الفهرس 
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Abstract
Sepsis is a major health-care problem across the world accounting for an average 1 in 5 admissions to intensive care unit and it is the most severe expression of acute infection, can lead to multi-organ dysfunction and ends in death in 30–50% of ICU cases.. Sepsis defines as life-threatening organ dysfunction caused by a dysregulated host response to infection. The new definition abandoned use of host inflammatory response syndrome criteria (SIRS) in identification of sepsis and eliminated the term severe sepsis.
Report of The Agency for Healthcare Research and Quality (AHRQ) about sepsis showed that the sixth most common principal reason for hospitalization in the United States with an economic burden of $15.4 billion in 2009. Several studies have reported an increase in hospitalizations for sepsis in recent years. Data from the AHRQ Healthcare Cost and Utilization Project (HCUP) indicated a 32% increase in the rate of sepsis hospitalizations, from 492 per 100,000 populations in 2005 to 651 per 100,000 populations in 2010.
According to data from the Surviving Sepsis Campaign, mortality rates from sepsis are 41% in Europe and 28.3% in the USA. In Australia and New Zealand, a multi-center study which included 101,064 critical patients revealed that mortality rates decreased over the years and finally reached 18-20%.
The Surviving Sepsis Campaign (SSC) is a joint collaboration of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) committed to reducing mortality and morbidity from sepsis and septic shock worldwide. The elements of the 2018 bundle, intended to be initiated within the first hour, “time zero” or “time of presentation” is defined as the time of triage in the emergency department or, if referred from another care location, from the earliest chart annotation consistent with all elements of sepsis (formerly severe sepsis) or septic shock ascertained through chart review. It includes five key elements;
1- Measure lactate level (remeasure if initially > 2 mmol/L)
2- Obtain blood cultures prior to administration of antibiotics.
3- Administer broad-spectrum antibiotics.
4- Begin rapid administration of 30 mL/kg crystalloid fluids for hypotension or lactate ≥ 4 mmol/L.
5- Apply vasopressors if the patient is hypotensive during or after fluid resuscitation to target mean arterial pressure (MAP) ≥ 65 mm Hg.
APACHE IV score was designed to assess the severity of illness as well as the prognosis in the ICU and it has 17 physiological criteria, adding new variables such as mechanical ventilation, thrombolysis, impact of sedation on Glasgow Coma Scale, rescaled
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Glasgow Coma Scale, PaO2/ FiO2 ratio and disease-specific subgroups, to the existing. According to recent studies, APACHE IV exhibits satisfactory diffrentiation performance in the United States, where it was first developed, and outside the United States.
The main aim is to assess the impact of implementing the surviving sepsis campaign (SSC) guideline (2018 update) on the mortality and length of stay of ICU patients suffering from sepsis. Specific aims include; comparing the adherence of ICU physicians with the hour 1 sepsis bundle before and after the implementing of surviving sepsis campaign (SSC) guideline. comparing the achievement of the goal objective therapy before and after the intervention phase. comparing the mortality and length of stay before and after the implementing of surviving sepsis campaign (SSC) guideline.
The study is conducted in the intensive care unit (ICU) in a health insurance hospital (Karmoz Hospital with total 311 beds and 14 ICU beds capacity) in Alexandria, Egypt. It is an intervention study performed in three phases (pre intervention, intervention phase and post intervention phase)
Pre intervention phase: assessment of the current management of septic patients admitted to ICU and the compliance of physicians with SSC guideline within 6 months duration. The intervention phase: active and passive intervention through orientation in the form of short orientation sessions to ICU physicians about the SSC sepsis bundles, pocket cards and the use of applications of smart phone and Post intervention phase: re-assessment of compliance to SSC sepsis bundles after the intervention within 6 months duration. This study included a total sample of 200 cases, (90 cases in the pre intervention phase and 110 case in the post intervention phase. Data collected by using a predesigned data collection sheet for all septic patients. from the data collected, APACHE IV score calculated by using online calculator to calculate the corresponding score for each patient. Statistical analysis was done using SPSS version 20.
The demographic characteristics of the study population. Males were 56 (62.2%) in pre-intervention phase (phase Ι) and 70(63.6%) in post intervention phase (phase П), Patients from 61-80 years in pre intervention phase were 66(73.3%) and post intervention phase 79(71.8%), patients classified according to their origin of admission from emergency departments 74(82.2%)in phase Ι versus 90(81.8%) in phase П, or admission to ICU by transformation from ward 16(17.8%) in phase Ι and 20(18.2%) in phase П. Sources of infections in the two phases, pneumonia and urinary tract infection (UTI) were the major sources of infection in pre and post intervention phases, pneumonia was 32(35.6%) in pre intervention versus 55(50%) in post intervention phase while UTI was 40(44.4%) in pre intervention and 37(33.6%) in post intervention phase revealed no significant association between the two phases (x2=7.41, p=0.17)
Patients screened on admission showed that 76(84.4%) of met the criteria of quick sofa in pre intervention phase and (92.7%) met the criteria in post intervention phase with no significant association between the 2 phases (x2=3.46, p=0.06) by performing chi-square test. Another tool was used (SIRS criteria) showed 84(93.6%) matched with SIRS criteria in pre intervention phase and 110(100%) matched cases with SIRS criteria in post intervention phase revealed a significant association between the two phases (x2=3.46, p=0.06).
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Mean of APACHE IV score in phase Ι was 80(41-132), compared to phase П 74.5(20-146) showed no significant difference between the two phases after doing student t test (t=1.917, p=0.057). Median of expected length of stay (LOS) was significantly differ between phase one and phase two 5.65(2-8.2) and 4.75(1.3-10) respectively after performing Mann Whitney test (U= 378.5, p=0.004). mean expected mortality in phase Ι 31.9(5.5-80.8) is not statistically significant from mean expected mortality of phase П 23.4(1.1-84) (t=1.5, p=0.135). for actual length of stay Mann Whitney test showed a significant difference in mean length of stay between the two phases (U= 376.3, p=0.003).
Adherence of physicians to SSC hour-1 bundle, for the first element of the bundle, measure lactate level the compliance before the intervention was 81 (90%) vs 96 (87.2%) after the intervention and there were non-significant association between the 2 phases (x2 = 2.7, p=0.28). For the second element, the compliance was 4 (4.4%) in the first phase, before intervention vs 24(21.8%) after intervention and a significant association revealed after performing chi square rest (x2 = 12.4, p<0.001). Regarding the third element, administration of broad-spectrum antibiotics though the first hour, the compliance before the intervention was 27(30%) vs 66 (60%) after intervention showed a significant association (x2 =17.9, p ≤ 0.001). For the forth element, begin rapid administration of 30 mL/kg crystalloid fluids for hypotension or lactate ≥ 4 mmol/L, before the intervention phase, the compliance was 79(87.8%) and after intervention phase was 109(99.1%) with significant difference between the two phases (x2 = 11.23, p=0.001).The last element in hour 1 was, apply vasopressors if hypotensive during or after fluid resuscitation to maintain a mean arterial pressure ≥ 65 mm Hg, the compliance before the intervention was 48 (24%) and after intervention was 100(50%) with significant difference between them (x2 = 57.4, p=0.001).
Analyzing success goals achieved after 6 hours from ICU admission shows that in case of CVP in vented and non-vented patients, the achievement before the intervention was 26 (28.7%) and after the intervention 85(77.2%), For MAP (mean arterial pressure) goal, the achievement before the intervention was 76(84.4%) of cases and after the intervention was 89 (80.9%) with non-significant association between the two phases.
Oxygen saturation goal, achieved in 85 (94.4%) cases in the first phase and in 97(88.2%) in the second phase with no significant difference between the two phases (x2 = 2.4, p=0.1). Blood sugar level achieved in 125 cases from total 200 case, 52 (57.8%) before the intervention and 73 (67%) cases after the intervention with no significant association (x2 = 1.8, p=0.2). Urine output (greater than 0.5 ml/kg/ hour) achieved in 69(76.7%) of cases before the intervention in 87(79.1%) after the intervention with no significant association.
Testing compliance of physicians to SSC guideline management from 6-24 hours from ICU admission, considering hydrocortisone if vasopressor not responsive, an increases in compliance after intervention 104(94.5%) than before the intervention 62(68.9%), revealed a significant association (x2 = 23.1, p>0.001). For beginning of blood glucose chart, from total 152 diabetic patients, there were an increase in compliance after the intervention 79(96.3%) than before the intervention 64 (91.4%), revealed no significant association. for giving insulin drip if patients glucose greater than 180 mg/dl, there were 80 (97.6%) compliance after the intervention greater than before the intervention 49(70%). revealed a significant association (x2 = 22.34, p>0.001).
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Binary logistic regression analysis performed to assess various predictors to mortality revealed that age group (61-80 years) more likely to affect mortality by 3.9 odds (p=0.003) and age group more than 80 years affect mortality by 5.83 odds (p =.004) more than the reference group (age from 40-60). Before intervention (phase one) affect mortality by 6.19 odds than after intervention, p< 0.001. More than one organ dysfunction significantly affect mortality (OR=6.6, p=0.006) more likely than patients with no organ dysfunctions (reference group), administration of vasopressor was significantly affect mortality (OR)=8.95, p= 0.001) when compared to patients with normal blood pressure as a reference group. The degree of achieved goals after 6 hours shows a significant effect on mortality as two goals achieved has odds of 10.2, p=0.003, three goals has odds 13.7, p>0.001, four goals 4.56, p>0.001, when compared to full goals achievement as a reference group.
Multiple logistic regression illustrates that, patients with age group more than 80 years have more risk for mortality than age group 40-60 years by 7.6 and significance 0.002. in phase one has a significant effect on mortality more likely than phase two group with odds= 11.2, p>0.001. degree of achieved goals after 6 hours of ICU admission affect mortality as 2 or less goals (OR=11.6, p=0.005) three and four goals OR=5.1, p>0.001, when compared to full goals achievement. Administration of vasopressor had a significant effect on mortality (OR=11.3, p=0.004).
The overall survival after follow up of 30 days. It revealed that the cumulative survival at the end of 3 days was 84%, at the end of 6 days 56%, at the end of 15 days 31% and finally at the end of 1 month the cumulative survival was 29%. The median time was 7 days. in phase one the cumulative survival at the end of 3 days was 90% versus 79% in phase two, at the end of 6 days, the cumulative survival was 49% in phase one versus 62% phase two, at the end of 15 days 12%, 46% in phase one and two respectively and at the end of follow up period the cumulative survival was 11% in phase one and 43% in phase two. There is an increase of median survival in phase two (5.9 days in phase one versus 8.7 days in phase two, with a significant difference between the two phases. (log rank testp>
Matching with qSOFA score showed significant effect (p= 0.02). Different levels of consciousness showed a significant result (x2 = 25.4, p <0.001) considered as a prognostic factor for survival rate, by performing pairwise comparison, there was a significant difference between conscious patient and ALOC patients (x2 = 20.2, p> 0.001) and a significant difference between conscious patients and comatose patients (x2 = 25.8, p> 0.001) and a significant difference between comatose and ALOC patients (x2 =4.04, p= 0.04). Organ dysfunction was significantly affect survival rate (x2 = 9.3, p=0.009), pairwise comparison revealed a significant difference between patients with no organ dysfunction and patients with more than one organ dysfunction (x2 = 8.2, p= 0.004) and between one organ dysfunction and more than one organ dysfunction group (x2 = 4.9, p= 0.026). Different sources of infection may have considered as a prognostic factor on survival rate (x2 = 19.5, p= 0.002).
Measure lactate level, obtaining blood culture before administration of the first dose of antibiotic Begin rapid administration of 30 mL/kg crystalloid fluids and level of achievement of SSC hour 1 bundle not significantly affect survival rate of patients with sepsis. Only vasopressor administration affects median survival time (x2=13.7, p=0.001),
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central venous pressure goal was not significantly affect survival. mean arterial pressure considered as independent prognostic factor for survival (x2=54.8, p>0.001). Goal of oxygen saturation affect survival (x2=4.4, 0.03). by analyzing whether glucose level influenced the prognostic value of overall survival, results confirmed that the glucose level was an independent prognostic factor for survival rate (x2=16.9, p>0.001). urine output goal influenced the prognostic value of overall survival, (x2=40.01, p>0.001). degree of achievement goals had a significant effect on survival rates (x2=56.8, p>0.001), pairwise comparison revealed a significant difference between three and four goals group and full achieved group (x2=33.4, p>0.001), and between (one and two) group and full achieved goals group (x2=47.2, p>0.001). There is no significant effect of hydrocortisone administration if vasopressor not responsive and beginning of blood glucose chart on mean survival time of patients with sepsis. Insulin drip admiration considered as a prognostic factor on survival (x2=7.2, p=0.02), Degree of the achieved goals shows significant difference (x2=11.5, p=0.009), pairwise comparison revealed that there was a significant difference between full achievement and no achieved group (x2=6.7, p=0.009). cox regression analysis done showed that more than one organ dysfunction affect survival of patients with sepsis (HR= 2.6, p=0.02), achievement of oxygen saturation goal affect the survival (HR= 2.03, p=0.029) the risk of mortality increased in patients that not reached the proper oxygen saturation (HR=2.03, p=0.029), urine output goal (HR= 2.03, p =0.005) and mean arterial blood pressure goal (HR=5.04, p =0.001) all considered as factors affecting survival of patients with sepsis and degree of achievement of goals from 6-24 hours considered as factor affecting survival rates especially three and four goals (HR=2.08, p =0.005).
APACHE IV score ranged from 19 to 147 in our present study (normal range APACHE IV score from 0 to 286), Receiver operating characteristic analysis revealed that, APACHE IV score has Sensitivity 97.9% and Specificity of 58.6%, AUC, 0.887, Cut off 41 with (p < 0.001) had a high ability to predict mortality within 24 hours of ICU admission with accuracy of 88.7%
Fishbone diagram or Ishikawa diagram, performed to detect the root cause of non or low compliance of physicians to guideline, showed many reasons concerning the man power as (staff resistant to any change, low income of physician plays an important role in making physicians busy all the time, Inadequate staff to patient ratio, not all physicians have received enough training and medical staff knowledge about evidence based medicine is still poor) and other reasons concerned by measurement (Absence of any tool to measure the adequate medical management and assessment of patients), methods (Absence of clear and sustained system in work), material (no clinical guidelines available and no policies of clinical practice) , patient (patient variation, poor patient and family culture about health is very low) and environment ( highly populated area) .
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6.2. Conclusion
Implementation of SSC hour 1 bundle has a positive impact on mortality and survival of patients with sepsis admitted to ICU.
Screening tools in triage in emergency department are very useful in primary diagnosis for sepsis patients and help in earlier management for patients as time is an important factor in treatment. As qSOFA scores
APACHE IV score has high ability to predict mortality in patients in ICU with sensitivity 97.9% and specificity of 58.6% and overall accuracy 88.7%
Early goals oriented therapy (EGOT) considered as prognostic factors in survival of patients with sepsis as early management of blood sugar level, mean arterial blood pressure and oxygen saturation affect positively the survival of patients with sepsis
Organ dysfunction, early administration of vasopressor and insulin drip administration are factors that affect survival in patients with sepsis
Educational programs and training sessions has a direct impact on increasing compliance of physician to guidelines and increasing survival rate of patients with sepsis from 11% to 43%.