SERUM LACTATE ALBUMIN RATIO AS A PREDICTOR OF MORTALITY IN SEVERE SEPSIS AND SEPTIC SHOCK AT TRIBHUWAN UNIVERSITY TEACHING HOSPITAL , KATHMANDU Affiliation

Methodology It was a hospital based cross sec onal study done at Tribhuvan University Teaching Hospital, Kathmandu from November 2015 to October 2016. The consent was taken from pa ents. Acute Physiology and Chronic Health Evalua on II score, serum lactate and serum albumin levels on first day of arrival in emergency room were calculated. Pa ents were classified as severe sepsis and sep c shock and treated according to Surviving Sepsis Campaign 2012 guideline. The pa ent were follow up at 28 day, The associa ons of 28-day outcome with Acute Physiology and Chronic Health Evalua on II score, serum lactate value, serum albumin value and serum lactate albumin ra o value were derived.


Objec ve
The objec ve of the study was to predict the serum lactate albumin ra o as an indicator of mortality in severe sepsis and sep c shock.

Methodology
It was a hospital based cross sec onal study done at Tribhuvan University Teaching Hospital, Kathmandu from November 2015 to October 2016.The consent was taken from pa ents.Acute Physiology and Chronic Health Evalua on II score, serum lactate and serum albumin levels on first day of arrival in emergency room were calculated.Pa ents were classified as severe sepsis and sep c shock and treated according to Surviving Sepsis Campaign 2012 guideline.The pa ent were follow up at 28 day, The associa ons of 28-day outcome with Acute Physiology and Chronic Health Evalua on II score, serum lactate value, serum albumin value and serum lactate albumin ra o value were derived.

Results
Out of total 240 severe sepsis and sep c shock pa ents it is found that increased serum lactate/albumin ra o was an independent predictor of the mortality with cut off value of 0.07.Furthermore serum lactate albumin ra o shows strong correla on with APACHE 2 score in predic ng mortality in severe sepsis and sep c shock.

Conclusion
Increased lactate/albumin ra o predicts mortality in pa ents with severe sepsis and sep c shock.

INTRODUCTION
Severe sepsis and sep c shock, are the major cause of emergency room admission and are associated with high 1 morbidity and mortality worldwide.Severe sepsis and sep c shock has been recognized to have a high risk of death with high mortality rate of 20-30% with overall hospital death of 2-4 30-50%.Similarly mortality rate of sepsis in Nepal found to 5,6 be 40%, so sepsis is s ll the leading cause of death.Furthermore majority of those who survives a er the diagnosis of severe sepsis have poor quality of life who frequently develop cogni ve and func onal disability As the incidences of severe sepsis and sep c shock are increasing much things remains to be done to decreasing the 11 mortality rate.One way to accomplish this is the early iden fica on of severe sepsis and sep c shock pa ents likely to die.There are lots of studies about sepsis done in developed countries but data are lacking in developing 12 countries.There are currently inadequate data outlining the incidence, prevalence, predic ng factors and mortality from severe sepsis and sep c shock alone with bacteriological profiles, an bio c sensi vity pa erns of isolates from blood cultures in Nepal.The most important factor in decreasing mortality among severe sepsis and sep c shock pa ents is the implementa on of care bundle approaches of the 13 Surviving Sepsis Campaign.If we can predict the mortality of pa ents with severe sepsis and sep c shock in the emergency room and aggressively resuscitate them, the survival rate can be expected to increase.Authen c risk stra fica on tool could be used which recognizes the seriousness of the condi on and assist in the best choice of early management.When there is low oxygen satura on and oxygen supply is inadequate to ssue demand anaerobic metabolism will occur, and subsequently increase in lactate produc on.It is established that the increased lactate is prognos c marker of generalized ssue hypoxia in 14 distribu ve shock.There is significant increase in mortality rate in normotensive pa ents in the presence of systemic inflammatory response syndrome when lactate concentra on 15 is greater than 4 mmol/l.Serum albumin comprises 75-80% of normal plasma colloid onco c pressure and the degree of low serum albumin in cri cally ill pa ents directly related 16 with the severity of infec on.It is a nega ve acute phase protein and marker of outcome of severe sepsis and sep c shock which decrease during the response of ac ve phase of 17 infec ons.Therefore, serum lactate and albumin levels which diverge during severe sepsis and sep c shock merges together and provide an prognos c index that correlate posi vely with infec on, that are inexpensive and readily available in most emergency room, with and without scoring systems.

METHODOLOGY
This was a hospital based prospec ve, cross sec onal study approved by the ins tu onal review board of ins tute of medicine tribhuvan university.The study was conducted at Department of Emergency and General Prac ce, Tribhuvan University Teaching Hospital (TUTH), Maharajgunj, Kathmandu Nepal, from November 2015 to October 2016.Wri en consent was obtained from par cipants.Pa ents with an age less than 16 years, do-not-resuscitate order, acute coronary syndrome, referred to other center, le against the medical advice, were excluded.For each pa ent, at emergency room conscious level, temperature, heart rate, respiratory rate, systemic blood pressure, capillary refill me, hematocrit, blood glucose level, total leukocyte counts, serum sodium, serum potassium, serum crea nine, platelets count, serum bicarbonate, Fio2, arterial PH, serum lactate level, serum albumin alone with comorbidity like chirrosis of liver, chronic kidney disease, chronic obstruc ve pulmonary diseases, immune-compromised status were recorded.All pa ents were resuscitated according to surviving sepsis campaign 2012 guideline.0.9% normal saline at the rate of 30 ml per kg was used for fluid resuscita on for the first three hours, if mean arterial pressure (MAP) is not increased by 65 mm of Hg then inj.Noradrenalin was started within first 6 hours with target MAP of >65 mm of Hg.Acute physiological and chronic health evalua on (APACHE) II score was calculated by using APACHE II scoring system calculator -MD Calc.Serum Lactate, serum albumin and serum lactate albumin ra o was calculated within first 6 hours period.The pa ent were admi ed in intensive care unit (ICU), medical intensive care unit (MICU), surgical intensive care unit (SICU) of TUTH a er fully resuscita on in emergency room.The pa ent were th follow up at 28 day in terms of mortality outcome by using hospital land line phone.The associa ons of 28-day outcome with APACHE II score, serum lactate value, serum albumin value and serum lactate albumin ra o value is examined.

RESULTS
From Nov 2015 to Oct 2016, two hundred forty criteria fulfilled pa ents were included in the study.There were fi yseven pa ents with severe sepsis and one hundred eighty three pa ents with sep c shock.Out of 240 pa ents 53.8 percent in male group and 46.2 percent in female were expired with p value of 0.128 (Table 1).

Original Research Article
In table 2, it was found that as there is gradually increase in serum lactate albumin ra o there is corresponding increase in mortality, when the serum lactate albumin ra o is in range of 0.01-0.20 mortality in severe sepsis and sep c shock were 43.1 and 58.1% respec vely.

DISCUSSION
With the gradual introducing ini al resuscita on methods, which decreases mortality in severe sepsis and sep c shock, the focus has now moved to predic ng mortality.Our study shows that in the pa ents with severe sepsis and sep c shock lactate/albumin ra o obtained at admission in the emergency room can be used as an independent predictor of 28-day mortality.Lots of studies have been done to inves gate the procalcitonin, pro-BNP, CRP to predict 18 mortality in cri cally ill pa ents.But only few studies have evaluate the prognos c significance of serum lactate albumin ra o in a pa ent with severe sepsis and sep c shock treated with end goal directed therapy.
Hypoalbuminaemia represent the inflammatory status and use in predic ng outcomes in chronic and inflammatory 19,20 disease.As the albumin levels are affected by both the chronic inflammatory and nutri onal status this marker alone can create bias.The measurement of single lactate value in emergency room has several limita on, pa ent with trauma, seizure, cardiac arrest, excessive muscle ac vity, regional ischemia, burn and smoke inhala on, diabe c ketoacidosis, thiamine deficiency, liver dysfunc on and pa ent under me ormin all have a higher lactate.Hyperlactemia may also occur despite of hypoxia like upregula on in epinephrine-s mulated Na/K-adenosine triphosphatase ac vity in skeletal muscle and inhibi on of

RECOMMENDATION
Such studies could be done in mul ple centre so that conclusion can be generalized.Number of the study subject could be increased to increase the power of the study.

LIMITATION OF THE STUDY
Here are several limita ons to our study.First, Pa ents who were admi ed to different unit of hospital might get different level of care which might have the effect on outcome.Second Pa ents with comorbid like chirrosis of liver, CKD, malnutri on were included in the study which might effect lactate albumin levels.Third all pa ents of severe sepsis and sep c shock were generalized once they come to emergency room in spite of their level of treatment outside the hospital.In addi on, this was a single-center and rela vely small-sized study.

7 - 9 require
substan al ongoing acute and long-term care.Similar to polytrauma, acute myocardial infarc on or stroke, early administered resuscita on in the ini al hours a er severe sepsis and sep c shock develops are likely to 2 influence outcome.Delayed iden fica on and inadequate resuscita on in severe sepsis and sep c shock leads to the 10 high mortality.

Figure 2 :
Figure 2: ROC analysis between serum lactate, serum lactate albumun ra o and APACHE II score On correla ng between APACHE II score and serum lactate albumin ra o it shows posi ve deflec on with correla on coefficient of 0.637 and P value <0.01 indica ng that serum lactate albumin ra o shows strong correla on with APACHE II score in predic ng mortality in severe sepsis and sep c shock (Figure 3).

Figure 3 :
Figure 3: Pearson correla on between APACHE II score and serum lactate albumin ra o

Table 1 : Distribu on of gender among expired and improved pa ents (n=240)Table 2 : Associa on of Serum lactate albumin ra o with mortality in severe sepsis and sep c shock (n=240) age
range par cipants was 18 to 92 years and a mean age of 49.60 years.There is increase in mortality rate as age increases with highest mortality of 73.52% is found in age group of 58-77 years and low mortality of 46.3% in age group of 18-27 years (Figure1).Receiver opera ng characteris cs (ROC) curve analysis comparing serum lactate, serum lactate albumin ra o and APACHE II score in predic ng mortality shows in Table3(n=240, mortality=143).The area under the ROC curve as shown in figure2for lactate and lactate albumin ra o were

Table3: Receiver opera ng characteris cs curve (ROC) analysis between APACHE II score, serum lactate and serum lactate albumin ra o (n=240)
able to show lactate as predic ve value of mortality.APACHE II scoring system were used widely to assess out come in severe sepsis and sep c shock but this is me consuming, expensive and lengthy process having mul ple variables to calculate, so it is very imprac cal to use APACHE It is known that taking measurement of single lactate has several limita ons.Lactate is found to be increase in numerous physiological and pathological condi on as well as increased by using different types of drugs.With a cutoff value of 0.07, this study has shows that pa ents with lactate/albumin ra o greater than 0.07 on day 1 had a more chance of mortality within 28 days.In the very busy emergency room where calcula ng APACHE 2 score is me consuming and expensive, serum lactate albumin ra o could be used as alterna ve marker to predict mortality in severe sepsis and sep c shock.
not II scoring system in busy emergency room.So we use serum lactate albumin ra o as a marker of outcome in sepsis.It is found that as there is gradually increase in serum lactate albumin ra o there is corresponding increase in mortality.Our study findings were similar with study done by B wang et CONCLUSION