Study to evaluate post operative drop in serum albumin as a marker for surgical stress and predictor for clinical outcome in laparatomy patients

(1)

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A Dissertation on

STUDY TO EVALUATE POST OPERATIVE DROP IN SERUM ALBUMIN AS A MARKER FOR SURGICAL STRESS

AND PREDICTOR FOR CLINICAL OUTCOME IN LAPARATOMY PATIENTS

Submitted to

THE TAMILNADU DR. M.G.R. MEDICAL UNIVERSITY In partial fulfillment of the requirements

For the award of degree of M.S. (BRANCH-I) GENERAL SURGERY

GOVERNMENT STANLEY MEDICAL COLLEGE &

HOSPITAL

THE TAMILNADU DR. M.G.R. MEDICAL UNIVERSITY, CHENNAI, TAMILNADU.

MAY 2018

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CERTIFICATE

This is to certify that this dissertation titled “STUDY TO EVALUATE POST OPERATIVE DROP IN SERUM ALBUMIN AS A MARKER FOR SURGICAL STRESS AND PREDICTOR FOR CLINICAL OUTCOME IN LAPARATOMY PATIENTS” is a bona-fide research work carried out by Dr.M.VINOTH KUMAR

under our direct supervision and guidance, submitted to The Tamil Nadu Dr. M.G.R.

Medical University, Chennai, in partial fulfilment of the requirements in the award of degree of M.S. (GENERAL SURGERY) Branch -I for the May 2018 examination.

Prof. Dr .A.K.RAJENDRAN M.S., D.ORTHO., Professor and HOD,

Department of General Surgery,

Government Stanley Medical College and Hospital, Chennai – 600 001.

Dr. S. PONNAMBALAM NAMASIVAYAM M.D., D.A., DNB.

DEAN

Government Stanley Medical College and Hospital, Chennai – 600 001.

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DECLARATION

I,DR.M.VINOTH KUMAR solemnly declare that the dissertation “STUDY TO EVALUATE POST OPERATIVE DROP IN SERUM ALBUMIN AS A MARKER FOR SURGICAL STRESS AND PREDICTOR FOR CLINICAL OUTCOME IN LAPARATOMY PATIENTS”is a bonafide work done by me.

I also declare that this bonafide work or a part of this work was not submitted by me or any other for any award, degree, diploma to any university board either in India or abroad.

This thesis is submitted to The Tamil Nadu Dr .M.G.R. Medical University in partial fulfilment of the rules and regulations for the award of Master of Surgery degree Branch-I (General Surgery) to be held in May 2018.

DR.M.VINOTH KUMAR

Chennai-1 DATE:

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ACKNOWLEDGEMENT

I wish to thank Dr. PONNAMBALAM NAMASIVAYAM M.D., D.A., DNB.

Dean, Stanley Medical College and Hospital, Chennai for permitting me to carry out this study.

With sincere gratitude, I wish to acknowledge the expert guidance and suggestions of my HOD and Chief Prof. Dr .A.K.RAJENDRAN M.S., D.ORTHO., Without whose guidance this study would not have been possible.

I am deeply indebted to and highly grateful to Dr. ARUN BABU M.S., Dr.

VIJAYALAKSHMI M.S., and Dr. JAYALAKSHMI M.S., Assistant Professors, Department of General Surgery, Stanley Medical College, without whom this work would not be in the present shape.

I wish to thank all my co-post graduates for helping me in this work.

I gratefully acknowledge all patients and participants who gave their consent and co-operation for this study.

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LIST OF ABBREVIATIONS

ANOVA- Analysis of Variance POD- Post Operative Day

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(7)

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(8)

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TABLE OF CONTENTS

S.No CONTENTS Page No

1 Introduction 1

2 Review of literature 6

3 Aims and Objectives 21

4 Materials and Methods 23

5 Results 29

6 Discussion 43

7 Summary 54

8 Conclusions 57

9 Limitations 60

10 Future

Recommendations

62

11 References 64

12 Annexures 68

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LIST OF TABLES

Sl.No Title of Table Page number

1 Indication for surgery 34

2 Surgery performed 35

3 Dindo-Clavien Scoring 36

4 Complications present 37

5 Within-Subjects Factors 39

6 Descriptive statistics 39

7 Within-subjects effects 40

8 Tests of Between-Subjects Effects 41

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LIST OF FIGURES

Sl.No Title of Figure Page number

1 Age distribution of the sample 32

2 Gender distribution of the sample 33

3 Duration of stay in hospital 38

4 Repeated measures ANOVA 42

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INTRODUCTION

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Introduction

Surgical interventions trigger a metabolic stress response of

varying magnitude which contributes to complications, delayed

recovery and prolonged hospital stay.

The information of the major surgeries and their outcome is

scarce in India. Publicly available data on post operative

complications, their predictors and outcomes are scanty which

has hindered in deciding the parameters to follow or observe in

a patient undergoing major surgeries.

A number of preoperative interventions allow modulating an

excessive stress response, some of them having an important

(13)

13

positive impact on clinical outcome. Therefore, a trustworthy

forecast of the surgical stress response is of high interest.

The ideal marker has to be easy to measure, available early in

the preoperative course, and economical. It should be

robustly correlated with the extent of surgical trauma and be

a reliable predictor of complications and prolonged hospital

stay. So far, no such parameter is available.

Stress response subsequent to surgery and trauma has been

widely studied, and it involve vital electrolytic, hormonal, and

metabolic changes and liberation of cytokines. While IL-6, a

pro-inflammatory cytokine correlates with postoperative

inflammation and the magnitude of (surgical) trauma, its

(14)

14

sophisticated and expensive measuring precludes its routine use.

CRP levels correlate closely with the magnitude of surgery and

are routinely assessed to monitor postoperative systemic

inflammatory response. However, the dynamics are rather

sluggish, and plasma peak are only attained between POD 2 and

POD 3.

This is an important limitation, as potential therapeutic

interventions should be launched as early as possible. Albumin,

the most abundant protein in humans, is widely used as a

nutritional marker and an outcome predictor. Albumin also

shows an instantaneous response to surgical tension and could,

therefore, meet the criteria to determine surgical stress and to

predict a complicated postoperative course. The present study

(15)

15

aims to assess serum albumin levels as response marker for

surgical stress and as a predictor of adverse outcomes.

(16)

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REVIEW OF

LITERATURE

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Review of literature

Manufactured by the liver, albumin is a protein that is essential

for performing many functions in the body. One of the main

functions is to maintain the osmotic pressure which prevents the

leakage of fluid from the blood into the tissues.

Here are few salient features of albumin;

- The levels are measured in grams per deciliter with a

normal range between 3.4 g/dL to 5.4 g/dL. When the

albumin reduces, the fluid is lost from circulation.

- Albumin is encoded in the gene ALB, and it is a type of

globular protein. Albumin is also a carrier of plasma that

non-specifically binds to steroid hormones (hydrophobic)

and also transports hemin and fatty acids.

(18)

18

- Albumin is mainly synthesized in the liver as a compound

called preproalbumin that has an N-terminal peptide. This

terminal peptide is removed before it is released from the

endoplasmic reticulum as proalbumin.

- The secreted albumin is then synthesized in the Golgi

vesicles by cleaving the proalbumin.

- The final product albumin is a globular protein that is

unglycosylated and water-soluble and negatively charged.

- Structurally it is made up of alpha helices which help it to

maintain static shape.

(19)

19

- It has binding domains (eleven in numbers) to attach with

hydrophobic compounds. Fatty acids (six) and hemin (one)

can attach at any point in time.

Surgery brings about metabolic stress responses depending on

the nature of surgery, time of surgery, the magnitude of surgery,

complications, co morbid conditions, duration of illness, etc^1-3.

The nomenclature for major abdominal surgery is yet to be

clearly defined. The following factors determine the outcome of

a surgery which makes it the definition of abdominal surgery

difficult^4-7;

- procedure-related factors

- type of surgical approach

(20)

20 - type of organ resection,

- the extent of organ resection

- operative time

- blood loss

- patient-related factors like underlying disease

- benign versus malignant

- nutritional status

- pre-existing co morbidities

The perioperative care has fairly advanced to address the

ambiguity through the use of recovery pathways (eras) that has

shown to reduce the surgical stress, complications, duration of

hospital stay and overall cost of the management^8-10. In addition

(21)

21

to this, nutritional support and other formulas have shown to

impact the clinical outcomes.

The real challenge lies in identifying an easy to monitor and

reliable variable that can be used to find out the patients at risk

and customize the perioperative care for them. Initially, insulin

was proposed by Thorell et al. (1999)¹¹. But the cost of tests

and the reliability factor has made it difficult to measure insulin.

Sometimes the peak values are observed only after the golden

period is crossed.

This is why albumin is proposed as a reliable predictor as it is

abundantly available and easy to measure. Albumin is known to

(22)

22

react immediately to surgical stress and has been instrumental in

predicting clinical course and outcome^12-14.

Not many studies are available that uses serum albumin level to

understand the response to surgical stress and related clinical

outcomes. There are not many studies that focus on the

postoperative albumin drop that can be used as a predictor or

indicator of surgical stress and the outcome of surgery. One

study by Martin Hubner et al. (2016)¹⁵ has been referred to for

this study of 70 patients who underwent abdominal surgeries.

Their albumin levels were measured from the day of surgery and

followed up daily till five post operative days. The results

showed that the values of albumin dropped post operatively by

(23)

23

10g/dL which correlated with the length of operation,

complications and clinical outcomes.

A study conducted at the department of visceral surgery, to

compare the patients regarding clinical, surgical and metabolic

profiles undergoing abdominal surgery focussed on how the

serum albumin levels vary before and after surgery, how much it

varies, its clinical correlation with symptoms, the severity of

disease, the operation performed, the outcome and other related

factors.

It was conducted between December 2011 and July 2012 among

70 patients, consecutively chosen (ten of them) during seven

abdominal surgical procedures of differing magnitude. The

following surgeries were performed;

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- laparoscopic cholecystectomy

- extraperitoneal incisional hernia repair

- laparoscopic colectomy

- Open colectomy

- Upper Gastrointestinal resections

- Gastrectomy

- Esophagectomy

- Liver resections

- Pancreas resections

In this study, the levels of serum albumin (g/l) were measured at

7 o clock in the morning before breakfast in a state of fasting.

The first measure was on the day before surgery, then the

(25)

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albumin levels were measured at the same time on subsequent

days namely;

- Postoperative day 0

The values were calculated in a standardised way as per the

guidelines outlined in the hospital. The relevant statistical

parameters regarding age, gender, surgical parameters,

surgery was done, clinical outcomes were also documented.

(26)

26

The duration of surgery was determined from the time of

incision to the closure of skin. This was done by the

anaesthetist. The decision to measure blood loss

intraoperatively was done collaboratively by the surgeon and

the anaesthetist. The blood loss was ascertained by the

measurement of the aspiration fluids and the gauze materials

that were soaked.

Based on the surgery and the complications that developed

after that, Dindo-Clavien method was used to assess and

grade the severity of the complications. Minor complications

were graded as one and two while major complications were

graded as three and four. Grade five denoted death.

(27)

27

In this study, serum albumin was used as a marker for the

surgical stress and the postoperative complications that

developed after that. Seven different surgeries were taken into

account. The level of albumin was measured on the day of

surgery (before), after the surgery on day 0 and subsequently on

day 1, day 2, day 3, day 4 and day 5. All of them were measured

at 7 am in the morning to help standardise the tests. It was found

out that the serum albumin showed significant results right after

4 to 6 hours of surgery.

Secondly,, the level of serum albumin drop closely related to the

duration of surgery, intraoperative complications, blood loss, the

severity of the operation and with the clinical outcome. All of

them positively correlated while prognosis was negatively

(28)

28

correlated. Since serum albumin could reliably predict the

outcome and other related factors, it was said to be a reliable

indicator for assessing the severity of surgery.

The serum albumin measurement is simple, easy and cost-

effective. It is also easy to perform anywhere unlike like other

methods that require state of the art care. Using the serum

albumin as a marker, reliable predictions can be made regarding

the surgical complications, duration of stay in the hospital, the

severity of surgical stress, etc.

Postoperative hemodilution may act as a confounding factor

which can be circumvented by using other parameters and

correlating with the clinical findings for confirmation.

(29)

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There were also several limitations in this study where only a

single set of surgical procedures were evaluated. The other

surgical procedures were not considered as a part of this study.

The smaller sample size leaves us with only a hypothesis. False

positives and false negatives are yet to be addressed with more

sensitivity, reliability, validity and specificity. Testing in larger

patients is required and also in other critically ill patients. How

far these values can be used to decide therapeutic procedures

remains a query.

In this study, the fall in serum albumin levels was related to the

magnitude of surgery and the surgical stress associated with it.

Clinical outcomes were also related to the postoperative albumin

levels.

(30)

30

There are no studies in India that have been done to evaluate

this. This present study focuses on bridging the gap in this

knowledge.

(31)

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AIMS AND

OBJECTIVES

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Aims and Objectives

a) To assess serum albumin levels as a marker for surgical stress

b) To assess serum albumin levels as a potential predictor of

adverse outcomes like delayed wound healing, increased

hospital stay and organ dysfunction.

(33)

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MATERIALS AND

METHODS

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Materials and Methods

Place of study:

Department of General Surgery, Stanley medical college

and hospital

Duration:

November 2016 to July 2017

Study design:

Prospective observational study

Selection of cases

From cases undergoing laparotomy both electively and in

emergency

Sample size

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50 cases

• Inclusion criteria:

•age group 16-70 years

•laparatomies both elective and emergencies

• Exclusion criteria:

• Age < 16 years or > 70 years.

• HIV patients with CD count < 200

• Patients with known decompensated liver disease

Study group

• Preoperative and postoperative albumin levels were

measured for the patients and correlation between the

post-op fall in albumin level was compared with the

(36)

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incidence of post-op complications as determined by

Dindo-Clavien scoring.

Methodology

 Patients were made to understand in their local language,

and informed consent was obtained before beginning the

study

 Study included patients who underwent laparotomies from

November 2016 to July 2017

 Serum albumin (g/L) levels were measured in preoperative

period in a homogeneous manner as per the hospital

technical guidelines. Samples on Post Operative Day 0

were taken 4–6 hours postoperatively. Subsequently, daily

albumin level was monitored up to POD - 5

(37)

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 Complications after surgery were graded by severity by

the apply of the validated Dindo-Clavien system; grades

I-II were measured as minor and III-IV were measured as

major complications, respectively. Mortality was

documented as grade V. Hospital stay was counted from

the day of surgery.

(38)

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DINDO-CLAVIEN System of grading

Statistical Analysis

Pre and Post operative albumin levels and its statistical

significance in predicting outcome was evaluated using SPSS

software analysis of repeated measures ANOVA.

(39)

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RESULTS

(40)

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Findings

A prospective study was done for nine months of cases

undergoing laparotomy both electively and in an emergency

between the age group of 16 to 70 years. Serum albumin (g/L)

levels were measured in preoperative period in a homogeneous

manner as per the hospital technical guidelines. Blood samples

on Post Operative Day were taken 4–6 hours postoperatively.

Subsequently, daily albumin level was monitored up to POD –

5. Complications after surgery were graded by use of validated

Dindo-Clavien system; grades I-II were measured as minor and

III-IV were measured as major complications, respectively.

Mortality was documented as grade V. Hospital stay was

counted from the day of surgery. Preoperative and postoperative

(41)

41

albumin levels were measured for the patients and correlation

between the post-op fall in albumin level was compared with the

incidence of post-op complications as determined by Dindo-

Clavien scoring. Following results were obtained.

(42)

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Age distribution of the sample

The following figure illustrates the age distribution of the participants with mean age of 45 (S.D=15.905).

Figure 1: Age distribution of the sample

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Gender distribution of the sample

Majority of them were males (60%, n=30). The following figure illustrates the gender distribution of the sample.

Figure 2: Gender distribution of the sample

Female 40%

Male 60%

Gender

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Indication for surgery

The following table shows the indication for surgery of the fifty cases.

SURGERY INDICATION Frequency Percent Illeocaecil TB with perforation (query) 1 2.0

(Rt) torsion ovarian cyst 1 2.0

Acute abdomen (ruptured ectopic pregnancy) 3 6.0

Acute abdomen (torsion ovarian cyst) 1 2.0

Acute abdomen Appendicular perforation 1 2.0

Acute intestinal obstruction 1 2.0

Adhesive intestinal obstruction 1 2.0

Appendicular perforation 1 2.0

Assault stab injury abdomen 1 2.0

Assault stab injury abdomen (illeal perforation) 1 2.0

CA rectum 1 2.0

CA Stomach Antropyloric growth stage II 1 2.0

DU Perforation 7 14.0

DU Perforation( 4 days old) 2 4.0

Fall from height 1 2.0

gastric perforation 1 2.0

Hollow viscus perforation 1 2.0

Hollow viscus perforation (sigmoid growth) 1 2.0

Internal hernia with pain abdomen 1 2.0

intestinal obstruction(adhesions) 1 2.0

Intussusceptions (colo colic ) 1 2.0

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Lt torsion ovarian cyst 1 2.0

Obstructed (R) inguinal hernia 1 2.0

obstructed incisional hernia 2 4.0

obstructed inguinal hernia 1 2.0

obstructed inguinal hernia(bowel gangrene) 1 2.0

obstructed umbilical hernia 1 2.0

obstructed umbilical hernia(bowel gangrene) 1 2.0

Rt torsion ovarian cyst 1 2.0

RTA blunt injury abdomen (illeal perforation) 1 2.0 RTA blunt injury abdomen (liver laceration) 1 2.0

ruptured ectopic pregnancy 1 2.0

Ruptured liver abscess 2 4.0

sigmoid volvulus 3 6.0

SMV thrombosis 2 4.0

stab injury abdomen 1 2.0

Table 1: Indication for surgery

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Surgery Performed

The following table depicts the type of surgery done for the patients.

Surgery Performed Frequency Percent

(Rt) herniorapphyomentectomy done 1 2.0

Adhesiolysis 1 2.0

Diversion colostomy 1 2.0

Double barrel colostomy 1 2.0

Graham's omental patch closure 11 22.0

Jejunostomy with resection of 100cm gangrene bowel 1 2.0 Jejunostomy with resection of gangrene bowel up to terminal

ileum

1 2.0

Laporotomy(L) salpingectomy 1 2.0

Laporotomy(Lt) oopherectomy 1 2.0

Laporotomy(R ) oophorectomy done 1 2.0

Laporotomy(R) salpingectomy 3 6.0

Laporotomy (Rt) oophorectomy 2 4.0

Laporotomyadhesiolysis 3 6.0

Laparotomy and proceed 1 2.0

Laporotomyappendicectomy 1 2.0

Laporotomyappendicectomy done 1 2.0

Laporotomyomentectomy 2 4.0

Laporotomy packing done 1 2.0

Laporotomyresection anastomosis 2 4.0

Laporotomywash given DT kept 2 4.0

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Laporotomywound wash 1 2.0

Limited resection with ileostomy 1 2.0

Polytraumatransverse colon laceration resection anastomosis 1 2.0 Primary suturing in transverse colon done 1 2.0

Resection anastamosis 1 2.0

Resection anastamosis done 1 2.0

Resection anastomosis of jejunum done 1 2.0

Resection anastomosis 1 2.0

Resection and primary anastamosis 1 2.0

Segmentelilleal resection done 1 2.0

Subtotal gastrectomy with D2 clearance 1 2.0 Table 2: Surgery performed

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Dindo-Clavien Scoring

The following table illustrates the Dindo-Clavien Scoring of the patients

Dindo-Clavien Scoring Frequency Percent

Grade I 19 38.0

Grade II 17 34.0

Grade III 3 6.0

Grade IIIa 6 12.0

Grade IV 1 2.0

Grade IV b 2 4.0

Grade IVa 1 2.0

Grade V 1 2.0

Total 50 100.0

Table 3: Dindo-Clavien Scoring

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Complications present

The following table demonstrates the complications present in the patients.

Complications if any Frequency Percent

AKI dialysis done 1 2.0

AKI underwent dialysis 1 2.0

AKI wound gapping 1 2.0

AKI wound infection 1 2.0

Blood transfusion done 6 12.0

Burst abdomen secondary suturing done 1 2.0

Elevated renal parameters, wound infection 2 4.0

Mild fever 1 2.0

MODS 3 6.0

MODS (ventilator support) 1 2.0

NIL 17 34.0

Post op fever 4 8.0

Wound gapping secondary suturing done 8 16.0

Wound infection 3 6.0

Table 4: Complications present

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Duration of stay in the hospital

The duration of the stay is depicted in the following figure with a mean of 8.32 days (S.D=4.468) for 47 patients while two of them died on 10^th post operative day and one of them on 12^th post operative day.

Figure 3:Duration of stay in hospital

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General Linear Model of comparing serum albumin levels pre-operatively and post operatively

The following table shows the within-subjects factors based on which analysis was done.

Within-Subjects Factors Measure: SERUM ALBUMIN

Time Dependent Variable

1 Pre Operative

2 POD0

3 POD1

4 POD2

5 POD3

6 POD4

7 POD5

POD= Post Operative Day Table 5: Within-Subjects Factors

(52)

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Descriptive Statistics of the measures

The following table shows the descriptive statistics of the measures.

Time Mean Std. Deviation N

PREOP ALBUMIN 3.874 .4615 50

POD 0 3.466 .5255 50

POD 1 3.324 .6029 50

POD 2 3.376 .6063 50

POD 3 3.368 .6242 50

POD 4 3.344 .6566 50

POD 5 3.374 .6417 50

Table 6: Descriptive statistics

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Tests of Within-Subjects Effects

The following table shows the results of within-subjects effects.

Measure: SERUM ALBUMIN

Source Type

III Sum of Squares

df Mean

Square

F Sig. Partial Eta Squared

Time Sphericity Assumed

11.252 6 1.875 69.895 .000 .588

Greenhouse- Geisser

11.252 2.321 4.847 69.895 .000 .588

Huynh-Feldt 11.252 2.444 4.604 69.895 .000 .588 Lower-

bound

11.252 1.000 11.252 69.895 .000 .588

Error(Time) Sphericity Assumed

7.888 294 .027

Greenhouse- Geisser

7.888 113.750 .069

Huynh-Feldt 7.888 119.744 .066 Lower-

bound

7.888 49.000 .161

Table 7: Within-subjects effects

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Tests of Between-Subjects Effects

The following table shows the tests of Between-Subjects Effects.

Measure: SERUM ALBUMIN Transformed Variable: Average

Source Type III Sum of Squares

df Mean

Square

F Sig. Partial Eta Squared

Intercept 4157.599 1 4157.599 1814.238 .000 .974

Error 112.291 49 2.292

Table 8: Tests of Between-Subjects Effects

Repeated measures ANOVA of serum albumin levels pre-operatively and postoperatively.

(55)

55 (1=Pre operative, 2-7= Post operative days 0 to 5)

Figure 4: repeated measures ANOVA

A repetitive measures ANOVA with a Greenhouse-Geisser correction determined that mean serum albumin differed statistically significantly between time points (F(2.321, 113.750) = 69.895, P < 0.0005).

(56)

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DISCUSSION

(57)

57

Discussion

A prospective study was done for nine months of cases

undergoing laparotomy both electively and in an emergency

between the age group of 16 to 70 years. Serum albumin (g/L)

levels were measured in preoperative period in a homogeneous

manner as per the hospital technical guidelines. Blood Samples

on POD 0 were taken 4–6 hours postoperatively. Subsequently,

daily albumin level was monitored up to POD – 5.

Complications after surgery were graded by the use of validated

Dindo-Clavien system; grades I-II were considered as minor

and III-IV were measured as major complications, respectively.

Mortality was documented as grade V. Hospital stay was

counted from the day of surgery. Preoperative and postoperative

(58)

58

albumin levels were measured for the patients and correlation

between the post-op fall in albumin level was compared with the

incidence of post-op complications as determined by Dindo-

Clavien scoring.

The age distribution of the participants was with a mean age of

45 (S.D=15.905). Majority of them were males (60%, n=30).

The Dindo-Clavien Scoring of the patients showed that 19 of

them were in grade I. The duration of the stay was a mean of

8.32 days (S.D=4.468) for 47 patients while two of them died on

10^thpost-operative day and one of them on 12^thpost-operative

day. A repetitive measures ANOVA with a Greenhouse-Geisser

correction determined that mean serum albumin differed

statistically significantly between time points (F(2.321,

(59)

59

113.750) = 69.895, P < 0.0005). In this study, the fall in serum

albumin levels was related to the magnitude of surgery and the

surgical stress associated with it. Clinical outcomes were also

related to the postoperative albumin levels.

This correlates with most of the previous studies that used serum

albumin as a marker for post-operative complications.

Manufactured by the liver, albumin is a protein that is essential

for performing many functions in the body. One of the main

functions is to maintain the osmotic pressure which prevents the

leakage of fluid from the blood into the tissues.

Here are few salient features of albumin;

(60)

60

- The levels are measured in grams per deciliter with a

normal range between 3.4 g/dL to 5.4 g/dL. When the

albumin reduces, the fluid is lost from circulation.

- Albumin is encoded in the gene ALB, and it is a type of

globular protein. Albumin is also a carrier of plasma that

non-specifically binds to steroid hormones (hydrophobic)

and also transports hemin and fatty acids.

- Albumin is mainly synthesized in the liver as a compound

called preproalbumin that has an N-terminal peptide. This

terminal peptide is removed before it is released from the

endoplasmic reticulum as proalbumin.

- The secreted albumin is then synthesized in the Golgi

vesicles by cleaving the proalbumin.

(61)

61

- The final product albumin is a globular protein that is

unglycosylated and water-soluble and negatively charged.

- Structurally it is made up of alpha helices which help it to

maintain static shape.

- It has binding domains (eleven in numbers) to attach with

hydrophobic compounds. Fatty acids (six) and hemin (one)

can attach at any point in time.

Surgery brings about metabolic stress responses depending on

the nature of surgery, time of surgery, the magnitude of surgery,

complications, co morbid conditions, duration of illness, etc^1-3.

The nomenclature for major abdominal surgery is yet to be

clearly defined. The following factors determine the outcome of

(62)

62

a surgery which makes it the definition of abdominal surgery

difficult^4-7;

- procedure-related factors

- type of surgical approach

- type of organ resection,

- the extent of organ resection

- operative time

- blood loss

- patient-related factors like underlying disease

- benign versus malignant

- nutritional status

- pre-existing co morbidities

(63)

63

The perioperative care has fairly advanced to address the

ambiguity through the use of recovery pathways (eras) that has

shown to reduce the surgical stress, complications, duration of

hospital stay and overall cost of the management^8-10. In addition

to this, nutritional support and other formulas have shown to

impact the clinical outcomes.

The real challenge lies in identifying an easy to monitor and

reliable variable that can be used to find out the patients at risk

and customize the perioperative care for them. Initially, insulin

was proposed by Thorell et al. (1999)¹¹. But the cost of tests

and the reliability factor has made it difficult to measure insulin.

(64)

64

Sometimes the peak values are observed only after the golden

period is crossed.

This is why albumin is proposed as a reliable predictor as it is

abundantly available and easy to measure. Albumin is known to

react immediately to surgical stress and has been instrumental in

predicting clinical course and outcome^12-14.

Not many studies are available that uses serum albumin level to

understand the response to surgical stress and related clinical

outcomes. There are not many studies that focus on the

postoperative albumin drop that can be used as a predictor or

indicator of surgical stress and the outcome of surgery.

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Albumin is known to react immediately to surgical stress and

has been instrumental in predicting clinical course and

outcome^12-14. One study by Martin Hubner et al. (2016)¹⁵ has

been referred to for this study of 70 patients who underwent

abdominal surgeries. Their albumin levels were measured from

the day of surgery and followed up daily till five post operative

days. The results showed that the values of albumin dropped

post operatively by 10g/dL which correlated with the length of

operation, complications and clinical outcomes. The present

study correlates with this quoted literature.

A study conducted at the department of visceral surgery, to

compare the patients regarding clinical, surgical and metabolic

profiles undergoing abdominal surgery focussed on how the

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serum albumin levels vary before and after surgery, how much it

varies, its clinical correlation with symptoms, the severity of

disease, the operation performed, the outcome and other related

factors.

It was conducted between December 2011 and July 2012 among

70 patients, consecutively chosen (ten of them) during seven

abdominal surgical procedures of differing magnitude. The

following surgeries were performed;

- laparoscopic cholecystectomy

- extraperitoneal incisional hernia repair

- laparoscopic colectomy

- Open colectomy

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- Upper Gastrointestinal resections

- Gastrectomy

- Esophagectomy

- Liver resections

- Pancreas resections

In this study, the levels of serum albumin (g/l) were measured at

7 o clock in the morning before breakfast in a state of fasting.

The first measure was on the day before surgery, then the

albumin levels were measured at the same time on subsequent

days namely;

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The values were calculated in a standardised way as per the

guidelines outlined in the hospital. The relevant statistical

parameters regarding age, gender, surgical parameters,

surgery was done, clinical outcomes were also documented.

The duration of surgery was determined from the time of

incision to the closure of skin. This was done by the

anaesthetist. The decision to measure blood loss

intraoperatively was done collaboratively by the surgeon and

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the anaesthetist. The blood loss was ascertained by the

measurement of the aspiration fluids and the gauze materials

that were soaked.

Based on the surgery and the complications that developed

after that, Dindo-Clavien method was used to assess and

grade the severity of the complications. Minor complications

were graded as one and two while major complications were

graded as three and four. Grade five denoted death.

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There were also several limitations in this study where only a

single set of surgical procedures were evaluated. The other

surgical procedures were not considered as a part of this study.

The smaller sample size leaves us with only a hypothesis. False

positives and false negatives are yet to be addressed with more

sensitivity, reliability, validity and specificity. Testing in larger

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patients is required and also in other critically ill patients. How

far these values can be used to decide therapeutic procedures

remains a query.

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SUMMARY

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Summary

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CONCLUSIONS

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Conclusions

1. From this study, Albumin is known to react immediately to

surgical stress and has been instrumental in predicting clinical

course and outcome.

2. Their albumin levels were measured from the day of surgery

and followed up daily till five post operative days.

3. The results showed that the values of albumin dropped post

operatively by 10g/dL which correlated with the length of

operation, complications and clinical outcomes.

4. In this study, the fall in serum albumin levels was related to

the magnitude of surgery and the surgical stress associated

with it.

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5. Clinical outcomes were also related to the postoperative

albumin levels.

6. Future studies should be focussed on correlating the results

from multi-site, multi-city studies to prove albumin as a

reliable indicator of post operative surgical stress.

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LIMITATIONS

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Limitations

1. There were also several limitations in this study where

only a single set of surgical procedures were evaluated.

2. The other surgical procedures were not considered as a

part of this study.

3. The smaller sample size leaves us with only a hypothesis.

4. False positives and false negatives are yet to be addressed

with more sensitivity, reliability, validity and specificity.

5. Testing in larger patients is required and also in other

critically ill patients.

6. How far these values can be used to decide therapeutic

procedures remains a query.

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FUTURE

RECOMMENDATIONS

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Future recommendations

1. This study should be replicated for other major surgical

procedures as well.

2. A larger sample size should be selected for better

understanding.

3. False positives and false negatives are to be addressed with

more sensitivity, reliability, validity and specificity.

4. Testing in larger patients is required and also in other

critically ill patients.

5. Translating these findings into decision making protocols

for therapeutic procedures is important.

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REFERENCES

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References

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18, no. 7, pp. 1022–1028, 2004.

2. J. P. Desborough, “The stress response to trauma and surgery,” British Journal of Anaesthesia, vol. 85, no. 1, pp. 109–117, 2000.

3. Y. Haga, T. Beppu, K. Doi et al., “Systemic inflammatory response syndrome and organ dysfunction following gastrointestinal surgery,” Critical Care Medicine, vol. 25, no. 12, pp. 1994–2000, 1997.

4. R. Hall, “Identification of inflammatory mediators and their modulation by strategies for the management of the systemic inflammatory response during cardiac surgery,” Journal of Cardiothoracic and Vascular Anesthesia, vol. 27, no. 5, pp. 983–1033, 2013.

5. S. Karanika, T. Karantanos, and G. E. Theodoropoulos, “Immune response after laparoscopic colectomy for cancer: a review,” Gastroenterology Report, vol. 1, no. 2, pp. 85–94, 2013.

6. E. Lin, S. E. Calvano, and S. F. Lowry, “Inflammatory cytokines and cell response in surgery,” Surgery, vol. 127, no. 2, pp. 117–126, 2000.

7. P. E. Marik and M. Flemmer, “The immune response to surgery and trauma: implications for treatment,” Journal of Trauma and Acute Care Surgery, vol. 73, no. 4, pp. 801–808, 2012.

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8. M. M. E. Coolsen, R. M. van Dam, A. A. van der Wilt, K. Slim, K.

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10. S. Muller, M. P. Zalunardo, M. Hubner, P. A. Clavien, and N.

Demartines, “A fast-track program reduces complications and length of hospital stay after open colonic surgery,” Gastroenterology, vol. 136, no.

3, pp. 842–847, 2009.

11. Thorell, J. Nygren, and O. Ljungqvist, “Insulin resistance: a marker of surgical stress,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 2, no. 1, pp. 69–78, 1999.

12. Fleck, G. Raines, F. Hawker et al., “Increased vascular permeability: a major cause of hypoalbuminaemia in disease and injury,” The Lancet, vol. 325, no. 8432, pp. 781–784, 1985.

13. M. Ryan, A. Hearty, R. S. Prichard, A. Cunningham, S. P. Rowley, and J. V. Reynolds, “Association of hypoalbuminemia on the first

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postoperative day and complications following esophagectomy,” Journal of Gastrointestinal Surgery, vol. 11, no. 10, pp. 1355–1360, 2007.

14. H. J. Smeets, J. Kievit, F. T. Dulfer, J. Hermans, and A. J. Moolenaar,

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15. Martin Hübner, Styliani Mantziari, Nicolas Demartines, François Pralong, Pauline Coti-Bertrand, and Markus Schäfer, “Postoperative Albumin Drop Is a Marker for Surgical Stress and a Predictor for Clinical Outcome: A Pilot Study,” Gastroenterology Research and Practice, vol. 2016, Article ID 8743187, 8 pages, 2016.

doi:10.1155/2016/8743187

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ANNEXURES

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PROFORMA

1. Name:

2. Age : 3. Sex:

4. IP No:

5. Indication for surgery:

6. Surgical procedure done:

7. Albumin Level (g/dl)

Preop POD0 POD1 POD2 POD3 POD4 POD5

8. Post operative complications (As per DINDO-CLAVIEN classification)

a) Type of complication b) No complications c) Grading

1 2 3a/3b 4a/4b 5

9. Duration of stay in hospital from the day of surgery: