Mendez D and Lapus R, J Emerg Med Trauma Surg Care 2015, 2: 010

DOI: 10.24966/ETS-8798/100010

HSOA Journal of
Emergency Medicine Trauma and Surgical Care
Research Article

goal-directed therapy in 102 children with severe sepsis or

Sepsis in Children fluid-refractory septic shock treated in two pediatric intensive
care units, 28-day mortality was lower in patients who received
Donna Mendez* and Robert Lapus goal-directed therapy versus therapy guided by blood pressure
(12 versus 39 percent) [9]. In another study, the implementation of
Department of Pediatric Emergency Medicine, The University of T
exas-Health Science Center at Houston Medical School, Houston, timely goal directed interventions by a mobile intensive care team
Texas, USA compatible with the ACCM 2002 guidelines for 331 children with
meningococcemia in the United Kingdom was associated with a
decrease in the case fatality rate from 23 to 2 percent over five years
(annual reduction in the odds of death 0.41, 95% CI: 0.27-0.62) [10].

Abstract Date Collection

Background: Sepsis in children still accounts for a substantial
We collected all the articles that were published from January
morbidity and mortality despite the advances in treatment. Rapidly 1997 to January 2015, which described children with SIRS or sepsis.
recognizing a child with SIRS or sepsis is key to having favorable These articles were obtained by searching PUBMED using key words
outcomes. The purpose of this review is to provide the most current “sepsis”, “pediatric sepsis”, “SIRS”, “pediatric SIRS” “CRP and sepsis”,
recommendations for evaluation and treatment including differences “Procalcitonin and sepsis”, “CRP and sepsis”, and “Lactate and
in the American College of Critical Care Medicine (ACCM) and sepsis.” Retrospective and prospective studies were included. We
Pediatric Advanced Life Support (PALS) sepsis guidelines. excluded studies which did not include children. Opinion articles
Methods: The literature is from a range of sources that was were also excluded from this review. After selecting the articles,
reviewed and synthesized to provide an overview of the most current the relevant information was extracted and classified according to
methods for evaluation and treatment of sepsis in children. evaluation and treatment. After screening the articles, a total of 60
Results: This review summarizes the definitions, clinical articles were considered to be relevant.
manifestations, evaluation and treatment of sepsis in children.
Inclusion of the most recent biomarkers of sepsis are included and Definitions
reviewed.
As stated before the early recognition of SIRS and sepsis is key
to a favorable outcome. In order to identify SIRS and sepsis their
Introduction definitions will be reviewed. These definitions have been developed
Systemic Inflammatory Response (SIRS) and Sepsis are important by the International Consensus Conference on Pediatric Sepsis
to recognize early and treat aggressively since without treatment it (Systemic Inflammatory Response Syndrome-SIRS). SIRS is a
can lead to increased morbidity and mortality. Even though widespread inflammatory response that may or may not be associated
pediatric mortality has decreased with the advent of antibiotics and with infection. Two or more of following criteria (one which needs to
better management, the mortality is still 4-10 percent in pediatric be abnormal temp or leukocyte count) indicate SIRS (Table 1).
patients with severe sepsis [1-3] and 13 to 34 percent in pediatric • Core temp of >38.5˚C (100.4˚F) or <36˚C (96.8˚F)
patients with septic shock [1-8].
• Tachycardia (mean HR more than 2 SD above normal for age),
It is important to rapidly recognize SIRS and sepsis early to have or for children younger than 1 year, bradycardia (mean HR <10th
favorable outcomes in children. Early recognition and treatment with percentile for age).
the American Critical Care Medicine (ACCM)-PALS guidelines has
improved outcomes in children. In a study by Han and colleague, they • Mean RR more than 2 SD above normal for a age or mechanical
showed a 92% survival versus 62% survival among patients who did ventilation for acute pulmonary process.
not receive ACCM-PALS guidelines [8]. In a prospective study of 91 • Leukocyte count elevated or depressed for age or >10 % immature
infants and children presenting to community hospitals with septic neutrophils.
shock, each hour delay in initiation of appropriate resuscitation or
persistence of hemodynamic abnormalities was associated with a Sepsis is defined as SIRS in the presence of suspected or proven
clinically significant increased risk of death [8]. In a trial of infection. Severe sepsis is sepsis with cardiovascular dysfunction,
Acute Respiratory Distress Syndrome (ARDS), or dysfunction in
*Corresponding author: Donna Mendez, Department of Pediatric Emergency 2 or more other organ systems [11]. Septic shock is sepsis with
Medicine, The University of Texas-Health Science Center at Houston cardiovascular dysfunction that persists despite the administration
Medical School, Houston, Texas 77030, USA, Tel: +44 7137044060;
E-mail: [email protected] of ≥40cc/kg of isotonic fluid in 1 hour. Refractory septic shock
can be divided into fluid refractory and catecholamine resistant.
Citation: Mendez D, Lapus R (2015) Sepsis in Children. J Emerg Med Trauma Fluid-refractory shock is when cardiovascular dysfunction persists
Surg Care 2: 010. despite at least 60cc/kg of fluids. Catecholamine-resistant shock is
Received: March 15, 2015; Accepted: August 17, 2015; Published: August 31, when shock persists despite therapy with dopamine >10mcg/kg/min
2015 and/or direct-acting catecholamines (epinephrine, norepinephrine).
Citation: Mendez D, Lapus R (2015) Sepsis in Children. J Emerg Med Trauma Surg Care 2: 010.

• Page 2 of 10 •

Pediatric Systemic Inflammatory Response Syndrome Criteria

Heart Rate
(beats/min) Leukocyte Count (Leukocytes Systollic Blood Pressure
Age Group Respiratory Rate (beats/min)
X 103/mm3) (mmHg)
Tachycardia Bradycardia

Newborn (0 days to 1 week) >180 <100 >50 >34 <59

Neonate (1 week to 1 month) >180 <100 >40 >19.5 or <5 <79

Infant (1 month to 1 year) >180 <90 >34 >17.5 or <5 <75

Toddler and preschool (>1 to 5 years) >140 NA >22 >15.5 or <6 <74

School age (<5 to 12 years) >130 NA >18 >13.5 or <4.5 <83

Adolescent (>12 to <18 years) >110 NA >14 >11 or <4.5 <90

Table 1: Demonstrates the SIRS criteria according to age [11].

NA: Not Applicable
Multiple organ failure is useful for tracking clinical changes and increasing heart rate as fever becomes elevated. This rise in heart
response to treatment in children with septic shock. The International rate can be adjusted for fever. For each 1 degree F above 100 F, the
Consensus on Pediatric Sepsis developed criteria for organ correction was 5 beats per minute or 9.6-10 beats per minute for each
dysfunction [11]. 1 degree C [12,13] (Table 2).
Temperature (F) 0-1 year old 2-5 year old 6-12 year old ≥12 year old
Cardiovascular
<100 180 140 130 110
Hypotension or reliance on a vasoactive drug to maintain blood
101 185 145 135 115
pressure, or two of the following: metabolic acidosis, elevated arterial
102 190 159 140 120
lactate, oliguria, or prolonged capillary refill.
103 195 155 145 125
Respiratory 104 200 160 150 130
Arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) 105 205 165 155 135
<300, arterial carbon dioxide tension (PaCO2) >65 torr or 20mmHg 106 210 165 155 140
over baseline PaCO2, need for >50 percent FiO2 to maintain oxygen
Table 2: Heart rate corrected for temperature [12].
saturation ≥92 percent, or need for nonelective mechanical
ventilation. Other physical findings

Neurologic Other physical findings of shock include: Ill appearance, prolonged

Glasgow coma score ≤11 or acute change in mental status. capillary refill (>3 sec), diminished peripheral pulses, mottled
extremities and altered mental status (irritability, anxiety, confusion,
Hematologic lethargy, and somnolence).
Platelet count <80,000/microL or a decline of 50 percent from
Presentation of shock in children versus adults
highest value recorded over the past three days or Disseminated
Intravascular Coagulation (DIC), a consumptive coagulopathy Early in shock, children have circulatory compromise which is
diagnosed by clinical findings of hemorrhage and microthrombi and exhibited by tachycardia and subtle alteration in mental status. When
laboratory abnormalities including thrombocytopenia, prolongation stroke volume is decreased because of hypovolemia or reduced
of clotting times (PT and aPTT), and evidence of fibrinolysis (low cardiac function, tachycardia is the compensatory mechanism used to
fibrinogen with elevated fibrin degradation products), which is a maintain cardiac output (cardiac output = heart rate X stroke volume).
common hematologic manifestation in sepsis. The ability of children to compensate with tachycardia is less than in
Renal adults. Adults can easily double their heart rate but children cannot.
This tachycardia in children may compromise cardiac output because
Serum creatinine ≥2 times upper limit of normal for age or twofold of inadequate ventricular filing time. Because of this “limited cardiac
increase in baseline creatinine. reserve,” as cardiocirculatory compromise progresses, children
Hepatic vasoconstrict their peripheral tissue microvascular beds in attempt to
maintain cardiac preload and perfusion pressure to central organs. If
Total bilirubin ≥4mg/dL (not applicable to newborn) or Alanine circulatory insufficiency progresses, hypotension occurs, circulatory
Aminotransferase (ALT) >2 times upper limit of normal for age. collapse, circulatory failure and eventual cardiac arrest.
Clinical Diagnostics of Septic Shock Types of shock and clinical findings
Vital signs Distributive shock which is also called warm shock is
Children with septic shock have alterations in their vital signs. characterized by hyperdynamic physiology with decreased systemic
Tachycardia is a sensitive, though non-specific indicator in early vascular resistance and elevated cardiac output. The physical findings
stages of shock. Hypotension is a late sign. Tachypnea, bradypnea, or for warm shock are: flash capillary refill (<1 second), bounding pulses,
apnea are other signs of septic shock. Fever or hypothermia (especially warm dry extremities, and wide pulse pressure (typically greater than
in infants) are also signs of shock. Fever effects heart rate by 40 mmHg in older children and adults).
Volume 2 • Issue 2 • 100010
J Emerg Med Trauma Surg Care ISSN: 2378-8798, Open Access Journal
DOI: 10.24966/ETS-8798/100010
Citation: Mendez D, Lapus R (2015) Sepsis in Children. J Emerg Med Trauma Surg Care 2: 010.

• Page 3 of 10 •

Cold shock is characterized by an increased systemic vascular • Arterial Blood Gas (ABG) or Venous Blood Gas (VBG)-Children
resistance and decreased cardiac output. The physical findings are: with sepsis frequently have acidosis from poor tissue perfusion.
delayed capillary refill (>2 seconds), diminished pulses and mottled
or cool extremities. • Complete Blood Count (CBC)-Sepsis in children frequently is
associated with leukocytosis or leukopenia.
Etiology
• Blood lactate -Elevation of blood lactate (arterial >3.5mmol/L or
Bacteria and viruses are the most frequent cause of sepsis. venous >4.0mmol/L) is associated with sepsis.
Bacteria • Serum Electrolytes-Electrolyte abnormalities (eg: Hyponatremia,
In table 3, the most common bacteria by age group is listed. Also hyperkalemia, hypokalemia, and hypophosphatemia) may be
listed are the recommended antibiotic coverage for each bacterium. associated with sepsis through syndrome of inappropriate secretion
of antidiuretic hormone and capillary leak.
Viruses
• Serum calcium-Ionized calcium <1.1mml/L, or nonionized (4.8mg/
Viral pathogens can present with the same symptoms as bacterial dL) may affect myocardial function & vascular tone. Treat with
sepsis. The following viral etiologies are: calcium gluconate 10% at dose of 50-100mg/kg up to 2g slowly by
• Respiratory (RSV, influenza, parainfluenza, adenovirus, metapneu- IV or IO (don’t give with bicarbonate). Treat hypocalcemia with
movirus) calcium chloride 10% in dose of 10-20mg/kg up to 1g in central line
or IO. Infants under 12 months may rely on extracellular calcium
• H1N1 to maintain cardiac contractility. Animal models suggest
improvement, but no human studies do, so it is recommended only
• EBV, CMV
to treat if hypocalcemia.
• Herpes simplex, enterovirus.
• Serum creatinine-Renal insufficiency suggested by a serum
Fungi creatinine >2 times upper limit of normal for age or twofold increase
in baseline creatinine is support the diagnosis of septic shock.
Fungal infections more common in children with the following
risk factors: • Alanine Serum total bilirubin and Alanine aminotransferase- A
• Malignancy total bilirubin ≥4mg/dL, (not in newborn) or Alanine aminotrans-
ferase (ALT) >2 time upper limit of normal for age indicates liver
• Indwelling vascular catheters dysfunction in sepsis.
• Prolonged neutropenia (>4 days) [14] • Prothrombin Time (PT) Partial Thromboplastin Time (aPTT), and
• Other - Parasitic or Rickettsial International Normalized Ratio (INR)-An elevation of PT and aPTT
or INR suggests Disseminated Intravascular Coagulopathy (DIC).
Culture negative sepsis
• Fibrinogen & D-Dimer-Decreased fibrinogen and increased
Between 30-75% of children with sepsis have no infectious D-Dimer support DIC
etiology identified [5,15,16]. Culture negative sepsis may indicate
host response to bacterial components, such as endotoxin, or prior • Cultures- blood, urine, CSF, wound
antibiotic treatment. It may be due to insensitive detection with a Biomarkers
blood culture. New Polymerase Chain Reactant (PCR) testing may
improve detection of the organism [17,18]. Distinguishing SIRS from sepsis can be confusing because there
are a number of noninfectious conditions that present like SIRS,
Evaluation such as burns, trauma, pancreatitis, and autoimmune disorders. It is
Clinical evaluation important to make the distinction between SIRS and sepsis because
it would dictate whether antibiotics would be administered and the
As the definition of SIRS and sepsis include the vital signs duration of antibiotic therapy. Diagnostic biomarkers establish the
parameters, this emphasizes how important the clinical evaluation presence or absence of clinical conditions and in this case, sepsis, they
is. Evaluating the patient for prolonged capillary refill, diminished would help in distinguishing SIRS from sepsis.
peripheral pulses, change in mental status and mottled extremities is
vital prior to using laboratory studies as a guide in defining SIRS and C-reactive protein CRP
sepsis. Some of the first applications of CRP in pediatrics were related to
identifying neonates with sepsis in whom clinical manifestations of
Laboratory Studies
severe illness were often nonspecific. CRP was also used in a variety
• Rapid glucose-Hypoglycemia is associated with sepsis in of other clinical scenarios to distinguish infection from inflammation.
children. Children have less glycogen stores than adults so they CRP alone lacks the specificity to consistently discriminate between
become hypoglycemia more frequently those adults with sepsis. infection and non-infection [19] McCabe and Remington reported
Hypoglycemia is defined as < 60 mg/dl in children, < 45 mg/dl in that CRP values did not differ significantly among patients with or
neonates. Treat hypoglycemia with 2.5-5mL/kg of 10% Dextrose without bacteremia [20]. Owing to its poor specificity, it is often used
solution (D10W) for infants to children up to 12 years, and 1-2mL/ in combination with other biomarkers as part of a panel of tests to
kg of 25 percent Dextrose (D25W) in adolescents. assist clinicians with diagnosis [21,22].
Volume 2 • Issue 2 • 100010
J Emerg Med Trauma Surg Care ISSN: 2378-8798, Open Access Journal
DOI: 10.24966/ETS-8798/100010
Citation: Mendez D, Lapus R (2015) Sepsis in Children. J Emerg Med Trauma Surg Care 2: 010.

• Page 4 of 10 •

Age Pathogen Antibiotic Coverage Adminster

Vancomycin Ampicillin & Gentamicin

Staphylococcus aureus Listeria Gram negative (especially E Coli) Ampicillin & Gentamicin
Gentamicin or Cefotaxime
≤28 days Group B Streptococcus Or Cefotaxime
Ampicillin & Gentamicin
Herpes simplex virus +/-Acyclovir
Acyclovir with clinical signs

Vancomycin
Staphylococcus aureus
Gent or Cefotaxime Vancomycin &
29 days- 3 mos Gram negative (especially E Coli)
Zosyn for GI source Ceftriaxone or Cefepime
Group B Streptococcus (rare)
Ampicillin & Gentamicin

Streptococcus pneumonia Cefotaxime/Ceftriaxone & Vanc (meningitis) Vancomycin

>3 mos
Neisseria meningitidis Cefotaxime/Ceftriaxone Ceftriaxone or Cefepime

Gram positive (Coagulase-negative staphylococci, Staphylococcus aureus,

Vancomycin Vancomycin
Febrile neutropenia Streptococcus pneumonia, viridans streptococci)
Cefepime or Ceftazidime Cefepime or Ceftazidime
Gram negative (Pseudomonas aureus, E coli, Klebsiella)

Vancomycin
Vancomycin
In hospital-acquired Coagulase-negative staphylococci Gram negatives Cefepime or Ceftazidime
Cefepime or Ceftazidime

Table 3: Bacterial etiology based on age.

Information from up to Date 2014, Septic Shock: Rapid recognition and initial resuscitation in children
CRP and Procalcitonin (PCT) Soluble adhesion molecules
These inflammatory biomarkers are not recommended in routine During sepsis it is postulated that aberrant leukocyte activation
testing [23,24]. CRP and procalcitonin have been helpful in certain and recruitment into host tissues plays a role in causing breakdown
cases. Procalcitonin and C-reactive protein have been shown to be of the vascular endothelium [30]. Inflammatory leukocyte
useful in predicting serious bacterial infection in infants and young recruitment is initiated by soluble mediators (for example, cytokines
children who present to an emergency department with fever and or bacteria-derived lipopolysaccharide) which upregulate
no apparent source of infection [25,26]. In a study by Luaces-Cubells adhesion molecule expression on both leukocytes and the
and colleagues, 868 children were studied. In this study, either PCT endothelium. This upregulation results in a multistep adhesion cascade
or CRP had a higher diagnostic reliability than WBC and Absolute whereby circulating immune cells sequentially roll on, firmly adhere
Neutrophil Count (ANC). More importantly, in children with to, and transmigrate across the endothelium [31-33] during the
duration of fever <8 hours, PCT was the biomarker with the highest progression of inflammatory responses, soluble isoforms of the leukocyte
predictive value. CRP and PCT may also be useful in predicting recruitment adhesion molecules are shed from cell surfaces and
bacterial infection in patients with fever and neutropenia [27,28]. accumulate within the circulating blood plasma [34]. These soluble
isoforms have been considered promising as biomarkers of sepsis.
Procalcitonin (PCT) Five soluble adhesion molecules are associated with sepsis:
PCT elevation has been associated with sepsis. In a prospective E-selectin, L-selectin, intercellular adhesion molecule-1 and
study in children, procalcitonin’s usefulness in distinguishing vascular cell adhesion molecule-1. Briassoulis and colleagues
bacteria from viral infection in early and rapid diagnosis in showed significant increase of sE-selectin, as well as sL-selectin and
neutropenic children with Acute Lymphoblastic Leukemia (ALL) was ICAM-1, especially amongst survivors [35]. The authors concluded that
shown. The study included five groups (A, B, C, D and E) of children with inadequate or suppressed shedding during sepsis might be
ALL undergoing intensive chemotherapy. Groups A and B consisted associated with increased mortality, and they hypothesize that
of neutropenic children with bacterial and viral infection, respectively. the shedding process is indeed protective for the host. Similarly,
Groups C and D consisted of non neutropenic children with in a large pediatric ICU study on microcirculatory dysfunction in
bacterial and viral infection, respectively. Group E consisted of meningococcal sepsis in children, levels of sE-selectin, sVCAM-1 and
children without neutropenia and without fever. In all groups, blood sICAM-1,but not sP-selectin, were significantly increased in septic
samples were collected upon admission and then for 7 days on a patients but negatively correlated with the degree of microcirculatory
daily basis. Levels of CRP, PCT, Tumor Necrosis Factor (TNF)-a, dysfunction (a measure of sepsis severity), as assessed by sublingual
Interleukin (IL)-1b, IL-8, and sTNFRII were determined in all blood imaging [36].
samples. They found a highly significant difference in PCT levels
between bacterial and nonbacterial episodes. Sensitivity and Interleukin 6 (IL-6)
specificity of PCT were 94 and 96.5%, respectively [27]. In a Cytokines are diagnostic markers and their levels are increased
study by Samransamruajkit and colleagues, they investigated the early in the infectious process [37,38], Interleukins are
prognostic value of initial plasma N-terminal (NT) pro- B-type pro-inflammatory cytokines predominantly produced by monocytes,
Natriuretic Peptide (BNP) and procalcitonin in children. activated macrophages and endothelial cells. IL-6 has been shown to
Infants and children (0-15 years with severe sepsis or septic be a sensitive marker in the early phase of infection but cannot be
shock) were prospectively enrolled and treated according to the used as a reliable marker in the later stages of disease, due to its short
ACCM guidelines. Initial blood drawn was saved for NT-pro-BNP, half-life [37,39,40]. In a study by Hassan Boskabadi and colleagues
procalcitonin measurements and clinical data were also recorded. A they showed that the median serum level of IL-6 is higher in cases
total of 47 subjects were recruited. There was a significant difference with sepsis in comparison with control healthy infants. IL-6 has also
between the initial NT-proBNP levels between survivors and non the highest sensitivity (89%) and negative predictive value (91%) at
survivors, (6280.3 ± 9597ng/L, P < 0.001), but not for procalcitonin the onset of infection compared with other biochemical markers,
(12.7 ± 24.8, 29.3 ± 46μg/L, P = 0.1), respectively [29]. including CRP, TNF, and E-selectin [41]. Maamouri and colleagues
Volume 2 • Issue 2 • 100010
J Emerg Med Trauma Surg Care ISSN: 2378-8798, Open Access Journal
DOI: 10.24966/ETS-8798/100010
Citation: Mendez D, Lapus R (2015) Sepsis in Children. J Emerg Med Trauma Surg Care 2: 010.

• Page 5 of 10 •

reported a higher mean serum level of IL-6 in clinical sepsis compared Endotracheal intubation with Rapid Sequence Intubation (RSI) is
with a control group (185 vs. 5Pg/ml) [42]. In a study by Krueger often necessary in children with septic shock to protect the airway,
et al., infants were classified into documented infection, possible assist with ventilation and/or promote oxygenation. Endotracheal
infection and healthy groups and mean serum IL-6 levels were found intubation and sedation reduces the work of breathing which will
to be 1920, 50 and 8Pg/ml, respectively [43]. In another study by retain cardiac output to other organs than the muscles of respiration.
Romagnoli et al., higher serum IL-6 and 10 levels were associated with As per the updated CCM guidelines in 2007, high-flow heated and
neonatal sepsis [44]. humidified oxygen is recommended by nasal cannula until intubation
is done [18].
IL-6 has been shown to be a sensitive biomarker for predicting
bacteremia/clinical sepsis in children with febrile neutropenia [45,46]. The decision to intubate and ventilate should be based on
In severe sepsis, the best diagnostic accuracies were found for I-6 clinical assessment of increased work of breathing, hypoventilation or
and procalcitonin and these were significantly higher than those for impaired mental status. Waiting for confirmatory laboratory tests is
Lipopolysaccharide-Binding Protein (LBP) on admission [46]. discouraged since 40% of cardiac output is used for work of breathing
and delay of intubation could be deleterious [18].
Lactate Overview of RSI:
Blood lactate may help identify presence and severity of septic • Preoxygenate: Preoxygenate with 100% for 2-5 minutes. Also preox-
shock at presentation but evidence is limited in children. A ygenate with high flow oxygen 15L/min with Nasal Cannula (NC).
study of 239 children younger than 19 years of age with SIRS who Preoxygenation is essential due to a child’s intolerance for apnea. A
presented to a pediatric ED, investigated whether early hyper- high-flow NC (15L in adolescents, up to 8L in toddlers) can be used
lactatemia (serum lactate 4.0mmol/L) would be associated with for preoxygenation in addition to the face mask and while intubat-
increased risk of organ dysfunction. The primary outcome was ing. It has been shown to decrease apnea and desaturations during
organ dysfunction within 24 hours of triage; secondary outcomes RSI [50,51].
included disposition, Serious Bacterial Infection (SBI), treatments,
• Preparation of equipment and medications
and mortality. The hyperlactatemia group had a relative risk of
5.5 (95% Confidence Interval [CI] = 1.9 to 16.0) of developing • Pretreatment: Atropine- All children <1 year, children <5 receiving
24-hour organ dysfunction. As a test for organ dysfunction, succinylcholine and older children receiving a second dose of
hyperlactatemia had a positive likelihood ratio of 5.0, a sensitivity of succinylcholine. Dose: 0.02mg/k IV (Minimum single dose
31% (95% CI = 13% to 58%), and specificity of 94% (95% CI = 90% 0.1mg, Maximum single dose child 0.5mg, Maximum singledose
to 96%). Subjects with hyperlactatemia were significantly more likely adolescent 1.0 mg; if no IV access, can be given IM).
to receive Intravenous (IV) antibiotics and fluid boluses; despite • Sedation
increased therapy, they were at significantly increased risk for
• Etomidate- Not recommended per the 2007 Clinical Guidelines
Intensive Care Unit (ICU) admission and bacterial infection.
for Hemodynamic Support of Neonates and Children with Septic
They concluded among undifferentiated children with SIRS, early
Shock from American College of Critical Care Medicine.
hyperlactatemia is significantly associated with increased risk of organ
dysfunction, resuscitative therapies, and critical illness [47]. • Ketamine: Safe with hemodynamic instability if patient is not cat-
echolamine depleted. Dose 1-2mg/kg IV (If no IV access, can be
In another study by Duke and colleagues of children with sepsis given IM at dose of 3-7mg/kg)
syndrome or septic shock, blood lactate level was the earliest predictor
of outcome in children with sepsis. The following data were recorded • Midazolam- May cause hemodynamic instability at doses required
at admission, 12, 24 and 48 h: heart rate, mean arterial pressure, for sedation. Dose: 0.2-0.3mg/kg IV (maximum dose 2mg, onset of
arterial pH, base deficit, arterial lactate, gastric intramucosal pH effect requires 2-3 minutes).
(pHi) and DCO (intramucosal carbon dioxide tension minus arterial • Thioopental- Not recommended with hemodynamic instability.
partial pressure of carbon dioxide). The principal outcome measure Dose: 3-5mg/kg iV.
was survival. The secondary outcome measure was the number of • Paralytic
organ systems failing at 48 h after admission. There were 10 deaths
and 21 survivors. No variable discriminated survival from death at • Succinycholine- Not recommended with chronic myopathy or de-
presentation. Blood lactate level was the earliest discriminator of nervating neuromuscular disease: 48-72 hours after burn, crush or
survival. Using univariate logistic regression, lactate discriminated denervating injury: malignant hyperthermia; or pre-existing hy-
survivors from those who died at 12 and 24 h after admission, but not perkalemia. Dose: infants and young children: 2mg/kg IV, older
at 48 h (p = 0.049, 0.044 and 0.062, respectively [48,49]. children: 1-1.5mg/kg IV. (If IV access unobtainable, can be given
IM at dose of 3-5mg/kg)
Management • Rocuronium- Has none of the adverse effects of succinylcholine,
Clinical management making it an ideal alternative. Dose: 1mg/kg.
Management of hemodynamic support: Goal-directed therapy
Airway and breathing: Patients with septic shock should receive
for septic shock involves an aggressive systematic approach to
100 percent supplemental oxygen to optimize blood oxygen content
resuscitation targeted to improve physiologic indicators of perfusion
and delivery to tissues. Once adequate perfusion has been restored,
and vital organ function within the first six hours.
supplemental oxygen should be titrated to avoid SpO2>97 percent
to prevent the adverse effects (eg: lung injury and oxygen and The first hour goals include restoring and maintaining normal
microcirculatory vasoconstriction) associated with hyperoxia and free heart rate, capillary refill <2 seconds, and normal blood pressure. Also
radical generation [32]. this includes support of oxygenation and ventilation.
Volume 2 • Issue 2 • 100010
J Emerg Med Trauma Surg Care ISSN: 2378-8798, Open Access Journal
DOI: 10.24966/ETS-8798/100010
Citation: Mendez D, Lapus R (2015) Sepsis in Children. J Emerg Med Trauma Surg Care 2: 010.

• Page 6 of 10 •

The following therapeutic endpoints should be targeted goals: Implementation of the PALS septic shock guidelines has also
shown a reduction in mortality and morbidity. In a retrospective study
• Strong, distal pulses equal to central pulses
over a 4-year period from 5 regional pediatric centers’ specialty care
• Capillary refill <2 seconds transport teams showed a significant decrease in morbidity and
mortality. Four thousand eight hundred fifty-six patients ranging
• Normal mental status in age from newborn to 18 years of age were included. Use of the
• Urine output (>1mL/kg/hour, up to 40mL per hour). PALS guidelines resulted in a 2 fold reduction in mortality (5.06% vs
16.37%) and functional morbidity (1.56% vs 4.11%) [54].
• Blood pressure in children 1 month to 10 years (systolic pressure at
least fifth percentile for age: 60 mmHg<1month of age, 70 mmHg + Comparing the ACCM and PALS Guidelines
(2 x age in years). Blood pressure in children 10 years of age or older
The 2007 American College of Critical Care Medicine (ACCM)
(90 mmHg)
guidelines and Pediatric Advanced Life Support are similar but the
• Lactate (<4mmol/L or ≥10 percent decrease per hour until normal) ACCM guidelines provide a tighter time frame of delivery of initial
intravenous fluids boluses. The ACCM guidelines recommend fluid
• Central venous oxygen saturation (ScvO2), (≥70 percent)
boluses within the first 15 minutes and PALS recommend fluid
Treatment Guidelines boluses within first 60 minutes. Literature has shown the quicker
shock treatment is administered the better the morbidity and
There are 2 guidelines for goal directed treatment for sepsis in mortality in children with septic shock. Acting quickly and it’s relation
children. to morbidity was shown in a study by Han. Every hour’s delay in
resuscitation was associated with a 40% increase in mortality [8].
The 2007 American College of Critical Care Medicine
Other observational evidence from pediatric studies suggest that
(ACCM) guidelines vigorous fluid resuscitation may play a major role in preventing
The ACCM guidelines emphasize early goal-directed therapy end-organ damage and improve survival in sepsis [9,10,37]. In a
(Figure 1). The guidelines recommend: 1) Recognition of sepsis recent quality improvement study, a reduction in severe sepsis
in the first 5 minutes, begin oxygen and establish IV/IO; 2) Initial mortality (4.0-2.4%) was shown with the delivery of fluid boluses and
resuscitation with 20cc/kg boluses up to and over 60cc/kg until antibiotics in the first hour in a pediatric emergency department [55].
perfusion improves or unless rales or hepatomegaly develop within The improved morbidity and mortality associated with fluid boluses
the first 15 minutes; 3) If the child is fluid refractory start low dose is due to it disrupting the normal progression of sepsis. The normal
dopamine or epinephrine. If dopamine resistant start an epinephrine progression of patients in shock is for them to be initially tachycardic
drip. One must monitor for peripheral infiltration/ischemia and then as shock progresses; they become vasoconstricted (prolonged
reduce the dose if this occurs. Central dopamine, epinephrine or capillary refill of more than 3 seconds) and then eventually
norepinephrine can be administered as a first line drug as indicated hypotensive. Mortality risks increase as the patient progresses through
by hemodynamic state. For cold shock with normal blood pressure shock. Carcillo and colleagues examined over 5,000 children and
epinephrine is recommended. For cold shock with low blood pressure found the mortality with tachycardia alone was 4.5% and increased
epinephrine is recommended. For warm shock with low blood to 33.7% when tachycardia was associated with hypotension and
pressure norepinephrine is recommended; 4) If patient is prolonged capillary refill. If shock treatment guidelines are initiated
catecholamine resistant then hydrocortisone is recommended. rapidly one can reverse this mortality. By treating with normal saline
boluses early when the patient is tachycardic prevents their
Using these ACCM guidelines has shown a reduction in mortality progression to tachycardia associated with hypotension and prolonged
of severe sepsis in children [9,52,53]. In a trial of goal-directed capillary refill. It makes sense that the ACCM guidelines would prove
therapy in 102 children with severe sepsis or fluid-refractory septic to be superior to the PALS guidelines since the ACCM guidelines
shock treated in two pediatric intensive care units, 28-day mortality recommend fluid boluses be administered in the first 15 minutes and
was lower in patients who were treated by the ACCM guideline versus the PALS guidelines recommend this within the first 60 minutes.
therapy guided by blood pressure (12 versus 39 percent, respectively)
[9]. In a single centered center in Pittsburgh, patients treated Pharmacological Treatment
according to ACCM guidelines found that every hour’s delay in
Antibiotics
resuscitation in the emergency room was associated with a 40%
increase in mortality in children with septic shock [8]. In another The recommended antibiotics are listed in the table under
study, institution of the ACCM guidelines by a mobile intensive care bacterial pathogens. Current guidelines recommend obtaining blood,
team, in the care for 331 children with meningococcemia in the urine and other cultures and administer empiric broad-spectrum
United Kingdom was associated with a decrease in the case fatality antibiotics within one hour of presentation [56]. Antibiotic therapy
rate from 23 to 2 percent over five years (annual reduction in the odds should not be delayed beyond one hour and not delayed waiting for
of death 0.41, 95% CI: 0.27-0.62) [10]. cultures to be obtained. Mortality increases for each hour that the
patient does not receive appropriate antibiotics [57,58]. If IV access
Pediatric Advanced Life Support (PALS) guidelines for is limited, consider administration of cephalosporin prior to
septic shock vancomycin, due to the former’s shorter infusion time.
The PALS guidelines are comparable to the American College Corticosteroids
of Critical Care Medicine guidelines but do not have as tight a
time frame for optimal delivery of initial intravenous fluid boluses Patients who persist with shock in spite of rapid fluid
(Figure 2). administration and continuous infusions of epinephrine or
Volume 2 • Issue 2 • 100010
J Emerg Med Trauma Surg Care ISSN: 2378-8798, Open Access Journal
DOI: 10.24966/ETS-8798/100010
Citation: Mendez D, Lapus R (2015) Sepsis in Children. J Emerg Med Trauma Surg Care 2: 010.

• Page 7 of 10 •

0 min
Recognize decreased mental status and perfusion.
Emergency Department

Begin high flow O2. Establish IV/IO access.

Initial resuscitation: Push blouses of 20cc/kg isotonic

saline or colloid up to and over 60cc/kg until
perfusion improves or unless rales or hepatomegaly If 2nd PIV, start inotrope.
develop. Correction hypoglycemia and hypocalcemia.
Begin antibiotics.
5 min
Shock not Reversed?

Fluid refractory shock: Begin inotrope IV/IO. Use

atropine/Ketamine IV/IO/IM to obtain central access Dose range: Dopamine up
and airway if needed.
to 10mcg/kg/min,
Reverse cold shock by titrating central dopamine or,
epinephrine 0.05 to
if resistant, titrate central epinephrine.
Reverse warm Shock by titrating central 0.3mcg/kg/min
15 min norepinephrine.
Shock not Reversed?

Catecholamine resistant shock: Begin hydrocortisone

if at risk for absolute adrenal insufficiency

Monitor CVP in PICU. Attain normal MAP-CVP and

SevO2 > 70 Percenrt
60 min
Pediatric Intensive Care Unit

Cold Shock with Cold Shock with low Warm Shock with Low
normal blood pressures blood pressures blood pressures
1. Titrate fluid and 1. Titrate fluid and 1. Titrate fluid and
epinephrine, Scvo2 > 70 epinephrine, Scvo2 > 70 epinephrine, Scvo2 > 70
percent, Hgb > 10 g/dl. percent, Hgb > 10 g/dl. percent, Hgb > 10 g/dl.
2. If Scvo2 still< 70 2. If still hypotensive, 2. If still hypotensive,
percent, add vasodilator consider norepinephrine. consider vasopressin,
with volume loading terlipressin or
3. If scvo2 still< 70
(nitrosovasodilators, angiotensin.
percent, consider
milrininone, imrinone
dobutamine, 3. If scvo2 still< 70
and others) consider
milrininone, enoximone percent, consider low
levosemindone
or levosemindone. dose of epinephrine.

Shock not Reversed?

Persistant Catecholamine resistant shock:

Rule out and correct pericardial effusion, pneumothorax and intra abdominal
pressure > 12 mmHg. Consider pu;monary artery, PICCO or FATD catheter,
and/or Doppler ultrasound to guide fluid, inotrope, vasopressure, vasodilator
and hormonal therapies, Goal CI > 3.3 and < 6.0 L/min/m2.

Shock not Reversed?

Refractory Shock: ECMO

Figure 1: ACCM Guidelines.

Volume 2 • Issue 2 • 100010

J Emerg Med Trauma Surg Care ISSN: 2378-8798, Open Access Journal
DOI: 10.24966/ETS-8798/100010
Citation: Mendez D, Lapus R (2015) Sepsis in Children. J Emerg Med Trauma Surg Care 2: 010.

• Page 8 of 10 •

Pediatric Advance Lifes Support septic shock algorithm

- Recognize altered mental status and perfusion

First hour - Give oxygen and support ventilation, establish
vascular access and begin resuscitation according

First hour: Push repeated 20mg/kg boluses of isoton-

ic fluid up to 3,4, or more boluses based on patient
response
Additional therapies:
- Correct hypoglycemia and hypocalcemia
- Administer first-dose antibiotics STAT
- Consider ordering STAT vasopressor drip and
stress-dose hydrocortisone*

Fluid refractory shock: Being

Consider ICU
inotrope IV/IO. Use s
monitoring
atropine/Ketamine IV/IO/IM to

No

Being vasoactive drug therapy and titrate to correct

hypotension/poor perfusion; consider establishing
arterial and central venous access
- Normotensive: Begin dopamine
- Hypotensive vasodialted (warm) shock:
Being norepinephrine
- Hypotensive vasodialted (cold) shock:
Being epinephrine rather than norepinephrine

Evaluate ScvO2; goalScvO2 sat > 70 percent

ScvO2 > 70 percent ScvO2 > 70 percent ScvO2 > 70 percent

Low BP Normal BP Low BP/Poor perfusion
“Warm shock” Poor perfusion “Cold shock”

Additional fluid boluses Transfuse to Hgb > 10g/dl Transfuse to Hgb > 10g/dl
Norepinephrine +/-vasopressin Optimize arterial oxygen saturation Optimize arterial oxygen saturation
Additional fluid boluses Additional fluid boluses
Consider milrinone or nitroprusside Consider milrinone or dobutarmine +
Consider dobutarmine norepinephrine

Figure 2: PALS Guidelines.

norepinephrine may have adrenal insufficiency. Risk factors include 2mg/kg per day, intermittent or continuous infusion, maximum dose
purpura fulminans, recent or chronic treatment with corticosteroids, 50mg/kg per day) is suggested [59]. Although evidence is lacking
hypothalamic or pituitary abnormalities, or adrenal insufficiency regarding the best method to identify adrenal insufficiency in
children with refractory septic shock, assessment of adrenal status
(congenital or acquired). When adrenal insufficiency is suspected, (either baseline serum cortisol or adrenocorticotropin hormone
administration of hydrocortisone in stress doses (50mg/m2/day or stimulation testing) is advised prior to corticosteroid administration.
Volume 2 • Issue 2 • 100010
J Emerg Med Trauma Surg Care ISSN: 2378-8798, Open Access Journal
DOI: 10.24966/ETS-8798/100010
Citation: Mendez D, Lapus R (2015) Sepsis in Children. J Emerg Med Trauma Surg Care 2: 010.

• Page 9 of 10 •

References 21. Jaye DL, Waites KB (1997) Clinical applications of C-reactive protein in pedi-
atrics. Pediatr Infect Dis J 16: 735-746.
1. Hartman ME, Linde-Zwirble WT, Angus DC, Watson RS (2013) Trends in the
epidemiology of pediatric severe sepsis*. Pediatr Crit Care Med 14: 686-693. 22. Hofer N, Zacharias E, Müller W, Resch B (2012) An update on the use of
C-reactive protein in early-onset neonatal sepsis: current insights and new
2. Ruth A, McCracken CE, Fortenberry JD, Hall M, Simon HK, et al. (2014) Pe- tasks. Neonatology 102: 25-36.
diatric severe sepsis: current trends and outcomes from the Pediatric Health
Information Systems database. Pediatr Crit Care Med 15: 828-838. 23. Marshall JC, Reinhart K, International Sepsis Forum (2009) Biomarkers of
sepsis. Crit Care Med 37: 2290-2298.
3. Balamuth F, Weiss SL, Neuman MI, Scott H, Brady PW, et al. (2014) Pediatric
severe sepsis in US children’s hospitals. Pediatr Crit Care Med 15: 798-805. 24. Kaplan JM, Wong HR (2011) Biomarker discovery and development in pedi-
atric critical care medicine. Pediatr Crit Care Med 12: 165-173.
4. Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, et al.
(2003) The epidemiology of severe sepsis in children in the United States. 25. Luaces-Cubells C, Mintegi S, García-García JJ, Astobiza E, Garrido-Romero
Am J Respir Crit Care Med 167: 695-701. R, et al. (2012) Procalcitonin to detect invasive bacterial infection in non-tox-
ic-appearing infants with fever without apparent source in the emergency de-
5. Weiss SL, Parker B, Bullock ME, Swartz S, Price C, et al. (2012) Defining
partment. Pediatr Infect Dis J 31: 645-647.
pediatric sepsis by different criteria: discrepancies in populations and implica-
tions for clinical practice. Pediatr Crit Care Med 13: 219-226. 26. Maniaci V, Dauber A, Weiss S, Nylen E, Becker KL, et al. (2008) Procalci-
6. Kutko MC, Calarco MP, Flaherty MB, Helmrich RF, Ushay HM, et al. (2003) tonin in young febrile infants for the detection of serious bacterial infections.
Mortality rates in pediatric septic shock with and without multiple organ sys- Pediatrics 122: 701-710.
tem failure. Pediatr Crit Care Med 4: 333-337.
27. Hatzistilianou M, Rekliti A, Athanassiadou F, Catriu D (2010) Procalcitonin as
7. Jaramillo-Bustamante JC, Marín-Agudelo A, Fernández-Laverde M, an early marker of bacterial infection in neutropenic febrile children with acute
Bareño-Silva J (2012) Epidemiology of sepsis in pediatric intensive care lymphoblastic leukemia. Inflamm Res 59: 339-347.
units: first Colombian multicenter study. Pediatr Crit Care Med 13: 501-508.
28. Juutilainen A, Hämäläinen S, Pulkki K, Kuittinen T, Nousiainen T, et al. (2011)
8. Han YY, Carcillo JA, Dragotta MA, Bills DM, Watson RS, et al. (2003) Early Biomarkers for bacteremia and severe sepsis in hematological patients with
reversal of pediatric-neonatal septic shock by community physicians is asso- neutropenic fever: multivariate logistic regression analysis and factor analy-
ciated with improved outcome. Pediatrics 112: 793-799. sis. Leuk Lymphoma 52: 2349-2355.

9. de Oliveira CF, de Oliveira DS, Gottschald AF, Moura JD, Costa GA, et al. 29. Samransamruajkit R, Uppala R, Pongsanon K, Deelodejanawong J, Sritip-
(2008) ACCM/PALS haemodynamic support guidelines for paediatric septic payawan S, et al. (2014) Clinical outcomes after utilizing surviving sepsis
shock: an outcomes comparison with and without monitoring central venous campaign in children with septic shock and prognostic value of initial plasma
oxygen saturation. Intensive Care Med 34: 1065-1075. NT-proBNP. Indian J Crit Care Med 18: 70-76.

10. Booy R, Habibi P, Nadel S, de Munter C, Britto J, et al. (2001) Reduction 30. Aird WC (2003) The role of the endothelium in severe sepsis and multiple
in case fatality rate from meningococcal disease associated with improved organ dysfunction syndrome. Blood 101: 3765-3777.
healthcare delivery. Arch Dis Child 85: 386-390.
31. Carman CV, Springer TA (2008) Trans-cellular migration: cell-cell contacts
11. Goldstein B, Giroir B, Randolph A, International Consensus Conference on get intimate. Curr Opin Cell Biol 20: 533-540.
Pediatric Sepsis (2005) International Consensus Conference on Pediatric
Sepsis. International pediatric sepsis consensus conference: definitions for 32. Springer TA (1990) Adhesion receptors of the immune system. Nature 346:
sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 6: 2-8. 425-434.

12. Hanna CM, Greenes DS (2004) How much tachycardia in infants can be at- 33. Springer TA (1990) Traffic signals for lymphocyte recirculation and leukocyte
tributed to fever? Ann Emerg Med 43: 699-705. emigration: the multi-step paradigm. Nature 346:425-433.

13. Davies P, Maconochie I (2009) The relationship between body temperature, 34. Garton KJ, Gough PJ, Raines EW (2006) Emerging roles for ectodomain
heart rate and respiratory rate in children. Emerg Med J 26: 641-643. shedding in the regulation of inflammatory responses. J Leukoc Biol 79:
1105-1116.
14. Zaoutis TE, Prasad PA, Localio AR, Coffin SE, Bell LM, et al. (2010) Risk
factors and predictors for candidemia in pediatric intensive care unit patients: 35. Briassoulis G, Papassotiriou I, Mavrikiou M, Lazaropoulou C, Margeli A
implications for prevention. Clin Infect Dis 51: 38-45. (2007) Longitudinal course and clinical significance of TGF-beta1, sL- and
sE-Selectins and sICAM-1 levels during severe acute stress in children. Clin
15. Gaines NN, Patel B, Williams EA, Cruz AT (2012) Etiologies of septic shock in
Biochem 40: 299-304.
a pediatric emergency department population. Pediatr Infect Dis J 31: 1203-
1205. 36. Paize F, Sarginson R, Makwana N, Baines PB, Thomson AP, et al. (2012)
Changes in the sublingual microcirculation and endothelial adhesion mole-
16. Nadel S, Goldstein B, Williams MD, Dalton H, Peters M, et al. (2007) Dro-
cules during the course of severe meningococcal disease treated in the pae-
trecogin alfa (activated) in children with severe sepsis: a multicentre phase III
diatric intensive care unit. Intensive Care Med 38: 863-871.
randomised controlled trial. Lancet 369: 836-843.

17. Lucignano B, Ranno S, Liesenfeld O, Pizzorno B, Putignani L, et al. (2011) 37. Ng PC, Cheng SH, Chui KM, Fok TF, Wong MY, et al. (1997) Diagnosis of
Multiplex PCR allows rapid and accurate diagnosis of bloodstream infections late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive
in newborns and children with suspected sepsis. J Clin Microbiol 49: 2252- protein in preterm very low birthweight infants. Arch Dis Child Fetal Neonatal
2258. Ed 77: 221-227.

18. Brierley J, Carcillo JA, Choong K, Cornell T, Decaen A, et al. (2009) Clinical 38. Gonzalez BE, Mercado CK, Johnson L, Brodsky NL, Bhandari V (2003) Early
practice parameters for hemodynamic support of pediatric and neonatal sep- markers of late-onset sepsis in premature neonates: clinical, hematological
tic shock: 2007 update from the American College of Critical Care Medicine. and cytokine profile. J Perinat Med 31: 60-68.
Crit Care Med 37: 666-688.
39. Ng PC (2004) Diagnostic markers of infection in neonates. Arch Dis Child
19. Standage SW, Wong HR (2011) Biomarkers for pediatric sepsis and septic Fetal Neonatal Ed 89: 229-235.
shock. Expert Rev Anti Infect Ther 9: 71-79.
40. Bhartiya D, Kapadia C, Sanghvi K, Singh H, Kelkar R, et al. (2000) Prelimi-
20. McCabe RE, Remington JS (1984) C-reactive protein in patients with bacte- nary studies on IL-6 levels in healthy and septic Indian neonates. Indian Pe-
remia. J Clin Microbiol 20: 317-319. diatr 37: 1361-1367.

Volume 2 • Issue 2 • 100010

J Emerg Med Trauma Surg Care ISSN: 2378-8798, Open Access Journal
DOI: 10.24966/ETS-8798/100010
Citation: Mendez D, Lapus R (2015) Sepsis in Children. J Emerg Med Trauma Surg Care 2: 010.

• Page 10 of 10 •

41. Buck C, Bundschu J, Gallati H, Bartmann P, Pohlandt F (1994) Interleukin-6: 50. Lee JH, Rehder KJ, Williford L, Cheifetz IM, Turner DA (2013) Use of high
a sensitive parameter for the early diagnosis of neonatal bacterial infection. flow nasal cannula in critically ill infants, children, and adults: a critical review
Pediatrics 93: 54-58. of the literature. Intensive Care Med 39: 247-257.

42. Maamouri G, Boskabadi H, Tavakkolafshari J, Shakeri M (2006) Evaluation 51. Weingart SD, Levitan RM (2012) Preoxygenation and prevention of desatu-
Quantities Interleukin 6 in diagnosis of Neonatal sepsis. Med J Mashad Univ ration during emergency airway management. Ann Emerg Med 59: 165-175.
Med Sci 93: 253-260.
52. Booy R, Habibi P, Nadel S, de Munter C, Britto J, et al. (2001) Reduction
43. Krueger M, Nauck MS, Sang S, Hentschel R, Wieland H, et al. (2001) Cord in case fatality rate from meningococcal disease associated with improved
blood levels of interleukin-6 and interleukin-8 for the immediate diagnosis of healthcare delivery. Arch Dis Child 85: 386-390.
early-onset infection in premature infants. Biol Neonate 80: 118-123. 53. Maat M, Buysse CM, Emonts M, Spanjaard L, Joosten KF, et al. (2007) Im-
proved survival of children with sepsis and purpura: effects of age, gender,
44. Romagnoli C, Frezza S, Cingolani A, De Luca A, Puopolo M, et al. (2001)
and era. Crit Care 11: 112.
Plasma levels of interleukin-6 and interleukin-10 in preterm neonates evalu-
ated for sepsis. Eur J Pediatr 160: 345-350. 54. Carcillo JA, Kuch BA, Han YY, Day S, Greenwald BM, et al. (2009) Mortality
and functional morbidity after use of PALS/APLS by community physicians.
45. Kitanovaski L, Jazbec J, Hojker S, Dergane M (2014) Diagnostic accuracy of
Pediatrics 124: 500-508.
lipopolysaccharide-binding protein for predicting bacteremia/clinical sepsis in
children with febrile neutropenia: comparison with interleukin-6, procalcitonin, 55. Cruz AT, Perry AM, Williams EA, Graf JM, Wuestner ER, et al. (2011) Imple-
and C-reactive protein. Support Care Cancer 22:269-277. mentation of goal-directed therapy for children with suspected sepsis in the
emergency department. Pediatrics 127: 758-766.
46. Kitanovski L, Jazbec J, Hojker S, Gubina M, Derganc M (2006) Diagnostic ac-
curacy of procalcitonin and interleukin-6 values for predicting bacteremia and 56. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, et al. (2013) Sur-
clinical sepsis in febrile neutropenic children with cancer. Eur J Clin Microbiol viving sepsis campaign: international guidelines for management of severe
Infect Dis 25: 413-415. sepsis and septic shock 2012. Crit Care Med 41: 580- 637.

47. Scott HF, Donoghue AJ, Gaieski DF, Marchese RF, Mistry RD (2012) The 57. Deminger RF, Levy MM, Rhodes A, Annane D, Gerlach H, et al. (2013) Sur-
utility of early lactate testing in undifferentiated pediatric systemic inflamma- viving sepsis campaign international guidelines for management of severe
tory response syndrome. Acad Emerg Med 19: 1276-1280. sepsis and septic shock 2012. Intensive Care Med 3: 165-228.

48. Duke TD, Butt W, South M (1997) Predictors of mortality and multiple organ 58. Russell JA (2006) Management of sepsis. N Engl J Med 355: 1699-1713.
failure in children with sepsis. Intensive Care Med 23: 684-692.
59. Brierley J, Carcillo JA, Choong K, Cornell T, Decaen A, et al. (2009) Clinical
49. Asfar P, Calzia E, Huber-Lang M, Ignatius A, Radermacher P (2012) Hyper- practice parameters for hemodynamic support of pediatric and neonatal sep-
oxia during septic shock--Dr. Jekyll or Mr. Hyde? Shock 37: 122-123. tic shock: 2007 update from the American College of Critical Care Medicine.
Crit Care Med 37: 666-688.

Volume 2 • Issue 2 • 100010

J Emerg Med Trauma Surg Care ISSN: 2378-8798, Open Access Journal
DOI: 10.24966/ETS-8798/100010