Preoperative factors associated with intraoperative maximum arterial pressures in patients with pheochromocytoma and paraganglioma: a single-center retrospective study

Preoperative factors associated with intraoperative maximum arterial pressures in patients with pheochromocytoma and paraganglioma: a single-center retrospective study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Preoperative factors associated with intraoperative maximum arterial pressures in patients with pheochromocytoma and paraganglioma: a single-center retrospective study Haruyuki Ohsugi, Nae Takizawa, Tadashi Matsuda, Hidefumi Kinoshita This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-894894/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Surgery for pheochromocytoma and paraganglioma (PPGL) can lead to life-threatening complications, such as intraoperative hypertensive crises, even when adequate doses of preoperative α-receptor blockades are administered. The aim of this study was to identify preoperative factors associated with maximum arterial pressure (AP) during surgery in patients with PPGL. We retrospectively reviewed the cases of 61 PPGL patients who underwent surgical resection in our hospital between 2006 and 2020. The primary outcome was intraoperative maximum AP as a single index for continuous variables. The normal distribution of the results was confirmed by the Kolmogorov–Smirnov test. Simple and multiple linear regression model were used for statistical analysis. The median maximum systolic AP during surgery was 165 mmHg (interquartile range: 150–180 mmHg). Although the 24-h urinary-fractionated metanephrine (MN) and normetanephrine (NMN) (mg/day) was not normally distributed, the logarithmic representation (base = 10) of the combination of these continuous variables showed a normal distribution (p = 0.549). Log 24 − h urinary−fractionated MN and NMN was correlated with intraoperative maximum AP (R = 0.481, p < 0.001). Multiple regression analyses showed that diabetes mellitus (β = 15.835, standard error [SE] = 7.550, t statistic = 2.097, P = 0.040), the classic triad (β = 14.081, SE = 5.668, t statistic = 2.484, P = 0.016), and log 24 − h urinary−fractionated MN and NMN (β = 14.641, SE = 5.842, t statistic = 2.506, P = 0.015) were independent factors associated with intraoperative maximum AP. Patients with PPGL accompanied by diabetes mellitus, the classic triad, and high log 24−h urinary−fractionated MN and NMN values may be at risk for hypertensive crises during surgery regardless of whether preoperative α-receptor blockades are used. Clinicians should manage these patients more carefully and effectively. Urology & Nephrology PPGL arterial pressure (AP) metanephrine (MN) normetanephrine (NMN) Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Pheochromocytomas are catecholamine-secreting neoplasms arising from chromaffin cells of the adrenal medulla, and paraganglioma are defined as tumors arising from extra-adrenal chromaffin tissue. These catecholamine-secreting neoplasms are rare, and the incidence of pheochromocytoma and paraganglioma (PPGL) is about 0.6 cases per 100,000 person-years [1]. Excessive catecholamine secretion causes various symptoms, including hypertension (HTN) and the classic triad of palpitation (tachycardia), headache, and sweating [2]. It also presents comorbidities of diabetes mellitus (DM) or cardiovascular events. Complete surgical resection is the definitive treatment for PPGL. However, unavoidable intraoperative manipulation of the tumor can cause catecholamine release and hypertensive crises. Therefore, surgery for PPGL has long been considered a challenging procedure [3]. In the 21st century, the mortality associated with surgery for PPGL has dramatically decreased to a rate of 0–3.0%, which has resulted from improvements in treatment, such as surgical techniques, preoperative management including α-receptor blockades, and anesthesia [2]. Regardless of these clinical efforts, surgery for PPGL can lead to intraoperative hypertensive crises, which cause life-threatening complications [4]. Although the guidelines issued by the Endocrine Society recommend preoperative α-receptor blockades as a prophylactic for all patients [5], a recent observational study showed that there was only a slight difference in maximum arterial pressure (AP) between patients who had been administered α-receptor blockades and those who had not [6]. These results are important because not only might there be asymptomatic patients who do not need preoperative α-receptor blockades but also severe patients who experience intraoperative hypertensive episodes despite adequate doses of preoperative α-receptor blockades. In the current study, we retrospectively reviewed the clinical and operative records of patients with PPGL. Using this data set, we identified preoperative factors associated with intraoperative maximum arterial pressure (AP) in patients with PPGL who received adequate doses of preoperative α-receptor blockades. Results Patient characteristics The clinical and tumor characteristics of the PPGL patients are shown in Table 1 . The median intraoperative maximum AP was 165 mmHg (interquartile ranges [IQR] : 150–180 mmHg). Of 61 patients, 18 (29.5%) had hypertensive episodes with intraoperative maximum APs above 180 mmHg. Preoperative hypertension and DM were shown in 28 (45.9%) and 9 (9.8%) patients, respectively. There were 16 (26.2%) patients exhibiting one or more of the classic triad. No postoperative complications greater than Grade 3 by the Clavien–Dindo classification were observed. Table 1 Clinical and tumor characteristics in patients with PPGL. Variables n = 61 Age, years, median (IQR) 54.0 (44.0 − 65.0) Sex, n (%) Female 32 (52.5) Male 29 (47.5) BMI, kg/m 2 , median (IQR) 21.4 (19.7 − 24.8) ASA, n (%) 1 1 (1.6) 2 59 (96.7) 3 1 (1.6) Cerebro-cardiovascular events, n (%) Absent 58 (95.1) Present 3 (4.9) Hypertension, n (%) Absent 33 (54.1) Present 28 (45.9) Diabetes mellitus, n (%) Absent 55 (90.2) Present 6 (9.8) Classic triad*, n (%) Absent (none of the symptoms) 45 (73.8) Present (at least one of symptom) 16 (26.2) Hereditary, n (%) Unknown 54 (88.5) MEN 5 (8.2) VHL 1 (1.6) SDH 1 (1.6) Tumor location, n (%) Pheochromocytoma 52 (85.2) Paraganglioma 9 (14.8) Type of surgery, n (%) Laparoscopic 51 (83.6) Open 10 (16.4) Surgical approach, n (%) Transperitoneal 54 (88.5) Retroperitoneal 7 (11.5) Tumor size, mm (IQR) 38.0 (28.0 − 52.0) Urinary-fractionated MN in 24-h urine, mg/day (IQR) 0.32 (0.14 − 0.97) Urinary-fractionated NMN in 24-h urine, mg/day (IQR) 1.40 (0.65 − 3.60) Preoperative systolic blood pressure, mmHg (IQR) 120 (112 − 130) Preoperative diastolic blood pressure, mmHg (IQR) 72 (67 − 81) Intraoperative maximum arterial pressure, mmHg (IQR) 165 (150 − 180) Abbreviations: ASA, American Society of Anesthesiologists; BMI, body mass index; IQR, interquartile range; MEN, multiple endocrine neoplasia; MN, metanephrines; NMN, normetanephrines; PPGL; pheochromocytoma and paraganglioma; SDH, succinate dehydrogense; VHL, von Hipple–Lindau. *Palpitation (tachycardia), headache, and episode of sweating. Relationship between preoperative blood pressure and intraoperative maximum AP Intraoperative maximum AP showed a normal distribution (P = 0.618; Fig. 1 A). Preoperative systolic blood pressure and diastolic blood pressure also showed normal distributions (P = 0.836 and P = 0.603, respectively; Fig. 1 B and 1 C). Neither preoperative systolic blood pressure nor diastolic blood pressure was correlated with intraoperative maximum AP (Fig. 2 A and 2 B). Normal distributivity of preoperative continuous variables Among the continuous variables of preoperative clinical factors, age, and body mass index (BMI) showed normal distributions (P = 0.976 and 0.332, respectively; Fig. 3 A and 3 B). However, tumor size, the 24-h urinary-fractionated metanephrine (MN), and the 24-h urinary-fractionated normetanephrine (NMN) were not normally distributed (all P < 0.01; S. Figure 1 A, 1 B, and 1 C). The logarithmic representation (log 10 ) of these three continuous variables showed a normal distribution (P = 0.201–0.715; Fig. 3 C, 3 D, and 3 E). Similarly, the 24-h urinary-fractionated MN and NMN was not normally distributed, but the logarithmic representation of this continuous variable also showed a normal distribution (P = 0.549; Fig. 3 F). Correlations between intraoperative maximum APs and preoperative variables Log 24 − h urinary−fractionated MN and NMN was correlated with intraoperative maximum AP (R = 0.481, P < 0.001; Fig. 4 ). The correlation coefficient index was higher than each of log 24 − h urinary−fractionated MN and log 24 − h urinary−fractionated NMN (R = 0.204 and R = 0.412, respectively). Next, preoperative variables were investigated by linear regression analyses. Simple linear regression analyses showed that comorbidities of DM, the classic triad, and log 24 − h urinary−fractionated MN and NMN were significantly associated with intraoperative maximum AP (all P < 0.05; Table 2 ). Log 24 − h urinary−fractionated MN and NMN showed the highest t statistic among the preoperative variables ( t statistic, 4.212). Then, multiple regression analyses showed that DM (β = 15.835, standard error [SE] = 7.550, t statistic = 2.097, P = 0.040), the classic triad (β = 14.081, SE = 5.668, t statistic = 2.484, P = 0.016), and log 24 − h urinary−fractionated MN and NMN (β = 14.641, SE = 5.842, t statistic, 2.506, P = 0.015) were independent factors associated with intraoperative maximum AP (Table 2 ). Table 2 Simple and multiple linear regression analyses to assess the association between intraoperative maximum arterial pressure and preoperative variables in patients with PPGL. Variable Simple linear regression analysis Multiple linear regression analysis* β SE t statistic P value β SE t statistic P value Age (years) −0.111 0.173 −0.643 0.522 BMI (kg/m 2 ) 0.613 0.706 0.868 0.389 Cerebro-cardiovascular events (absent vs. present) −2.724 12.261 −0.222 0.825 Comorbidity of hypertension (absent vs. present) 8.416 5.209 1.616 0.112 Comorbidity of DM (absent vs. present) 17.461 8.612 2.028 0.047 15.835 7.550 2.097 0.040 Classic triad** (absent vs. present) 19.788 5.452 3.629 0.015 14.081 5.668 2.484 0.016 Type of surgery (open vs. laparoscopic) −3.241 7.152 −0.453 0.652 Surgical approach (transperitoneal vs. retroperitoneal) 8.854 8.242 1.074 0.287 Log (tumor size, base = 10) 4.955 12.115 0.409 0.684 Log (24-h urinary-fractionated MN and NMN, base = 10) 22.765 5.404 4.212 < 0.001 14.641 5.842 2.506 0.015 Preoperative systolic blood pressure (mmHg) −0.202 0.175 −1.155 0.253 BMI, body mass index; DM, diabetes mellitus; MN, metanephrines; NMN, normetanephrines; PPGL; pheochromocytoma and paraganglioma. *Backward step-down selection was used. **Palpitation (tachycardia), headache, and episode of sweating. Discussion The present study found that either preoperative systolic or diastolic blood pressure was basically stable when adequate doses of α-receptor blockades had been administered, and neither was correlated with intraoperative maximum AP in patients with PPGL. We also demonstrated that log 24−h urinary−fractionated MN and NMN was correlated with intraoperative maximum AP. In addition, log 24−h urinary−fractionated MN and NMN , DM, and the classic triad were independent factors associated with intraoperative maximum AP. Thus, PPGL patients with these clinical factors might be at risk for hypertensive crises during surgery regardless of preoperative α-receptor blockades. PPGL presents with various life-threatening complications, including cerebro-cardiovascular disease, HTN, and DM. Falhammar et al. showed that HTN and DM were present in 67% and 27% of patients with PPGL, respectively [7]. Although our results showed that the incidence of these comorbidities were lower than reported (45.9% and 9.8%, respectively), in our cohort, tumor size was smaller than that of the cohort of Falhammar et al. (median tumor sizes of 38 mm vs. 49 mm). These results indicated that patients in our cohort were diagnosed relatively early, and detecting the tumor while still small might reduce the prevalence of complications associated with PPGL. PPGL also presents with a wide spectrum of symptoms related to excessive catecholamine secretion. The classic triad, which include p alpitation, h eadaches, and e pisode of sweating (the acronym PHE is reminiscent of pheochromocytoma), is valuable for screening symptoms for PPGL diagnosis. All three symptoms have specificities and sensitivities of more than 90% [8]. However, recent retrospective reports have indicated that only 17–24% of pheochromocytoma cases exhibit all three symptoms [7,9]. In our cohort, the percentage of patients exhibiting all three symptoms of the classic triad was even lower; patients exhibiting at least one of the three symptoms accounted for only 26.2% of cases. This could be because the patients in our cohort were diagnosed with PPGL relatively early, as mentioned earlier. Taken together, the results indicate that the classic triad is unreliable for modern PPGL diagnosis. However, our study revealed that the presence at least one symptom of the classic triad was associated with intraoperative maximum AP. Consequently, the presence or absence of the classic triad should be confirmed to assess the preoperative severity of PPGL, even after it has been diagnosed. In our study, intraoperative maximum AP was a primary outcome and assessed as a continuous variable; we confirmed that it was normally distributed. To examine the association of preoperative continuous variables with intraoperative maximum AP, it was necessary to validate their distributions. Factors that might be related to tumor growth, such as tumor size or 24-h urinary-fractionated metabolism of catecholamines, did not show normal distributions. However, the logarithmic representation of these continuous variables showed normal distributions. Interestingly, the logarithmic representation of tumor markers is important in assessing the progression or stage of particular types of cancer [10, 11, 12]. Twenty-four-hour urinary-fractionated MN or NMN is used for biochemical screening but not disease progression or severity. Therefore, these values are considered important only for functional diagnosis of PPGL and evaluation of how many folds higher they are above the upper limit of normal (the cut-off value suggested by Japanese guidelines is three-fold). However, our results indicated that the 24-h urinary-fractionated metabolism of catecholamines should be evaluated as a logarithmic representation, similar to tumor markers; moreover, the logarithms of these variables were correlated with intraoperative maximum AP. Additionally, it was also indicated that evaluation of the sum of MN and NMN could reflect the severity of hormone secretion more accurately than either value alone. Many experts, as well as Endocrine Society guidelines, continue to recommend preoperative α-receptor blockades to prevent hemodynamic instability and hypertensive crises for all patients with PPGL [5, 13]. In an observational study, Groeben et al. reported that there was no difference in the incidence of excessive hypertensive crises between pheochromocytoma patients who had been administered α-receptor blockades and those who had not [6]. They questioned whether all patients with pheochromocytoma require preoperative α-receptor blockades as prophylaxis. They also proposed that preoperative α-receptor blockades might not be mandatory for patients with low endocrine activity because of minimally invasive surgical techniques and highly effective drugs for intraoperative control of hemodynamic conditions. Unfortunately, we were not able to assess mild cases that might not require preoperative treatment. Meanwhile, our results revealed severe cases that were at risk for intraoperative hypertensive episodes regardless of preoperative α-adrenergic receptor blockers; therefore, patient selection is essential when considering precision preoperative management. We believe that PPGL patients can be divided into at least two categories: moderate and severe cases. Based on the opinion that there are some patients who would not require preoperative α-receptor blockades, mild cases can be added. Thus, there could be three categories. Adequate doses of preoperative α-receptor blockades would be expected to have an effect on moderate cases. However, preoperative α-receptor blockades alone might not be enough in severe cases, which have high levels of log 24−h urinary−fractionated MN and NMN , DM, or the classic triad. In these cases, additional preoperative interventions, such as metyrosine, which is catecholamine synthesis inhibitor, might help to stabilize intraoperative blood pressure. Our results should be interpreted with caution because of several limitations. There were some ascertainment biases, which are inherent limitations of all retrospective observational analyses. Even though this study was not small compared with similar single-center studies, validation with a larger cohort would be required, mainly due to the rarity of PPGL. Also, we could not assess plasma free MN in most cases due to the system of Japanese insurance. Moreover, we were not able to decide the cut-off reference for log 24−h urinary−fractionated MN and NMN . To resolve these limitations, we will need to compare the accuracy of plasma free MN or urinary-fractionated MN for predicting intraoperative maximum AP in a larger cohort through a multi-center study. Conclusion Log 24 − h urinary−fractionated MN and NMN , DM, and the classic triad were independent factors associated with intraoperative maximum AP in patients with PPGL. Patients with these factors might be at risk for hypertensive crises during surgery regardless of preoperative α-receptor blockades. Clinicians should confirm these independent factors before surgery for PPGL and manage these patients more carefully and effectively. Methods Patient selection. The medical records of 66 patients with PPGL who underwent surgical resection at Kansai Medical University Hospital between September 2006 and September 2020 were retrospectively reviewed. Among these, five patients received partial adrenalectomies (adrenal-sparing surgeries) and were excluded from the analysis. Ultimately, the records of 61 patients were analyzed. All patients enrolled were identified as having pheochromocytoma from the pathological specimens. Clinical parameters. The preoperative clinical data (sex, age, BMI, American Society of Anesthesiologists (ASA) score, comorbidity, PPGL-associated classic triad, tumor size, and 24-h urinary-fractionated MN and NMN) were analyzed. Comorbidities included cerebro-cardiovascular events, HTN, and DM. HTN was diagnosed as a systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher without antihypertensive drugs at the time of medical examination. HTN was also defined as patients taking antihypertensive drugs. DM was diagnosed in patients taking DM-related drugs or insulin treatments. The classic triad was diagnosed in patients exhibiting at least one of the following symptoms: palpitations, headache, and episode of sweating. Tumor size was measured with preoperative computed tomography (CT) or magnetic resonance imaging (MRI). These clinical data were obtained from the patients’ medical records. Preoperative management, surgery, and anesthesia. All patients were treated with the maximum dose of doxazosin (16 mg/day) at least 2 weeks before surgery. Patients were admitted to the hospital the day before surgery, and preoperative systolic and diastolic blood pressure was measured at rest during the daytime. Retroperitoneoscopic and laparoscopic surgical techniques have been described in detail [14]. Intraoperatively, the arterial pressure and heart rate were automatically recorded with an arterial line. Intravenous vasodilators, such as sodium nitroprusside, were administered to control undesirable increases in systolic AP. All procedures were performed by experienced surgeons and anesthesiologists at a single institution. Statistical analysis. The primary outcome measure was intraoperative maximum AP for continuous variables. It was defined as the highest blood pressure recorded via the arterial line during surgery, excluding the time of intubation and extubation. All continuous data are shown as median values and IQRs. The normal distribution of the results was confirmed by the Kolmogorov–Smirnov test. The logarithmic representation of continuous variables was calculated with base 10. Simple and multiple linear regression analyses were performed to evaluate the relationship between intraoperative maximum APs and preoperative variables. In linear regression analysis, the t statistic, which was calculated as the ratio of an estimated coefficient (β) to its standard error, was used to test the hypothesis that a coefficient was equal to zero. All statistical analyses were performed using EZR version 1.37 [15]. A two-sided P value < 0.05 was considered statistically significant. Ethics approval. All procedures performed in the present study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the institutional review board of the Kansai Medical University Hospital, Japan (Approval No. 2015607), and informed consent was obtained from all individual patients prior to surgery. Abbreviations AP arterial pressure ASA American Society of Anesthesiologists BMI body mass index CT computed tomography DM diabetes mellitus HTN hypertension IQR interquartile range MN metanephrine MRI magnetic resonance imaging NMN normetanephrine PPGL pheochromocytoma and paraganglioma SE standard error Declarations Data Availability The datasets analysed during the current study are not publicly available but are available from the corresponding author on reasonable request. Author contributions H Ohsugi: project development, data collection, and manuscript writing. N Takizawa: data collection, data management, and manuscript editing. T Matsuda: study supervision. H Kinoshita: manuscript editing and study supervision. Competing interests This research did not receive any specific grants and fellowships from any funding agency in the public, commercial or not-for-profit sector. References 1. Berends AMA, Buitenwerf E, de Krijger RR, et al. Incidence of pheochromocytoma and sympathetic paraganglioma in the Netherlands: A nationwide study and systematic review. Eur J Intern Med. 51 , 68-73 (2018). 2. Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet. 366, 665-675 (2005). 3. Roizen MF, Schreider BD, Hassan SZ. Anesthesia for patients with pheochromocytoma. Anesthesiol Clin North America. 5 , 269–75 (1987). 4. Conzo G, Musella M, Corcione F, et al. Role of preoperative adrenergic blockade with doxazosin on hemodynamic control during the surgical treatment of pheochromocytoma: a retrospective study of 48 cases. Am Surg. 79 , 1196-1202 (2013). 5. Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 99 , 1915-1942 (2014). 6. Groeben H, Nottebaum BJ, Alesina PF, et al. Perioperative α-receptor blockade in phaeochromocytoma surgery: an observational case series. Br J Anaesth. 118 , 182-189 (2017). 7. Falhammar H, Kjellman M, Calissendorff J. Initial clinical presentation and spectrum of pheochromocytoma: a study of 94 cases from a single center. Endocr Connect. 7 , 186-192 (2018). 8. Plouin PF, Degoulet P, Tugayé A, Ducrocq MB, Ménard J. Le dépistage du phéochromocytome: chez quels hypertendus? Etude sémiologique chez 2585 hypertendus dont 11 ayant un phéochromocytome [Screening for phaeochromocytoma: in which hypertensive patients? A semiological study of 2585 patients, including 11 with phaeochromocytoma (author's transl)]. Nouv Presse Med. 10 , 869-872 (1981). 9. Baguet JP, Hammer L, Mazzuco TL, et al. Circumstances of discovery of phaeochromocytoma: a retrospective study of 41 consecutive patients. Eur J Endocrinol. 150 , 681-686 (2004). 10. Laird AK. DYNAMICS OF TUMOR GROWTH. Br J Cancer. 13 , 490-502 (1964). 11. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol. 15 , 594-603 (1997). 12. Stein WD, Figg WD, Dahut W, et al. Tumor growth rates derived from data for patients in a clinical trial correlate strongly with patient survival: a novel strategy for evaluation of clinical trial data. Oncologist. 13 , 1046-1054 (2008). 13. Neumann HPH, Young WF Jr, Eng C. Pheochromocytoma and Paraganglioma. N Engl J Med. 381 , 552-565 (2019). 14. Gagner M, Pomp A, Heniford BT, Pharand D, Lacroix A. Laparoscopic adrenalectomy: lessons learned from 100 consecutive procedures. Ann Surg. 226 , 238-246 (1997). 15. Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant. 48 , 452-458 (2013). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-894894","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":52176031,"identity":"7b540b16-e437-49c1-928e-ab29e8a7ecdd","order_by":0,"name":"Haruyuki Ohsugi","email":"","orcid":"","institution":"Kansai Medical University","correspondingAuthor":false,"prefix":"","firstName":"Haruyuki","middleName":"","lastName":"Ohsugi","suffix":""},{"id":52176033,"identity":"073025ae-30f2-4c9a-8f0a-9ed399738e97","order_by":1,"name":"Nae Takizawa","email":"","orcid":"","institution":"Kansai Medical University","correspondingAuthor":false,"prefix":"","firstName":"Nae","middleName":"","lastName":"Takizawa","suffix":""},{"id":52176034,"identity":"ed4c9a64-eadc-4831-8817-c362e1a63182","order_by":2,"name":"Tadashi Matsuda","email":"","orcid":"","institution":"Kansai Medical University","correspondingAuthor":false,"prefix":"","firstName":"Tadashi","middleName":"","lastName":"Matsuda","suffix":""},{"id":52176040,"identity":"1a644348-4c53-493c-ab6c-e87fb6e36403","order_by":3,"name":"Hidefumi Kinoshita","email":"data:image/png;base64,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","orcid":"","institution":"Kansai Medical University","correspondingAuthor":true,"prefix":"","firstName":"Hidefumi","middleName":"","lastName":"Kinoshita","suffix":""}],"badges":[],"createdAt":"2021-09-11 02:29:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-894894/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-894894/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":13720811,"identity":"b91100b7-267c-48bf-8936-f281adb08fc7","added_by":"auto","created_at":"2021-09-17 16:46:51","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":132897,"visible":true,"origin":"","legend":"The P values of continuous variables regarding blood pressure were above 0.05, and the continuous variables were confirmed to be normally distributed by the Kolmogorov–Smirnov test.\n(A) Intraoperative maximum arterial pressure. (B) Preoperative systolic blood pressure. (C) Preoperative diastolic blood pressure.\n","description":"","filename":"OhsugiFig.1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-894894/v1/43a8742dd92fa8c548ca706f.jpg"},{"id":13720599,"identity":"67475c81-2fbe-4a3b-a95d-48a897c512be","added_by":"auto","created_at":"2021-09-17 16:43:52","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":196828,"visible":true,"origin":"","legend":"Correlation analysis between intraoperative maximum arterial pressure and preoperative systolic blood pressure (A) or preoperative diastolic blood pressure (B). *R indicates the correlation coefficient index.","description":"","filename":"OhsugiFig.2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-894894/v1/64b16152ad5e78670598eae6.jpg"},{"id":13720598,"identity":"1080f058-74af-48fb-947d-fa0efbf97f30","added_by":"auto","created_at":"2021-09-17 16:43:51","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":161619,"visible":true,"origin":"","legend":"The P values of continuous preoperative variables were above 0.05, and the continuous variables were confirmed to be normally distributed by the Kolmogorov–Smirnov test.\n(A) BMI. (B) Age. (C) Logtumor size. (D) Log24-h urinary-fractionated MN. (E) Log24-h urinary-fractionated NMN. (F) Log24-h urinary-fractionated MN+NMN. BMI, body mass index. MN, metanephrine. NMN, normetanephrine.\n","description":"","filename":"OhsugiFig.3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-894894/v1/02da35600a0915be08f1a2a4.jpg"},{"id":13720596,"identity":"f4cd99d2-d767-4edf-89a0-d4d12cfda24f","added_by":"auto","created_at":"2021-09-17 16:43:51","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":71357,"visible":true,"origin":"","legend":"Correlation analysis between intraoperative maximum arterial pressure and log24-h urinary-fractionated MN+NMN. *R indicates the correlation coefficient index.","description":"","filename":"OhsugiFig.4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-894894/v1/6197df9793f2cb43382b2a62.jpg"},{"id":14745178,"identity":"d03195c5-7a88-41a5-8d4c-97d8aeb0825b","added_by":"auto","created_at":"2021-10-21 08:59:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":573711,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-894894/v1/9d8b8d45-add2-43d0-8777-0146c0557935.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Preoperative factors associated with intraoperative maximum arterial pressures in patients with pheochromocytoma and paraganglioma: a single-center retrospective study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePheochromocytomas are catecholamine-secreting neoplasms arising from chromaffin cells of the adrenal medulla, and paraganglioma are defined as tumors arising from extra-adrenal chromaffin tissue. These catecholamine-secreting neoplasms are rare, and the incidence of pheochromocytoma and paraganglioma (PPGL) is about 0.6 cases per 100,000 person-years [1]. Excessive catecholamine secretion causes various symptoms, including hypertension (HTN) and the classic triad of palpitation (tachycardia), headache, and sweating [2]. It also presents comorbidities of diabetes mellitus (DM) or cardiovascular events.\u003c/p\u003e \u003cp\u003eComplete surgical resection is the definitive treatment for PPGL. However, unavoidable intraoperative manipulation of the tumor can cause catecholamine release and hypertensive crises. Therefore, surgery for PPGL has long been considered a challenging procedure [3]. In the 21st century, the mortality associated with surgery for PPGL has dramatically decreased to a rate of 0\u0026ndash;3.0%, which has resulted from improvements in treatment, such as surgical techniques, preoperative management including α-receptor blockades, and anesthesia [2]. Regardless of these clinical efforts, surgery for PPGL can lead to intraoperative hypertensive crises, which cause life-threatening complications [4].\u003c/p\u003e \u003cp\u003e Although the guidelines issued by the Endocrine Society recommend preoperative α-receptor blockades as a prophylactic for all patients [5], a recent observational study showed that there was only a slight difference in maximum arterial pressure (AP) between patients who had been administered α-receptor blockades and those who had not [6]. These results are important because not only might there be asymptomatic patients who do not need preoperative α-receptor blockades but also severe patients who experience intraoperative hypertensive episodes despite adequate doses of preoperative α-receptor blockades.\u003c/p\u003e \u003cp\u003eIn the current study, we retrospectively reviewed the clinical and operative records of patients with PPGL. Using this data set, we identified preoperative factors associated with intraoperative maximum arterial pressure (AP) in patients with PPGL who received adequate doses of preoperative α-receptor blockades.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eThe clinical and tumor characteristics of the PPGL patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median intraoperative maximum AP was 165 mmHg (interquartile ranges [IQR] : 150\u0026ndash;180 mmHg). Of 61 patients, 18 (29.5%) had hypertensive episodes with intraoperative maximum APs above 180 mmHg. Preoperative hypertension and DM were shown in 28 (45.9%) and 9 (9.8%) patients, respectively. There were 16 (26.2%) patients exhibiting one or more of the classic triad. No postoperative complications greater than Grade 3 by the Clavien\u0026ndash;Dindo classification were observed.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical and tumor characteristics in patients with PPGL.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;61\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.0 (44.0\u0026thinsp;\u0026minus;\u0026thinsp;65.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (52.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (47.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.4 (19.7\u0026thinsp;\u0026minus;\u0026thinsp;24.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (96.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebro-cardiovascular events, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (95.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (4.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (54.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (45.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (90.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (9.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClassic\u0026nbsp;triad*, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent (none of the symptoms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (73.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent (at least one of symptom)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (26.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHereditary, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (88.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMEN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (8.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVHL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSDH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePheochromocytoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (85.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParaganglioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (14.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of surgery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaparoscopic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (83.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (16.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical approach, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransperitoneal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (88.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetroperitoneal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (11.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size, mm (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.0 (28.0\u0026thinsp;\u0026minus;\u0026thinsp;52.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary-fractionated MN in 24-h urine, mg/day (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.32 (0.14\u0026thinsp;\u0026minus;\u0026thinsp;0.97)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary-fractionated NMN in 24-h urine, mg/day (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.40 (0.65\u0026thinsp;\u0026minus;\u0026thinsp;3.60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative systolic blood pressure, mmHg (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e120 (112\u0026thinsp;\u0026minus;\u0026thinsp;130)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative diastolic blood pressure, mmHg (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (67\u0026thinsp;\u0026minus;\u0026thinsp;81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative maximum arterial pressure, mmHg (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e165 (150\u0026thinsp;\u0026minus;\u0026thinsp;180)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAbbreviations: ASA, American Society of Anesthesiologists; BMI, body mass index; IQR, interquartile range; MEN, multiple endocrine neoplasia; MN, metanephrines; NMN, normetanephrines; PPGL; pheochromocytoma and paraganglioma; SDH, succinate dehydrogense; VHL, von Hipple\u0026ndash;Lindau.\u003c/p\u003e \u003cp\u003e*Palpitation (tachycardia), headache, and episode of sweating.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eRelationship between preoperative blood pressure and intraoperative maximum AP\u003c/h2\u003e \u003cp\u003eIntraoperative maximum AP showed a normal distribution (P\u0026thinsp;=\u0026thinsp;0.618; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Preoperative systolic blood pressure and diastolic blood pressure also showed normal distributions (P\u0026thinsp;=\u0026thinsp;0.836 and P\u0026thinsp;=\u0026thinsp;0.603, respectively; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Neither preoperative systolic blood pressure nor diastolic blood pressure was correlated with intraoperative maximum AP (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eNormal distributivity of preoperative continuous variables\u003c/h2\u003e \u003cp\u003eAmong the continuous variables of preoperative clinical factors, age, and body mass index (BMI) showed normal distributions (P\u0026thinsp;=\u0026thinsp;0.976 and 0.332, respectively; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). However, tumor size, the 24-h urinary-fractionated metanephrine (MN), and the 24-h urinary-fractionated normetanephrine (NMN) were not normally distributed (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.01; S. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB, and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). The logarithmic representation (log\u003csub\u003e10\u003c/sub\u003e) of these three continuous variables showed a normal distribution (P\u0026thinsp;=\u0026thinsp;0.201\u0026ndash;0.715; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD, and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eE). Similarly, the 24-h urinary-fractionated MN and NMN was not normally distributed, but the logarithmic representation of this continuous variable also showed a normal distribution (P\u0026thinsp;=\u0026thinsp;0.549; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eF).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eCorrelations between intraoperative maximum APs and preoperative variables\u003c/h2\u003e \u003cp\u003eLog\u003csub\u003e24\u0026thinsp;\u0026minus;\u0026thinsp;h urinary\u0026minus;fractionated MN and NMN\u003c/sub\u003e was correlated with intraoperative maximum AP (R\u0026thinsp;=\u0026thinsp;0.481, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The correlation coefficient index was higher than each of log\u003csub\u003e24\u0026thinsp;\u0026minus;\u0026thinsp;h urinary\u0026minus;fractionated MN\u003c/sub\u003e and log\u003csub\u003e24\u0026thinsp;\u0026minus;\u0026thinsp;h urinary\u0026minus;fractionated NMN\u003c/sub\u003e (R\u0026thinsp;=\u0026thinsp;0.204 and R\u0026thinsp;=\u0026thinsp;0.412, respectively). Next, preoperative variables were investigated by linear regression analyses. Simple linear regression analyses showed that comorbidities of DM, the classic triad, and log\u003csub\u003e24\u0026thinsp;\u0026minus;\u0026thinsp;h urinary\u0026minus;fractionated MN and NMN\u003c/sub\u003e were significantly associated with intraoperative maximum AP (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Log\u003csub\u003e24\u0026thinsp;\u0026minus;\u0026thinsp;h urinary\u0026minus;fractionated MN and NMN\u003c/sub\u003e showed the highest \u003cem\u003et\u003c/em\u003e statistic among the preoperative variables (\u003cem\u003et\u003c/em\u003e statistic, 4.212). Then, multiple regression analyses showed that DM (β\u0026thinsp;=\u0026thinsp;15.835, standard error [SE]\u0026thinsp;=\u0026thinsp;7.550, \u003cem\u003et\u003c/em\u003e statistic\u0026thinsp;=\u0026thinsp;2.097, P\u0026thinsp;=\u0026thinsp;0.040), the classic triad (β\u0026thinsp;=\u0026thinsp;14.081, SE\u0026thinsp;=\u0026thinsp;5.668, \u003cem\u003et\u003c/em\u003e statistic\u0026thinsp;=\u0026thinsp;2.484, P\u0026thinsp;=\u0026thinsp;0.016), and log\u003csub\u003e24\u0026thinsp;\u0026minus;\u0026thinsp;h urinary\u0026minus;fractionated MN and NMN\u003c/sub\u003e (β\u0026thinsp;=\u0026thinsp;14.641, SE\u0026thinsp;=\u0026thinsp;5.842, \u003cem\u003et\u003c/em\u003e statistic, 2.506, P\u0026thinsp;=\u0026thinsp;0.015) were independent factors associated with intraoperative maximum AP (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSimple and multiple linear regression analyses to assess the association between intraoperative maximum arterial pressure and preoperative variables in patients with PPGL.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eSimple linear regression analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c11\" namest=\"c7\"\u003e \u003cp\u003eMultiple linear regression analysis*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003et\u003c/em\u003e statistic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003et\u003c/em\u003e statistic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;0.111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.173\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;0.643\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.522\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.613\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.706\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.868\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.389\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebro-cardiovascular events (absent vs. present)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;2.724\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.261\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;0.222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.825\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidity of hypertension (absent vs. present)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.416\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.616\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidity of DM (absent vs. present)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.461\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.612\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15.835\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.550\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.097\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClassic triad** (absent vs. present)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.788\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.452\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.629\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14.081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.668\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.484\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of surgery (open vs. laparoscopic)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;3.241\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;0.453\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.652\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical approach (transperitoneal vs. retroperitoneal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.242\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.074\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.287\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLog (tumor size, base\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.955\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.409\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.684\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLog (24-h urinary-fractionated MN and NMN, base\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.765\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.404\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14.641\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.842\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.506\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative systolic blood pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026minus;0.202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;1.155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.253\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eBMI, body mass index; DM, diabetes mellitus; MN, metanephrines; NMN, normetanephrines; PPGL; pheochromocytoma and paraganglioma.\u003c/p\u003e \u003cp\u003e*Backward step-down selection was used.\u003c/p\u003e \u003cp\u003e**Palpitation (tachycardia), headache, and episode of sweating.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study found that either preoperative systolic or diastolic blood pressure was basically stable when adequate doses of α-receptor blockades had been administered, and neither was correlated with intraoperative maximum AP in patients with PPGL. We also demonstrated that log \u003csub\u003e24\u0026minus;h urinary\u0026minus;fractionated MN and NMN\u003c/sub\u003e was correlated with intraoperative maximum AP. In addition, log \u003csub\u003e24\u0026minus;h urinary\u0026minus;fractionated MN and NMN\u003c/sub\u003e, DM, and the classic triad were independent factors associated with intraoperative maximum AP. Thus, PPGL patients with these clinical factors might be at risk for hypertensive crises during surgery regardless of preoperative α-receptor blockades.\u003c/p\u003e \u003cp\u003ePPGL presents with various life-threatening complications, including cerebro-cardiovascular disease, HTN, and DM. Falhammar et al. showed that HTN and DM were present in 67% and 27% of patients with PPGL, respectively [7]. Although our results showed that the incidence of these comorbidities were lower than reported (45.9% and 9.8%, respectively), in our cohort, tumor size was smaller than that of the cohort of Falhammar et al. (median tumor sizes of 38 mm vs. 49 mm). These results indicated that patients in our cohort were diagnosed relatively early, and detecting the tumor while still small might reduce the prevalence of complications associated with PPGL.\u003c/p\u003e \u003cp\u003ePPGL also presents with a wide spectrum of symptoms related to excessive catecholamine secretion. The classic triad, which include \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ep\u003c/span\u003ealpitation, \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eh\u003c/span\u003eeadaches, and \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ee\u003c/span\u003episode of sweating (the acronym PHE is reminiscent of pheochromocytoma), is valuable for screening symptoms for PPGL diagnosis. All three symptoms have specificities and sensitivities of more than 90% [8]. However, recent retrospective reports have indicated that only 17\u0026ndash;24% of pheochromocytoma cases exhibit all three symptoms [7,9]. In our cohort, the percentage of patients exhibiting all three symptoms of the classic triad was even lower; patients exhibiting at least one of the three symptoms accounted for only 26.2% of cases. This could be because the patients in our cohort were diagnosed with PPGL relatively early, as mentioned earlier. Taken together, the results indicate that the classic triad is unreliable for modern PPGL diagnosis. However, our study revealed that the presence at least one symptom of the classic triad was associated with intraoperative maximum AP. Consequently, the presence or absence of the classic triad should be confirmed to assess the preoperative severity of PPGL, even after it has been diagnosed.\u003c/p\u003e \u003cp\u003eIn our study, intraoperative maximum AP was a primary outcome and assessed as a continuous variable; we confirmed that it was normally distributed. To examine the association of preoperative continuous variables with intraoperative maximum AP, it was necessary to validate their distributions. Factors that might be related to tumor growth, such as tumor size or 24-h urinary-fractionated metabolism of catecholamines, did not show normal distributions. However, the logarithmic representation of these continuous variables showed normal distributions. Interestingly, the logarithmic representation of tumor markers is important in assessing the progression or stage of particular types of cancer [10, 11, 12]. Twenty-four-hour urinary-fractionated MN or NMN is used for biochemical screening but not disease progression or severity. Therefore, these values are considered important only for functional diagnosis of PPGL and evaluation of how many folds higher they are above the upper limit of normal (the cut-off value suggested by Japanese guidelines is three-fold). However, our results indicated that the 24-h urinary-fractionated metabolism of catecholamines should be evaluated as a logarithmic representation, similar to tumor markers; moreover, the logarithms of these variables were correlated with intraoperative maximum AP. Additionally, it was also indicated that evaluation of the sum of MN and NMN could reflect the severity of hormone secretion more accurately than either value alone.\u003c/p\u003e \u003cp\u003e Many experts, as well as Endocrine Society guidelines, continue to recommend preoperative α-receptor blockades to prevent hemodynamic instability and hypertensive crises for all patients with PPGL [5, 13]. In an observational study, Groeben et al. reported that there was no difference in the incidence of excessive hypertensive crises between pheochromocytoma patients who had been administered α-receptor blockades and those who had not [6]. They questioned whether all patients with pheochromocytoma require preoperative α-receptor blockades as prophylaxis. They also proposed that preoperative α-receptor blockades might not be mandatory for patients with low endocrine activity because of minimally invasive surgical techniques and highly effective drugs for intraoperative control of hemodynamic conditions. Unfortunately, we were not able to assess mild cases that might not require preoperative treatment. Meanwhile, our results revealed severe cases that were at risk for intraoperative hypertensive episodes regardless of preoperative α-adrenergic receptor blockers; therefore, patient selection is essential when considering precision preoperative management. We believe that PPGL patients can be divided into at least two categories: moderate and severe cases. Based on the opinion that there are some patients who would not require preoperative α-receptor blockades, mild cases can be added. Thus, there could be three categories. Adequate doses of preoperative α-receptor blockades would be expected to have an effect on moderate cases. However, preoperative α-receptor blockades alone might not be enough in severe cases, which have high levels of log \u003csub\u003e24\u0026minus;h urinary\u0026minus;fractionated MN and NMN\u003c/sub\u003e, DM, or the classic triad. In these cases, additional preoperative interventions, such as metyrosine, which is catecholamine synthesis inhibitor, might help to stabilize intraoperative blood pressure.\u003c/p\u003e \u003cp\u003eOur results should be interpreted with caution because of several limitations. There were some ascertainment biases, which are inherent limitations of all retrospective observational analyses. Even though this study was not small compared with similar single-center studies, validation with a larger cohort would be required, mainly due to the rarity of PPGL. Also, we could not assess plasma free MN in most cases due to the system of Japanese insurance. Moreover, we were not able to decide the cut-off reference for log \u003csub\u003e24\u0026minus;h urinary\u0026minus;fractionated MN and NMN\u003c/sub\u003e. To resolve these limitations, we will need to compare the accuracy of plasma free MN or urinary-fractionated MN for predicting intraoperative maximum AP in a larger cohort through a multi-center study.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eLog\u003csub\u003e24\u0026thinsp;\u0026minus;\u0026thinsp;h urinary\u0026minus;fractionated MN and NMN\u003c/sub\u003e, DM, and the classic triad were independent factors associated with intraoperative maximum AP in patients with PPGL. Patients with these factors might be at risk for hypertensive crises during surgery regardless of preoperative α-receptor blockades. Clinicians should confirm these independent factors before surgery for PPGL and manage these patients more carefully and effectively.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ePatient selection.\u003c/span\u003e The medical records of 66 patients with PPGL who underwent surgical resection at Kansai Medical University Hospital between September 2006 and September 2020 were retrospectively reviewed. Among these, five patients received partial adrenalectomies (adrenal-sparing surgeries) and were excluded from the analysis. Ultimately, the records of 61 patients were analyzed. All patients enrolled were identified as having pheochromocytoma from the pathological specimens.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eClinical parameters.\u003c/span\u003e The preoperative clinical data (sex, age, BMI, American Society of Anesthesiologists (ASA) score, comorbidity, PPGL-associated classic triad, tumor size, and 24-h urinary-fractionated MN and NMN) were analyzed. Comorbidities included cerebro-cardiovascular events, HTN, and DM. HTN was diagnosed as a systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher without antihypertensive drugs at the time of medical examination. HTN was also defined as patients taking antihypertensive drugs. DM was diagnosed in patients taking DM-related drugs or insulin treatments. The classic triad was diagnosed in patients exhibiting at least one of the following symptoms: palpitations, headache, and episode of sweating. Tumor size was measured with preoperative computed tomography (CT) or magnetic resonance imaging (MRI). These clinical data were obtained from the patients\u0026rsquo; medical records.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ePreoperative management, surgery, and anesthesia.\u003c/span\u003e All patients were treated with the maximum dose of doxazosin (16 mg/day) at least 2 weeks before surgery. Patients were admitted to the hospital the day before surgery, and preoperative systolic and diastolic blood pressure was measured at rest during the daytime. Retroperitoneoscopic and laparoscopic surgical techniques have been described in detail [14]. Intraoperatively, the arterial pressure and heart rate were automatically recorded with an arterial line. Intravenous vasodilators, such as sodium nitroprusside, were administered to control undesirable increases in systolic AP. All procedures were performed by experienced surgeons and anesthesiologists at a single institution.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eStatistical analysis.\u003c/span\u003e The primary outcome measure was intraoperative maximum AP for continuous variables. It was defined as the highest blood pressure recorded via the arterial line during surgery, excluding the time of intubation and extubation. All continuous data are shown as median values and IQRs. The normal distribution of the results was confirmed by the Kolmogorov\u0026ndash;Smirnov test. The logarithmic representation of continuous variables was calculated with base 10. Simple and multiple linear regression analyses were performed to evaluate the relationship between intraoperative maximum APs and preoperative variables. In linear regression analysis, the \u003cem\u003et\u003c/em\u003e statistic, which was calculated as the ratio of an estimated coefficient (β) to its standard error, was used to test the hypothesis that a coefficient was equal to zero. All statistical analyses were performed using EZR version 1.37 [15]. A two-sided P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics approval.\u003c/strong\u003e \u003cp\u003e All procedures performed in the present study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the institutional review board of the Kansai Medical University Hospital, Japan (Approval No. 2015607), and informed consent was obtained from all individual patients prior to surgery.\u003c/p\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAP arterial pressure\u003c/p\u003e\n\u003cp\u003eASA American Society of Anesthesiologists\u003c/p\u003e\n\u003cp\u003eBMI body mass index\u003c/p\u003e\n\u003cp\u003eCT computed tomography\u003c/p\u003e\n\u003cp\u003eDM diabetes mellitus\u003c/p\u003e\n\u003cp\u003eHTN hypertension\u003c/p\u003e\n\u003cp\u003eIQR\u0026nbsp;interquartile range\u003c/p\u003e\n\u003cp\u003eMN metanephrine\u003c/p\u003e\n\u003cp\u003eMRI magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eNMN normetanephrine\u003c/p\u003e\n\u003cp\u003ePPGL pheochromocytoma and paraganglioma\u003c/p\u003e\n\u003cp\u003eSE standard error\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eH Ohsugi: project development, data collection, and manuscript writing. N Takizawa: data collection, data management, and manuscript editing. T Matsuda: study supervision. H Kinoshita: manuscript editing and study supervision.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grants and fellowships from any funding agency in the public, commercial or not-for-profit sector.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1. Berends AMA, Buitenwerf E, de Krijger RR, et al. Incidence of pheochromocytoma and sympathetic paraganglioma in the Netherlands: A nationwide study and systematic review. \u003cem\u003eEur J Intern Med.\u003c/em\u003e \u003cstrong\u003e51\u003c/strong\u003e, 68-73 (2018).\u003c/p\u003e\n\u003cp\u003e2. Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. \u003cem\u003eLancet.\u003c/em\u003e \u003cstrong\u003e366,\u0026nbsp;\u003c/strong\u003e665-675 (2005).\u003c/p\u003e\n\u003cp\u003e3. Roizen MF, Schreider BD, Hassan SZ. Anesthesia for patients with pheochromocytoma. \u003cem\u003eAnesthesiol Clin North America.\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e5\u003c/strong\u003e, 269\u0026ndash;75 (1987).\u003c/p\u003e\n\u003cp\u003e4. Conzo G, Musella M, Corcione F, et al. Role of preoperative adrenergic blockade with doxazosin on hemodynamic control during the surgical treatment of pheochromocytoma: a retrospective study of 48 cases. \u003cem\u003eAm Surg.\u003c/em\u003e \u003cstrong\u003e79\u003c/strong\u003e, 1196-1202 (2013).\u003c/p\u003e\n\u003cp\u003e5. Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. \u003cem\u003eJ Clin Endocrinol Metab.\u003c/em\u003e \u003cstrong\u003e99\u003c/strong\u003e, 1915-1942 (2014).\u003c/p\u003e\n\u003cp\u003e6. Groeben H, Nottebaum BJ, Alesina PF, et al. Perioperative \u0026alpha;-receptor blockade in phaeochromocytoma surgery: an observational case series. \u003cem\u003eBr J Anaesth.\u003c/em\u003e \u003cstrong\u003e118\u003c/strong\u003e, 182-189 (2017).\u003c/p\u003e\n\u003cp\u003e7. Falhammar H, Kjellman M, Calissendorff J. Initial clinical presentation and spectrum of pheochromocytoma: a study of 94 cases from a single center. \u003cem\u003eEndocr Connect.\u003c/em\u003e \u003cstrong\u003e7\u003c/strong\u003e, 186-192 (2018).\u003c/p\u003e\n\u003cp\u003e8. Plouin PF, Degoulet P, Tugay\u0026eacute; A, Ducrocq MB, M\u0026eacute;nard J. Le d\u0026eacute;pistage du ph\u0026eacute;ochromocytome: chez quels hypertendus? Etude s\u0026eacute;miologique chez 2585 hypertendus dont 11 ayant un ph\u0026eacute;ochromocytome [Screening for phaeochromocytoma: in which hypertensive patients? A semiological study of 2585 patients, including 11 with phaeochromocytoma (author\u0026apos;s transl)]. \u003cem\u003eNouv Presse Med.\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 869-872 (1981).\u003c/p\u003e\n\u003cp\u003e9. Baguet JP, Hammer L, Mazzuco TL, et al. Circumstances of discovery of phaeochromocytoma: a retrospective study of 41 consecutive patients. \u003cem\u003eEur J Endocrinol.\u003c/em\u003e \u003cstrong\u003e150\u003c/strong\u003e, 681-686 (2004).\u003c/p\u003e\n\u003cp\u003e10. Laird AK. DYNAMICS OF TUMOR GROWTH. \u003cem\u003eBr J Cancer.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 490-502 (1964).\u003c/p\u003e\n\u003cp\u003e11. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. \u003cem\u003eJ Clin Oncol.\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, 594-603 (1997).\u003c/p\u003e\n\u003cp\u003e12. Stein WD, Figg WD, Dahut W, et al. Tumor growth rates derived from data for patients in a clinical trial correlate strongly with patient survival: a novel strategy for evaluation of clinical trial data. \u003cem\u003eOncologist.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 1046-1054 (2008).\u003c/p\u003e\n\u003cp\u003e13. Neumann HPH, Young WF Jr, Eng C. Pheochromocytoma and Paraganglioma. \u003cem\u003eN Engl J Med.\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e381\u003c/strong\u003e, 552-565 (2019).\u003c/p\u003e\n\u003cp\u003e14. Gagner M, Pomp A, Heniford BT, Pharand D, Lacroix A. Laparoscopic adrenalectomy: lessons learned from 100 consecutive procedures. \u003cem\u003eAnn Surg.\u0026nbsp;\u003c/em\u003e\u003cstrong\u003e226\u003c/strong\u003e, 238-246 (1997).\u003c/p\u003e\n\u003cp\u003e15. Kanda Y. Investigation of the freely available easy-to-use software \u0026apos;EZR\u0026apos; for medical statistics. \u003cem\u003eBone Marrow Transplant.\u003c/em\u003e \u003cstrong\u003e48\u003c/strong\u003e, 452-458 (2013).\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"PPGL, arterial pressure (AP), metanephrine (MN), normetanephrine (NMN)","lastPublishedDoi":"10.21203/rs.3.rs-894894/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-894894/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSurgery for pheochromocytoma and paraganglioma (PPGL) can lead to life-threatening complications, such as intraoperative hypertensive crises, even when adequate doses of preoperative α-receptor blockades are administered. The aim of this study was to identify preoperative factors associated with maximum arterial pressure (AP) during surgery in patients with PPGL. We retrospectively reviewed the cases of 61 PPGL patients who underwent surgical resection in our hospital between 2006 and 2020. The primary outcome was intraoperative maximum AP as a single index for continuous variables. The normal distribution of the results was confirmed by the Kolmogorov\u0026ndash;Smirnov test. Simple and multiple linear regression model were used for statistical analysis. The median maximum systolic AP during surgery was 165 mmHg (interquartile range: 150\u0026ndash;180 mmHg). Although the 24-h urinary-fractionated metanephrine (MN) and normetanephrine (NMN) (mg/day) was not normally distributed, the logarithmic representation (base\u0026thinsp;=\u0026thinsp;10) of the combination of these continuous variables showed a normal distribution (p\u0026thinsp;=\u0026thinsp;0.549). Log\u003csub\u003e24\u0026thinsp;\u0026minus;\u0026thinsp;h urinary\u0026minus;fractionated MN and NMN\u003c/sub\u003e was correlated with intraoperative maximum AP (R\u0026thinsp;=\u0026thinsp;0.481, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Multiple regression analyses showed that diabetes mellitus (β\u0026thinsp;=\u0026thinsp;15.835, standard error [SE]\u0026thinsp;=\u0026thinsp;7.550, \u003cem\u003et\u003c/em\u003e statistic\u0026thinsp;=\u0026thinsp;2.097, P\u0026thinsp;=\u0026thinsp;0.040), the classic triad (β\u0026thinsp;=\u0026thinsp;14.081, SE\u0026thinsp;=\u0026thinsp;5.668, \u003cem\u003et\u003c/em\u003e statistic\u0026thinsp;=\u0026thinsp;2.484, P\u0026thinsp;=\u0026thinsp;0.016), and log\u003csub\u003e24\u0026thinsp;\u0026minus;\u0026thinsp;h urinary\u0026minus;fractionated MN and NMN\u003c/sub\u003e (β\u0026thinsp;=\u0026thinsp;14.641, SE\u0026thinsp;=\u0026thinsp;5.842, \u003cem\u003et\u003c/em\u003e statistic\u0026thinsp;=\u0026thinsp;2.506, P\u0026thinsp;=\u0026thinsp;0.015) were independent factors associated with intraoperative maximum AP. Patients with PPGL accompanied by diabetes mellitus, the classic triad, and high log \u003csub\u003e24\u0026minus;h urinary\u0026minus;fractionated MN and NMN\u003c/sub\u003e values may be at risk for hypertensive crises during surgery regardless of whether preoperative α-receptor blockades are used. Clinicians should manage these patients more carefully and effectively.\u003c/p\u003e","manuscriptTitle":"Preoperative factors associated with intraoperative maximum arterial pressures in patients with pheochromocytoma and paraganglioma: a single-center retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-09-17 16:43:49","doi":"10.21203/rs.3.rs-894894/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"524fd2ea-aed8-424d-95e1-7658fc9c9e25","owner":[],"postedDate":"September 17th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":7252743,"name":"Urology \u0026 Nephrology"}],"tags":[],"updatedAt":"2021-10-21T08:59:17+00:00","versionOfRecord":[],"versionCreatedAt":"2021-09-17 16:43:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-894894","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-894894","identity":"rs-894894","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}