AJA Asian Journal of Anesthesiology

Advancing, Capability, Improving lives

Research Paper
Volume 58, Issue 1, Pages 14-23
Eriko Takeyama 1 , Chiaki ito 1 , Eizo Amano 1 , Hiromi Shibuya 1
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Abstract

Objective: We sometimes encounter cases with unexpected increase in intraoperative urine output during tympanoplasty. However, no previous study has evaluated whether intraoperative urine output during tympanoplasty is higher than that during other surgeries. Thus, this study aimed to evaluate the association between tympanoplasty and intraoperative urine output.

Methods: This single-center retrospective cohort study was conducted by assessing the records of patients who underwent tympanoplasty, sinus surgery, or thyroidectomy under general anesthesia between April 2013 and March 2017. We defined intraoperative polyuria as a urine output rate of ≥ 2.5 mL/kg/h. The factors associated with high urine output were investigated using multivariable analysis. The influence of tympanoplasty on intraoperative urine output was evaluated after propensity score matching that excluded confounding factors, except the surgical procedure.

Results: Intraoperative polyuria occurred in 48 of 173 patients (27.7%) who underwent tympanoplasty. Multivariable analysis revealed that tympanoplasty (p = 0.001), operative time of ≥ 3 h (p = 0.010), and fluid infusion volume of ≥ 5 mL/kg/h (p = 0.029) were risk factors for polyuria. Among the study patients, 100 who underwent tympanoplasty (tympanoplasty group) and 100 who underwent sinus surgery or thyroidectomy (control group) were matched by propensity score analysis. The intraoperative urine output rate was significantly higher in the tympanoplasty group than in the control group (1.2 [0.51–2.20] mL/kg/h vs. 0.70 [0.32–1.60] mL/kg/h, p = 0.010).

Conclusion: Our findings indicate that intraoperative urine output is higher during tympanoplasty than that during other otologic surgeries.

Keywords

polyuria, tympanoplasty, otologic surgery, intraoperative urine output


Introduction

The release of antidiuretic hormone (ADH) has been shown to increase in response to surgical stress, and this is followed by an increase in tubular reabsorption of water, leading to a sharp decrease in urine output.1-3 Therefore, oliguria is common during surgery. In contrast, anesthesiologists sometimes encounter cases of intraoperative polyuria during tympanoplasty. As factors related to increase of intraoperative urine output, some drugs such as remifentanil and dexmedetomidine4-9 are reported. However, to our knowledge, no previous study has evaluated the association between specific surgery type including tympanoplasty and intraoperative urine output. If intraoperative urine output increases during tympanoplasty, anesthesiologists need to pay attention to the urine output and ensure sufficient hydration to prevent hypovolemia.

Therefore, the present study retrospectively evaluated the association between tympanoplasty and intraoperative urine output.

Methods

We retrospectively reviewed the medical records of adult patients (aged ≥ 20 years) who underwent tympanoplasty, sinus surgery, or thyroidectomy under general anesthesia in our hospital between April 2013 and March 2017. Patients with renal failure (estimated glomerular filtration rate [eGFR] of < 60 mL/min/1.73 m2) were excluded.

Patients were allowed solid foods for up to the night before surgery. Patients scheduled for induction of anesthesia between 8:30 AM and 12:00 AM were allowed clear water until 6:00 AM. Patients scheduled for induction of anesthesia after 12:00 AM were allowed clear water until 9:00 AM.

Urine catheter is placed after the induction of general anesthesia and recorded the urine output during surgery routinely.

The present study was approved by the Medical Ethics Committee of Osaka National Hospital (approval number: 18079). Considering the retrospective design of the study, the requirement for informed consent was waived by the Institutional Review Board.

Data Collection

The following available data were collected from the medical records of each patient: sex, age, body mass index (BMI), American Society of Anesthesiologists Physical Status (ASA-PS), comorbidities, preoperative eGFR, anesthesia type (total intravenous anesthesia or inhalational anesthesia), operative time, anesthesia time, total infusion volume, colloid use, total urine output volume, total amount of fentanyl and remifentanil, intraoperative heart rate (HR), and intraoperative mean blood pressure (mBP). Intraoperative urine output was calculated from the start of surgery until discharge from the operating room. The HR ratio was calculated as the ratio of the intraoperative mean HR to the preoperative HR. Similarly, the mBP ratio was calculated as the ratio of the intraoperative mBP to the preoperative mBP. We defined intraoperative polyuria as an intraoperative urine output rate of ≥ 2.5 mL/kg/h, which is calculated as hourly urine amount of the definition of polyuria (3 L/day) when the weight was assumed to be 50 kg.

Statistical Analysis

Data on patient characteristics are expressed as medians (interquartile range). Logistic regression analysis was performed to evaluate the factors related to high urine output. For this analysis, the original cohort was divided into a polyuria group (urine output rate of ≥ 2.5 mL/kg/h) and a non-polyuria group (urine output rate of < 2.5 mL/kg/h). Univariate analysis was conducted for each evaluated parameter. Categorical variables were compared using Fisher’s test, whereas continuous variables were compared using the Wilcoxon rank test. Variables with a p value < 0.05 in the univariate analysis were entered into the multivariable analysis involving logistic regression.

The association between polyuria and each factor is expressed as odds ratio (OR) with 95% confidence interval (CI).

Subsequently, propensity score matching was performed to assess the difference in intraoperative urine output between tympanoplasty and other surgeries. For propensity score matching, the original cohort was divided into a tympanoplasty group (those who underwent tympanoplasty) and a control group (those who underwent sinus surgery or thyroidectomy). Propensity score matching enabled elimination of the confounding effects of sex, age, BMI, ASA-PS, preoperative eGFR, anesthesia type, operative time, anesthesia time, infusion volume, colloid use, opioid amount (fentanyl and remifentanil), HR ratio, and mBP ratio.

Patients were matched 1:1, and the caliper was set as the standard deviation of the logit conversion value of the propensity score multiplied by 0.2.10 Intraoperative urine output was designated as the primary endpoint, and polyuria incidence was designated as the secondary endpoint.

All statistical analyses were performed using JMP Pro software (version 14; SAS Inc., Cary, NC, USA). All tests were two-tailed, and a p value < 0.05 was considered statistically significant.

Results

A flow chart describing the patient selection process is presented in Figure 1. A total of 410 patients who underwent tympanoplasty, sinus surgery, or thyroidectomy under general anesthesia during the study period were initially screened. Among these patients, 79 had renal failure and were excluded. Eventually, 331 adult patients were included in the final cohort. Of these 331 patients, 62 were included in the polyuria group and 269 were included in the non-polyuria group (Figure 1).

Figure 1.
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Figure. 1. Flow Chart for Patient Selection

Abbreviation: eGFR, estimated glomerular fi ltration rate.

Comparisons of patient demographics between the polyuria and non-polyuria groups are presented in Table 1. There were more female patients in the polyuria group than in the non-polyuria group (69.3% vs. 55.0%; p = 0.046). However, there were no significant differences in other patient characteristics and preoperative conditions. Intraoperative polyuria occurred in 48 of 173 patients (27.7%) who underwent tympanoplasty. The polyuria incidence was significantly higher in patients who underwent tympanoplasty than in those who underwent other otologic surgeries (p < 0.001). When comparing the polyuria group and non-polyuria group, it was found that the polyuria group had longer operative time (p< 0.001) and anesthesia time (p < 0.001), higher infusion volume (p< 0.001), lower fluid balance (p < 0.001), and greater remifentanil use (p < 0.001). Information on comorbidities is shown in Supplement Table 1.

Table 1. Comparison of Preoperative and Postoperative Characteristics Between Patients With and Without Intraoperative Polyuriaa
Table 1.
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Tables 2 and 3 present the results of the univariate and multivariable logistic regression analyses for polyuria, respectively. The univariate analysis showed an association between polyuria and tympanoplasty (OR, 3.92; 95% CI, 2.1–7.5; p < 0.001). Furthermore, female sex, operative time of ≥ 3 h, fluid infusion rate of ≥ 5 mL/kg/h, and remifentanil use of ≥ 1 mg were associated with the polyuria incidence. Multivariable logistic regression analysis was performed using the following variables: sex, surgery type, operative time of ≥ 3 h, fluid infusion rate of ≥ 5 mL/kg/h, and remifentanil use of ≥ 1 mg. The analysis revealed that the independent risk factors for intraoperative polyuria were tympanoplasty (p = 0.001), operative time of ≥ 3 h (p = 0.010), and fluid infusion rate of ≥ 5 mL/kg/h (p = 0.029). Tympanoplasty was the most significant predictive factor of intraoperative polyuria according to the OR.

Table 2. Univariate Logistic Regression Analysis for Occurrence of Intraoperative Polyuria
Table 2.
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Table 3. Multivariable Model Evaluating the Risk Factors for Occurrence of Intraoperative Polyuria
Table 3.
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The results of propensity score matching conducted to investigate the effect of tympanoplasty on urine output are shown in Tables 4 and 5. The original cohort before matching included 173 patients in the tympanoplasty group and 158 patients in the control group (Figure 1).

After propensity score matching, none of the factors (sex, age, BMI, ASA-PS, preoperative eGFR, anesthesia type, operative time, anesthesia time, fluid infusion, fentanyl and remifentanil amounts, HR ratio, and mBP ratio) showed a significant difference between the two groups (Table 4). Comparisons of the endpoints are shown in Table 5. Before matching, the intraoperative urine output and polyuria incidence were significantly higher in the tympanoplasty group than in the control group (urine output rate: 1.4 [0.67–2.60] mL/kg/h vs. 0.65 [0.30–1.50] mL/kg/h, p < 0.001; polyuria incidence: 27.8% vs. 8.9%, p < 0.001). After matching, both the intraoperative urine output and polyuria incidence remained significantly higher in the tympanoplasty group than in the control group (urine output rate: 1.2 [0.51–2.20] mL/kg/h vs. 0.70 [0.32–1.60] mL/kg/h, p = 0.010; polyuria incidence: 23% vs. 10%, p = 0.021).

Table 4. Patient Demographics and Intraoperative Characteristics of the Original Cohort Before and After Propensity Score Matchinga
Table 4.
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Table 5. Patient Outcomes Before and After Propensity Score Matchinga
Table 5.
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Discussion

During surgery, urine output has been shown to decrease because of ADH secretion associated with surgical stress. As low urine output during surgery is a natural stress response to surgery, restricted fluid infusion during surgery is considered more beneficial than fluid replacement targeting high urine output.11-13 However, anesthesiologists sometimes experience cases of unexpectedly high urine output during tympanoplasty. The present study attempted to evaluate whether tympanoplasty is associated with an increase in intraoperative urine output. The study found that the incidence of intraoperative polyuria was higher in patients who underwent tympanoplasty than in those who underwent other otologic surgeries. Multivariable analysis showed that operative time of ≥ 3 h and fluid infusion rate of ≥ 5 mL/kg/h were also risk factors for intraoperative polyuria. To eliminate the influence of factors other than surgery type, propensity score analysis was performed. Following matching, intraoperative urine output remained higher in patients who underwent tympanoplasty, even after infusion volume and operative time were adjusted. These results indicated an association between urine output increase and tympanoplasty.

One of the possible factors associated with polyuria during tympanoplasty is ADH. ADH represents one of the homeostatic systems for controlling extracellular volume. Recently, it was found that the ADH receptor is present throughout the inner ear tissue.14,15 ADH and its receptor play significant roles in local fluid homeostasis by controlling the elimination/reabsorption of fluid in the inner ear, likely similar to the mechanism that occurs in the kidney.16 In an animal model, pressure changes in the inner ear were found to control ADH release.17 Thus, we assumed that surgical procedures in the inner ear could drastically change the environment, resulting in the transmission of signal through the ADH receptor and a subsequent decrease in ADH release. The increase in urine output during tympanoplasty might be explained by this decrease in ADH release despite surgical stress.

Remifentanil has been reported to increase urine output during surgery by suppressing the surgical stress response, as a low urine output during surgery has been shown to be caused by the surgical stress response.5,8,9 These reports revealed that the endocrine stress response, including release of adrenocorticotropic hormone, cortisol, and ADH, increased during surgery, and this was suppressed by remifentanil. Additionally, it was shown that remifentanil use is related with low intraoperative mBP and high intraoperative urine output.5 In the present study, univariate logistic regression analysis showed a significant association between polyuria and remifentanil dose, although multivariable analysis showed no significant association. In addition, no significant differences in the intraoperative mBP and HR ratio were observed between the polyuria and non-polyuria groups. Remifentanil might be associated with an increase in intraoperative urine output, although it was not an independent risk factor for polyuria. As hormonal changes associated with the stress response were not measured, the precise mechanism by which remifentanil increases urine output during tympanoplasty remains unclear.

Dexmedetomidine is also reported to increases urine output in the perioperative period.4,6 Additionally, it has been reported that intraoperative hypernatremia and polyuric syndrome are induced by dexmedetomidine.18 Before surgery, there is a dehydration tendency owing to fasting, and it is easy to experience hypertonic dehydration due to polyuria. Furthermore, supplementing water lost as urine with extracellular fluid might easily cause hypernatremia. In the present study, no patient used dexmedetomidine; however, it is important to be aware of electrolyte disturbance due to increased urine output during tympanoplasty.

The present study has some limitations. First, the study did not examine the mechanism involved in increase of urine output. We did not measure serum ADH levels, stress hormones, plasma and urine osmolality, and electrolytes. We could not determine the correlation between tympanoplasty and ADH release. Although we could not exclude the possibility of an unknown factors related to specific procedures during tympanoplasty, we still expect that an association exists based on previous studies. Second, we could not completely exclude the influence of infusion volume on urine output because of the study design. In fact, the total infusion volume was higher in the polyuria group. However, the total fluid balance was lower in the polyuria group, suggesting that the attending anesthesiologist increased the infusion volume considering the urine output. Furthermore, the urine output was significantly higher in the tympanoplasty group after propensity score matching that excluded the influence of factors, such as infusion volume. These results suggest that the influence of tympanoplasty is greater than the influence of infusion volume. Third, we did not investigate the clinical outcome of polyuria. In our study, infusion volume was higher in polyuria group, suggesting anesthesiologists increased infusion volume as urine output increased. Therefore, it is difficult to discuss about the clinical impact of increase in urine output on volume status. On the other hand, our data suggest the possibility to cause hypovolemia unless careful observation of intraoperative urine output. In addition, electrolytes were not analyzed intraoperatively or immediately after surgery, and the effect of polyuria induced by tympanoplasty on electrolytes was unclear. There were few reports about intraoperative polyuria and some of them reported intraoperative hypernatremia due to polyuria. Granger and Ninan reported that the serum potassium level increased from 136 to 148 mmol/L when 965 mL urine output was observed in 4 hours.19 In our study, 25 patients secreted more than 900 mL urine. Polyuria as high as that in patients who developed hypernatremia owing to dexmedetomidine (urine output rate: 7.6 mL/kg/h)18 was also noted in the present study. In addition, if tympanoplasty caused polyuria through ADH and free water secreted, suggesting extracellular fluid replacement exacerbate hypernatremia. No patient had a problematic clinical course after surgery in our study, and we could not conclude any clinical impact of intraoperative polyuria during tympanoplasty. However, our data suggest the risk that tympanoplasty can cause polyuria and thus electrolytes abnormalities including hypernatremia. Further study to evaluate the clinical impact of intraoperative polyuria due to tympanoplasty will be needed.

Conclusion

The findings of the present study suggest that intraoperative urine output and polyuria incidences are higher in patients undergoing tympanoplasty than in those undergoing other surgeries. Considering the risk of an unexpected increase in urine output during surgeries involving the inner ear, such as tympanoplasty, careful fluid management is required to avoid dehydration, especially in elderly patients and patients with heart diseases.

Author Contributions

Eriko Takeyama designed the work, collected and analyzed the data, and wrote the initial draft of the manuscript. Eizo Amano contributed to analysis and interpretation of data, and assisted in preparation of the manuscript. All authors revised the manuscript critically and approved the final version for publication.

Conflicts of Interest

The authors declare that they have no competing interests.

Ethics Approval and Consent to Participate

This study was approved by the Medical Ethics Committee of Osaka National Hospital (approval number: 18079).

Funding

This research did not receive any specific grant from agencies in the public, commercial, or not-for profit sectors.

Supplement

Supplement Table 1. Comorbidities and Intraoperative Polyuriaa
Supplement Table 1.
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