Prognostic Impact of Admission Glucose Level in Septic Patients Admitted to the Intensive Care Unit
Prognostic Impact of Admission Glucose Level in Septic Patients Admitted to the Intensive Care Unit
Background:

 Sepsis is one of the most common reasons for admission to intensive care units (ICU)
 worldwide. About 30% of all patients admitted to intensive care suffer from sepsis (1).
 Sepsis causes an extreme physiological stress response, with significant changes in
 metabolism and disruption in glucose regulation. Disorder of glucose regulation can lead to
 hyperglycemia, hypoglycemia and glucose variability (2). All of these conditions are
 associated with increased mortality (3). In critically-ill patients, the glucose threshold
 from which damage may be caused remains controversial.

 Hyperglycemia often occurs in critically-ill patients suffering from sepsis, even in those
 who were not diabetic before, for several reasons. Sepsis causes massive activation of
 anti-inflammatory mediators which enhances the activity of counter-regulatory hormones,
 including cortisol, glucagon and catecholamines. Those hormones increase both hepatic
 gluconeogenesis and peripheral resistance to insulin (4). Some of the detrimental effects of
 hyperglycemia in septic patients are mediated via hyperglycemia-induced blood hypercoagulable
 state, decrease of vascular endothelial responsiveness and disrupted process of phagocytosis
 and chemotaxis of white blood cells, especially neutrophils (5).

 It is widely accepted that disordered blood glucose regulation increases mortality and
 morbidity, as well as hospital admission times and associated financial expenses (2,6). Blood
 glucose level at ICU admission was found to be a poor prognostic factor at various studies on
 different ICU patient populations (7-9). For example, in ICU patients admitted due to acute
 myocardial infarction, cardiogenic shock and need for urgent cardiac catheterization, high
 blood glucose levels at admission, even in non-diabetic patients, were associated with both
 increased in- hospital and long-term mortality (7). Among patients admitted due to acute
 heart failure, high admission glucose levels (above 200 mg / dL), in both diabetic and
 non-diabetic patients, were associated with higher mortality from cardio-vascular etiologies
 within one year of admission (8). Among non-diabetic patients admitted to the hospital due to
 acute myocardial infarction, admission glucose levels above 180 mg / dL were associated with
 a significant increase in all-causes in-hospital mortality (9). However, there is currently
 insufficient information regarding the prognostic impact of high admission glucose levels of
 non-diabetic septic patients admitted to the ICU (10).
Background:

 Sepsis is one of the most common reasons for admission to intensive care units (ICU)
 worldwide. About 30% of all patients admitted to intensive care suffer from sepsis (1).
 Sepsis causes an extreme physiological stress response, with significant changes in
 metabolism and disruption in glucose regulation. Disorder of glucose regulation can lead to
 hyperglycemia, hypoglycemia and glucose variability (2). All of these conditions are
 associated with increased mortality (3). In critically-ill patients, the glucose threshold
 from which damage may be caused remains controversial.

 Hyperglycemia often occurs in critically-ill patients suffering from sepsis, even in those
 who were not diabetic before, for several reasons. Sepsis causes massive activation of
 anti-inflammatory mediators which enhances the activity of counter-regulatory hormones,
 including cortisol, glucagon and catecholamines. Those hormones increase both hepatic
 gluconeogenesis and peripheral resistance to insulin (4). Some of the detrimental effects of
 hyperglycemia in septic patients are mediated via hyperglycemia-induced blood hypercoagulable
 state, decrease of vascular endothelial responsiveness and disrupted process of phagocytosis
 and chemotaxis of white blood cells, especially neutrophils (5).

 It is widely accepted that disordered blood glucose regulation increases mortality and
 morbidity, as well as hospital admission times and associated financial expenses (2,6). Blood
 glucose level at ICU admission was found to be a poor prognostic factor at various studies on
 different ICU patient populations (7-9). For example, in ICU patients admitted due to acute
 myocardial infarction, cardiogenic shock and need for urgent cardiac catheterization, high
 blood glucose levels at admission, even in non-diabetic patients, were associated with both
 increased in- hospital and long-term mortality (7). Among patients admitted due to acute
 heart failure, high admission glucose levels (above 200 mg / dL), in both diabetic and
 non-diabetic patients, were associated with higher mortality from cardio-vascular etiologies
 within one year of admission (8). Among non-diabetic patients admitted to the hospital due to
 acute myocardial infarction, admission glucose levels above 180 mg / dL were associated with
 a significant increase in all-causes in-hospital mortality (9). However, there is currently
 insufficient information regarding the prognostic impact of high admission glucose levels of
 non-diabetic septic patients admitted to the ICU (10).

 Outcomes:

 Main outcome: To study the correlation between high blood glucose levels (above 180 mg / dL)
 upon ICU admission of non-diabetic patients with sepsis, and 28-day mortality, compared to
 ICU admitted septic patients with normal blood glucose levels upon admission (less than 180
 mg / dL and above 70 mg / dL).

 Secondary outcomes: To study the correlation between high blood glucose levels (above 180 mg
 / dL) upon ICU admission of non-diabetic patients with sepsis, and morbidity parameters, such
 as ventilation days, vasopressor and inotropic support, need for dialysis, need for
 tracheostomy, APACHE-2 score and admission lactate level compared to ICU admitted septic
 patients with normal blood glucose levels upon admission (less than 180 mg / dL and above 70
 mg / dL).

 Materials and methods:

 Study design: Cohort retrospective study. Study population: Non-diabetic patients aged 18-99
 who were admitted to the ICU between 1.1.2014 and 30.1.2020 due to sepsis or septic shock.

 Study groups: Group A - Patients with admission blood glucose level lower than 180 mg / dL
 (but higher than 70 mg / dL).

 Group B- Patients with admission blood glucose level higher than 180 mg / dL. Inclusion
 criteria: 1. Patients admitted to the ICU between 1.1.2014-30.1.2020. 2. Diagnosis of sepsis
 or septic shock upon admission. 3. Age over 18 years. 4. No previous diagnosis of diabetes
 mellitus. Exclusion criteria: 1. Patients with prior diagnosis of diabetes mellitus. 2.
 Admission hypoglycemia (blood glucose levels below 70 mg / dL). 3. Patients who were given
 insulin or intravenous glucose before the first ICU blood glucose measured level.

 Data collection: Observational data collection format from hospital files and computerized
 systems (Chameleon system and iMDsoft software).

 Data to be collected: age, gender, ICU and hospital admission times, source of infection,
 ventilation days, pressor or inotropic support, 28-day mortality, past medical history
 including regular medications, APACHE-2 score, admission lactate level, need for dialysis and
 need for tracheostomy.

 Study group size: 1000 patients. Statistical analysis: All the parameters will be
 statistically examined by a qualified statistician depending on the type of data. We will use
 the Chi square test to analyze the individual data and the Mann-Whitney test to analyze the
 continuous data.
Inclusion Criteria:1. Patients admitted to the ICU between 1.1.2014-30.1.2020. 2. Diagnosis
 of sepsis or septic shock upon admission. 3. Age over 18 years. 4. No previous diagnosis of
 diabetes mellitus.

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 Exclusion Criteria:1. Patients with prior diagnosis of diabetes mellitus. 2. Admission
 hypoglycemia (blood glucose levels below 70 mg / dL). 3. Patients who were given insulin or
 intravenous glucose before the first ICU blood glucose measured level.

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