PDF
Citation
Print
INTRODUCTION
Pancreaticoduodenectomy (PD) is a major surgical procedure with significant postoperative complications. Despite reduced mortality of 2% to 3% in high-volume centers, postoperative morbidity remains high (30%–40%) [1]. Most patients undergoing PD are elderly, but not all elderly individuals develop major complications after the procedure. Outcomes of PD are often estimated using risk prediction tools that include both patient and tumor-related factors, some of which cannot be assessed preoperatively [2]. While recent studies have introduced preoperative risk prediction models, these models heavily depend on high-quality imaging and expert interpretation, and their validation in large, general patient populations remains limited [3-5].
Frailty, a multifactorial measure of overall physiologic reserve, has emerged as a strong predictor of outcomes following high-risk surgeries like PD [6]. Frail individuals, with reduced physiologic reserves, are less capable of maintaining homeostasis and are more vulnerable to acute stressors such as surgery [7-9]. The Modified Frailty Index (mFI) was developed by aligning variables from the Canadian Study on Health and Aging with 11 corresponding variables in the American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) database [10-12]. The mFI is a simple frailty assessment tool that uses readily available historical variables, which can be reliably and consistently collected in the preoperative setting. Retrospective studies have shown that mFI accurately predicts postoperative morbidity and mortality after PD [6,13]. However, robust prospective data to confirm these findings is still lacking.
Sarcopenia, characterized by the loss of muscle mass and function, is known to increase the risk of postoperative complications after major gastrointestinal surgeries and is a key component of frailty [14]. While the authors have previously examined radiologically assessed muscle mass as a predictor of complications after PD, no significant association was found between muscle loss and the development of major complications [15]. Recent sarcopenia consensus guidelines highlight the importance of functional assessments, such as measuring muscle strength, as a more accurate indicator of sarcopenia [14]. It has been suggested that functional changes may occur earlier than measurable alterations in muscle mass or other anthropometric parameters [16]. Hand grip strength (HGS) measurement helps evaluate these early functional changes in the muscle strength of the small muscles of the hand, which is a surrogate marker of the patient’s physiological status. HGS has been used to predict the outcomes of major digestive tract surgeries [16]. However, its role in predicting complications after PD remains unexplored.
The present study aimed to assess the impact of the mFI and HGS on postoperative outcomes following PD.
MATERIALS AND METHODS
This prospective observational study was conducted in the Department of Gastrointestinal Surgery at Medanta-The Medicity Hospital. All consecutive patients undergoing elective PD from June 2021 to March 2023 were included. Patients with American Society of Anesthesiology grade 4, preoperative sepsis, post-neoadjuvant chemotherapy, and those undergoing emergency PDs were excluded. The primary outcome measure was major complications, defined as Clavien-Dindo (CD) grade 3 and above [17]. Secondary outcomes of the study included overall complications (CD grades 1 to 5), 90-day mortality, length of hospital stay (LOS), and 90-day re-admission rate. The Institutional Review Board approved the study, and a clearance from the Ethics committee was obtained (Ref No. 1289/2021).
Data collection and definitions deployed in the study
Data collected included clinico-demographic characteristics, mFI, and HGS. Additionally, data were maintained regarding laboratory investigations, primary diagnosis, surgical procedure, and postoperative outcomes.
The mFI used for the study, as described previously by Velanovich et al. [12], includes the following 11 items: diabetes; functional status (not independent); chronic obstructive pulmonary disease or pneumonia; congestive heart failure; history of myocardial infarction; hypertension requiring medication; peripheral vascular disease or rest pain; impaired sensorium; history of either transient ischemic attack or cerebrovascular accident; history of the cerebrovascular accident with the neurologic deficit; and prior percutaneous coronary intervention, previous coronary surgery, or history of angina. Each item was assigned 1 point in the index calculation. The mFI was calculated as the proportion of the total 11 items used in the study that were present in an individual patient (total points as the sum of all the items divided by 11). An mFI cut-off of 0.27 (3/11) was used, based on previous data demonstrating overlap in deficit accumulation between individuals who are ‘‘robust’’ and those who are ‘‘frail’’ [11]. Patients with a high mFI (> 0.27) were identified as frail.
For HGS evaluation, patients were seated with their elbows flexed at a 90-degree angle and supported during measurement. The patient was instructed to grip the hand grip dynamometer with the maximum possible strength using the dominant hand and hold the grip for 3 seconds, and the findings were recorded. A new standardized and calibrated CAMRY electronic hand grip dynamometer MODEL EH101 (CAMRY) was used for measurement. HGS was graded as weak, normal, or strong based on age and sex. A table of age and sex-standardized cut-off values for the device is attached in the Supplementary Table 1.
Postoperative complications were graded according to the CD classification [17]. Major complications were defined as CD grade 3 and above. Post-pancreatectomy complications, such as postoperative pancreatic fistula, delayed gastric emptying, and post-pancreatectomy hemorrhage, were defined according to the International Study Group of Pancreatic Surgery classifications [18-20]. LOS was defined as the number of days spent as an inpatient from the day of surgery until discharge. The 90-day mortality was defined as either in-hospital deaths or deaths from any cause within 90 days of the surgery.
All patients underwent open PD. Preoperative care, operative procedure, and postoperative management using enhanced recovery pathways have been described in previous publications [21-23]. A standard institutional protocol was followed until discharge and during follow-up for 3 months after surgery. In cases of re-admission due to surgical complications, the necessary data were collected. The sample size was calculated based on a major complication rate of 8% [21]. As previously published by the department, the estimated sample size was 180 with a 95% confidence interval and a precision of ± 4%.
Statistical analysis
Data were analyzed using R software version 4.1.1. R Core Team (2021), R: A language and environment for statistical computing, R Foundation for Statistical Computing, Vienna, Austria (https://www.R-project.org/). Categorical variables were presented as frequencies and percentages, and associations were tested using the chi-square test or Fisher’s exact test. Continuous data were expressed as mean ± standard deviation, and associations were tested using the Independent Student’s t-test. For nonparametric data, the median and interquartile range were used, and the Mann–Whitney U test was employed to compare groups. Significant risk factors identified in univariate analysis were included in a multivariate logistic regression analysis to test independent associations. Statistical significance was set at a p-value of 5%.
RESULTS
A total of 180 patients were enrolled in the study, with the majority being men (126, 70.0%). The mean age of the cohort was 58.1 ± 12.3 years. The mean body mass index was 25.6 ± 4.2 kg/m2. Eighteen patients (10.0%) had an American Society of Anaesthesiologists (ASA) grade of 3, and 16 (8.9%) had three or more comorbidities. Eight patients (4.4%) had an albumin level of < 3 g/dL. Cholangitis was the initial presentation in 18 patients (10.2%). Preoperative endobiliary stenting was performed in 78 patients (48.3%) (for patients with bilirubin >15 g/dL [42], medically intractable cholangitis [18], renal failure [5], and if planned for neoadjuvant chemotherapy [13]). The most common disease etiology was a periampullary tumor (100, 55.6%), followed by a pancreatic head tumor (47, 26.1%; Table 1).
The distribution of mFI and HGS is shown in Table 1. High mFI (≥ 0.27; 3 or more positive factors of 11 for mFI) was observed in 11 patients (6.1%). Weak HGS was observed in 42 patients (23.4%). No patient had strong HGS.
Table 2 shows postoperative complications graded according to the CD classification. Major complications occurred in 19 patients (10.5%). CD grade 5 (90-day mortality) was observed in six patients (3.3%).
Major complications
The association of patient mFI, HGS, and clinico-demographic parameters with major complications in univariate analysis is shown in Table 1. Although the proportion of patients with high mFI was higher in those who developed major complications than in those who did not, it was not statistically significant (p = 0.063). In contrast, the proportion of patients with weak HGS was significantly higher in those who developed major complications than in those who did not (p < 0.001).
There was no other factor significantly associated with major complications at a 5 percent significance level in univariate analysis. High mFI, history of cholangitis, and weak HGS were significantly associated in univariate analysis at the 10 percent significance level. Multivariate analysis of these factors showed that weak HGS was the only factor independently associated with major complications post-PD (adjusted odds ratio [OR] = 11.5, p < 0.0001; Table 3).
Major complications, including 90-day mortality classified based on weak and normal HGS, are tabulated in Table 4.
Overall complications
The association of patient mFI, HGS, and clinico-demographic parameters with overall complications in univariate analysis is shown in Table 5. Weak HGS, mean age, and duration of surgery > 360 minutes were significantly associated with overall complications.
On multivariate analysis, surgery duration > 360 minutes (adjusted OR = 2.9, p = 0.005) and weak HGS (adjusted OR = 6.61, p = 0.003) were independently associated with overall complications (Table 6).
Ninety-day mortality, ninety-day re-admissions, and length of hospital stay
High mFI did not show a statistically significant association with 90-day mortality (9.1% vs. 3.0%, p = 0.268), LOS > 8 days (60% vs. 35.4%, p = 0.117), and 90-day re-admission (10.0% vs. 7.3%, p = 0.748) when compared to low mFI.
Whereas weak HGS showed a statistically significant association with 90-day mortality (14.3% vs. 0%, p < 0.001), LOS > 8 days (83.3% vs. 24.6%, p < 0.001), and 90-day re-admission (19.4% vs. 4.3%, p = 0.002) compared to normal HGS.
DISCUSSION
This study is the first prospective study to assess the impact of the mFI and HGS on major complications of PD; weak HGS was found to be independently associated with major complications. In contrast, a statistically significant association of high mFI with major complications after PD could not be established. The rate of major complications was 10.5%, and the 90-day mortality rate was 3.3%, consistent with previously published literature [21,24-26].
Frailty and sarcopenia are complementary but not synonymous phenomena. Frailty is characterized by decreased reserves in multiple organ systems caused by illness, lack of activity, inadequate nutrition, stress, and the physiological changes of aging [9]. Two well-validated frailty models are widely used in geriatric literature. The first, a “phenotypic” model, involves a prospective clinical questionnaire about exhaustion and weight loss and tests of physical ability, including walking speed and grip strength [7]. Conceptually, this is the easiest to understand because the attributes are physical characteristics driven by a causal, age-related, and biological set of changes (frailty). The second frailty model is based on ‘accumulating deficits,’ which include surveyed medical, functional, and social deficits that culminate in accelerated aging [27]. The mFI is based on the second model and is an abbreviated, simplified frailty assessment tool that uses readily available historical variables, which can be reliably and consistently collected in the preoperative setting, including 11 items in NSQIP as described by Velanovich et al. [12], and is validated by level II studies for its impact on surgical outcomes. Sarcopenia is characterized by muscle failure and affects muscle mass and strength [28]. The latest sarcopenia consensus guidelines recommend that assessment of functional muscle strength should be essential in evaluating sarcopenia [14]. Sarcopenia increases the risk of postoperative complications from any major surgery [14]. HGS measurement helps assess functional changes in muscle strength, and the rationale for using HGS is that functional muscle strength changes may be evident earlier than changes in anthropometry and laboratory variables [16].
In previous retrospective studies, high mFI has been significantly associated with major complications and overall complications [6,13]. However, in our prospective study, this association was not statistically significant. Nevertheless, patients who developed major complications, 90-day mortality, and overall complications were found to have a higher proportion of high mFI compared to those without complications. We probably could not achieve statistical significance because only 6.1% of the study cohort had high mFI.
The aging process is associated with physiological changes and changes in body composition [29]. Males also tend to have larger anthropometric measurements than females [30]. Both parameters significantly influence HGS. This study used an average of three handgrip dynamometer readings with age and sex-standardized cut-offs to ensure a fair comparison. Although a statistically significant association of weak HGS with major complications and overall complications has been observed in a previous study, their study cohort included major general surgical patients and not specifically for PD [16]. Our study is the first prospective study demonstrating a significant independent association between weak HGS and major complications of PD. Additionally, it was significantly associated with overall complications, 90-day mortality, 90-day re-admission, and hospital stay > 8 days after PD. HGS is a simple and easy preoperative tool for assessing sarcopenia, objectively identifying patients at risk of developing major complications. It is important to note that a previous study from our center evaluating the role of radiologically assessed muscle loss did not find low muscle mass or ‘radiological’ sarcopenia to be a risk factor for major complications [15]. On the other hand, a ‘functional assessment’ in the form of HGS testing is a better method for identifying patients with poor muscle strength. This finding demonstrates that functional sarcopenia is a more critical component than volumetric and anthropometric sarcopenia.
The objective assessment of ‘functional muscle weakness’ can assist in better decision-making and risk stratification, which are crucial for preoperative counseling. In the weak HGS group, prehabilitation strategies and preoperative nutritional support can be considered to prepare patients before surgical intervention for optimal postoperative outcomes.
The study’s strength lies in its prospective design, utilizing a standardized method to assess HGS. The HGS readings were also adjusted for sex and age (Supplementary Material 1). The study was conducted at a high-volume center with protocolized perioperative care [21]. This is a potential criticism because the results cannot be generalized to low-volume centers. Nevertheless, the study focuses on a relatively simple test—HGS testing, which can be performed at the bedside, is easy to interpret, and is independently associated with postoperative complications. Additionally, we recommend future multicenter validation studies and longitudinal research to evaluate whether interventions based on HGS status (such as prehabilitation) can enhance outcomes.
In conclusion, HGS, measured using a handgrip dynamometer, is a simple tool for evaluating functional sarcopenia. It was found to be an independent predictor of major and overall complications. It was also significantly associated with 90-day mortality, LOS, and re-admission rate.
SUPPLEMENTARY DATA
Supplementary data related to this article can be found at https://doi.org/10.14701/ahbps.25-117.
XML Download