Preoperative risk factors for hemodynamic instability ...

DR MINCHUN

JIANG (Orcid ID : 0000-0002-6726-7266)

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Article type

: 15 Original Article - Asia (rest of)

Title page

Title: Preoperative risk factors for hemodynamic instability during pheochromocytoma surgery in Chinese patients

Running title: Risk factors for hemodynamic instability

Authors: Minchun Jiang*, Huanyu Ding+, Ying Liang*, Juying Tang*, Ying Lin*, Kexu Xiang*, Ying Guo*, Shaoling Zhang*

Additional authorship options: Minchun Jiang and Huanyu Ding should be considered joint first author.

Affiliations: * Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University and +Department of Cardiology, Vascular Center, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/cen.13544 This article is protected by copyright. All rights reserved.

Correspondence: Ying Guo, Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun

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Yat-sen University, 107 Yanjiang West Road, Guangzhou, People's Republic of China. Tel: 86-20-81332286; E-mail: [email protected]

Acknowledgments: None.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or nonprofit sector.

Conflict of Interest Statement: The authors have no conflict of interest or financial statements to disclose.

Summary

Objective: Pheochromocytoma surgery carries a high risk of hemodynamic instability (HI). However, there are few studies investigating the risk factors of HI for pheochromocytoma surgery in a Chinese population. Therefore, our objective was to identify preoperative risk factors for HI during surgery in a Chinese population with pheochromocytoma.

Patients and methods: In this retrospective study, 134 patients undergoing surgery for pheochromocytoma at a single university-affiliated hospital between November 2002 and July 2017 were enrolled. Demographics, comorbidities, preoperative medical preparation, operation details and perioperative hemodynamics of these patients were retrospectively collected and analyzed.

This article is protected by copyright. All rights reserved.

Multivariable logistic regression analysis was performed to identify the preoperative risk factors of

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intraoperative HI.

Results: 32.8% (44/134) patients suffered from intraoperative HI. According to the result of multivariate analysis, tumor diameter >50 mm (odds ratio [OR] 2.526; 95% confidence interval [CI] 1.163–5.485; P = 0.019), diabetes / prediabetes (OR 2.251; 95% CI 1.039–4.876; P = 0.040), and preoperative systolic blood pressure fluctuation >50 mmHg (OR 3.163; 95% CI 1.051–9.522, P = 0.041) were independent predictors for intraoperative HI. The observed incidence of HI was 8.9%, 42.6%, 47.8 % and 60% when zero, one, two or three risk factors were present, respectively.

Conclusions: HI is common among Chinese patients undergoing surgery for pheochromocytoma. Our study identified three predictive factors for intraoperative HI: a large tumor diameter, diabetes / prediabetes and a great preoperative systolic blood pressure fluctuation. Furthermore, patients are more likely to suffer from HI when they have more predictive risk factors. Identification of these risk factors can help to improve perioperative management.

Keywords: pheochromocytoma; hemodynamics; risk factors; blood pressure fluctuation

Introduction Pheochromocytoma is rare neuroendocrine tumor that originates from chromaffin cells of the adrenal medulla. Pheochromocytoma synthesizes and secretes large amounts of catecholamines, such as norepinephrine, epinephrine, and dopamine, causing a series of clinical symptoms such as


elevated blood pressure, palpitation, headache, as well as heart, brain, kidney and other organ

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complications.

The main treatment strategy for pheochromocytoma is surgery.1 However, surgery carries a

high risk of evoking a massive release of catecholamines into circulation during the pheochromocytoma resection.2 Hemodynamic instability (HI) may occur during surgery for pheochromocytoma, resulting in life-threatening complications. According to current guidelines, patients with pheochromocytoma should undergo preoperative medical treatment consisting of αand β-adrenergic blockades to prevent perioperative cardiovascular complications.1

It was reported that historically the mortality associated with the resection of

pheochromocytoma was as high as 50%.3 Inspiringly, widespread application of preoperative medical management has significantly reduced the operative mortality rate to 0–2.9%.4 Nevertheless, HI during operations is still common.5 Determinants of hemodynamic stability in this clinical situation remain unclear. Previous studies revealed some risk factors that may be associated with this issue including: tumor size, preoperative blood pressure, surgical approach and catecholamine levels.6-8 However, some results from previous studies are conflicting, which still requires further exploration. Specifically, there are few studies in the literature investigating risk factors among Chinese patients with pheochromocytoma.7 Therefore the aim of this study is to identify the preoperative risk factors of HI during surgery for pheochromocytoma in Chinese patients with a relatively large sample size.


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Methods

Patients

We reviewed the medical records of 203 consecutive patients who underwent surgical resection for pheochromocytoma at a single university-affiliated hospital (Sun Yat-sen Memorial Hospital, Sun Yat-sen University) between November 2002 and July 2017. Retrospective data on demographics, coexisting medical conditions, preoperative medical preparation, operation details, perioperative hemodynamics and postoperative complications were collected and analyzed after obtaining informed consent by participants. The study protocol was approved by the institutional review board.

Patients with malignant or metastatic tumors (n=7), or with incomplete medical records (n=29),

were excluded. Patients who underwent surgery with atypical or complicated procedures were also excluded (n=4, one required hepatic lobectomy; two underwent nephrectomy; the other one was a pregnant woman who required cesarean section). Additionally, patients undergoing surgery for paraganglioma (n=16), recurrent tumors (n=4) or bilateral tumors (n=9) were excluded. Therefore, a total of 134 patients were included in this study. The diagnosis of pheochromocytoma in all patients was confirmed pathologically.

Preoperative medical preparation

A non-selective α-adrenergic receptor blocker, phenoxybenzamine, was started at least seven days before surgery in all patients to normalize blood pressure, and was titrated according to blood pressure. A β-adrenergic receptor blocker was added in patients with tachycardia after


administration of phenoxybenzamine. If the use of phenoxybenzamine in a sufficient dose did not

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achieve normotension, a calcium channel blocker was added to further control blood pressure. A preoperative high-sodium diet and fluid intake were encouraged to reverse catecholamine-induced blood volume contraction. Preoperative hemodynamic parameters were assessed one week before surgery. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were monitored non-invasively four times a day. The blood pressure (BP) was recorded at sitting position under the same condition (including having the patient sit quietly for more than 5 minutes before measurement, and avoid caffeine, exercise, eating, and smoking for at least 30 min before measurement).9 Range of preoperative BP fluctuation was defined as: maximum BP minus the minimum BP. The preinduction BP was defined as the value measured in the morning of the surgery. Adequate preoperative medical preparation was reflected by the normalization of preoperative BP. The target preinduction BP was 130/85 mmHg.6, 10According to American Diabetes Association (ADA) guidelines updated in 201711, diabetes was defined as (1) a self-reported previous diagnosis by health care professionals, (2) fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L), (3) 2h plasma glucose ≥200 mg/dL (11.1 mmol/L) during an OGTT, (4) a random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis. Prediabetes is the term used for individuals with impaired fasting glucose (IFG) and / or impaired glucose tolerance (IGT). IFG was defined as FPG between 100 and 125 mg/dL (between 5.6 and 6.9 mmol/L). IGT was defined as 2h plasma glucose

after OGTT between 140 and 199 mg/dL (between 7.8 and 11.0

mmol/L).


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Operative details

All surgeries were conducted under general anesthesia. Furthermore, all operations were performed by the same surgical team with experience in the treatment of pheochromocytoma. Two chief surgeons were involved in the pheochromocytoma surgery. And the choice to operate laparoscopically or with an open approach was based on the size and location of the tumor. To monitor intraoperative hemodynamics, a radial arterial line was routinely inserted. Intraoperative SBP, DBP, and mean arterial pressure were invasively measured and recorded every 5 min, and were monitored more frequently if obvious fluctuations occurred. Intraoperative vasopressors and vasodilators, estimated blood loss, as well as infusion volume of colloid and crystalloid were evaluated. According to previous studies, intraoperative HI was defined as the presence of at least one intraoperative SBP > 200 mmHg episode and/or at least one intraoperative DBP < 80 mmHg episode.12-15 Postoperative complications were collected and classified using the Clavien-Dindo classification.12, 16-18

Statistical analysis

Mean ± standard deviation(SD) or median (interquartile range) was used to describe continuous variables; intergroup differences were evaluated by use of Student’s t test or nonparametric Mann-Whitney U test, depending on the distribution of variables. Categorical variables were presented as frequencies and percentages, and intergroup differences were compared by Fisher’s exact or χ2 test. Stepwise multivariate logistic regression variables were fitted from variables found to have marginal associations with HI on univariate testing (P < 0.10). Odds ratio (OR), 95%


confidence interval (CI) and probability values were calculated. All statistical tests were 2-sided, and

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P < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS software, version 19.0 (IBM Inc., Chicago, IL, USA).

Results

A total of 134 patients with pheochromocytoma were included in our analysis. The diagnosis of pheochromocytoma was confirmed by histopathological evaluation. 32.8% (44/134) of patients were found to have HI. The demographics and clinical characteristics of patients with pheochromocytoma are shown in Table 1. 46.3% (62/134) patients were male. Mean age was 43.1 ± 14.9 years, and patients with HI were older than those without HI (47.4 ± 13.5 vs. 40.9 ± 15.1 years; P = 0.017). Hypertension, clinical symptoms and catecholamines excess were observed in most patients (80.6%, 73.9% and 81.3%, respectively). The mean tumor diameter was 52.3 ± 26.9 mm. Patients with HI had larger tumor diameters than those patients without HI (64.3 ± 32.2 vs. 46.5 ± 21.8 mm; P = 0.002). The most common comorbidities were diabetes / prediabetes (40.3%, 54/134). More than half of the patients with HI were accompanied with diabetes / prediabetes (54.5%, 24/44). There was no significant difference in other comorbidities between the two groups including: coronary artery disease, heart failure, chronic kidney disease and chronic obstructive pulmonary disease.

Preoperative medical preparation and preoperative hemodynamic data are summarized in

Table 2. All recruited patients had received a diagnosis of pheochromocytoma. No significant difference was observed in the daily dose of phenoxybenzamine or duration of phenoxybenzamine


before surgery between patients with HI and without HI. β-blockade and calcium channel blockade

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were administered in 48.5% and 23.1% of the patients, respectively. Range of preoperative SBP fluctuation was greater in patients with HI (37.5 ± 15.2 vs. 31.1 ± 13.5 mmHg; P = 0.014). About a quarter of patients with HI experienced preoperative SBP fluctuation greater than 50 mmHg (22.7%, 10/44). About half of patients (49.3%, 66/134) achieved a target BP (preinduction BP < 130/85 mmHg) after preoperative medical preparation. With regard to preinduction SBP, preinduction DBP and preinduction heart rate, there was no significant difference between HI and non-HI patient groups.

Characteristics associated with surgery in all patients are listed in Table 3. No significant

difference was observed between patients with HI and without HI when comparing American Society of Anesthesiologists (ASA) score, surgical approach, or duration of surgery. However, the postoperative hospital stay was longer in patients with HI (10.2 ± 5.4 vs. 8.0 ± 2.8 days; P = 0.018). More intraoperative vasopressors were used in patients with HI (1.18 ± 0.79 vs. 0.74 ± 0.59; P < 0.001), although there was no significant difference in intraoperative vasodilators administered in two groups. No mortality was observed within 30 days after surgery. 20.9% (28/134) patients were diagnosed with postoperative complications (data shown in Supplementary Table 1). Only three patients suffered from major complications (Clavien-Dindo ≥ 3). Two patients had heart failure while the other one suffered from ischemic stroke. All of them required postoperative management in intensive care unit.

Intraoperative hemodynamics and administered fluids for all patients are shown in Table 4.

Maximum SBP, maximum DBP were greater in HI group (174.3 ± 36.9 vs. 154.2 ± 22.3 mmHg, P =


0.002; 96.3 ± 18.2 vs. 88.4 ± 11.9 mmHg, P = 0.001, respectively). Accordingly, both minimum SBP

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and minimum DBP were lower in HI group (79.5 ± 13.2 vs. 95.4 ± 9.2 mmHg, P < 0.001; 48.2 ± 8.3 vs. 54.9 ± 7.6 mmHg, P < 0.001, respectively). Patients with HI had a wider range of SBP fluctuation (94.8 ± 31.1 vs. 58.8 ± 24.3 mmHg, P < 0.001). SBP ≥ 180 mmHg and SBP ≤ 90 mmHg were more frequent in patients with HI (50.0% vs. 17.8%, P < 0.001; 90.9% vs. 48.9%, P < 0.001, respectively). Larger amounts of patients with HI experienced mean arterial pressure ≤ 60 mmHg (40.9% vs. 13.3%, P = 0.001). Estimated blood loss was greater in HI group (574 ± 845 vs. 172 ± 242 ml, P = 0.003). With respect to administered fluids, both the volume of intraoperative crystalloids and intraoperative colloids were larger in the HI group.

The independent predictors identified for intraoperative HI are summarized in Table 5. On

multivariate analysis, tumor diameter > 50 mm (OR 2.526; 95% CI 1.163–5.485; P=0.019), diabetes / prediabetes (OR 2.251; 95% CI 1.039–4.876; P = 0.040), and preoperative SBP fluctuation > 50 mmHg (OR 3.163; 95% CI 1.051–9.522; P=0.041) remained independent predictors for intraoperative HI. Based on this result, correlation between the number of risk factors and the incidence rate of HI was identified (Figure 1). The observed incidence of HI was 8.9%, 42.6%, 47.8 % and 60% when zero, one, two or three risk factors were present, respectively.

Discussion

Surgery carries a high risk of HI during the procedure for patients with pheochromocytoma. Intraoperative HI is still common for pheochromocytoma although preoperative medical preparation, perioperative anesthetic care and surgical techniques have progressed considerably in


recent years.5, 6 Identifying the risk factors for HI will lead to a better perioperative management.

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Unfortunately, there are only a few retrospective studies on this subject in the literature. Therefore current knowledge is based on retrospective studies and institutional experience. Furthermore, risk factors for HI are not yet clear, especially in the Chinese population. In the current study, we present data from a large group of patients from a single-institution undergoing surgery for pheochromocytoma from China. Our study revealed a number of risk factors for intraoperative HI, specifically: having a tumor diameter greater than 50 mm, patients with diabetes / prediabetes and a preoperative SBP fluctuation greater than 50 mmHg.

There is no evidence from randomized controlled studies to determine the criteria for HI

because of the low incidence of pheochromocytoma. Thus no consensus has been reached about the criteria for HI. In our study, intraoperative HI was assessed using the definition of hemodynamic parameters determined from previous studies.12-15 Some recent studies suggest that HI should be defined as a morbidity-related variable.18, 19 That point of view stresses the definition should be relevant to clinical outcomes. In this study, we confirmed that our HI criterion was the only independent predictor for postoperative complications (data shown in Supplementary Table 2). Therefore our criterion was significantly associated with clinical outcomes. Our results showed that 32.8% patients suffered from HI, which supported the fact that HI was still common in pheochromocytoma surgery.

In our study, tumor diameter (larger than 50mm) was an independent risk factor for

intraoperative HI, which was in accordance with previous studies.6, 8, 20 Kiernan C.M. et al.8 reported that larger tumor size was independently associated with HI during pheochromocytoma resection,


without mentioning a clear cutoff value for tumor size. Bruynzeel et al.6 and Anouk Scholten et al.20

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found similar results using the cutoff size of 40 mm and 30 mm, respectively. It was reported that tumor diameter was correlated with catecholamines level.20-22 Manipulation of larger tumors may lead to the release of catecholamines during surgery resulting in an increase of HI incidences. Further studies are needed to evaluate this correlation and to identify the proper cutoff of tumor size for HI indication.

This study also showed that diabetes / prediabetes was a significant predictor for intraoperative

HI. The prevalence of diabetes has increased significantly in recent decades around the world, especially in China. In a national survey conducted in 2010, the estimated prevalence of diabetes among Chinese adults was 11.6% and the prevalence of prediabetes was 50.1%.23 Moreover, pheochromocytoma itself can cause hyperglycemia due to the high levels of catecholamines in circulation, which increases the prevalence of diabetes / prediabetes. Similar to prior reports, our study demonstrated that 40.3% patients with pheochromocytoma were diagnosed with diabetes / prediabetes.24 More importantly, our study revealed that diabetes and prediabetes were significantly associated with HI in patients with pheochromocytoma. Prior studies suggested that diabetes was associated with increased risk of HI during surgery.25-27 It was also reported that cardiovascular autonomic neuropathy was involved in HI in patients with diabetes.27, 28 Additionally, decreased capacitance response and decreased net fluid absorption from tissues to blood during hypovolemic circulatory stress were associated with the pathophysiology of HI in diabetes.29, 30

Preoperative SBP fluctuation (greater than 50 mmHg) was another independent risk factor for

intraoperative HI in this study. To our knowledge, we are the first to identify preoperative SBP


fluctuation as an independent risk factor for intraoperative HI in patients with pheochromocytoma.

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Prior studies mainly focused on relationship between preoperative BP level and HI.6, 19, 31 However, our findings showed that greater preoperative SBP fluctuation was significantly correlated with intraoperative SBP fluctuation (data shown in Supplementary Figure 1). Previous studies suggested that desensitization of adrenergic functions and impaired baroreceptor function might be responsible for abnormal BP response in pheochromocytoma.32 In addition, impairment of endothelial function and vascular remodeling caused by hypercatecholaminemia might be involved in vascular structural changes and dysfunction.33-37 All of the above mentioned could result in disorders of vasoconstriction and vasodilatation, appearing as greater perioperative BP fluctuations. The precise mechanisms for this correlation are unclear. Therefore, further studies are needed.

Our results demonstrated that the incidence rate of intraoperative HI was up to 60% when all

three predictive factors were found in our patient group. The number of predictive factors presented was associated with incidence rate of intraoperative HI. This significant outcome has direct implications for clinical practice. Identification of these risk factors can help to improve perioperative management. Preoperative assessment of the relevant conditions and complications, especially cardiovascular complications, should be conducted for patients with risk factors. Additionally, we need to attach importance to adequate glycemic control. Preoperative medical management is required to be more precise to control preoperative BP fluctuations. During surgery, anesthesia and operation should be performed more carefully. Furthermore, perioperative hemodynamics is supposed to be monitored intensively in patients presenting with risk factors. Accordingly, treatment should be timely, aggressive and adequate when HI occurs during surgery.


There are several limitations to our study. First, there are biases in our study due to the

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retrospective nature of the study design and enrollment from a single center. Second, uniform quantification of levels of catecholamines and metanephrines was not available in this study. Since our study spanned over a relatively long period, different methods of detecting hormones were used at different times. Therefore, we could not quantitatively analyze the difference of hormones between the two groups. Third, some data about the dose of each intraoperative vasopressor and vasodilator were missing. Hence, our study was not sufficiently powered to assess differences in the doses of drugs administrated between two groups. Fourth, since our study was a retrospective study without long-term follow-up results, we could not draw the conclusion that diabetes or prediabetes would improve after surgery. Finally, we were unable to investigate the precise mechanisms for the correlation between risk factors and HI.

In conclusion, our study confirmed that HI was common among patients undergoing surgery for

pheochromocytoma. This study identified three risk factors predictive of intraoperative HI: a large tumor diameter, diabetes / prediabetes and a great preoperative SBP fluctuation. Patients are more likely to suffer from HI when they have more risk factors. Identification of these risk factors can help to improve perioperative management. However, randomized controlled trials and further studies are needed to confirm the predictive value of these variables and to investigate the precise mechanisms behind their correlation. Besides, the proportion of severe postoperative complications is relatively small in our study. The predictive factors of severe postoperative events need to be further explored.


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Table 1.Demographics and clinical characteristics in patients with pheochromocytoma All patients

HI

Non-HI

N=134

N=44

N=90

Male

62(46.3)

18(40.9)

44(48.9)

0.462

Age (year)

43.1±14.9

47.4±13.5

40.9±15.1

0.017

Age > 45years

59(44.0)

25(56.8)

34(37.8)

0.043

Body mass index (kg/m2)

21.9±2.8

22.2±3.3

21.7±2.4

0.379

Family history

7(5.2)

2(4.5)

5(5.6)

1.000

Hypertension

108(80.6)

39(88.6)

69(76.7)

0.110

Palpitation / hyperhidrosis / headache

99(73.9)

35(79.5)

64(71.1)

0.403

Catecholamines excess

109(81.3)

38(86.4)

71(78.9)

0.352

Tumor diameter (mm)

52.3±26.9

64.3±32.2

46.5±21.8

0.002

Tumor diameter > 50mm

51(38.1)

23(52.3)

28(31.1)

0.023

Diabetes / prediabets

54(40.3)

24(54.5)

30(33.3)

0.024

Coronary artery disease

3(2.2)

2(4.5)

1(1.1)

0.251

Heart failure

8(6.0)

4(9.1)

4(4.4)

0.438

Stroke

8(6.0)

3(6.8)

5(5.6)

0.717


P-value

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Chronic kidney diseases

4(3.0)

0(0)

4(4.4)

0.302

Chronic obstructive pulmonary disease

2(1.5)

1(2.3)

1(1.1)

0.551

HI, hemodynamic instability.

Table 2. Preoperative medical preparation and preoperative hemodynamic data All patients

HI

Non-HI

N=134

N=44

N=90

α-blockade (phenoxybenzamine)

134(100.0)

44(100.0)

90(100.0)

1.000

Daily dose of phenoxybenzamine (mg)

40.5±20.2

41.1±19.3

40.2±20.8

0.795

Duration of phenoxybenzamine before surgery (days)

20.5±12.0

20.5±13.3

20.4±11.3

0.984

β-blockade

65(48.5)

26(59.1)

39(43.3)

0.100

Duration of β-blockade before surgery (days)

4.7±8.7

4.1±5.9

5.0±9.9

0.588

Calcium channel blockade

31(23.1)

14(31.8)

17(18.9)

0.126

Duration of calcium channel blockade before surgery (days)

1.6±3.8

2.2±4.0

1.3±3.7

0.227


P-value

ccepted Articl

Range of preoperative SBP fluctuation (mmHg)

33.2±14.4

37.5±15.2

31.1±13.5

0.014

Range of preoperative DBP fluctuation (mmHg)

22.3±9.1

23.6±9.6

21.7±8.8

0.266

Preoperative SBP fluctuation > 50mmHg

17(12.7)

10(22.7)

7(7.8)

0.025

Preoperative DBP fluctuation > 30mmHg

27(20.1)

12(27.3)

15(16.7)

0.172

Preinduction SBP (mmHg)

128.8±18.0

132.0±16.2

127.2±18.7

0.146

Preinduction DBP (mmHg)

79.7±13.0

82.2±10.3

78.4±14.0

0.109

Preinduction HR (bpm)

83.3±11.6

84.3±10.9

82.8±11.9

0.475

Preinduction SBP > 130mmHg

59(44.0)

22(50.0)

37(41.1)

0.359

Preinduction SBP > 140mmHg

32(23.9)

14(31.8)

18(20.0)

0.138

Preinduction DBP < 85mmHg

92(68.7)

28(63.6)

64(71.1)

0.430

Preinduction DBP < 90mmHg

103(76.9)

31(70.5)

72(80.0)

0.276

Preinduction BP < 130/85mmHg

66(49.3)

19(43.2)

47(52.2)

0.361

HI, hemodynamic instability; SBP, systolic blood pressure; DBP, diastolic blood pressure; BP, blood pressure; HR, heart rate; bpm, beats per minute.


ccepted Articl

Table 3. Characteristics associated with surgery in all patients All patients

HI

Non-HI

N=134

N=44

N=90

American Society of Anesthesiologists score

P-value 0.539

II

25(18.7)

6(13.6)

19(21.1)

III

99(73.9)

34(77.3)

65(72.2)

IV

10(7.5)

4(9.1)

6(6.7)

Surgical approach

0.206

Laparoscopic

104(77.6)

31(70.5)

73(81.1)

Laparoscopic converted to open

5(3.7)

3(6.8)

2(2.2)

Open

25(18.7)

10(22.7)

15(16.7)

Duration of surgery (min)

152.1±73.7

166.1±70.6

145.2±74.6

0.125

Intraoperative vasopressors

0.89±0.69

1.18±0.79

0.74±0.59