Google Scholar
51Choi HR, Cho JK, Lee S, Yoo BH, Yon JH, Kim KM. The effect of remifentanil versus N(2)O on postoperative pain and emergence agitation after pediatric tonsillectomy/adenoidectomy. Korean J Anesthesiol. 2011; 61(2): 148-153. doi:10.4097/kjae.2011.61.2.148
Google Scholar
52Cicekci F, Sizer C, Atici SS, Arican S, Karaibrahimoglu A, Kara I. Comparison of the perioperative and postoperative effects of levobupivacaine and of levobupivacaine + adrenaline in pediatric tonsillectomy: a double-blind randomized study. Pain Res Manag. 2017; 2017:8431823. doi:10.1155/2017/8431823
Google Scholar
53Cocelli LP, Ugur BK, Durucu C, Kul S, Arik H, Mumbuc S. Comparison of pre-emptive tonsillar lodge infiltration with ropivacaine versus intravenous tramadol in pediatric tonsillectomies: a randomized placebo-controlled study. Int J Pediatr Otorhinolaryngol. 2012; 76(5): 653-657. doi:10.1016/j.ijporl.2012.01.031
Google Scholar
54Conceição DA, Bruggemann MJ, Conceição DA, Carneiro Leão C D. Effect of an intravenous single dose of ketamine on postoperative pain in tonsillectomy patients. Paediatr Anaesth. 2006; 16(9): 962-967. doi:10.1111/j.1460-9592.2006.01893.x
Google Scholar
55Dahi-Taleghani M, Mousavifard S, Tahmoureszade S, Dabbagh A. Rectal acetaminophen versus peritonsillar infiltration of bupivacaine for postoperative analgesia after adenotonsillectomy in children. Eur Arch Otorhinolaryngol. 2011; 268(4): 581-584. doi:10.1007/s00405-010-1434-5
Google Scholar
56Dal D, Celebi N, Elvan EG, Celiker V, Aypar U. The efficacy of intravenous or peritonsillar infiltration of ketamine for postoperative pain relief in children following adenotonsillectomy. Paediatr Anaesth. 2007; 17(3): 263-269. doi:10.1111/j.1460-9592.2006.02095.x
Google Scholar
57Dashti GA, Amini S, Zanguee E. The prophylactic effect of rectal acetaminophen on postoperative pain and opioid requirements after adenotonsillectomy in children. Middle East J Anaesthesiol. 2009; 20(2): 245-249.
Google Scholar
58Dawson GS, Seidman P, Ramadan HH. Improved postoperative pain control in pediatric adenotonsillectomy with dextromethorphan. Laryngoscope. 2001; 111(7): 1223-1226. doi:10.1097/00005537-200107000-00015
Google Scholar
59de Oliveira Araújo MC, de Sousa Caixeta JA, Vilarinho BF, Gomes Avelino MA. Single dose of intraoperative intravenous morphine for analgesia in children undergoing tonsillectomy: randomized, double-blind clinical trial. Braz J Otorhinolaryngol. 2020; S1808-8694(20): 30173-30177. doi:10.1016/j.bjorl.2020.09.007
Google Scholar
60Aysenur D, Mine C, Ozgur Y, et al. Pre-emptive peritonsillar dexamethasone vs. levobupivacaine infiltration for relief of post-adenotonsillectomy pain in children: a controlled clinical study. Int J Pediatr Otorhinolaryngol. 2014; 78(9): 1467-1471. doi:10.1016/j.ijporl.2014.06.010
Google Scholar
61Dsida RM, Wheeler M, Birmingham PK, et al. Premedication of pediatric tonsillectomy patients with oral transmucosal fentanyl citrate. Anesth Analg. 1998; 86(1): 66-70. doi:10.1097/00000539-199801000-00013
Google Scholar
62Egeli E, Harputluoglu U, Oghan F, Demiraran Y, Guclu E, Ozturk O. Does topical lidocaine with adrenaline have an effect on morbidity in pediatric tonsillectomy. Int J Pediatr Otorhinolaryngol. 2005; 69(6): 811-815. doi:10.1016/j.ijporl.2005.01.014
Google Scholar
63Egeli E, Harputluoglu U, Ozturk O, Oghan F, Kocak S. Can post-adenotonsillectomy morbidity be reduced by intravenous 24 h hydration in pediatric patients following adenotonsillectomy. Int J Pediatr Otorhinolaryngol. 2004; 68(8): 1047-1051. doi:10.1016/j.ijporl.2004.03.012
Google Scholar
64Eghbal MH, Taregh S, Amin A, Sahmeddini MA. Ketamine improves postoperative pain and emergence agitation following adenotonsillectomy in children. A randomized clinical trial. Middle East J Anaesthesiol. 2013; 22(2): 155-160.
Google Scholar
65El Sonbaty MI, Abo el Dahab H, Mostafa A, Abo Shanab O. Preemptive peritonsillar ketamine infiltration: postoperative analgesic efficacy versus meperidine. Middle East J Anaesthesiol. 2011; 21(1): 43-51.
Google Scholar
66Eladi IA, Mourad KH, Youssef AN, Abdelrazek AA, Ramadan MA. Efficacy and safety of intravenous ketorolac versus nalbuphine in relieving postoperative pain after tonsillectomy in children. Open Access Maced J Med Sci. 2019; 7(7): 1082-1086. doi:10.3889/oamjms.2019.243
Google Scholar
67El-Fattah AM, Ramzy E. Pre-emptive triple analgesia protocol for tonsillectomy pain control in children: double-blind, randomised, controlled, clinical trial. J Laryngol Otol. 2013; 127(4): 383-391. doi:10.1017/S0022215113000364
Google Scholar
68Elhakim M, Khalafallah Z, El-Fattah HA, Farouk S, Khattab A. Ketamine reduces swallowing-evoked pain after paediatric tonsillectomy. Acta Anaesthesiol Scand. 2003; 47(5): 604-609. doi:10.1034/j.1399-6576.2003.00111.x
Google Scholar
69Elshammaa N, Chidambaran V, Housny W, Thomas J, Zhang X, Michael R. Ketamine as an adjunct to fentanyl improves postoperative analgesia and hastens discharge in children following tonsillectomy—a prospective, double-blinded, randomized study. Paediatr Anaesth. 2011; 21(10): 1009-1014. doi:10.1111/j.1460-9592.2011.03604.x
Google Scholar
70Engelhardt T, Crawford M. Sublingual morphine may be a suitable alternative for pain control in children in the postoperative period. Paediatr Anaesth. 2001; 11(1): 81-83. doi:10.1046/j.1460-9592.2001.00598.x
Google Scholar
71Engelhardt T, Steel E, Johnston G, Veitch DY. Tramadol for pain relief in children undergoing tonsillectomy: a comparison with morphine. Paediatr Anaesth. 2003; 13(3): 249-252. doi:10.1046/j.1460-9592.2003.00983.x
Google Scholar
72Ergil J, Akkaya T, Gozaydin O, et al. Vasoconstrictive and analgesic efficacy of locally infiltrated levobupivacaine in tonsillectomy patients. Int J Pediatr Otorhinolaryngol. 2012; 76(10): 1429-1433. doi:10.1016/j.ijporl.2012.06.016
Google Scholar
73Erhan OL, Göksu H, Alpay C, Beştaş A. Ketamine in post-tonsillectomy pain. Int J Pediatr Otorhinolaryngol. 2007; 71(5): 735-739. doi:10.1016/j.ijporl.2007.01.008
Google Scholar
74Ertugrul F, Akbas M, Karsli B, Kayacan N, Bulut F, Trakya A. Pain relief for children after adenotonsillectomy. J Int Med Res. 2006; 34(6): 648-654. doi:10.1177/147323000603400610
Google Scholar
75Faiz SH, Rahimzadeh P, Alebouyeh MR, Sedaghat M. A randomized controlled trial on analgesic effects of intravenous acetaminophen versus dexamethasone after pediatric tonsillectomy. Iran Red Crescent Med J. 2013; 15(11):e9267. doi:10.5812/ircmj.9267
Google Scholar
76Farmawy MS, Rashad MM. Preemptive analgesia by peritonsillar ketamine versus ropivacaine for post-tonsillectomy pain in children. Egypt J Anaesth. 2014; 30(1): 1-5.
Google Scholar
77Fazi L, Jantzen EC, Rose JB, Kurth CD, Watcha MF. A comparison of oral clonidine and oral midazolam as preanesthetic medications in the pediatric tonsillectomy patient. Anesth Analg. 2001; 92(1): 56-61. doi:10.1097/00000539-200101000-00011
Google Scholar
78Freeman KO, Connelly NR, Schwartz D, Jacobs BR, Schreibstein JM, Gibson C. Analgesia for paediatric tonsillectomy and adenoidectomy with intramuscular clonidine. Paediatr Anaesth. 2002; 12(7): 617-620. doi:10.1046/j.1460-9592.2002.00914.x
Google Scholar
79Gao W, Zhang QR, Jiang L, Geng JY. Comparison of local and intravenous dexamethasone for postoperative pain and recovery after tonsillectomy. Otolaryngol Head Neck Surg. 2015; 152(3): 530-535. doi:10.1177/0194599814567856
Google Scholar
80Gemma M, Piccioni LO, Gioia L, Beretta L, Bussi M. Ropivacaine peritonsillar infiltration for analgesia after adenotonsillectomy in children: a randomized, double-blind, placebo-controlled study. Ann Otol Rhinol Laryngol. 2009; 118(3): 227-231. doi:10.1177/000348940911800311
Google Scholar
81Giannoni C, White S, Enneking FK. Does dexamethasone with preemptive analgesia improve pediatric tonsillectomy pain. Otolaryngol Head Neck Surg. 2002; 126(3): 307-315. doi:10.1067/mhn.2002.122700
Google Scholar
82Giannoni C, White S, Enneking FK, Morey T. Ropivacaine with or without clonidine improves pediatric tonsillectomy pain. Arch Otolaryngol Head Neck Surg. 2001; 127(10): 1265-1270. doi:10.1001/archotol.127.10.1265
Google Scholar
83Gökçe Kütük S, Özdaş T. The impact of platelet-rich plasma therapy on short-term postoperative outcomes of pediatric tonsillectomy patients. Eur Arch Otorhinolaryngol. 2019; 276(2): 489-495. doi:10.1007/s00405-018-5211-1
Google Scholar
84Greenwell AG, Isaiah A, Pereira KD. Recovery after adenotonsillectomy-do steroids help? Outcomes from a randomized controlled trial. Otolaryngol Head Neck Surg. 2021; 165(1): 83-88. doi:10.1177/0194599820973250
Google Scholar
85Gross CW, Gallagher R, Schlosser RJ, et al. Autologous fibrin sealant reduces pain after tonsillectomy. Laryngoscope. 2001; 111(2): 259-263. doi:10.1097/00005537-200102000-00014
Google Scholar
86Lowman JD, Solomon GM, Rowe SM, Yuen HK. Gaming console home-based exercise for adults with cystic fibrosis: study protocol. Int J Caring Sci. 2020; 13(2): 1530-1540.
Google Scholar
87Haddadi S, Marzban S, Karami MS, Heidarzadeh A, Parvizi A, Naderi Nabi B. Comparing the duration of the analgesic effects of intravenous and rectal acetaminophen following tonsillectomy in children. Anesth Pain Med. 2014; 4(1):e13175. doi:10.5812/aapm.13175
Google Scholar
88Haddadi S, Marzban S, Parvizi A, et al. Effects of gabapentin suspension and rectal acetaminophen on postoperative pain of adenotonsillectomy in children. Iran J Otorhinolaryngol. 2020; 32(111): 197-205. doi:10.22038/ijorl.2020.38811.2283
Google Scholar
89Hadi BA, Sbeitan SM. Clinical pharmacy intervention post tonsillectomy: a randomized control trial. Int J Clin Pharm. 2015; 37(1): 133-138. doi:10.1007/s11096-014-0051-6
Google Scholar
90Haksever M, Özmen S, Akduman D, Solmaz F. Topical bupivacaine compared to bupivacaine infiltration for post-tonsillectomy pain relief in children: a prospective randomized controlled clinical study. Eur Arch Otorhinolaryngol. 2014; 271(9): 2555-2559. doi:10.1007/s00405-014-3022-6
Google Scholar
91Hamed MA, Al-Saeed MA. The efficacy of intravenous magnesium sulfate versus intravenous paracetamol on children posttonsillectomy pain and analgesic requirement: a randomized controlled study. Anesth Essays Res. 2018; 12(3): 724-728. doi:10.4103/aer.AER_113_18
Google Scholar
92Hamers JP, Huijer Abu-Saad H, Geisler FE, et al. The effect of paracetamol, fentanyl, and systematic assessments on children's pain after tonsillectomy and adenoidectomy. J Perianesth Nurs. 1999; 14(6): 357-366. doi:10.1016/s1089-9472(99)80097-5
Google Scholar
93Hao J, Wu Z, Luo Z, Dong B. Addition of dexmedetomidine to ropivacaine for local infiltration anaesthesia improves analgesic efficacy after tonsillectomy and adenoidectomy: a randomized controlled trial. Int J Pediatr Otorhinolaryngol. 2020; 137:110168. doi:10.1016/j.ijporl.2020.110168
Google Scholar
94Harley EH, Dattolo RA. Ibuprofen for tonsillectomy pain in children: efficacy and complications. Otolaryngol Head Neck Surg. 1998; 119(5): 492-496. doi:10.1016/S0194-5998(98)70107-X
Google Scholar
95Heidari SM, Mirlohi SZ, Hashemi SJ. Comparison of the preventive analgesic effect of rectal ketamine and rectal acetaminophen after pediatric tonsillectomy. Int J Prev Med. 2012; 3(suppl 1): S150-S155.
Google Scholar
96Hermans V, De Pooter F, De Groote F, De Hert S, Van der Linden P. Effect of dexamethasone on nausea, vomiting, and pain in paediatric tonsillectomy. Br J Anaesth. 2012; 109(3): 427-431. doi:10.1093/bja/aes249
Google Scholar
97Honarmand A, Safavi M, Kashefi P, Hosseini B, Badiei S. Comparison of effect of intravenous ketamine, peritonsillar infiltration of tramadol and their combination on pediatric posttonsillectomy pain: a double-blinded randomized placebo-controlled clinical trial. Res Pharm Sci. 2013; 8(3): 177-183.
Google Scholar
98Honarmand A, Safavi M, Naghibi K, et al. Preemptive peritonsillar infiltration with bupivacaine in combination with tramadol improves pediatric post-tonsillectomy pain better than using bupivacaine or tramadol alone: a randomized, placebo-controlled, double blind clinical trial. Adv Biomed Res. 2015; 4: 132. doi:10.4103/2277-9175.161518
Google Scholar
99Honarmand A, Safavi MR, Jamshidi M. The preventative analgesic effect of preincisional peritonsillar infiltration of two low doses of ketamine for postoperative pain relief in children following adenotonsillectomy. A randomized, double-blind, placebo-controlled study. Paediatr Anaesth. 2008; 18(6): 508-514.
Google Scholar
100Hong B, Lim CS, Kim YH, et al. Comparison of topical ropivacaine with and without ketamine on post-surgical pain in children undergoing tonsillectomy: a randomized controlled double-blind study. J Anesth. 2017; 31(4): 559-564. doi:10.1007/s00540-017-2353-z
Google Scholar
101Hosseini Jahromi SA, Hosseini Valami SM, Hatamian S. Comparison between effect of lidocaine, morphine and ketamine spray on post-tonsillectomy pain in children. Anesth Pain Med. 2012; 2(1): 17-21. doi:10.5812/aapm.4092
Google Scholar
102Hullett BJ, Chambers NA, Pascoe EM, Johnson C. Tramadol vs morphine during adenotonsillectomy for obstructive sleep apnea in children. Paediatr Anaesth. 2006; 16(6): 648-653. doi:10.1111/j.1460-9592.2005.01827.x
Google Scholar
103Inanoglu K, Ozbakis Akkurt BC, Turhanoglu S, Okuyucu S, Akoglu E. Intravenous ketamine and local bupivacaine infiltration are effective as part of a multimodal regime for reducing post-tonsillectomy pain. Med Sci Monit. 2009; 15(10): CR539-CR543.
Google Scholar
104Ince I, Yoruk O, Ahiskalioglu A, Aksoy M, Dostbil A, Celik M. Does montelukast have an effect on post-tonsillectomy pain control in children? A randomized trial study. Otolaryngol Head Neck Surg. 2015; 153(2): 269-274. doi:10.1177/0194599815580976
Google Scholar
105Jahanshahi J, Pazira S, Farahani F, et al. Effect of topical sucralfate vs clindamycin on posttonsillectomy pain in children aged 6 to 12 years: a triple-blind randomized clinical trial. JAMA Otolaryngol Head Neck Surg. 2014; 140(8): 698-703. doi:10.1001/jamaoto.2014.979
Google Scholar
106Javid MJ, Hajijafari M, Hajipour A, Makarem J, Khazaeipour Z. Evaluation of a low dose ketamine in post tonsillectomy pain relief: a randomized trial comparing intravenous and subcutaneous ketamine in pediatrics. Anesth Pain Med. 2012; 2(2): 85-89. doi:10.5812/aapm.4399
Google Scholar
107Jebeles JA, Reilly JS, Gutierrez JF, Bradley EL, Jr., Kissin I. The effect of pre-incisional infiltration of tonsils with bupivacaine on the pain following tonsillectomy under general anesthesia. Pain. 1991; 47(3): 305-308. doi:10.1016/0304-3959(91)90220-R
Google Scholar
108Jebeles JA, Reilly JS, Gutierrez JF, Bradley EL, Jr., Kissin I. Tonsillectomy and adenoidectomy pain reduction by local bupivacaine infiltration in children. Int J Pediatr Otorhinolaryngol. 1993; 25(1-3): 149-154. doi:10.1016/0165-5876(93)90048-8
Google Scholar
109Joshi W, Connelly NR, Reuben SS, Wolckenhaar M, Thakkar N. An evaluation of the safety and efficacy of administering rofecoxib for postoperative pain management. Anesth Analg. Table of contents. 2003; 97(1): 35-38. doi:10.1213/01.ane.0000069507.93582.6e
Google Scholar
110Jotić A, Savić Vujović K, Milovanović J, et al. Pain management after surgical tonsillectomy: is there a favorable analgesic. Ear Nose Throat J. 2019; 98(6): 356-361. doi:10.1177/0145561319846065
Google Scholar
111Ju NY, Cui GX, Gao W. Ropivacaine plus dexamethasone infiltration reduces postoperative pain after tonsillectomy and adenoidectomy. Int J Pediatr Otorhinolaryngol. 2013; 77(11): 1881-1885. doi:10.1016/j.ijporl.2013.08.037
Google Scholar
112Kaan MN, Odabasi O, Gezer E, Daldal A. The effect of preoperative dexamethasone on early oral intake, vomiting and pain after tonsillectomy. Int J Pediatr Otorhinolaryngol. 2006; 70(1): 73-79. doi:10.1016/j.ijporl.2005.05.013
Google Scholar
113Kang Y, Ku EJ, Jung IG, Kang MH, Choi YS, Jung HJ. Dexamethasone and post-adenotonsillectomy pain in children: double-blind, randomized controlled trial. Medicine (Baltimore). 2021; 100(2):e24122. doi:10.1097/MD.0000000000024122
Google Scholar
114Karaaslan K, Yilmaz F, Gulcu N, Sarpkaya A, Colak C, Kocoglu H. The effects of levobupivacaine versus levobupivacaine plus magnesium infiltration on postoperative analgesia and laryngospasm in pediatric tonsillectomy patients. Int J Pediatr Otorhinolaryngol. 2008; 72(5): 675-681. doi:10.1016/j.ijporl.2008.01.029
Google Scholar
115Kasapoglu F, Kaya FN, Tuzemen G, Ozmen OA, Kaya A, Onart S. Comparison of peritonsillar levobupivacaine and bupivacaine infiltration for post-tonsillectomy pain relief in children: placebo-controlled clinical study. Int J Pediatr Otorhinolaryngol. 2011; 75(3): 322-326. doi:10.1016/j.ijporl.2010.11.015
Google Scholar
116Kaygusuz I, Susaman N. The effects of dexamethasone, bupivacaine and topical lidocaine spray on pain after tonsillectomy. Int J Pediatr Otorhinolaryngol. 2003; 67(7): 737-742. doi:10.1016/s0165-5876(03)00091-0
Google Scholar
117Kelly LE, Sommer DD, Ramakrishna J, et al. Morphine or Ibuprofen for post-tonsillectomy analgesia: a randomized trial. Pediatrics. 2015; 135(2): 307-313. doi:10.1542/peds.2014-1906
Google Scholar
118Khademi S, Ghaffarpasand F, Heiran HR, Yavari MJ, Motazedian S, Dehghankhalili M. Intravenous and peritonsillar infiltration of ketamine for postoperative pain after adenotonsillectomy: a randomized placebo-controlled clinical trial. Med Princ Pract. 2011; 20(5): 433-437. doi:10.1159/000327657
Google Scholar
119Khalili G, Sajedi P, Shafa A, Hosseini B, Seyyedyousefi H. A randomized evaluation of intravenous dexamethasone versus oral acetaminophen codeine in pediatric adenotonsillectomy: emergence agitation and analgesia. Middle East J Anaesthesiol. 2012; 21(4): 499-504.
Google Scholar
120Kilinc L, Türk B, Türk HS, Cinar S, Turgut S, İslamoğlu S. Peritonsillar dexamethasone-bupivacaine vs. bupivacaine infiltration for post-tonsillectomy pain relief in children: a randomized, double-blind, controlled study. Eur Arch Otorhinolaryngol. 2019; 276(7): 2081-2089. doi:10.1007/s00405-019-05472-y
Google Scholar
121Kim MS, Coté CJ, Cristoloveanu C, et al. There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting, reducing pain, shortening time to first liquid intake, or the incidence of voice change. Anesth Analg. Tables of contents. 2007; 104(5): 1052-1058. doi:10.1213/01.ane.0000263276.52287.3b
Google Scholar
122Koceroglu I, Devrim S, Bingol Tanriverdi T, Gura Celik M. The effects of dexmedetomidine and tramadol on post-operative pain and agitation, and extubation quality in paediatric patients undergoing adenotonsillectomy surgery: a randomized trial. J Clin Pharm Ther. 2020; 45(2): 340-346. doi:10.1111/jcpt.13080
Google Scholar
123Kokki H, Salonen A. Comparison of pre- and postoperative administration of ketoprofen for analgesia after tonsillectomy in children. Paediatr Anaesth. 2002; 12(2): 162-167. doi:10.1046/j.1460-9592.2002.00804.x
Google Scholar
124Komazaki M, Mihara T, Nakamura N, Ka K, Goto T. Preventive effect of ramelteon on emergence agitation after general anaesthesia in paediatric patients undergoing tonsillectomy: a randomised, placebo-controlled clinical trial. Sci Rep. 2020; 10(1):21996. doi:10.1038/s41598-020-79078-4
Google Scholar
125Krishnan A, Tolhurst-Cleaver CL, Kay B. Controlled comparison of nalbuphine and morphine for post-tonsillectomy pain. Anaesthesia. 1985; 40(12): 1178-1181. doi:10.1111/j.1365-2044.1985.tb10654.x
Google Scholar
126Lee IH, Sung CY, Han JI, Kim CH, Chung RK. The preemptive analgesic effect of ketorolac and propacetamol for adenotonsillectomy in pediatric patients. Korean J Anesthesiol. 2009; 57(3): 308-313. doi:10.4097/kjae.2009.57.3.308
Google Scholar
127Lee YS, Kim WY, Choi JH, Son JH, Kim JH, Park YC. The effect of ketamine on the incidence of emergence agitation in children undergoing tonsillectomy and adenoidectomy under sevoflurane general anesthesia. Korean J Anesthesiol. 2010; 58(5): 440-445. doi:10.4097/kjae.2010.58.5.440
Google Scholar
128Li X, Zhou M, Xia Q, Li J. Parecoxib sodium reduces the need for opioids after tonsillectomy in children: a double-blind placebo-controlled randomized clinical trial. Can J Anaesth. 2016; 63(3): 268-274. doi:10.1007/s12630-015-0560-3
Google Scholar
129Liu CM, Su CY. Post-operative pain control with topical steroid injection after hot dissection tonsillectomy. J Laryngol Otol. 1996; 110(11): 1038-1040. doi:10.1017/s0022215100135704
Google Scholar
130Mahgoobifard M, Mirmesdagh Y, Imani F, Najafi A, Nataj-Majd M. The analgesic efficacy of preoperative oral Ibuprofen and acetaminophen in children undergoing adenotonsillectomy: a randomized clinical trial. Anesth Pain Med. 2014; 4(1):e15049. doi:10.5812/aapm.15049
Google Scholar
131Maryam H, Amin J, Sedighe V, Vida A. Comparing the effects of peritonsillar infiltration of tramadol before and after the surgery on post-tonsillectomy pain. Eur Arch Otorhinolaryngol. 2017; 274(6): 2521-2527. doi:10.1007/s00405-017-4477-z
Google Scholar
132Mendham JE, Mather SJ. Comparison of diclofenac and tenoxicam for postoperative analgesia with and without fentanyl in children undergoing adenotonsillectomy or tonsillectomy. Paediatr Anaesth. 1996; 6(6): 467-473. doi:10.1046/j.1460-9592.1996.d01-22.x
Google Scholar
133Merry AF, Edwards KE, Ahmad Z, Barber C, Mahadevan M, Frampton C. Randomized comparison between the combination of acetaminophen and ibuprofen and each constituent alone for analgesia following tonsillectomy in children. Can J Anaesth. 2013; 60(12): 1180-1189. doi:10.1007/s12630-013-0043-3
Google Scholar
134Miura MS, Saleh C, de Andrade M, Assmann M, Ayres M, Lubianca Neto JF. Topical sucralfate in post-adenotonsillectomy analgesia in children: a double-blind randomized clinical trial. Otolaryngol Head Neck Surg. 2009; 141(3): 322-328. doi:10.1016/j.otohns.2009.05.032
Google Scholar
135Miura MS, Saleh C, de Andrade M, Assmann M, Lima LH, Lubianca Neto JF. Topical clindamycin in post-adenotonsillectomy analgesia in children: a double-blind, randomized clinical trial. Otolaryngol Head Neck Surg. 2009; 141(4): 509-515. doi:10.1016/j.otohns.2009.06.082
Google Scholar
136Mohamed SK, Ibraheem AS, Abdelraheem MG. Preoperative intravenous dexamethasone combined with glossopharyngeal nerve block: role in pediatric postoperative analgesia following tonsillectomy. Eur Arch Otorhinolaryngol. 2009; 266(11): 1815-1819. doi:10.1007/s00405-009-0937-4
Google Scholar
137Mohebbi S, Nia FH, Kelantari F, Nejad SE, Hamedi Y, Abd R. Efficacy of honey in reduction of post tonsillectomy pain, randomized clinical trial. Int J Pediatr Otorhinolaryngol. 2014; 78(11): 1886-1889. doi:10.1016/j.ijporl.2014.08.018
Google Scholar
138Moss JR, Cofer S, Hersey S, et al. Comparison of clonidine, local anesthetics, and placebo for pain reduction in pediatric tonsillectomy. Arch Otolaryngol Head Neck Surg. 2011; 137(6): 591-597. doi:10.1001/archoto.2011.45
Google Scholar
139Moss JR, Watcha MF, Bendel LP, McCarthy DL, Witham SL, Glover CD. A multicenter, randomized, double-blind placebo-controlled, single dose trial of the safety and efficacy of intravenous ibuprofen for treatment of pain in pediatric patients undergoing tonsillectomy. Paediatr Anaesth. 2014; 24(5): 483-489. doi:10.1111/pan.12381
Google Scholar
140Murto K, Lamontagne C, McFaul C, et al. Celecoxib pharmacogenetics and pediatric adenotonsillectomy: a double-blinded randomized controlled study. Can J Anaesth. 2015; 62(7): 785-797. doi:10.1007/s12630-015-0376-1
Google Scholar
141Nikandish R, Maghsoodi B, Khademi S, Motazedian S, Kaboodkhani R. Peritonsillar infiltration with bupivacaine and pethidine for relief of post-tonsillectomy pain: a randomised double-blind study. Anaesthesia. 2008; 63(1): 20-25. doi:10.1111/j.1365-2044.2007.05283.x
Google Scholar
142O'Flaherty JE, Flaherty JE, Lin CX. Does ketamine or magnesium affect posttonsillectomy pain in children. Paediatr Anaesth. 2003; 13(5): 413-421. doi:10.1046/j.1460-9592.2003.01049.x
Google Scholar
143Oghan F, Harputluoglu U, Guclu E, Kocaman B, Ozturk O. Does topical ropivacaine reduce the post-tonsillectomy morbidity in pediatric patients. Int J Pediatr Otorhinolaryngol. 2008; 72(3): 361-365. doi:10.1016/j.ijporl.2007.11.011
Google Scholar
144Öksüz H, Şeneǧlu N, Doǧan Z. Comparison of the efficacies of ketamine and fentanyl on prevention of early post-operative pain after tonsillectomy. Erciyes Tip Dergisi. 2009; 31(1): 27-30.
Google Scholar
145Olutoye OA, Glover CD, Diefenderfer JW, et al. The effect of intraoperative dexmedetomidine on postoperative analgesia and sedation in pediatric patients undergoing tonsillectomy and adenoidectomy. Anesth Analg. 2010; 111(2): 490-495. doi:10.1213/ANE.0b013e3181e33429
Google Scholar
146Owczarzak V, Haddad J, Jr. Comparison of oral versus rectal administration of acetaminophen with codeine in postoperative pediatric adenotonsillectomy patients. Laryngoscope. 2006; 116(8): 1485-1488. doi:10.1097/01.mlg.0000227530.64179.1f
Google Scholar
147Ozalevli M, Unlügenç H, Tuncer U, Güneş Y, Ozcengiz D. Comparison of morphine and tramadol by patient-controlled analgesia for postoperative analgesia after tonsillectomy in children. Paediatr Anaesth. 2005; 15(11): 979-984. doi:10.1111/j.1460-9592.2005.01591.x
Google Scholar
148Ozkiriş M, Kapusuz Z, Saydam L. Comparison of ropivacaine, bupivacaine and lidocaine in the management of post-tonsillectomy pain. Int J Pediatr Otorhinolaryngol. 2012; 76(12): 1831-1834. doi:10.1016/j.ijporl.2012.09.011
Google Scholar
149Ozköse Z, Akçabay M, Kemaloğlu YK, Sezenler S. Relief of posttonsillectomy pain with low-dose tramadol given at induction of anesthesia in children. Int J Pediatr Otorhinolaryngol. 2000; 53(3): 207-214. doi:10.1016/s0165-5876(00)82008-x
Google Scholar
150Ozmen OA, Ozmen S. Topical bupivacaine compared to lidocaine with epinephrine for post-tonsillectomy pain relief in children: a randomized controlled study. Int J Pediatr Otorhinolaryngol. 2011; 75(1): 77-80. doi:10.1016/j.ijporl.2010.10.013
Google Scholar
151Ozmen S, Ozmen OA, Kasapoglu F. Effects of levobupivacaine versus bupivacaine infiltration on postoperative analgesia in pediatric tonsillectomy patients: a randomized, double-blind, placebo-controlled study. Ann Otol Rhinol Laryngol. 2011; 120(7): 489-493. doi:10.1177/000348941112000712
Google Scholar
152Patel A, Davidson M, Tran MC, et al. Dexmedetomidine infusion for analgesia and prevention of emergence agitation in children with obstructive sleep apnea syndrome undergoing tonsillectomy and adenoidectomy. Anesth Analg. 2010; 111(4): 1004-1010. doi:10.1213/ANE.0b013e3181ee82fa
Google Scholar
153Pestieau SR, Quezado ZM, Johnson YJ, et al. High-dose dexmedetomidine increases the opioid-free interval and decreases opioid requirement after tonsillectomy in children. Can J Anaesth. 2011; 58(6): 540-550. doi:10.1007/s12630-011-9493-7
Google Scholar
154Pickering AE, Bridge HS, Nolan J, Stoddart PA. Double-blind, placebo-controlled analgesic study of ibuprofen or rofecoxib in combination with paracetamol for tonsillectomy in children. Br J Anaesth. 2002; 88(1): 72-77. doi:10.1093/bja/88.1.72
Google Scholar
155Pieters BJ, Penn E, Nicklaus P, Bruegger D, Mehta B, Weatherly R. Emergence delirium and postoperative pain in children undergoing adenotonsillectomy: a comparison of propofol vs sevoflurane anesthesia. Paediatr Anaesth. 2010; 20(10): 944-950. doi:10.1111/j.1460-9592.2010.03394.x
Google Scholar
156Pirzadeh A, Mohammadi MA, Allaf-Akbari S, Entezariasl M. The effect of ketamine on posttonsillectomy pain in children: a clinical trial. Iran J Otorhinolaryngol. 2012; 24(66): 23-28.
Google Scholar
157Qian B, Zheng W, Shi J, Chen Z, Guo Y, Yao Y. Ketamine enhances intranasal dexmedetomidine-induced sedation in children: a randomized, double-blind trial. Drug Des Devel Ther. 2020; 14: 3559-3565. doi:10.2147/DDDT.S269765
Google Scholar
158Ramirez L, Cros J, Marin B, et al. Analgesic interaction between ondansetron and acetaminophen after tonsillectomy in children: the Paratron randomized, controlled trial. Eur J Pain. 2015; 19(5): 661-668. doi:10.1002/ejp.587
Google Scholar
159Rawlinson E, Walker A, Skone R, Thillaivasan A, Bagshaw O. A randomised controlled trial of two analgesic techniques for paediatric tonsillectomy. Anaesthesia. 2011; 66(10): 919-924. doi:10.1111/j.1365-2044.2011.06851.x
Google Scholar
160Reimer EJ, Dunn GS, Montgomery CJ, Sanderson PM, Scheepers LD, Merrick PM. The effectiveness of clonidine as an analgesic in paediatric adenotonsillectomy. Can J Anaesth. 1998; 45(12): 1162-1167. doi:10.1007/BF03012457
Google Scholar
161Rhendra Hardy MZ, Zayuah MS, Baharudin A, et al. The effects of topical viscous lignocaine 2% versus per-rectal diclofenac in early post-tonsillectomy pain in children. Int J Pediatr Otorhinolaryngol. 2010; 74(4): 374-377. doi:10.1016/j.ijporl.2010.01.005
Google Scholar
162Rizk SN, Samir EM. Use of ketofol to control emergence agitation in children undergoing adenotonsillectomy. Egypt J Anaesth. 2014; 30(1): 13-19.
Google Scholar
163Rømsing J, Ostergaard D, Drozdziewicz D, Schultz P, Ravn G. Diclofenac or acetaminophen for analgesia in paediatric tonsillectomy outpatients. Acta Anaesthesiol Scand. 2000; 44(3): 291-295. doi:10.1034/j.1399-6576.2000.440312.x
Google Scholar
164Rømsing J, Ostergaard D, Walther-Larsen S, Valentin N. Analgesic efficacy and safety of preoperative versus postoperative ketorolac in paediatric tonsillectomy. Acta Anaesthesiol Scand. 1998; 42(7): 770-775. doi:10.1111/j.1399-6576.1998.tb05320.x
Google Scholar
165Rose JB, Cuy R, Cohen DE, Schreiner MS. Preoperative oral dextromethorphan does not reduce pain or analgesic consumption in children after adenotonsillectomy. Anesth Analg. 1999; 88(4): 749-753. doi:10.1097/00000539-199904000-00012
Google Scholar
166Rusy LM, Houck CS, Sullivan LJ, et al. A double-blind evaluation of ketorolac tromethamine versus acetaminophen in pediatric tonsillectomy: analgesia and bleeding. Anesth Analg. 1995; 80(2): 226-229. doi:10.1097/00000539-199502000-00004
Google Scholar
167Safavi M, Honarmand A, Habibabady MR, Baraty S, Aghadavoudi O. Assessing intravenous ketamine and intravenous dexamethasone separately and in combination for early oral intake, vomiting and postoperative pain relief in children following tonsillectomy. Med Arh. 2012; 66(2): 111-115. doi:10.5455/medarh.2012.66.111-115
Google Scholar
168Sahmeddini MA, Panah A, Ghanbari A. Effects of low-dose propofol or ketamine on coughing at emergence from anesthesia in children undergoing tonsillectomy. Cureus. 2020; 12(4):e7842. doi:10.7759/cureus.7842
Google Scholar
169Samarkandi AH, Shaikh MA, Ahmad RA, Alammar AY. Use of dexamethasone to reduce postoperative vomiting and pain after pediatric tonsillectomy procedures. Saudi Med J. 2004; 25(11): 1636-1639.
Google Scholar
170Sampaio AL, Pinheiro TG, Furtado PL, Araújo MF, Olivieira CA. Evaluation of early postoperative morbidity in pediatric tonsillectomy with the use of sucralfate. Int J Pediatr Otorhinolaryngol. 2007; 71(4): 645-651. doi:10.1016/j.ijporl.2006.12.016
Google Scholar
171Schoem SR, Watkins GL, Kuhn JJ, Thompson DH. Control of early postoperative pain with bupivacaine in pediatric tonsillectomy. Ear Nose Throat J. 1993; 72(8): 560-563.
Google Scholar
172Semple D, Russell S, Doyle E, Aldridge LM. Comparison of morphine sulphate and codeine phosphate in children undergoing adenotonsillectomy. Paediatr Anaesth. 1999; 9(2): 135-138. doi:10.1046/j.1460-9592.1999.9220317.x
Google Scholar
173Şen B, Doǧru S, Koltka N, Güra M. The effect of intra-operative paracetamol on post operative pain, nausea and vomit in children who underwent adenotonsillectomy. Goztepe Tip Dergisi. 2012; 27(1): 16-21.
Google Scholar
174Sener M, Kocum A, Caliskan E, Yilmaz I, Caylakli F, Aribogan A. Administration of paracetamol versus dipyrone by intravenous patient-controlled analgesia for postoperative pain relief in children after tonsillectomy. Braz J Anesthesiol. 2015; 65(6): 476-482. doi:10.1016/j.bjane.2013.09.010
Google Scholar
175Sharma K, Kumar M, Gandhi R. Effect of single-dose dexmedetomidine on intraoperative hemodynamics and postoperative recovery during pediatric adenotonsillectomy. Anesth Essays Res. 2019; 13(1): 63-67. doi:10.4103/aer.AER_178_18
Google Scholar
176Siddiqui AS, Raees US, Siddiqui SZ, Raza SA. Efficacy of pre-incisional peritonsillar infiltration of ketamine for post-tonsillectomy analgesia in children. J Coll Physicians Surg Pak. 2013; 23(8): 533-537.
Google Scholar
177Sidman JD, Lander TA, Finkelstein M. Platelet-rich plasma for pediatric tonsillectomy patients. Laryngoscope. 2008; 118(10): 1765-1767. doi:10.1097/MLG.0b013e31817f18e7
Google Scholar
178Soltani R, Soheilipour S, Hajhashemi V, Asghari G, Bagheri M, Molavi M. Evaluation of the effect of aromatherapy with lavender essential oil on post-tonsillectomy pain in pediatric patients: a randomized controlled trial. Int J Pediatr Otorhinolaryngol. 2013; 77(9): 1579-1581. doi:10.1016/j.ijporl.2013.07.014
Google Scholar
179Sood AS, Pal P, Gill GS. Peritonsillar ropivacaine infiltration in paediatric tonsillectomy: a randomised control trial. Iran J Otorhinolaryngol. 2020; 32(111): 207-212. doi:10.22038/ijorl.2020.36577.2199
Google Scholar
180Stuart JC, MacGregor FB, Cairns CS, Chandrachud HR. Peritonsillar infiltration with bupivacaine for paediatric tonsillectomy. Anaesth Intensive Care. 1994; 22(6): 679-682. doi:10.1177/0310057X9402200606
Google Scholar
181Sun J, Wu X, Zhao X, Chen F, Wang W. Pre-emptive peritonsillar infiltration of magnesium sulphate and ropivacaine vs. ropivacaine or magnesium alone for relief of post-adenotonsillectomy pain in children. Int J Pediatr Otorhinolaryngol. 2015; 79(4): 499-503. doi:10.1016/j.ijporl.2015.01.009
Google Scholar
182Taheri R, Seyedhejazi M, Ghojazadeh M, Ghabili K, Shayeghi S. Comparison of ketamine and fentanyl for postoperative pain relief in children following adenotonsillectomy. Pak J Biol Sci. 2011; 14(10): 572-577. doi:10.3923/pjbs.2011.572.577
Google Scholar
183Tan L, Taylor E, Hannam JA, Salkeld L, Salman S, Anderson BJ. Pharmacokinetics and analgesic effectiveness of intravenous parecoxib for tonsillectomy ± adenoidectomy. Paediatr Anaesth. 2016; 26(12): 1126-1135. doi:10.1111/pan.13009
Google Scholar
184Tawalbeh MI, Nawasreh OO, Husban AM. Comparative study of diclofenac sodium and paracetamol for treatment of pain after adenotonsillectomy in children. Saudi Med J. 2001; 22(2): 121-123.
Google Scholar
185Tekelioglu UY, Apuhan T, Akkaya A, et al. Comparison of topical tramadol and ketamine in pain treatment after tonsillectomy. Paediatr Anaesth. 2013; 23(6): 496-501. doi:10.1111/pan.12148
Google Scholar
186Teunkens A, Vermeulen K, Peters M, Fieuws S, Van de Velde M, Rex S. Bupivacaine infiltration in children for postoperative analgesia after tonsillectomy: a randomised controlled trial. Eur J Anaesthesiol. 2019; 36(3): 206-214. doi:10.1097/EJA.0000000000000950
Google Scholar
187Thung AK, Elmaraghy CA, Barry N, et al. Double-blind randomized placebo-controlled trial of single-dose intravenous acetaminophen for pain associated with adenotonsillectomy in pediatric patients with sleep-disordered breathing. J Pediatr Pharmacol Ther. 2017; 22(5): 344-351. doi:10.5863/1551-6776-22.5.344
Google Scholar
188Tom LW, Templeton JJ, Thompson ME, Marsh RR. Dexamethasone in adenotonsillectomy. Int J Pediatr Otorhinolaryngol. 1996; 37(2): 115-120.
Google Scholar
189Topal K, Aktan B, Sakat MS, Kilic K, Gozeler MS. Post-operative pain control after tonsillectomy: dexametasone vs tramadol. Acta Otolaryngol. 2017; 137(6): 618-622. doi:10.1080/00016489.2016.1269945
Google Scholar
190Turan G, Yuksel G, Ormanci F. Preemptive analgesia with paracetamol and tramadol in pediatric adenotonsillectomy. J Anesth Clin Res. 2012; 3(8): 231.
Google Scholar
191Ubale P, Trasy V. Comparison of analgesic efficacy of diclofenac sodium suppository over acetaminophen suppository for post tonsillectomy pain relief in pediatric age group: randomized study. Anaesth Pain Intens Care. 2016; 20(2): 137-142.
Google Scholar
192Ugur KS, Karabayirli S, Demircioğlu Rİ, et al. The comparison of preincisional peritonsillar infiltration of ketamine and tramadol for postoperative pain relief on children following adenotonsillectomy. Int J Pediatr Otorhinolaryngol. 2013; 77(11): 1825-1829. doi:10.1016/j.ijporl.2013.08.018
Google Scholar
193Ugur MB, Yilmaz M, Altunkaya H, Cinar F, Ozer Y, Beder L. Effects of intramuscular and peritonsillar injection of tramadol before tonsillectomy: a double blind, randomized, placebo-controlled clinical trial. Int J Pediatr Otorhinolaryngol. 2008; 72(2): 241-248. doi:10.1016/j.ijporl.2007.11.002
Google Scholar
194Umuroğlu T, Eti Z, Ciftçi H, Yilmaz Göğüş F. Analgesia for adenotonsillectomy in children: a comparison of morphine, ketamine and tramadol. Paediatr Anaesth. 2004; 14(7): 568-573. doi:10.1111/j.1460-9592.2004.01223.x
Google Scholar
195Unal Y, Pampal K, Korkmaz S, Arslan M, Zengin A, Kurtipek O. Comparison of bupivacaine and ropivacaine on postoperative pain after tonsillectomy in paediatric patients. Int J Pediatr Otorhinolaryngol. 2007; 71(1): 83-87. doi:10.1016/j.ijporl.2006.09.005
Google Scholar
196Unsal O, Akpinar M, Bozkurt G, et al. Nasal sprays containing mometasone furoate for relief of post-adenotonsillectomy pain in children: a prospective controlled study. Sisli Etfal Hastan Tip Bul. 2021; 55(1): 101-107. doi:10.14744/SEMB.2020.75735
Google Scholar
197Uysal HY, Takmaz SA, Yaman F, Baltaci B, Başar H. The efficacy of intravenous paracetamol versus tramadol for postoperative analgesia after adenotonsillectomy in children. J Clin Anesth. 2011; 23(1): 53-57. doi:10.1016/j.jclinane.2010.07.001
Google Scholar
198Vahabi S, Shoja T, Chaibakhsh S, Khak M, Saljoughi N. Effect of postoperative topical administration of magnesium sulfate on pain relief in paediatric adenotonsillectomy: a randomised controlled study. Hong Kong J Paediatr. 2012; 17(2): 109-114.
Google Scholar
199Volk MS, Martin P, Brodsky L, Stanievich JF, Ballou M. The effects of preoperative steroids on tonsillectomy patients. Otolaryngol Head Neck Surg. 1993; 109(4): 726-730. doi:10.1177/019459989310900415
Google Scholar
200Wong AK, Bissonnette B, Braude BM, Macdonald RM, St-Louis PJ, Fear DW. Post-tonsillectomy infiltration with bupivacaine reduces immediate postoperative pain in children. Can J Anaesth. 1995; 42(9): 770-774. doi:10.1007/BF03011174
Google Scholar
201Wu J, Gui Q, Wang J, et al. Oxycodone preemptive analgesia after endoscopic plasma total adenotonsillectomy in children: a randomized controlled trial. Medicine (Baltimore). 2020; 99(6):e19004. doi:10.1097/MD.0000000000019004
Google Scholar
202Yenigun A, Et T, Aytac S, Olcay B. Comparison of different administration of ketamine and intravenous tramadol hydrochloride for postoperative pain relief and sedation after pediatric tonsillectomy. J Craniofac Surg. 2015; 26(1): e21-e24. doi:10.1097/SCS.0000000000001250
Google Scholar
203Yenigun A, Yilmaz S, Dogan R, Goktas SS, Calim M, Ozturan O. Demonstration of analgesic effect of intranasal ketamine and intranasal fentanyl for postoperative pain after pediatric tonsillectomy. Int J Pediatr Otorhinolaryngol. 2018; 104: 182-185. doi:10.1016/j.ijporl.2017.11.018
Google Scholar
204Yilmaz S, Demiraran Y, Akkan N, et al. The effects of topical levobupivacaine on morbidity in pediatric tonsillectomy patients. Int J Pediatr Otorhinolaryngol. 2009; 73(9): 1208-1210. doi:10.1016/j.ijporl.2009.05.006
Google Scholar
205Yücel Ekici N, Özdoğan H. Comparing local anesthetic infiltration of the peritonsillar region and glossotonsillar sulcus for post-tonsillectomy pain management. Eur Arch Otorhinolaryngol. 2020; 277(1): 255-260. doi:10.1007/s00405-019-05668-2
Google Scholar
206Zhuang PJ, Wang X, Zhang XF, Zhou ZJ, Wang Q. Postoperative respiratory and analgesic effects of dexmedetomidine or morphine for adenotonsillectomy in children with obstructive sleep apnoea. Anaesthesia. 2011; 66(11): 989-993. doi:10.1111/j.1365-2044.2011.06817.x
Google Scholar
207Seyberth HW, Kauffman RE. Basics and dynamics of neonatal and pediatric pharmacology. Handb Exp Pharmacol. 2011; 205: 3-49. doi:10.1007/978-3-642-20195-0_1
Google Scholar
208 Center for Disease Control and Prevention. Defining childhood obesity. 2021. Accessed June 13, 2021. https://www.cdc.gov/obesity/childhood/defining.html
Google Scholar
209Matson KL, Horton ER, Capino AC. Medication dosage in overweight and obese children. J Pediatr Pharmacol Ther. 2017; 22(1): 81-83. doi:10.5863/1551-6776-22.1.81
Google Scholar
210Voronov P, Przybylo HJ, Jagannathan N. Apnea in a child after oral codeine: a genetic variant—an ultra-rapid metabolizer. Paediatr Anaesth. 2007; 17(7): 684-687. doi:10.1111/j.1460-9592.2006.02182.x
Google Scholar
211Hermanns-Clausen M, Weinmann W, Auwärter V, et al. Drug dosing error with drops: severe clinical course of codeine intoxication in twins. Eur J Pediatr. 2009; 168(7): 819-824. doi:10.1007/s00431-008-0842-7
Google Scholar
212Kelly LE, Rieder M, van den Anker J, et al. More codeine fatalities after tonsillectomy in North American children. Pediatrics. 2012; 129(5): e1343-e1347. doi:10.1542/peds.2011-2538
Google Scholar
213Goldman JL, Baugh RF, Davies L, et al. Mortality and major morbidity after tonsillectomy: etiologic factors and strategies for prevention. Laryngoscope. 2013; 123(10): 2544-2553. doi:10.1002/lary.23926
Google Scholar
214Leung P, DeVore EK, Kawai K, et al. Does ibuprofen increase bleed risk for pediatric tonsillectomy. Otolaryngol Head Neck Surg. 2021; 165(1): 187-196. doi:10.1177/0194599820970943
Google Scholar
215Swanson RT, Schubart JR, Carr MM. Association of ibuprofen use with post-tonsillectomy bleeding in older children. Am J Otolaryngol. 2018; 39(5): 618-622. doi:10.1016/j.amjoto.2018.05.009
Google Scholar
216Stokes W, Swanson RT, Schubart J, Carr MM. Postoperative bleeding associated with ibuprofen use after tonsillectomy: a meta-analysis. Otolaryngol Head Neck Surg. 2019; 161(5): 734-741. doi:10.1177/0194599819852328
Google Scholar
217Mudd PA, Thottathil P, Giordano T, et al. Association between ibuprofen use and severity of surgically managed posttonsillectomy hemorrhage. JAMA Otolaryngol Head Neck Surg. 2017; 143(7): 712-717. doi:10.1001/jamaoto.2016.3839
Google Scholar
218Chan DK, Parikh SR. Perioperative ketorolac increases post-tonsillectomy hemorrhage in adults but not children. Laryngoscope. 2014; 124(8): 1789-1793. doi:10.1002/lary.24555
Google Scholar
219Jin F, Chung F. Multimodal analgesia for postoperative pain control. J Clin Anesth. 2001; 13(7): 524-539. doi:10.1016/s0952-8180(01)00320-8
Google Scholar
220Zhang LY, Zhong L, David M, Cervin A. Tonsillectomy or tonsillotomy? A systematic review for paediatric sleep-disordered breathing. Int J Pediatr Otorhinolaryngol. 2017; 103: 41-50. doi:10.1016/j.ijporl.2017.10.008
Google Scholar

Volume9, Issue1

March 2023

Pages 9-26

This article also appears in:

Obstructive Sleep Apnea

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wjo254-sup-0001-Tonsillectomy_search_appendix.docx17 KB	Supporting information.
wjo254-sup-0002-3Raw_Data.xlsx107.5 KB	Supporting information.

A scoping review of randomized clinical trials for pain management in pediatric tonsillectomy and adenotonsillectomy