Keywords

Sepsis, Septic shock, Microorganism, Morbidity, Mortality, Intensive care unit

Introduction

Sepsis is a systemic response of the host to infectious stimuli, which consists of clinical, hemodynamic, biochemical, and inflammatory components [1], but according to the new definition, sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection [2]. During this research, the new definition of sepsis was not applied because it was published in February 2016. The number of deaths from sepsis in the U.S. increased from 154.159 in 2000 to 207.427 in 2007 [3], and the numbers of hospitalizations with sepsis have overtaken those from cardial infarction [4]. In the U.S, sepsis accounts for far more deaths than the number of deaths from prostate cancer, breast cancer and AIDS combined. Sepsis strikes an estimated 30 million people worldwide every year. The sepsis syndrome, severe sepsis, and septic shock represent a major therapeutic and economic problem [5].

Literature Review

Literature review showed two large investigations of sepsis occurrence were performed in Croatia. In one study, 314 sepsis episodes that occurred between 2000 and 2005, analysis has shown that the number of admitted patients to ICUs was increased from 3.7% in 2000 to 11.7% in 2005, while the recorded mortality was 14.2% in 2000 and 20.3% in 2005 [6]. Second study conducted on 24 ICUs from a 1-year period (November 2004-October 2005) has shown that overall 8.6% of patients hospitalized in ICUs that were treated for septic syndrome or heavy sepsis what makes sepsis the third reason in occurrence for hospitalization in ICUs. Mortality was 29% for septic syndrome, 35% for heavy sepsis and 34% for septic shock [7]. Both surveys were performed before 10 years and more, so our research gives us new insights about epidemiology of sepsis. Looking at previous studies that show that the incidence of sepsis is growing in Croatia, but our research denies that. The reduced mortality may be due to changes in the definition of sepsis, better detection and treatment of the underlying infection, or improved supportive care, after all, 10 years has passed and something has changed given the continuous progress in medicine. Because of these new results, there was a need to describe the particularities of medical/health situation in Clinical Centre Zagreb, nursing at nursing field and infection control that could be important/relevant connection with results. Croatian Nurses Society of Anesthesia, Reanimation, Intensive Care and Transfusion (CNSARICT), one of the largest nurse’s societies in Croatia, is a part of a Global Sepsis Alliance and they had recognized the need to carry out this investigation about morbidity, mortality and other characteristics related to sepsis. Inside CNSARIST there's a Commission for intensive care that has initiated and developed this research. High number of members come from Clinical Hospital Centre Zagreb, where the research was conducted.

Clinical Hospital Centre Zagreb, in the end of April 2016, had over 3215 employed health workers and 1,795 beds in accordance with the National Plan of the Ministry of Health [8]. We know that optimal number of nurses is a prerequisite for the quality of health care. Increase in the number of elderly patients with multiple comorbidities who are admitted to ICU, leads to development of new therapeutic methods which increase nursing workload [9]. Optimal ratio of nurses ideally required in ICU is 1:1. Although there is progress towards establishing such working conditions, we are unable to achieve these criteria at this point. In complex situations that may require two nurses per patient, in our conditions we can provide only one nurse per 2,5 patients. In attempt to control infections, cooperation with the Clinic of Microbiology and Clinic of Pharmacology is of great importance. Department for Anesthesia every week has a meeting with microbiologists to detect patients with infections and pharmacologists to evaluate the best antibiotic therapy. Such medical meetings are conducted in presence of microbiologists, pharmacologists, intensive care specialists and team – leader nurse. ICU is department of higher risk, and that's why the Hospital Infection Control carried out numerous inspections, for example, every day one infection control nurse visits all ICUs and monitors all patients who remain more than 3 days in ICU. That kind of supervision is the part of European Surveillance of ICU acquired infections [10]. Furthermore, the inside Hospital Infection Control conducted quarterly reports about type of microorganism in each ICU; place of sampling; antibiotic consumption and other relevant data. There are numerous other monitoring carried out by nurses and doctors in Hospital Infection Control. With constant surveillance, we can recognize with which bacteria we have a problem and what measures we need to take to put it under control. As for working with septic patients, in Croatia doctor and nurses follow the leading guidelines. For doctors that is Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock [11], and for nurses that is 63 recommendations World Federation of Critical Care Nurse [12], that was translated by CNSARICT to Croatian language and was published on the official web site of CNSARICT, and delivered in every ICU in Croatia.

Methods

The study was a prospective, observational study, designed to define the epidemiology of sepsis and septic shock, and other clinical and microbiological characteristics of ICU surgical patients in 3 intensive care units and was approved by the Ethics Committee Clinical Hospital Centre Zagreb. Informed consent was not required because there was no deviation from routine medical practice and the personal data of patients was not shown in the research and they are protected by the Law on the Protection of Patients. The sample included all admitted ICU patients between January 1st and December 31st in 2015. The study followed up all patients (>0 yrs) until death or ICU discharge. Occurrence of sepsis and septic shock was monitored using criteria defined by Surviving Sepsis Campaign (Appendix 1 and 2). Sepsis was defined as the presence (probable or documented) of infection together with systemic manifestations of infection. Severe sepsis was defined as sepsis plus sepsis-induced organdys function or tissue hypo- perfusion. Septic shock was defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation. Sepsis-induced tissue hypo-perfusion was defined as infection-induced hypotension, elevated lactate, or oliguria. The term sepsis includes sepsis and severe sepsis for easier management of data. Fungal infection was diagnosed when a fungus was isolated in any sterile sample. Documented sepsis was considered when a relevant microorganism was isolated from blood and a suspected focus (urine, or quantitative tracheal aspirate in intubated patients), or when the patient has 2 or more clinical signs of systemic inflammation according to Surviving Sepsis I Campaign Guidelines 2012. A special form was made for the purpose of the research to collect data, and was approved by the Ethics Committee Clinical Hospital Centre Zagreb. The form collected following information: type of ICU; name of the patient; date and year of birth; patient identification number; sex; input SAPS score I; referral diagnosis; proven cause of infection; name of infectious agents; isolate of microorganism; diagnosis of sepsis, severe sepsis and septic shock; condition on the day of discharge from ICU; output SAPA score II. This form was used in general, cardiac and neurosurgical intensive care units in Clinical Hospital Center Zagreb. Since epidemiology, microbiology and surveillance data is a little different between these 3 surgical ICUs, each ICU was processed separately and mutually compared. Six investigators collected data throughout the study period, 2 per each ICU. All data was revised by two senior investigators in situations when data values were either questionable or missing for required fields.

Statistical Analysis

Data was analyzed descriptively and results for continuous variables with normal distribution were presented as means ± standard deviation (± SD). Clinical data was presented as the observed proportion with 95% confidence intervals and the p<0.05 was considered to be statistically significant. For clinical characteristics of the study groups (SAPS), differences between groups were assessed using a Student’s t-test. Data was analyzed in Excel (Microsoft) and SPSS 11.0 for Windows. Variables that were clinically significant were presented with odds ratio (OR) and 95% confidence interval (CI). We also used MedCalc (MedCalc Software) software for analyses.

Results

Through one-year period, a total of 3169 patients were hospitalized in the 3 ICUs; general, cardiac and neurosurgical intensive care unit in Clinical Hospital Center Zagreb. Of the total number of admitted patients 126 of them had a condition as bacteremia, sepsis, severe sepsis and septic shock. Table 1 shows the frequency of individual diagnoses in three ICUs. Obtained data shows the highest representation of sepsis and severe sepsis (53.96%), followed by bacteremia (33.33%) and septic shock placed in third place (12.69%). Of 126 infection affected patients, 83 (65.87%) were male, 43 (34.12%) were female. The median patient age was 65 Years (mean ± SD, 62.2 ± 15.7). There were 3042 (96%) ICU survivors, and 127 (4%) ICU non-survivors. Of 127 deceased patients, 31 (24.40%) of them died of infectious complications.

Table 1: Frequency of individual diagnoses in three ICUs.

There was a difference in ICU mortality in patients who died from infections complications (neurosurgical 6.4%, general 74.1% and cardiac 19.3%). Figure 1 shows relationship between intensive care unit morbidity and mortality rates of patients with sepsis, severe sepsis and septic shock in 3 ICUs. Cardiac ICU had the largest number of patients suffering from sepsis, severe sepsis and septic shock (52.3%), but only 4.7% of them died. Characteristics of all 126 patients with bacteremia, sepsis, severe sepsis and septic shock are shown in Table 2. From 126 patient who had sepsis, sever sepsis or septic shock, we isolated 418 positive cultures of various microorganisms. Table 3 shows the type of microorganism distributed in 3 ICUs. The microorganism was considered once per patient even if present in more than one site. The most common type of microorganism was gram negative bacteria. In 418 positive cultures, 216 (51.6%) were gram negative. Pseudomonas were the most common Gram-negative microorganism, found in 58 isolates in all 3 ICUs, followed by the Gram positive micro-organism Staphylococcus, found in 52 isolates. The third most common microorganism was Candida albicans, found in 51 isolate.

Figure 1: Frequency of morbidity and mortality from sepsis, severe sepsis and septic shock in 3 ICUs

Table 2: Number of patients, number of infective patients, Simplified Acute Physiology Score (SAPS I – II), frequency of bacteremia, sepsis, severe sepsis and septic shock, ICU mortality rates, and ICU mortality from sepsis, severe sepsis and septic shock according to ICUs.

Table 3: Distribution of microorganisms in 3 ICUs. Total number of micro-organisms findings was 418. Gram-negative bacteria were present in 216 isolates. Microorganism was considered once per patient even if present in more than one site.

We tested odds ratio between patients from whom we isolated gram negative, gram positive bacteria and patients who died from sepsis, severe sepsis and septic shock and had a gram positive or gram-negative bacterium (Table 4). We found no connects ion between those who had gram negative bacteria and died, and those who had gram positive bacteria and died.

Table 4: OR, odds ratio; CI, confidence interval and p Value between those who had gram-negative bacteria and died and those who had gram-positive bacteria and died.

The lung was the most common site of infection (67%), followed by the blood (48%) and urinary tract (46%) as we can see in Table 5. T test was used to test the difference between individual ICUs due to the input and output SAPS score of patients who suffered from sepsis, severe sepsis and septic shock (no=126), and we found significant differences between the intensive care units (Tables 6 and 7). T test shows difference in the output SAPS score II between cardiac and general ICU, t=2.06, p=0.43. The input SAPS score I has shown no difference between ICUs. The OR was calculated for each ICU regarding to the number of patients (Table 8).

Table 5: Site of infection in ICUs.

Table 6: Mean and SD for cardiac, general and neurosurgical ICU.

Table 7: Independent Sample Test. T test of input SAPS score I and output SAPS score II between cardiac and general ICU.