|Year : 2018 | Volume
| Issue : 1 | Page : 14-21
Impact of pre-pediatric ICU management on prognosis of sepsis and septic shock at Alexandria University Children’s Hospital
Hassan A El-Kinany, Amel A.A Mahfouz, Lamiaa E Abd El-Fattah
Department of Pediatrics, Alexandria University, Alexandria, Egypt
|Date of Web Publication||7-Sep-2018|
Amel A.A Mahfouz
Department of Pediatrics, Alexandria University, Alexandria 2164655
Source of Support: None, Conflict of Interest: None
Background Pre-pediatric ICU (PICU) management in cases of severe sepsis and septic shock is an extremely important factor in the outcome of the patients. Pre-PICU management can also be the direct cause of better outcome of cases with severe sepsis and septic shock.
Aim The purpose of this study was to evaluate the pre-PICU management in cases of severe sepsis and septic shock at Alexandria University Children’s Hospital and its association with the survival rate of the cases.
Patients and methods A cross-sectional study was conducted on 40 patients during 12 months period at PICU of Alexandria University Children’s Hospital with the diagnosis of severe sepsis and/or septic shock. Their age ranged from 1 month to 12 years, 21 were males and 19 were females. All cases were subjected to history taking stressing on time from the start of illness until the patient arrived to the hospital, pre-referral treatment, number and kind of medical centers that took care of the patient before admission. The clinical condition of the patient on admission was evaluated (with respect to the degree of sepsis) and the mortality probability on admission was performed using Pediatric Index of Mortality 2 (PIM-2) score. Routine investigations were done at admission. Follow-up of the cases in PICU was evaluated by PIM-2 score, length of stay and the prognosis of cases whether improvement or death.
Results Twenty-three (57.5%) cases presented with septic shock and 17 (42.5%) cases presented with severe sepsis. Gastrointestinal tract infection and chest infection were the most common clinical sources of sepsis (16 and 10 cases, respectively). The mean of the duration from start of illness until patient arrived to the hospital was 7 days in nonsurvivors versus 3 days in survivors. Eighteen (45%) patients did not receive any antibiotic therapy before admission, whereas 22 (55%) received antibiotics via different routes before admission.
Conclusion The results indicated that gastrointestinal tract infections and chest infection were the most common clinical sources of sepsis. Administration of intravenous antimicrobial therapy with the onset of sepsis is an important factor in better prognosis of septic shock and PIM-2 score is a good predictor of mortality on the first day of admission to PICU. Referral from a tertiary hospital to PICU is a good indicator for better prognosis.
Keywords: antibiotics, pre-pediatric ICU management, septic shock, severe sepsis
|How to cite this article:|
El-Kinany HA, Mahfouz AA, Abd El-Fattah LE. Impact of pre-pediatric ICU management on prognosis of sepsis and septic shock at Alexandria University Children’s Hospital. Alex J Pediatr 2018;31:14-21
|How to cite this URL:|
El-Kinany HA, Mahfouz AA, Abd El-Fattah LE. Impact of pre-pediatric ICU management on prognosis of sepsis and septic shock at Alexandria University Children’s Hospital. Alex J Pediatr [serial online] 2018 [cited 2018 Nov 15];31:14-21. Available from: http://www.ajp.eg.net/text.asp?2018/31/1/14/240746
| Introduction|| |
Sepsis is a major cause of ICU admission and is associated with high morbidity and mortality rates . Within the last decade, several trials and protocols have focused on this condition, aiming to establish better measures for its management and prevention of potential complications. Therapeutic measures with considerable positive impacts have been largely emphasized. Mastering this challenge is largely related to the art of medical practice and it leads to more objective care of the patients .
Severe sepsis and septic shock are medical emergency conditions that should alert any staff member working in the healthcare system at any level, and be treated with the highest priority in patient care. The golden hour: the time period within which rapid treatment can make an outcome difference between life and death, is nowadays a well-known term to describe the fact that within an hour the clinician has a good chance to reduce mortality and also morbidity (time is an organ). To influence outcome of the disease, the appropriateness and speed with which sepsis therapy is administered should be similar to that of other emergencies like stroke, acute myocardial infarction, and trauma. Early recognition and treatment of sepsis can be life-saving for children in developed and underdeveloped countries .
Pre-pediatric ICU (PICU) management in patients with severe sepsis and septic shock remains the cornerstone in the outcome of the patients, and it can also be the direct cause of better prognosis of the patients.
| Aim|| |
The purpose of this study was to evaluate the pre-PICU management in cases of severe sepsis and septic shock at Alexandria University Children’s Hospital (AUCH) and its association with the survival rate of the cases.
| Patients and methods|| |
This cross-sectional study was conducted in PICU which is located in a tertiary care teaching hospital AUCH), with a capacity of 220 beds and nine-bedded ICU. The range of yearly admissions to PICU is 300–350 cases. The study was conducted after the approval of the Ethical Committee of Alexandria University, Egypt.
This study was conducted from April 2016 to April 2017 on 40 pediatric patients aged 1 month to 12 years of both sexes with the diagnosis of severe sepsis or septic shock admitted to PICU at AUCH.
The selection criteria of the cases were the following.
Forty children were enrolled in the study who were referred to PICU at AUCH with confirmed diagnosis of sepsis syndrome based on pediatric organ dysfunction criteria .
- Infants less than 1 month old.
- Patients with history of accidents or trauma.
- Primary immunodeficiency patients.
All the data for this study were obtained by reviewing the records of patients of PICU after taking an oral consent from their parents.
All patients who were included in this study had been subjected to the following steps on the first day of admission and followed until discharge.
Evaluation of pre-ICU medical care by:
- Noting the history of the patient, stressing on age, sex, residence, risk factors, date of admission, clinical source of sepsis, time from the start of illness till patient arrived at the hospital, pre-referral treatment: medications given to the patients with special emphasis on antibiotic intake, types and routes of intake, number and kind of medical centers that took care of the patient before admission (clinic, polyclinic, or hospital), and the causes of referral.
- Investigations were done during admission and the mode of transportation was noted.
- The clinical condition of the patient on admission was evaluated (with respect to the degree of sepsis) and the mortality probability on admission was performed using Pediatric Index of Mortality (PIM-2) score .
- Routine laboratory investigations at PICU (on the day of admission and the same were repeated whenever indicated):
- Renal function tests, and liver function tests blood urea nitrogen, and serum creatinine.
- C-reactive protein, prothrombin time, and partial thromboplast in time.
- Blood gases.
- Complete blood count.
- Routine cultures on admission; blood and urine cultures. Nonbronchoscopicbroncho-alveolar lavage, stool cultures, and cerebrospinal fluid examination and culture were done (whenever indicated).
The following outcomes were reported
- Length of PICU stay.
- Fate of patients in PICU (discharged or deceased).
Data were collected and entered to the computer using statistical package for the social sciences (SPSS) program for statistical analysis (version 21) (IBM Corp. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.; Released 2012). Data were entered as numerical or categorical, as appropriate. Kolmogorov–Smirnov test of normality revealed significance in the distribution of some variables, so the nonparametric statistics were adopted .
- Data were described using minimum, maximum, median, and inter-quartile range for not-normally distributed data.
- Categorical variables were described using frequency and percentage of the total.
- Comparisons were carried out between two studied independent not-normally distributed subgroups using Mann–Whitney U-test.
- χ2-Test was used to test association between qualitative variables. Fisher exact test and Monte-Carlo correction were used whenever indicated.
The binary (Cox) logistic model was used to estimate the probability of a binary response (e.g. type of infection) based on one or more predictor (or independent) variables (features). The calibration was assessed by directly comparing the observed and the customized predicted mortality across subcategories of risk. We employed the Hosmer–Lemeshow goodness-of-fit test, where a P value more than 0.05 indicates acceptable calibration .
An alpha level was set to 5% with a significance level of 95%, and a β error was accepted up to 20% with a power of study of 80%.
| Results|| |
[Table 1] showed that there was no statistical significant relation between the rate of survival and the sex, age, and residence of the studied cases. In addition, there was no statistical significant relation between past medical history, clinical source of sepsis, and the rate of survival. Duration from start of illness till patients arrived hospital (days) was longer in cases who died than cases who survived but without significant relation. The state of immunity had a statistical significant relation with the rate of survival as immunodeficient cases had poorer outcomes than immuncompetent cases [χ2(d.f.=1)=5.230, P=0.022]. Mode of transportation and the number of previous medical centers had no statistical significant relation with the rate of survival. Patients who were referred from a tertiary center: AUCH had better outcomes than patients from other levels of referral (χ2=6.423, P=0.011).
|Table 1 Relation between outcome with historical data of the studied cases (n=40)|
Click here to view
[Table 2] revealed that patients who received antibiotics before admission to PICU had better survival than patients who did not receive antibiotics with a statistically significant relation (P=0.024).
|Table 2 Relation between the outcome and medical history of the studied cases (before admission)|
Click here to view
Significantly patients who received intravenous antibiotics had better outcomes than patients who received antibiotics by other routes [P(MC)=0.006].
There was no significant relation between interventions that were done to the cases and their outcomes ([Table 3]).
|Table 3 Relation between the outcome and interventions done to the studied cases|
Click here to view
[Table 4] showed that there was a significant relation between low Glasgow Coma Scale (GCS) after admission and poor outcomes [Z(MW)=3.461, P=0.001].
|Table 4 Relation between CRT and Glasgow Coma Scale of the studied cases and the outcome|
Click here to view
[Table 5] demonstrated that the degree of sepsis syndrome, presence of arrest and respiratory failure, increased the length of stay and high PIM-2 score had statistically significant impact on the outcome and they were strong predictors for mortality.
|Table 5 Relation between the outcome and certain parameters of the pediatric ICU (after admission)|
Click here to view
Multivariate analysis logistic regression was used to determine the most important factors predicting mortality ([Table 6]). GCS was a statistically significant predictor of death. Every unit increase in the GCS will decrease the probability of death by 0.406% (log-units) (odds ratio=0.666; 95% confidence interval: 0.480–0.925) (P=0.015).
| Discussion|| |
Sepsis is a major cause of ICU admission and is associated with high morbidity and mortality rates. Within the last decade, several trials and protocols have focused on this condition, aiming to establish better measures for its management and prevention of potential complications. Therapeutic measures with considerable positive impacts have been largely emphasized. Mastering this challenge is largely related to the art of medical practice and it leads to more objective care of the patients .
The aim of this study was to find a correlation between the pre-PICU management and the outcome in pediatric patients with severe sepsis and septic shock.
The study was an observational cross-sectional study that was conducted over a year from April 2016 to April 2017 on 40 patients with diagnosis of severe sepsis and septic shock.
Regarding demographic characteristics, there was no statistically significant difference between survivors and nonsurvivors with respect to age, sex, and residence. This was similar to what was found by Weiss et al. , Delgado et al. , and Pedro et al. , all cases in these studies had pediatric septic shock. Weiss in his study titled ‘global epidemiology of pediatric severe sepsis’; studied 569 patients, found that hospital mortality in patients with severe sepsis did not differ by age or residence. Also, Pedro in his study on the etiology and prognostic factors of sepsis among 115 children and adolescents admitted to the ICU established that no significant differences were found for sex, age, and mortality rate. On contrary to the present results, age was found to affect the outcome in several studies on septic shock in adults, as Kucukardali et al. , Sadaka et al. , Blanco et al. , and Kumar et al.  found a significant relation between higher ages and mortality.
In the current study, the clinical source of sepsis was insignificantly related with the occurrence of mortality and this was consistent with the results in other researchers’ studies ,,. Weiss in his study on global epidemiology of pediatric severe sepsis, found that the most frequent sites of infection were respiratory (40%) and bloodstream (19%), but with no statistical significant correlation with mortality. However, Esper et al.  found that respiratory tract infections particularly pneumonia were associated with the highest mortality.
Gastrointestinal tract infection was the main source of sepsis in the current study (36.8% in survivor group and 42.9% in nonurvivor group), followed by chest infections. This was similar to Randolph et al. , who found that diarrheal diseases are major cause of sepsis in infants and children, especially in the underdeveloped world. Other researchers found that chest infection was the primary source of sepsis as Weiss et al. , Blanco et al. , Kumar et al. , and Boechat et al. , Annane et al. . This could be attributed to more prevalence of diarrheal disease in underdeveloped world due to poverty, ignorance, and lack of sanitation. Wiess study  was a point prevalence study that was conducted for 5 days, whereas our study was observational clinically and the laboratory study was conducted over a year. Other factors that may increase the risk of chest infections, in other studies, include environmental factors, genetic susceptibility, ethnic causes, and also because these studies occurred in developed countries.
The adequacy of initial empirical antimicrobial treatment is crucial in terms of outcome. Timely antibiotic therapy has been shown to reduce a person’s risk of dying from sepsis by 50%. Empiric antimicrobial therapy should be initiated as soon as blood and other relevant sites are cultured and maximal recommended doses should be given parentally . In the current study, a statistical significant relation was found among those who received antibiotics before admission and had a better outcome. This was consistent with the results in other researcher’s studies as Weiss et al.  and Garnacho-Montero . Weiss in his study, found that hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with significant increase in PICU mortality.
Tertiary hospital is a referral hospital providing comprehensive, multidisciplinary, regionalized patient care to children up to 18 years of age. This includes the provision of a full range of medical and surgical care for severely ill children, pediatric residents present with 24 h pediatrician coverage, an organized pediatric research program, pediatric ICU, basic emergency medical service, and physical therapy. In the current study, 15 (37.5%) patients came to AUCH (tertiary hospital) before admission, 14 (35%) from polyclinics, five (12.5%) from primary or secondary hospitals and four (10%) from polyclinics. There was a statistically significant relation between higher survival rate and patients who were admitted at the tertiary hospital. This shows the importance of quality healthcare, providing healthcare services catering to the patient’s needs, at the right time and in a the right way .
In the current study regarding length of stay in PICU, it significantly affected mortality as median of days of survived cases was 8 versus 3 days in nonsurvivors. However, other studies by Weiss et al.  and Delgado et al.  found that length of stay did not affect mortality as there was no significant difference between survivors and nonsurvivors. This can be explained by severity of the disease in those patients who died so they stayed for short duration in PICU.
Regarding PIM-2 score, which was done on admission, it was significantly higher in the nonsurvivors and, the P value was 0.002, a finding that was similar to many other researchers as Leteurtre et al. , Slater et al. , Martha et al. , Rajasekaran et al. , and Alqahtani et al. . However, Delgado et al.  found that PIM-2 score had no significant difference between survivors and nonsurvivors and he attributed this result due to small sample size. The current study had relatively high mean PIM-2 score 35.3 (±29.7%) on the day of admission that reflects the severity of their condition. This is self-explanatory because this PICU is the referral center and the highest tertiary care center serving four governorates.
Pre-PICU management in cases of severe sepsis and septic shock remains the cornerstone in the outcome of the patients, and it can also be the direct cause of better outcome of cases of severe sepsis and septic shock. Vincent et al.  stated that, ‘if you want to change outcomes in ICU, look at what happens before the patient comes to the ICU’.
The following facts were obtained from the current study:
- Gastrointestinal tract and chest infection were the most common clinical sources of sepsis.
- Administration of proper intravenous antimicrobial therapy with the onset of sepsis is an important factor in better prognosis of septic shock.
- Referral from a tertiary hospital as AUCH to PICU is a good indicator of a better prognosis.
- PIM-2 score is a good predictor of mortality on the first day of admission to PICU.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003;348:1546–1554
Rocco J, Rocco P, Noé R, David C. Prognostic score for semi-intensive postoperative unit. Rev Bras Ter Intensiva 2003;15:153–167.
Wheeler DS Is the ‘golden age’ of the ‘golden hour’ in sepsis over? Crit Care 2015; 19:447.
Celik U, Yildizdas D, Alhan E, Celik T, Attila G, Sertdemir Y et al.
Genetic dilemma: eNOS gene intron 4a/b VNTR polymorphism in sepsis and its clinical features in Turkish children. Turk J Pediatr 2008;50:114–119.
Slater A, Shann F, Pearson G. PIM2: a revised version of the Paediatric Index of Mortality. Intensive Care Med 2003; 29:278–285.
IBM Corp. IBM SPSS statistics for Windows, version 21.0. Armonk, NY: IBM Corp. 2012.
Hosmer DW, Lemeshow S, Sturdivant RX. Applied logistic regression New Jersey, United State: John Wiley & Sons; 2013.
Weiss SL, Fitzgerald JC, Pappachan J, Wheeler D, Jaramillo-Bustamante JC, Salloo A et al.
Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med 2015;191:1147–1157.
Delgado I, Hon K, Raszynski A, Totapally B. Inotropes, absolute monocyte counts and survival of children with septic shock. J Paediatr 2016; 21:22–26.
Pedro Tda C, Morcillo AM, Baracat EC. Etiology and prognostic factors of sepsis among children and adolescents admitted to the intensive care unit. Rev Bras Ter Intensiva 2015; 27:240–246.
Kucukardali Y, Onem Y, Terekeci H, Tangi F, Sahan B, Erikci A. Mean Platelet Volume (MPV) in Intensive Care Unit (ICU) Patients: is it a useful parameter in assessing prediction for mortality? J Med Med Sci 2010;1:61–64.
Sadaka F, Donnelly P, Griffin M, O’Brien J, Lakshmanan R. Mean platelet volume is not a useful predictor of mortality in septic shock. J Blood Disord Transfus 2014;5:194.
Blanco J, Muriel-Bombin A, Sagredo V, Taboada F, Gandia F, Tamayo L et al.
Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care 2008; 12:R158.
Kumar A, Zarychanski R, Light B, Parrillo J, Maki D, Simon D et al.
Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Crit Care Med 2010;38:1773–1785.
Boechat Tde O, Silveira MF, Faviere W, Macedo GL. Thrombocitopenia in sepsis: an important prognosis factor. Rev Bras Ter Intensiva 2012; 24:35–42.
Esper AM, Moss M, Lewis CA, Nisbet R, Mannino DM, Martin GS. The role of infection and comorbidity: factors that influence disparities in sepsis. Crit Care Med 2006;34:2576–2582.
Randolph AG, McCulloh RJ. Pediatric sepsis: important considerations for diagnosing and managing severe infections in infants, children, and adolescents. Virulence 2014;5:179–189.
Annane D, Aegerter P, Jars-Guincestre MC, Guidet B. Current epidemiology of septic shock: the CUB-Rea Network. Am J Respir Crit Care Med 2003;168:165–172.
Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodovar A, Jimenez-Jimenez FJ, Perez-Paredes C, Ortiz-Leyba C. Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit Care Med 2003;31:2742–2751.
Weiss SL, Fitzgerald JC, Balamuth F, Alpern ER, Lavelle J, Chilutti M et al.
Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. Crit Care Med 2014;42:2409–2417.
Garnacho-Montero J, Aldabo-Pallas T, Garnacho-Montero C, Cayuela A, Jiménez R, Barroso S et al.
Timing of adequate antibiotic therapy is a greater determinant of outcome than are TNF and IL-10 polymorphisms in patients with sepsis. Crit Care 2006;10:R111.
Leteurtre S, Leclerc F, Martinot A, Cremer R, Fourier C, Sadik A et al.
Can generic scores (Pediatric Risk of Mortality and Pediatric Index of Mortality) replace specific scores in predicting the outcome of presumed meningococcal septic shock in children? Crit Care Med 2001;29:1239–1246.
Slater A. Monitoring outcome in paediatric intensive care. Paediatr Anaesth 2004;14:113–116.
Martha VF, Garcia PC, Piva JP, Einloft PR, Bruno F, Rampon V. Comparison of two prognostic scores (PRISM and PIM) at a pediatric intensive care unit. J Pediatr (Rio J) 2005;81:259–264.
Rajasekaran S, Kort E, Hackbarth R, Davis AT, Sanfilippo D, Fitzgerald R et al.
Red cell transfusions as an independent risk for mortality in critically ill children. J Intensive Care 2016;4:2.
Alqahtani MF, Smith CM, Weiss SL, Dawson S, Ralay Ranaivo H, Wainwright MS. Evaluation of new diagnostic biomarkers in pediatric sepsis: matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, mid-regional pro-atrial natriuretic peptide, and adipocyte fatty-acid binding protein. PLoS One 2016; 11:e0153645.
Vincent J, Rubenfeld GD. Does intermediate care improve patient outcomes or reduce costs? Crit Care 2015;19:89.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]