Evaluation of sepsis mortality in children

Transcription

1 Rom J Leg Med [26] [2018] DOI: /rjlm Romanian Society of Legal Medicine FORENSIC PATHOLOGY Mădălina Merișescu 1,2, Gheorghiță Jugulete 1,2,*, Alexandra Eugenia Bastian 1,3, Monica Luminos 1,2 Abstract: Sepsis in children is a relatively frequent condition which can associate mortality, imposing a properly administered treatment and empiric antibiotic therapy until diagnosis is established. Due to their severe condition, patients diagnosed with sepsis require extended hospital admission which entails significant resource use, often resulting in multiple complications and sequelae, sometimes even death and rarely in complete cure. Given this context, substantial human and material assets have been invested in the discovery process of new diagnostic methods, more rapidly and efficiently. The main objective was: identifying the clinical cases that meet sepsis criteria in children and evaluating the role and importance of modern diagnostic methods for the evolution and prognosis of paediatric sepsis. Another important objective is assessment of the mortality rate in patients under study. In order to accomplish the scientific objectives, we deployed a clinical prospective study on the paediatric wards in the National Institute for Infectious Diseases Prof. Dr. Matei Bals, Bucharest, during January December 2015 (60 months). The study focused on patients admitted for various evolving forms of sepsis. 263 eligible patients were registered, of whom 57 diagnosed by molecular methods. We recorded 24 deaths. We observed significant differences in patients diagnosed by molecular methods, for whom the number of admission days and implicitly associated costs decreased, as well as the number of days until the identification of the aetiological agent, specification of the molecular method and type of biological product under assay (molecular method is more permissive). In this context, the rate of mortality can decrease to a great extent. Key Words: sepsis mortality, child. INTRODUCTION Sepsis in children is a relatively frequent condition which can associate mortality, imposing a properly administered treatment and empiric antibiotic therapy until diagnosis is established. Based on the World Health Organization s latest statistics - 58% of infantile mortality cases are registered in children below 5 years of age due to infectious diseases. Furthermore, in 2011, 6.9% deaths were recorded globally in children younger than 5 years because of sepsis [3-5]. Despite the availability of modern therapeutic schemes and broad-spectrum antibiotics, the incidence of sepsis is continuously growing due to the resistant strain involved in severe systemic bacterial infections. Intensive care units are thus confronted with multiresistant germs that can determine hard-to-manage nosocomial infections which have an unfavourable evolution, associating a high risk of death. Due to their serious condition, patients diagnosed with sepsis require extended hospital admission which entails significant resource use, often resulting in multiple complications and sequelae, sometimes even death and rarely in complete cure. In this context, substantial human 1) Carol Davila University of Medicine and Pharmacy, Bucharest, Romania 2) Prof. Dr. Matei Balș Institute for Infectious Diseases, Bucharest, Romania * Corresponding author: georgejugulete@yahoo.com 3) Colentina University Hospital, Department of Pathology, Bucharest, Romania All authors had the same contribution to this article 37

2 Merișescu M. et al. and material assets have been invested in the discovery process of new diagnostic methods, more rapidly and efficiently [7, 8]. Sepsis diagnostic and treatment methods are in continuous evolution due to improved classical methods, in terms of specificity and sensitivity as well as the emergence of new modern PCR (polymerase chain reaction) techniques. The prognostic of a patient diagnosed with sepsis depends directly on the time until aetiology has been established, hence the rapid methods of diagnosis characterised by high sensitivity and specificity [6]. From a financial standpoint, the method is expected to determine rapid diagnostic certainty; correct therapeutic conduct that can lead to global decrease of hospital stay; assessment of the methods impact on the therapeutic requirements of a sepsis patient and decrease in the rate of morbidity associated with other therapeutic approaches. OBJECTIVES The focus of our study were paediatric cases of sepsis, admitted in National Institute for Infectious Diseases Prof. Dr. Matei Bals (INBIMB), Bucharest where we analysed the clinical signs and evolution of severe forms of septic shock, mortality rates, as well as medico-legal implications (correlation between necropsy results and clinical/laboratory diagnosis). The main objective was: identifying the clinical cases that meet sepsis criteria in children and evaluating the role and importance of modern diagnostic methods for the evolution and prognosis of paediatric sepsis. Another important objective is assessment of the mortality rate in patients under study MATERIAL AND METHOD We carried out a retrospective study over 5 years ( ) on all cases of sepsis in children admitted in INBIMB Bucharest. We analysed: age, sex, time lapsed Table 1. Number of deaths Death Lot: Absolute frequency patients (Relative frequency) Yes 24/263 (9.12) No 239/263 (90.88) Table 2. Time lapse until the establishment of diagnostic Time lapse until diagnostic PlexID Lot (hours) Median value (±SEM) [IC95%] 7.26 (±0.63) [5.98 la 8.55] Median (IQR) 6.00 (5.50) Min Max (Range) 2.00 la (16.00) Standard deviation (Variant) 4.06 (16.55) Skewness 1.02 Kurtosis 0.66 P value Shapiro-Wilk test from admission to death. Diagnosis was established based on clinical and laboratory criteria. Infectious aetiology was identified through specific diagnostic methods: blood cultures, cultures and smears from cutaneous lesions, PCR. RESULTS Throughout the study s 60 months of deployment we followed the evolution of 263 children, aged between 0-18 years who met sepsis and septic shock criteria, some of them being admitted in an extremely serious state. Twenty-three of these children required orotracheal intubation and VM (?), while other 63 presented multiple organ dysfunction syndromes (MODS). From the total number of patients, 263, 63 evinced severe stages of disease and from this number - 24 (0.912%) had an unfavourable evolution to exitus. (Table 1, Fig. 1). Sepsis mortality rates in US and Europe rises to 377/ cases/year, following cancer that records 331/ cases, CV (cerebrovascular accident) 223/100000, heart conditions 208/ and HIV 22, 8/ [1, 2, 6, 9]. We further investigated if and how the variables in our study influenced in any way the lot of patients. In this context, logistical regression was applied with a dependant variable- outcome and independent variablevarious studied parameters. The results can be consulted below (univariate analysis). Logistical regression allowed us to calculate odd-ratio for each predictor. Considering that mortality registered by the lot was 9%, odd-ratio is practically identical with risk-ratio. Number of treatment days until death In patients where sepsis proved fatal we calculated the number of treatment days, before exitus, considering that the initiation of specific therapy from the very first hours of admission may decrease lethality by 30%. We recorded 24 deaths, 8 being patients that died upon admission (30% of cases due to fulminate meningitis - meningococcal and pneumococcal). The same percentage was recorded in patients hospitalised for more than 21 days. The rest of percentages are equally Figure 1. Number of treatment days until death. 38

3 Romanian Journal of Legal Medicine Vol. XXVI, No 1(2018) Figure 2. Age recorded at the time of death. distributed among patients with hospital stay, namely 7, 14, 20 days (Fig. 2). In many cases the aetiological agent was isolated after death, when cultures were positive. For those 30% deceased upon admission, the death diagnostic was established solely by clinical suspicion and unspecific probes. Age at death Extreme ages can present severe forms of sepsis due to either immaturity or co-morbidities. Based on the age recorded at the time of death we observed a slightly higher value in small age patients. Thus, 12 patients accounting for 50% of the total number of deaths were younger than 3 years while 7, representing 29.16% were newborns and toddlers below 1 year of age which correlates with data in literature that highlights similar percentages (Fig. 3) [1, 2, 9]. The age groups 3-5 and 5-7 registered a small rate of deaths, namely 8% (2/24). However, for the age group 7-14 an increase of this rate can be observed % (4 cases) as well as in the age group- 25% (6 cases). Most cases were registered in the age groups 0-1 year and years. Distribution of deaths by years In reference to the distribution of deaths by years, in 2011 we registered a peak- 8 (33.33%) from the overall number. 20.8% (5) was the percentage that covered 2012 and 2014, while in 2013 and 2015 the rate decreased to 12.5% (Fig. 4). Between 2011 and 2015 the mortality rate declined significantly by approximately 20% due to improved diagnostic methods and implicitly to rapid initiation on specific antibiotic therapy. Anatomopathological examination Autopsy was performed in 9 cases, representing 37 %, 5 males and 4 females, aged 0-12 years of age. In all these cases the autopsy was performed in order to confirm or complete the diagnosis. Molecular methods One of the biggest advantages of molecular diagnostic methods is rapid detection of the etiologic agent, ultimately this representing an automatic method. Figure 3. Distribution of deaths by years. In the studied patients, the time span from the moment of sample collection until the probe s positive result ranged, on average, between 2-24 hours. In our study the time median was 6 hours, with an average of 7.26 hours and a variation from a minimum of 2 hours to maximum 18 hours (Table 2). DISCUSSION During the 60 months from study s initiation to the enrolment of the last patient we observed the evolution of 263 children, aged 0-18 years that matched the clinical and paraclinical criteria for sepsis, severe sepsis and septic shock. Twenty four deaths were registered. Of the cumulative total, 63 (23.95%) patients presented multiple organ dysfunction syndrome, 8.74% (23) sepsis and 36, 5% multiple organ failure requiring respiratory prothesis by intubation and mechanical ventilation, while 24 patients died. From the total number of 263 patients, 63 presented severe forms of disease and of them 24 (0.912%) had unfavourable evolution to exitus. The time span from the moment of sample collection until the probe s positive result ranged, on average, between 2-24 hours. Autopsy was performed in 9 cases, representing 37 % of the total of deaths. 5 were males and 4 females, aged 0-12 years of age. CONCLUSION The results from the univariate analysis indicate the following conclusions: Each day of hospital admission increases the death risk by 0.5% (p<0.05, IC95% does not contain 1). MODS increases the risk for death of, at least, 13 times (p<0.05, IC95% does not contain 1). Orotracheal intubation augments the risk of death by approximately 48 times (p<0.05, IC95% does not contain 1). In this case, we are not referring to the risk associated to the manoeuvre itself but to the risk for patients that required the procedure. In our studied patients, the time lapse from the moment of sample collection until the probe s positive result ranged between 2-24 hours which led to a decrease in the number of days spent in hospital and implicitly in the associated costs. 39

4 Merișescu M. et al. A B C D E F G H I J K L Figure 4. A, B. Cerebral abscess: circumscribed lesion with necrotic center and local inflammatory reaction consisting of neutrophils, lymphocytes and plasma cells, walled off by a vascular membrane. The brain parenchyma surrounding the abscess with reactive gliosis (Hematoxylin and eosin stain; magnification A x 100, B x 200. C, D. Purulent leptomeningitis: cerebral hemisphere with subarachnoidal space displaying vascular congestion and marked inflammatory exudate composed of neutrophils and fibrin (Hematoxylin and eosin stain; magnification C x 100, D x 200). E, F, G. Liver abscess: central area containing necrotic debris and numerous neutrophils, surrounded by a pyogenic membrane composed of granulation tissue. Adjacent liver with inflammatory infiltrate and dystrophic hepatocytes (Hematoxylin and eosin stain; magnification E, F x 100, G x400). H, I, J, K. Lung with abscessing bronchopneumonia: circumscribed suppurative inflammation with large areas of necrotic tissue, bordered by granulation tissue with numerous prominent capillaries filled with blood. The wall of the lung abscess is irregular, with a shaggy fibrinous lining and the area around the cavity shows acute and organizing bronchopneumonia (Hematoxylin and eosin stain, magnification H and J x 40, I x 100, J x 400). L. Abscessing myocarditis: diffuse myocardial infiltrate made predominantly by neutrophils among the cardiomyocytes (Hematoxylin and eosin stain, magnification x 400). Rapid diagnostic of patients with sepsis will not only diminish the number of admission days but it will also lead to a significant reduction in the rates of mortality and morbidity. One of the most important advantages of this method is rapid detection of the etiologic agent, ultimately this representing an automatic method. Conflict of interest. The authors declare that there is no conflict of interest. Acknowledgements. We would like to thank Prof. Dr. Sabina Zurac and Prof. Dr. Florica Staniceanu (Colentina University Hospital, Department of Pathology, Carol Davila University of Medicine and Pharmacy Bucharest) for supporting the cases of necropsy. 40

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