Title– Utility of  serum albumin levels to predict postoperative complications in pancreatic surgeries in a tertiary cancer institute

Background and rationale– Albumin is commonly known as  an acute phase reactant which is  down regulated by inflammatory signals. Trauma, burns and surgical stress are known to lead to immediate drop in serum albumin levels. The most important  cause of  postoperative serum  albumin losses  are due to sequestration into the third space. Capillary leak is a well known phenomenon which  accounts for  >75% of albumin decrease in the early postoperative phase and appears to be related to the magnitude of systemic inflammatory response.  Recent studies have suggested that it may be used to predict immediate post-surgical  outcomes. Since postoperative complications add further stress to post-surgical stress, a continued drop in serum albumin levels may be useful to predict post-surgical outcomes. We, therefore, want to assess whether serial measurement of decrease in serum albumin levels in the immediate postoperative period after pancreatic resections  are useful in predicting short term postoperative outcomes.

Aims of the study–To evaluate the utility of postoperative serum albumin decrease after pancreatic resections  on post operative day  1 ,3 and 5  for predicting immediate postoperative outcomes i.e morbidity and mortality within 30 days.

Outcomes – Primary outcomes measured will be short term postoperative complications as per Clavien Dindo classification

Secondary outcomes  - Need for vasopressors, need for postoperative ventilation, ICU and Hospital Length of Stay (LOS), status at hospital discharge or at 30 days, whichever is earlier (alive or dead)

STUDY DESIGN–Prospective Observational cohort study

STUDY PERIOD: Duration of study will be for 12 months.

Methods

Ethics-The study will be undertaken after obtaining approval from Institutional Ethics Committee(IEC).

Patients- The study will include all  patients at our institute posted for  pancreatic resections under general anaesthesia, within 12 months period, after approval from IEC. The study will be conducted in the Department of Anaesthesia, Critical Care and Pain at Tata Memorial Cancer Centre

Inclusion Criteria- All patients above 18 years undergoing elective major pancreatic resections under General Anaesthesia

Exclusion Criteria-           

Other abdominal surgeries (liver resections, gall bladder, gastrectomies, oesophagectomies and colorectal surgeries)

SAMPLE SIZE-  All pancreatic surgeries in a period of one year approximately 169  patients

Details of Study Procedures Involved-

Data will be collected from the electronic medical record system (EMR) of the hospital which contains patients’ clinical, laboratory and radiological data. Data will also be recorded from the patient’s case file, the anaesthesia and PACU (intraoperative and postoperative) management summaries, monitoring charts and the surgical notes and will be entered in a prospectively maintained database. There will be no change in routine anaesthesia practice and care. No additional interventions will be performed. No additional hospital visits will be required.

The following data will be collected

Demographics, Comorbidities,Charlson comorbidity index, preoperative Hemogram, Renal and Liver function tests, coagulation studies

Patient undergoing pancreatic resections  will be analysed  for the length of their hospital stay maximum upto 30 days.The  post operative morbidity, length of hospital stay, ICU stay and readmissions , duration of ventilation  and status at hospital discharge or at 30 days, whichever is earlier (alive or dead) will be noted.  

Postoperative complications noted will be graded by severity by use of the validated Clavien-Dindo system; grades I-II will be considered as minor and III-IV will be  considered as major complications, respectively. Mortality will be  noted as Clavien Dindo 5 complication

 The hospital stay will be counted from the day of surgery till discharge or death

The  most recent preoperative serum albumin level (POD -1)  and the serum albumin levels on the first, third and fifth postoperative day will be noted . The maximal difference between the preoperative and postoperative values  on day 1,3 and 5 will be considered. Δ Max: maximal difference between the preoperative and postoperative values. Δ POD 1: difference of concentration on POD −1 and POD 1 ; Δ POD3: difference of concentration on POD−1 and POD 3 and Δ POD 5- difference of concentration on POD −1 and POD 5.

Sample size

Total sample size 128 (64 in each group) will achieve 80% power with size effect of 0.5 and with a significance level (alpha) of 5% using a two-sided two-sample t-test. As per complication rate of 30%, the final sample size for this study was n=152. In order to adjust for 10% dropout or missing data, final sample size resulted in n=169 (51 patients complication vs 118 without complication).

Statistical analysis plan:

Continuous variables will be  presented as mean with SD or median value with IQR depending on the normality of the distribution and compared using Student’s t-test and Mann–Whitney U test, whereas categorical variables will be  given as frequencies with percentages and compared with χ2 test. Receiver operating characteristic (ROC) curves will be  applied to obtain the area under the curve (AUC) and to determine ideal cut-offs.  Univariate analysis of categorical variables will be compared by Pearson’s Χ2 test or Fisher’s exact test. Logistic regression will be  applied to identify independent predictors; variables with significance < 0.2 in univariate analyses will be further included in multivariable analyses. Multivariate logistic regression (adjusted for Albumin infusion) and major risk factors as independent variables. Predictive accuracy of a logistic regression model will be assessed using c-index. All analysis will two sided, and significance will set at a p-value of 0.05.Statistical analyses will be performed using SPSS (the statistical package for social sciences) IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp and R studio (version 1.2).

References

Hübner M, Mantziari S, Demartines N, Pralong F, Coti-Bertrand P, Schäfer M. Postoperative albumin drop is a marker for surgical stress and a predictor for clinical outcome: a pilot study. Gastroenterology research and practice. 2016 Oct;2016.

Labgaa I, Joliat G, Kefleyesus A, et alIs postoperative decrease of serum albumin an early predictor of complications after major abdominal surgery? A prospective cohort study in a European centreBMJ Open 2017;7.