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11 April 2023: Clinical Research  

Intraoperative Hypotension and Its Association with Postoperative Acute Kidney Injury in Patients Undergoing Pancreaticoduodenectomy: A 5-Year, Single-Center, Retrospective Cohort Study

Zbigniew Putowski1ABCDEF*, Karolina Majewska ORCID logo12ABCDE, Karol Gruca1ABCD, Aleksandra Zimnoch1ABC, Anna Szczepańska ORCID logo3DEF, Łukasz J. Krzych3ABCDE, Beata Jabłońska4DEF, Sławomir Mrowiec4DEF

DOI: 10.12659/MSM.938945

Med Sci Monit 2023; 29:e938945

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Abstract

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BACKGROUND: Intraoperative hypotension (IOH) is a common phenomenon in high-risk surgery and is often linked to postoperative acute kidney injury (AKI). Pancreaticoduodenectomy (PD), or Whipple’s procedure, is a lengthy and complex surgical procedure to remove the head of the pancreas, gallbladder and bile duct, and the first part of the duodenum. This retrospective 5-year study from a single center in Poland included 303 patients who underwent PD and evaluated IOH as a factor associated with AKI.

MATERIAL AND METHODS: We analyzed perioperative data to assess how various IOH thresholds can predict AKI (according to KDIGO criteria). Several IOH definitions were applied, including absolute and relative thresholds, based on the mean arterial pressure (MAP). Statistically significant IOH thresholds were inserted into multivariable logistic regression models with previously established independent variables.

RESULTS: We included 303 patients over a 5-year period (2016-2021). There were 58 (19.1%) cases of postoperative AKI. MAP <55 mmHg and a maximal% drop from preinduction MAP were the only IOH definitions associated with AKI. Multivariable analysis revealed that max% drop from preinduction MAP (per 10%, OR=1.65; AUROC=0.70) was the IOH definition best suited for AKI prediction in patients undergoing PD.

CONCLUSIONS: In patients undergoing PD, it is important to prevent excessive blood pressure drops in regards to preinduction blood pressure values. In this cohort, relative IOH thresholds were better suited for prediction of AKI than the absolute IOH thresholds.

Keywords: Acute Kidney Injury, Hypotension, Intraoperative Period, Pancreaticoduodenectomy, Humans, Cohort Studies, Intraoperative Complications, Postoperative Complications, Risk Factors

Background

Intraoperative hypotension (IOH) is a common phenomenon in patients undergoing surgical treatment and is a result of a combination of various factors altering blood pressure (BP). IOH can be induced by a variety of patient- and procedure-related factors, including hypovolemia, vasodilation, and myocardial depression [1,2]. One of the most distinct complications occurring in the perioperative period is acute kidney injury (AKI), which also seems to be closely related to IOH [3]. There is, therefore, a strong rationale for the perioperative hemodynamic optimization, but with no clear consensus on the best definition of clinically significant hypotension [4–6]. Numerous interpretations of IOH were proposed over the years, leading to disparity in the hypotension incidence (from 5% to 99%) and divergent conclusions [4]. Methods used to identify IOH include absolute thresholds and relative thresholds, defined as drop from preoperative/preinduction BP [3,7–9]. Most studies on IOH included patients undergoing overall noncardiac surgeries, with no specific focus on a specific subgroup [5,6,10].

Pancreaticoduodenectomy (PD) is one of the most complex and high-risk procedures in abdominal surgery. The advance in surgical technique and centralization of pancreatic cancer surgery resulted in decreased perioperative mortality after PD to 5% [11,12]. Nevertheless, perioperative morbidity remains high, affecting about 40% of patients, which is much higher than for other abdominal surgeries [13,14]. Such a long, extensive surgery, mostly performed in patients at an advanced age, and often associated with significant blood loss, may pose a considerable risk of hypotension and subsequent ischemic complications. Guidelines for perioperative care for PD were updated recently [15], but there are no specific recommendations regarding management of IOH during PD.

Therefore, the purpose of this study was to evaluate various definitions of IOH as factors associated with AKI in patients undergoing PD.

Material and Methods

ETHICS STATEMENT:

All patients gave their written informed consent for medical procedures and data management. No additional approval of the Ethics Committee was required due to the anonymous and non-interventional design of the project (PCN/0052/KB/116/22).

PATIENT SELECTION AND DATA ACQUISITION:

In this cohort study we screened adult patients who underwent pancreaticoduodenectomy between 1 January 2016 and 1 December 2021 in a university hospital. Patients who had end-stage renal disease (chronic kidney disease G5), died during the intraoperative period, underwent any re-operation before the onset of AKI, or had incomplete data in the medical records were excluded from the analysis [16]. Demographic and clinical data were recorded, including sex, age, body mass index (BMI), comorbidities (chronic arterial hypertension and its ongoing pharmacological therapy, chronic kidney disease CKD, coronary heart disease CHD, and diabetes mellitus DM), preoperative hemoglobin, any premedication, and any history of neoadjuvant chemotherapy. The Charlson Comorbidity Index (CCI) and Revised Cardiac Risk Index (RCRI) were subsequently calculated. The type and duration of anesthesia were recorded. Perioperative risk was assessed based on individual patient’s risk, according to the American Society of Anesthesiology (ASA) physical status (PS) classification [17]. Due to the nature of the procedure, in all cases, the procedural risk was ranked as “high” according to the European Society of Cardiology and European Society of Anesthesiology recommendations [18].

The blood pressure (BP) monitoring method used depended on the anesthesiologist’s decision. Patients had either non-invasive blood pressure measurements (via an automatic oscillometric method; Dräger Infinity Gamma XL) or invasive ones (by using an arterial catheter in the radial artery). BP was recorded before and after the induction of anesthesia and in 5-minute intervals until the patient was discharged from the operating theater. Recordings of MAP throughout the procedure were analyzed. Our study focused solely on MAP-derived IOH thresholds since these definitions seem to be the most well documented in the literature [9]. Hence, the most commonly applied IOH thresholds were distinguished: MAP <70 mmHg, <65 mmHg, <60 mmHg, and <55 mmHg [3,8,9]. Duration of such IOH events were calculated. Moreover, maximal% drops from the preinduction MAP values were analyzed. Intraoperative fluid dosing, diuresis, bleeding, and the use of norepinephrine (NE) was analyzed according to the dose and duration of infusion.

In the postoperative period, incidents of AKI were recorded. Preoperative creatinine was measured 1 day before the surgery. According to the KDIGO guidelines, AKI was defined as either a 0.3 mg/dL increase in the first 48 hours after surgery or a 1.5-fold increase in the first 7 days after surgery [19].

The STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) statement was applied for appropriate reporting [20].

STATISTICAL ANALYSIS:

Statistical analysis was performed using MedCalc Statistical Software version 18.1 (MedCalc Software Ltd., Ostend, Belgium). Continuous variables were expressed as median and interquartile range (IQR). Qualitative variables were expressed as absolute values and/or percent. Between-group differences for quantitative variables were assessed using the Mann-Whitney U-test or Kruskal-Wallis test. Their distribution was verified with the Shapiro-Wilk test. The χ2 test or Fisher’s exact test were applied for qualitative variables. All tests were two-tailed. A P value <0.05 was considered statistically significant. Multivariable logistic regression was implemented for each of the thresholds that achieved P values lower than 0.1. To control the potential confounding factors, we used variables regarded as independent risk factors for postoperative AKI: age, diabetes mellitus, RCRI, and ASA status [21,22]. Each of the multivariable models were then analyzed in terms of AUROC values.

Results

SUMMARY RESULTS:

The study group consisted of 303 patients (Figure 1). The median age was 64 (range, 57–69) years. There were 169 patients (55.7%) with chronic arterial hypertension, of which 94 were treated with ACEI/ARB (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers). In regards to ASA-PS class, 154 (50.8%) patients were classified as class III and 141 (46.5%) as class II. The most common indication for PD was tumor of the head of the pancreas (70.6%), followed by cancer of the ampulla of the duodenum (25.7%) and biliary tract cancer (3.6%). Invasive BP monitoring was applied in 55.4% of cases. The median duration of PD was 440 minutes. The outcome of interest was postoperative AKI, which was reported in 58 patients (19.1%). Based on KDIGO classification, 47 (81%) patients had stage I AKI, 9 (15.5%) had stage II AKI, and 2 (3.5%) had stage III AKI.

There were a number of factors associated with the postoperative AKI (Tables 1, 2). In terms of preoperative factors, age, CHD, use of ACEI/ARB, and ASA III and higher preinduction BP values were associated with increased risk of AKI. As for intraoperative factors, several hemodynamic parameters were found to be associated with AKI. Patients who experienced lower BP and greater drops in BP during the procedure were more likely to develop AKI. Lastly, patients who required more norepinephrine to maintain appropriate MAP were almost statistically significantly more likely to have AKI than the non-AKI individuals.

INTRAOPERATIVE HYPOTENSION:

In regards to absolute IOH thresholds, a MAP of <55 mmHg was statistically significantly associated with postoperative AKI (Table 2). Hence, only 2 IOH definitions were put into multivariable logistic regression models: 1) Max% drop from preinduction MAP and 2) MAP <55 mmHg. Each model consisted of an IOH definition along with other independent variables mentioned in the methods section. These 2 different multivariable models were associated with AKI: the first was the model with the maximal% drop from preinduction MAP (OR: 1.65 per 10%, AUROC for the model: 0.70) and the second was with MAP <55 mmHg (OR: 2.23, AUROC for the model: 0.65) (Table 3).

Discussion

LIMITATIONS:

In terms of limitations, this was a single-center study including 1 specific surgical procedure, which limited the size of the cohort and number of included cases of AKI, but such a design was essential to provide a fairly homogenous group. Additionally, due to the retrospective nature of the study, it contains variables that could not be controlled for. The fact that extensive hemodynamic monitoring is not routinely applied in patients after PD at surgery ward is the reason why our analysis was limited to intraoperative BP monitoring. For the best evaluation of the association between intraoperative hemodynamic parameters and AKI, the postoperative period should also be taken into account. Another limitation is that BP was recorded in a 5-minute interval, so available data may fail to fully capture the exact occurrence of hypotension. Moreover, different methods of BP monitoring were used, including non-invasive and invasive measurements, which could result in disparities in acquired values, as non-invasive monitoring is less precise [36].

Conclusions

In patients undergoing pancreaticoduodenectomy, it is important to prevent excessive blood pressure drops in regards to preinduction blood pressure values. For every 10% decrease in mean arterial pressure there was approximately 1.60 increased odds of generating acute kidney injury. In this cohort, relative blood pressure thresholds were better suited for prediction of postoperative acute kidney injury.

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