The horizontal axis denotes the duration (days) between initial tonsillectomy and surgery for hemostasis, while the vertical axis denotes the percentage of reoperations at each day after tonsillectomy.
Suzuki S, Yasunaga H, Matsui H, Horiguchi H, Fushimi K, Yamasoba T. Impact of Systemic Steroids on Posttonsillectomy BleedingAnalysis of 61 430 Patients Using a National Inpatient Database in Japan. JAMA Otolaryngol Head Neck Surg. 2014;140(10):906-910. doi:10.1001/jamaoto.2014.2009
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Although postoperative bleeding after tonsillectomy is rare, it is potentially life-threatening. The association between steroid administration and postoperative bleeding remains controversial. The findings of previous studies were limited by small sample sizes.
To examine the impact of intravenous steroid administration on posttonsillectomy bleeding requiring reoperation in children and adults.
Design, Setting, and Participants
Retrospective cohort study of 61 430 patients from 718 hospitals who underwent tonsillectomy between 2007 and 2013, using the Diagnosis Procedure Combination database in Japan.
Intravenous steroid administration on the day of tonsillectomy.
Main Outcomes and Measures
The main outcome measure was reoperation for hemostasis under general anesthesia. Patient characteristics (age, sex, comorbidities) and steroid use were examined. Patients were classified as children (age ≤15 years, n = 31 934) and adults (age >15 years, n = 29 496), and subclassified into those who received intravenous steroid therapy on the day of tonsillectomy (steroid group) and those who did not (control group). Multivariable logistic regression analysis was performed to analyze the association between steroid use and posttonsillectomy bleeding with adjustment for patient characteristics.
The rate of reoperation was significantly higher in the steroid group than in the control group for children (1.2% vs 0.5%) (P < .001) but not for adults (1.7% vs 1.4%) (P = .14). Reoperation was most frequently performed at about 7 days after tonsillectomy. After adjusting for patient characteristics, we found a significant increase in the rate of reoperation in the steroid group in children (adjusted odds ratio [OR], 2.50 [95% CI, 1.47-4.23]) (P = .001) but not in adults (OR, 1.18 [95% CI, 0.85-1.64]) (P = .31).
Conclusions and Relevance
Intravenous steroid administration on the day of tonsillectomy in children was an independent risk factor for severe bleeding requiring reoperation.
Tonsillectomy is one of the most frequent surgical procedures performed in the field of otorhinolaryngology worldwide. Tonsillectomy may result in postoperative pain and nausea, and systemic steroid administration is considered an effective treatment option for preventing these symptoms.1- 5
Although tonsillectomy is usually safe, postoperative bleeding is a rare but potentially life-threatening complication.6 Hemostasis is usually achieved by direct pressure or electrocautery, but reoperation may be required for severe bleeding.
There is ongoing controversy regarding whether perioperative systemic steroid administration increases posttonsillectomy bleeding. A meta-analysis of 29 randomized trials (n = 2674) found that steroid administration was related to increased frequency of reoperation,7 but the findings were limited by the small sample size. In the present retrospective observational study, we investigated whether systemic steroid administration increased the rate of posttonsillectomy bleeding requiring reoperation using a national inpatient database in Japan.
The University of Tokyo institutional review board approved this study, waiving patient informed consent owing to the retrospective design and the anonymous nature of the data.
This study analyzed data from the Diagnosis Procedure Combination (DPC) database, which is a national inpatient database in Japan that includes administrative claims data and discharge abstract data. For each patient, the database includes (1) main diagnoses, comorbidities at admission, and complications after admission, with the corresponding International Statistical Classification of Diseases, 10th Revision (ICD-10); (2) surgical interventions, with the original Japanese codes; (3) patient age and sex; (4) drugs and devices used; and (5) type of hospital (academic or nonacademic). The database information includes brand names of drugs, administration method for drugs (intravenous or oral), and the dates when each drug or device was used as well as the dates of surgery performed.
The DPC database was launched in 2002 by the Ministry of Health, Labor, and Welfare of Japan, and all 82 academic hospitals in the country are obliged to adopt it.8 Data were collected for 6 months each year (July 1 to December 31) between 2007 and 2010. In 2011, the duration of the survey for each year was extended to 12 months.9 The attending physicians are required to record all discharge abstract data for each patient once per admission, using medical records to optimize the accuracy of the data. The number of patients included in 2012 (6.8 million) represented more than 50% of all inpatient admissions to acute care hospitals in Japan.
Data were obtained for patients who underwent tonsillectomy between July and December from 2007 to 2009, during the entire year from 2010 to 2012, and from January to March in 2013 (51 months in total). Patients with benign or malignant pharyngeal tumors (ICD-10 codes D105, D107, D109, and D370) and all patients 50 years or older were excluded. Patients who received intravenous steroids on the day of tonsillectomy (steroid group) and those who did not receive steroids, neither intravenous nor oral, during the hospitalization (control group) were selected. Patients who received intravenous steroids on any day other than the day of tonsillectomy were excluded. Patients with asthma (ICD-10 code, J45x) were also excluded because they could be routine steroid users.
We note that IgA nephropathy (ICD-10 code N028) and palmoplantar pustulosis (ICD-10 code J403) belong to the tonsillar focal infections, as defined by disorders in distant organs caused by the tonsils without any symptoms of the tonsils themselves,10 and tonsillectomy combined with steroid pulse therapy is one of the treatment options for IgA nephropathy.11 Because the causes of these 2 diseases are different from that of tonsillitis, patients who were diagnosed with either disease were excluded. Finally, hereditary bleeding disorders including factor VIII deficiency, factor IX deficiency, von Willebrand disease, and deficiency of other clotting factors (ICD-10 codes D66, D67, D680, and D682, respectively) were excluded.
Patient age and sex were noted, as were the following comorbidities: adenoid hypertrophy (ICD-10 codes J352 and J358), sleep apnea syndrome (G473), tonsillar hypertrophy (J351), allergic rhinitis (J304), chronic rhinosinusitis (J329), and otitis media with effusion (H65x).
The primary outcome was postoperative bleeding requiring reoperation under general anesthesia, including reoperation during the same hospitalization and during rehospitalization for hemostasis. The period between tonsillectomy and reoperation for hemostasis was recorded. In the subgroup analyses, we set a cut-off age of 15 years for the children’s group because many previous studies have included patients 15 years or younger in the children’s group.7
Patient characteristics were compared between the steroid and control groups using the t test or χ2 test, as appropriate. Multivariable logistic regression analysis was performed to investigate the relationships between steroid administration and posttonsillectomy bleeding requiring reoperation in children (aged ≤15 years) and adults (aged >15 years) with adjustment for background characteristics, and also for within-hospital clustering using a generalized estimating equation. Additional subgroup analyses were performed for patients who received dexamethasone or hydrocortisone. The threshold for significance was set at P < .05. All statistical analyses were performed using the Statistical Package for Social Sciences, version 20.0 (IBM SPSS Corp).
A total of 85 808 patients who underwent tonsillectomy during the study period were identified. Of these, 378 patients with pharyngeal tumors and 5592 patients 50 years or older were excluded. A further 18 408 patients were excluded for the following reasons: intravenous steroid administration on a day other than the day of tonsillectomy (n = 10 531), oral steroid use (n = 802), asthma (n = 1831), IgA nephropathy (n = 4835), palmoplantar pustulosis (n = 398), hereditary factor VIII deficiency (n = 4), hereditary factor IX deficiency (n = 1), von Willebrand disease (n = 3), and hereditary deficiency of other clotting factors (n = 3).
The remaining 61 430 eligible patients from 718 hospitals were classified into those who received intravenous steroids on the day of tonsillectomy (steroid group, n = 4767) and those who did not (control group, n = 56 663). Table 1 summarizes the patient characteristics in the steroid and control groups. Patients in the steroid group had a significantly lower rate of adenoid hypertrophy and significantly higher rates of sleep apnea syndrome and tonsillar hypertrophy than those in the control group. Table 2 details how the rate of reoperation for hemostasis was significantly higher in the steroid group than in control group (1.6% vs 0.9% [P < .001] in all patients and 1.2% vs 0.5% [P < .001] in children, respectively), but this was not true in adults. Both the dexamethasone (1.7%; 18 of 1048) (P = .01) and hydrocortisone (1.7%; 34 of 1965) (P < .001) subgroups had significantly higher rates of reoperation than the control group (0.9%).
Table 3 lists the results of multivariable logistic regression analysis for reoperation according to age group. In children, steroid administration (odds ratio [OR], 2.50 [95% CI, 1.47-4.23]) (P = .001) and age (OR, 1.10 [95% CI, 1.04-1.17]) (P < .001) were independent predictors of severe bleeding requiring reoperation. Female patients were less likely to require reoperation than male patients in both children (OR, 0.73 [95% CI, 0.54-1.00]) (P = .048) and adults (OR, 0.41 [95% CI, 0.33-0.52]) (P < .001). Children who underwent tonsillectomy in an academic hospital had a significantly higher rate of reoperation than children who underwent the procedure in a nonacademic hospital (OR, 1.53 [95% CI, 1.02-2.29]) (P = .04), but this was not true for adults (OR, 0.66 [95% CI, 0.46-0.94]) (P = .02). Allergic rhinitis was associated with a lower risk of reoperation in adults (OR, 0.48 [95% CI, 0.25-0.92]) (P = .03), but other comorbidities were not associated with reoperation.
A total of 588 reoperations were performed, 382 during the same hospitalization and 206 during rehospitalization. The Figure shows the timing of posttonsillectomy reoperations. The reoperation rate was highest at about 7 days after tonsillectomy.
The present study investigated the impact of systemic steroid administration on posttonsillectomy bleeding in children and adults, using a large-scale data set from a nationwide inpatient database in Japan. Our analysis of 61 430 patients showed that intravenous steroid administration on the day of tonsillectomy was significantly associated with a higher rate of reoperation for hemostasis in children (age ≤15 years) but not in adults (age >15 years). The subgroup analyses divided by types of steroids (dexamethasone and hydrocortisone) showed similar results to those of the all-patient analysis.
The American,1 Italian,12 and Scottish13 tonsillectomy guidelines recommend a single intraoperative dose of dexamethasone in children to prevent postoperative nausea and vomiting (grade A). The Scottish guideline also recommends use of steroids to prevent postoperative nausea and vomiting in adults (grade B). Many previous studies have reported on the relationship between steroid administration and posttonsillectomy bleeding, but the findings were inconsistent.1- 5,7,14,15 A recent meta-analysis of 12 randomized trials (n = 1178) found that the incidence of reoperation for hemostasis was significantly higher in the steroid group than in the control group for children (OR, 3.43 [95% CI, 1.29-9.13]) but not for adults (OR, 1.07 [95% CI, 0.29-4.03]).7 Another meta-analysis including 270 adult patients showed that dexamethasone use was associated with a significantly lower rate of posttonsillectomy bleeding (relative risk, 0.45 [95% CI, 0.25-0.80]).3 Conversely, a recent meta-analysis including 1180 children in 12 prospective studies15 found that preoperative dexamethasone use did not increase the bleeding risk. Considering the fact that severe bleeding requiring reoperation is rare, a large-scale single study is needed to strictly evaluate the bleeding risk.
The present study included 61 430 patients. To our knowledge, this represents the largest study of tonsillectomy-related bleeding reported to date. Our results may not support the use of steroids in children because of the significant association with reoperation for hemostasis. However, steroid use may be acceptable for adult patients.
The lower proportion of steroid use in Japan may be caused by differences in the clinical practice and health care systems between the United States and Japan. A guideline for tonsillectomy has not been established in Japan, and patients usually stay in the hospital for about 7 days after tonsillectomy in case of bleeding. Steroid administration is not routine, and antiemetic drugs are commonly used to prevent postoperative nausea and vomiting on the day of or after tonsillectomy.
We did not use the rate of bleeding as an end point because the definition of bleeding may have varied among institutions. Instead, we used the rate of reoperation as the primary end point because this is an objective and reliable method of assessing clinically significant bleeding after tonsillectomy.
A previous study in the United States found that obstructive sleep apnea syndrome was associated with a lower rate of posttonsillectomy bleeding, which may be explained by the protective effect of upregulation of prothrombotic factors.16 However, sleep apnea syndrome was not associated with reoperation in the present study.
The proportion of patients with sleep apnea syndrome in the steroid group was higher than that in the control group, in both children and adults. In contrast, the proportion of children with adenoid hypertrophy or tonsillar hypertrophy in the steroid group was lower than that in the control group, while the proportion of adults with adenoid hypertrophy or tonsillar hypertrophy in the steroid group was higher. Although the reason for these relationships remains unclear, a possible explanation may be that patients with sleep apnea syndrome, both children and adults, could have a risk of postoperative airway obstruction, which may have affected the physicians’ choice of steroid use. Children with adenoid hypertrophy or tonsillar hypertrophy may have had less severe inflammation, while adults could have been more likely to have refractory tonsillitis. These factors may have resulted in the lower steroid use for children and greater steroid use for adults.
Posttonsillectomy bleeding is categorized as primary or secondary.1 Primary bleeding is defined as bleeding within 24 hours after tonsillectomy and is associated with surgical technique and reopening of blood vessels. Secondary bleeding occurs more than 24 hours after tonsillectomy, often between days 5 and 10,14,16- 18 and usually occurs when the primary scab or necrotic tissue on the tonsil bed sloughs off before the wound has completely healed. In our study, secondary bleeding requiring reoperation for hemostasis occurred in 537 patients (0.87%). Reoperation occurred most frequently during the first 7 days after tonsillectomy. If patients are discharged earlier than 7 days after tonsillectomy, they should be given detailed advice regarding the management of bleeding after discharge.
Several limitations of this study should be acknowledged. First, this study was based on retrospective observation, and the treatment assignment was not random. Unrecorded confounding factors such as obesity, preoperative inflammation, and surgical technique (electrocautery or sharp dissection) may have influenced the rates of steroid use. Second, comorbidities recorded in an administrative claims database are generally less accurate than those recorded in planned prospective studies.
Our results show that intravenous administration of steroids on the day of surgery was associated with an increased rate of posttonsillectomy reoperation for hemostasis in patients 15 years or younger. Further prospective studies are warranted to evaluate the potential risks and benefits of steroid use in children undergoing tonsillectomy.
Submitted for Publication: April 4, 2014; final revision received June 18, 2014; accepted July 22, 2014.
Corresponding Author: Sayaka Suzuki, MD, Department of Clinical Epidemiology and Health Economics, School of Public Health, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1130033, Japan (firstname.lastname@example.org).
Published Online: September 18, 2014. doi:10.1001/jamaoto.2014.2009.
Author Contributions: Drs Suzuki and Yasunaga had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Suzuki, Yasunaga, Fushimi, Yamasoba.
Acquisition, analysis, or interpretation of data: Suzuki, Yasunaga, Matsui, Horiguchi.
Drafting of the manuscript: Suzuki, Yasunaga, Matsui, Fushimi.
Critical revision of the manuscript for important intellectual content: Yasunaga, Horiguchi, Yamasoba.
Statistical analysis: Suzuki, Yasunaga, Matsui.
Obtained funding: Yasunaga.
Administrative, technical, or material support: Yasunaga, Matsui, Horiguchi, Yamasoba.
Study supervision: Yasunaga, Fushimi, Yamasoba.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was funded by grants from the Ministry of Health, Labor and Welfare, Japan (Research on Policy Planning and Evaluation grant No. H25-Policy-010), and the Council for Science and Technology Policy, Japan (Funding Program for World-Leading Innovative R&D on Science and Technology, FIRST program grant No. 0301002001001).
Role of the Funder/Sponsor: The funding institutions had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.