Diagnosis
We must remember, however, that even though countless laboratory and imaging tests
are available today, sepsis essentially remains a clinical diagnosis. Even consensus
criteria for diagnosis of sepsis and septic shock may fail. Only two-third of patients
treated at intensive care units for severe sepsis or septic shock satisfied the consensus
criteria.[22]
The systemic inflammatory response syndrome, which was first introduced by the American
College of Chest Physicians and the Society of Critical Care Medicine, helps us to
detect the systemic inflammatory response, its severity, and the choice of therapy.[23]
[24]
[25] In 2005, the International Pediatric Consensus Conference adapted the definition
of SIRS, sepsis, and related diagnoses to age-specific normal values of childhood
([Tables 1]
[2]
[3]
[4]).
Table 1
Definitions of SIRS, infection, sepsis, severe sepsis, and septic shock[a]
|
SIRS[a]
[c]
|
The presence of at least two of the following four criteria, one of which must be
abnormal temperature or leukocyte count:
|
|
Core[b] temperature of >38.5°C or <36°C
|
|
Tachycardia, defined as a mean heart rate >2 SD above normal for age in the absence
of external stimulus, chronic drugs, or painful stimuli, or otherwise unexplained
persistent elevation over a 0.5- to 4-h period or for children <1 y old: bradycardia, defined as a mean heart rate <10th percentile
for age in the absence of external vagal stimulus, beta-blocker drugs, or congenital
heart disease, or otherwise unexplained persistent depression over a 0.5-h time period
|
|
Mean respiratory rate >2 SD above normal for age or mechanical ventilation for an
acute process not related to underlying neuromuscular disease or the receipt of general
anesthesia
|
|
Leukocyte count elevated or depressed for age (not secondary to chemotherapy-induced
leukopenia) or >10% immature neutrophils
|
|
Infection
|
A suspected or proven (by positive culture, tissue stain, or polymerase chain reaction
test) infection caused by any pathogen or a clinical syndrome associated with a high probability of infection. Evidence of
infection includes positive findings on clinical exam, imaging, or laboratory tests
(e.g., white blood cells in a normally sterile body fluid, perforated viscus, chest
radiograph consistent with pneumonia, petechial or purpuric rash, or purpura fulminans)
|
|
Sepsis
|
SIRS in the presence of or as a result of suspected or proven infection
|
|
Severe sepsis
|
Sepsis plus one of the following: cardiovascular organ dysfunction or acute respiratory distress syndrome or two or more other organ dysfunctions; organ dysfunctions are defined in [Table 2]
|
|
Septic shock
|
Sepsis and cardiovascular organ dysfunction as defined in [Table 2]
|
Abbreviations: SD, standard deviation; SIRS, systemic inflammatory response syndrome.
a Based on data from Goldstein et al.[5]
b Core temperature must be measured by rectal, bladder, oral, or central catheter probe.
c See [Table 3] for age-specific ranges for physiological and laboratory variables.
Table 2
Organ dysfunction criteria[a]
|
Cardiovascular dysfunction
|
Despite administration of isotonic intravenous fluid bolus ≥40 mL/kg in 1 h:
|
|
Decrease in BP (hypotension) 5th percentile for age or systolic BP < 2 SD below normal
for age
|
|
or
|
|
Need for vasoactive drug to maintain BP in normal range (dopamine >5 µg/kg/min or
dobutamine, epinephrine, or norepinephrine at any dose)
|
|
or two of the following:
|
|
Unexplained metabolic acidosis: base deficit >5 mEq/L
|
|
Increased arterial lactate more than two times upper limit of normal
|
|
Oliguria: urine output <0.5 mL/kg/h
|
|
Prolonged capillary refill: >5 s
|
|
Core to peripheral temperature gap >3°C
|
|
Respiratory
|
PaO2/FIO2 < 300 in the absence of cyanotic heart disease or preexisting lung disease
|
|
or
|
|
PaCO2 >65 Torr or 20 mm Hg over baseline PaCO2
|
|
or
|
|
Proven need or >50% FiO2 to maintain saturation >92%
|
|
or
|
|
Need for nonelective invasive or noninvasive mechanical ventilation
|
|
Neurologic
|
Glasgow Coma Score < 11
|
|
or
|
|
Acute change in mental status with a decrease in Glasgow Coma Score ≥3 points from
abnormal baseline
|
|
Hematological
|
Platelet count of 80,000/mm3 or a decline of 50% in platelet count from highest value recorded over the past 3
d (for chronic hematology/oncology patients)
or
|
|
International Normalized Ratio > 2
|
|
Renal
|
Serum creatinine more than two times upper limit of normal for age or twofold increase
in baseline creatinine
|
|
Hepatic
|
Total bilirubin < 4 mg/dL (not applicable for newborn)
|
|
or
|
|
ALT two times upper limit of normal for age
|
Abbreviations: ALT, alanine aminotransferase; BP, blood pressure; SD, standard deviation.
a Goldstein et al.[5]
Table 3
Pediatric age groups for severe sepsis definitions[a]
|
Newborn
|
0 d to 1 wk
|
|
Neonate
|
1 wk to 1 mo
|
|
Infant
|
1 mo to 1 y
|
|
Toddler and preschool
|
2–5 y
|
|
School age child
|
6–12 y
|
|
Adolescent and young adult
|
13 to <18 y
|
a Goldstein et al.[5]
Table 4
Age-specific vital signs and laboratory variables[a]
[b]
|
Heart rate (beats/min)
|
Respiratory rate (breaths/min)
|
Leukocyte count (leukocytes 103/mm3)
|
Systolic blood pressure (mm Hg)
|
|
Age group
|
Tachycardia
|
Bradycardia
|
|
0 d to 1 wk
|
>180
|
<100
|
>50
|
>34
|
<65
|
|
1 wk to 1 mo
|
>180
|
<100
|
>40
|
>19.5 or <5
|
<75
|
|
1 mo to 1 y
|
>180
|
<90
|
>34
|
>17.5 or <5
|
<100
|
|
2–5 y
|
>140
|
NA
|
>22
|
>15.5 or <6
|
<94
|
|
6–12 y
|
>130
|
NA
|
>18
|
>13.5 or <4.5
|
<105
|
|
13 to <18 y
|
>110
|
NA
|
>14
|
>11 or <4.5
|
<117
|
a Goldstein et al.[5]
b Lower values for heart rate, leukocyte count, and systolic blood pressure are for
the fifth and upper values for heart rate, respiration rate, or leukocyte count for
the 95th percentile.
However, clinical presentation, physical examination findings, and laboratory test
results are neither specific nor sensitive. Initial symptoms such as fever, cold chills,
tachycardia and elevated respiratory rate are too general and often accompany merely
a trivial viral infection. Prompt antibiotic therapy started in general upon these
symptoms would only aggravate antibiotic resistance, a phenomenon already significantly
observed worldwide. This may also cause unnecessary hospitalizations, with financial
and social demands thereof. On the other hand, starting therapy only after occurrence
of obvious clinical symptoms such as hemodynamic instability or altered mental status
with impeding multiple organ failure unequivocally results in drastically elevated
mortality.
Due to the severe nature of this clinical diagnosis and the potential for complications,
all care providers should use a readily available, simple, rapidly and multiply repeatable,
internationally accepted system of criteria with which disease progression and therapeutic
efficacy could be monitored simply. Accepted in February 2016, the Third International
Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) are perfectly suitable
for this.[24]
This article summarizes the most important objective clinical parameters, thus facilitating
early recognition of sepsis.
Body Temperature
One of the key SIRS criteria is abnormal body temperature, be it hyperthermia or hypothermia.
Fever is an adaptive response to infection. In vitro and animal experimental data
confirm that cellular and humoral immunity shows increased antimicrobial activity
when temperature is higher.[25]
In children, the most frequent clinical sign of a septic patient is a change in body
temperature, mostly elevated core temperature. When assessing central body temperature,
tympanic, rectal, urinary cystic, oral, or esophageal measurement sites can be used.
Today, the tympanic temperature is most widely used during primary assessment.
Hypothermia is an independent prognostic factor in sepsis mortality assessment. Adult
studies report an increased 90-day mortality when hypothermia develops during sepsis.
One-fifth of septic patients are hypothermic at hospital admission. The mortality
of these patients is twice as high, independent of age, disease severity, and concomitant
diseases.[26]
[27]
[28] Relevant studies have found no underlying etiological or unambiguously abnormal
immunological reasons. Elevated levels of fractalkine have been confirmed in hypothermia;
it is a chemokine released upon endothelial cell damage with a possible role in the
ensuing vascular dysfunction, but its clinical significance requires further research.[26] Other studies on septic patients also reported increased mortality and hypothermia-associated
lymphopenia, which is an early clinical predictor of sepsis-induced immunosuppression.[29] Several studies reported on absolute leukocytopenia and lymphopenia in newborns
receiving therapeutic hypothermia for hypoxic–ischemic encephalopathy.[30]
Altered Mental Status
An important part of early assessment is the evaluation of mental status. It is outstandingly
important since it can be performed right upon contact with the patient, with no need
for major physical, equipment-based or laboratory methods. It also lends itself to
continuous, noninvasive monitoring of the mental status of the child.
In addition to the usual subjective description (irritability, nervousness, disorientation,
lethargy, somnolence, stupor, coma), it can be continuously objectivized in real time
using the internationally recognized Glasgow Coma Scale. Interestingly, in the emergency
room, patients more frequently presented with an altered mental status (38.2%) than
with excess of respiratory effort (30.2%).[31] Clinical observations indicate that Glasgow Coma Scale scores of 11 or less and
acute changes in mental status of at least two points are correlated with disease
severity. Changes in mental status are affected by the general effects of inadequate
tissue oxygenation in the body, insufficient tissue perfusion, potential hypoglycemia,
and significant electrolyte disturbances. Of course, in septic events with an accompanying
central nervous system infection (i.e., meningoencephalitis), local cerebral inflammation,
circulation, and coagulation disturbances may also alter mental status.
Respiratory System
The examination and continuous monitoring of the respiratory system is indispensable
when dealing with septic children. Strict observation and patency management of the
airways is a key factor to ensure gas exchange. Rapid and objective assessment of
the respiratory system is possible through tests such as age-specific respiratory
rate, respiratory effort, auscultation, transcutaneous oxygen saturation, or blood
gas analysis. Respiration rate is one of the most sensitive indicators of disease
severity.[32]
Surprisingly, respiratory alkalosis of a central origin is often observable in early
stage sepsis even before the onset of metabolic acidosis. As the disease progresses,
the release of proinflammatory factors (cytokine storm) leads to a compromised lung
compliance independent of age. In physical examination, nasal flaring, accessory respiratory
muscle use, and appearance of suprasternal, subcostal, and sternal retractions may
indicate, even before laboratory tests, the presence of acute lung injury (ALI) or
the acute respiratory distress syndrome (ARDS), which are frequent complications confirmable
by radiological (ultrasound, chest X-ray) and laboratory testing (arterial blood gas
analysis).[33] Peripheral circulatory failure developing as the process continues, coupled with
the onset of metabolic acidosis as its consequence, causes the respiratory rate to
increase further, now as a compensatory mechanism to maintain respiratory alkalosis.
This compensatory mechanism is dedicated to two possible reasons. A substantial number
of septic cases have lower respiratory tract infection in the background, and gas
exchange is compromised due to the primary involvement of the lungs. The most common
cause of the aforementioned ALI or ARDS is sepsis. Locally released proinflammatory
mediators are the underlying causes of diffuse alveolar and pulmonary capillary injury,
a process of exudative nature in the early phase. This results in an increased permeability
of the alveolar–capillary barrier, upon which the alveoli get filled up with a protein-rich
fluid. The process primarily affects type I pneumocytes. Type II, surfactant-producing
cells are more resilient against the injury; however, damages to surfactant production
lead to further deterioration of lung compliance and atelectasis. Neutrophils, tumor
necrosis factor (TNF), various leukotrienes, macrophage inhibition factor, and other
mediators released during sepsis have a substantial role in the process. The damaged
alveolus collapses and is unable to refill with air at the next inspiration, thus
escalating the ensuing atelectasis. This results in an early loss of functional residual
capacity, an already limited resource in children, and, finally, global respiratory
failure occurs. To compensate for the loss of lung compliance, accessory respiratory
muscle effort is necessary by increasing respiration minute volume.[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
The excessive respiratory effort may require up to 40% of the base metabolic rate
and cardiac output. To avoid fatigue and consequential cardiorespiratory collapse
in children, it is important to continuously monitor respiratory effort by physical
examination and noninvasive transcutaneous saturation measurement, which is also informative
of heart rate. Continuous observation helps determine when and how to start respiratory
support, as well as facilitates close therapeutic efficacy monitoring once started.[39]
[40]
[45]
[46]
[47]
Cardiovascular System
Knowledge of age-specific heart rate, stroke volume, blood pressure, and systemic
vascular resistance values, as well as their changes in response to the septic cascade
triggered by infectious agents is indispensable for disease recognition and appropriate
management. These are parameters with substantial differences between adults and various
pediatric groups.[41]
[42]
[43]
Clinically informative assessment of the cardiovascular system also relies on a simultaneous
evaluation of multiple parameters. During diagnosis and for rapid monitoring of therapeutic
efficacy, key markers include the physical examination of heart rate and capillary
refill time, and laboratory evaluation of arterial lactate levels and metabolic acidosis.
Assessment of the cardiovascular system is assisted by noninvasive or invasive blood
pressure measurement and continuous urinary output monitoring.
The triad triggered by inflammatory response, that is, fever, tachycardia, and altered
vasoregulation, is a common set of symptoms in incipient pediatric infection. Suspicion
of a septic event should be raised if these symptoms are accompanied by altered mental
status, irritability, disorientation, and disturbed interpersonal contact. Similar
to the respiratory system, the basis for the process is abnormal inflammation and
dysregulation triggered and maintained by pathogens. The mechanisms leading to cell
damage are not yet fully understood; however, postmortem data indicate a central role
of endothelial damage in the evolution of the process.
Provoked by the injury, abnormal vascular tone, increased microvascular permeability,
and leukocyte accumulation initially lead to relative and then absolute intravascular
fluid deficit. Early symptoms of fluid deficit include an elevated heart rate and
increased capillary refill time due to poor tissue perfusion. Owing to compensatory
mechanisms, blood pressure drop is a late-onset symptom in most pediatric cases, together
with reduced urinary output (< 1 mL/kg/hour).
Heart Rate
Similar to respiratory rate, heart rate values are strongly age-specific. Changes
in heart rate are a nonspecific sign, but it is a highly sensitive early stage indicator
of relative or absolute fluid deficit, a common accompanying feature of pediatric
shock; it is also one of the mechanisms to compensate for ongoing cardiac dysfunction
or altered vascular resistance.[43]
Heart rate variability (HRV) is an indicator of the heart's neurovegetative activity
and autonomous function. It describes the heart's ability to continuously vary the
time interval from heartbeat to heartbeat (RR interval) in response to changes in
internal and external environmental demand; it is thus a measure of cardiac adaptability.
Neither its etiology nor its exact clinical significance is clear yet; however, reduced
HRV shows an association with poor outcomes in septic patients. HRV can predict the
development of septic shock and multiple organ failure in sepsis.[44]
[48]
[49]
[50]
[51] In newborns, it predicts blood culture positive septic cases independent of laboratory
findings.[52]
[53]
[54] An association is also detectable between hypercytokinemia, elevated interleukin
(IL)-6, levels and reduced HRV in septic patients.[55]
Further research is needed to clarify the exact mechanisms of abnormal HRV and autonomous
nervous system disorders.[56]
[57]
[58]
Tissue Perfusion
Microcirculation is the most important target in the septic process. Reduction in
the number of functioning capillaries compromises oxygen utilization.
Several approaches exist to assess damaged microcirculation. The simplest, quickest,
and most reproducible one is the measurement of capillary refill time. A capillary
refill time of longer than 3 seconds is regarded as abnormal and prolonged.
Additional signs of disturbed microcirculation include altered skin temperature and
skin color (paleness, mottling). Prolonged capillary refill time in incipient sepsis
is a reliable indicator of vital organ microcirculation.
There are, of course, equipment-based tests available to assess the process. Spectrophotometry
and sublingual/gastric assessment of orthogonal spectral polarization have not been
established in daily routine diagnostics.[59]
[60]
[61]
[62]
[63]
Based on changes in hemodynamic response, cardiac output, and systemic vascular resistance,
two forms of shock can be distinguished.[64]
Clinical manifestation may identify shock as being of the warm (hyperdynamic) type,
characterized by low systemic vascular resistance, quick and prompt capillary refill
time, warm skin all over the body, Corrigan's pulse, and wide pulse pressure (difference
between systolic and diastolic blood pressure).
Children's heart rates are physiologically higher than those of adults. So there is
much less opportunity to further increase heart rate as a compensatory mechanism than
in adults. Children therefore tend to raise their systemic vascular resistance in
response to blood pressure decrease and to maintain it in the normal range.
In cold (hypodynamic) shock, systemic vascular resistance is high, the skin is cold
and damp, a so-called cold-warm boundary can be detected, the capillary refill time
is prolonged, the pulse is suppressible, and the pulse amplitude is narrow. There
is, of course, a limit beyond which further vasoconstriction leads to a decrease in
cardiac output, hypotension, circulatory failure, and eventually death, unless appropriate
intervention is made. Earliest possible recognition and treatment of cold shock persisting
in spite of normal blood pressures is therefore a key outcome factor.[65]
Tissue perfusion, capillary refill time, and cold–warm boundary assessment are excellent
markers in both shock severity evaluation and therapeutic efficacy monitoring.[66]
[67]
[68]
[69]
[70]
[71]
Blood Pressure
Blood pressure drop is a very late-phase manifestation in pediatric shock; therefore,
normal age-specific blood pressure values early in the process do not help to exclude
the diagnosis. They do help, however, differentiate between cold and warm shock in
a noninvasive way. Treatment goals include restoring an age-specific normal blood
pressure within the golden hour. Each hour spent outside the age-specific normal blood
pressure range and with a capillary refill time of at least 3 seconds will double
the mortality.[72]
Various hemodynamic values measured at emergency departments are characterized by
various mortality estimates: normal heart rate, 1%; tachycardia/bradycardia, 3%; hypotension
and capillary refill time <3 seconds, 5%; normotension and prolonged capillary refill
time, 7%; hypotension and prolonged capillary refill time, 33%. When hemodynamic values
are normalized by treatment based on ACCM/PALS (American College of Critical Care
Medicine-Pediatric Advanced Life Support) guidelines, a 40% reduction in mortality
can be observed, independent of the patient's group assignment at treatment initiation.[40]
[73]
Subcutaneous Bleeding
Skin changes, that is, color and temperature described previously, mainly depend on
shock type. In either type, thrombocytopenia developing as part of the septic process
causes petechiae, and an early physical symptom of disseminated intravascular coagulation
is the appearance of purpura. All patients developing purpurae should be considered
potentially severe cases. When suspecting invasive meningococcal infection, parenteral
antibiotic treatment must be started immediately, even before arrival at the hospital.
Likewise, upon detection of grave thrombocytopenia, extensive, cause-finding examinations
and coagulation tests must be performed.
Sepsis-induced disseminated intravascular coagulation may result in complement-mediated
thrombotic microangiopathy. The process may culminate in necrotizing fasciitis requiring
a surgical solution.[74]
[75]
[76]
The most severe manifestation of the process is purpura fulminans, a life-threatening
condition characterized by disseminated dermal and systemic thrombosis, skin bleeding
and dermal necrosis, systemic microcirculation disorder, and multiple organ failure.
The pathogenesis of the process is rooted in intrinsic coagulation cascade disorders
and hereditary or acquired protein C deficiency.[77]
[78]
[79]
[80]
Laboratory Investigations
Owing to the nature of the septic process, laboratory tests are run in parallel with
treatment initiation while diagnosis is still being established. In full-blown septic
shock, antimicrobial treatment and golden-hour therapy must not be delayed by laboratory
tests (blood panel, inflammatory parameters, liver and kidney function tests).
Microbiology
Microbiological tests should take place before the onset of antimicrobial treatment,
if possible, but must in no way cause significant delay (longer than 45 minutes).
It is recommended to collect an aerobic and an anaerobic blood culture sample from
at least one sampling site, but preferably from two different sampling sites.[81]
[82]
[83]
[84]
[85] From older children, volumes of 3 to 10 mL should be sampled, which reduces incidence
of false-negative cases.[86]
[87]
[88]
[89]
[90]
[91]
[92]
[93]
[94]
[95]
[96]
In addition to conventional microbiological diagnosis, an alternative way of pathogen
identification is PCR. Multiple PCR is well-known to deliver faster results, but requires
a greater volume of blood, and is more prone to false-positive results and does not
facilitate antibiogram assessment.[96]
[97]
[98]
[99]
[100]
[101]
[102]
White Blood Cell Count
Age-specific white blood cell count deviations and a percentage of immature forms
higher than 10% are included in SIRS criteria as well. In suspicion of sepsis, the
most fundamental laboratory test is total white blood cell count. Bacterial infection
may entail both neutrophilia and neutropenia. The greater the proportion of immature
white blood cells, the greater the chance of an infectious origin behind SIRS.[103]
Inflammatory Markers
Additional inflammatory markers recommended for use are sedimentation rate, C-reactive
protein, IL-1b, IL-6, IL-8, TNF-α, leukotriene B4, and procalcitonin (PCT). Because
early disease symptoms are nonspecific, combined use of biomarkers is recommended
for quick diagnostic judgment, rapid treatment initiation, and therapeutic efficacy
monitoring, thereby significantly improving specificity and sensitivity.[103]
[104]
[105]
[106]
Inflammatory marker assessment is useful in predicting severe bacterial infection
in infants and children with no clinically definite focal infectious lesions on hospital
admission.[107]
[108]
In children aged 2 to 17 years, combined use of metabolic and inflammatory parameters
helps identify patients who require intensive care. Information on multiple laboratory
parameters is especially helpful in determining disease severity also in situations
where care providers are less experienced in pediatric care.[109]
Patients who satisfy SIRS criteria and have elevated IL-6 levels are more likely to
develop complications (pneumonia, multiple organ failure) and have a greater mortality
risk.[110] On the other hand, declining levels are a good indicator of therapeutic efficacy
as early as day 2 of antibiotic treatment and have a positive predictive value in
SIRS with an infectious origin.[111]
The soluble form of the CD14 cellular surface antigen is called presepsin (P-SEP).
CD14 is a diagnostic and prognostic marker in adult sepsis. According to a prospective
study, P-SEP in late-onset sepsis of premature babies is a potentially useful biomarker
in both establishing diagnosis and treatment monitoring.[105]
Repeat assessment of markers with various half-lives helps confirm diagnosis and is
suitable for disease activity monitoring; on a longer run, it also assists in judging
the duration of antimicrobial therapy. PCT is more likely to help distinguish between
viral and bacterial pathologies, but has a limited significance in determining the
septic process in children as compared with adults.[103]
[106]
[107]
[108]
[109]
[110]
[111]
[112]
[113]
[114]
[115]
[116]
[117]
[118]
[119]
[120]
[121]
Platelet Count and Hemostasis
Disseminated intravascular coagulation developing during sepsis is affected not only
by basic coagulation factors but also by endothelial injury caused by thrombocytes
and proinflammatory factors. Coagulation system assessment is imperative in critically
ill patients. The most important tests include platelet count, partial thromboplastin
time, international normalized ratio, and activated partial thromboplastin time.
In sepsis, thrombocytopenia is well correlated with disease severity and is an early
predictor of poor outcomes. Of various other biomarkers, elevated levels of soluble
thrombomodulin were associated with higher 90-day mortality and multiple organ failure.
Endothelial injury and consequential coagulopathy play a central role in sepsis pathogenesis
and facilitate prognostic judgment.[122]
[123]
[124]
[125]
[126]
[127]
[128]
[129]
[130]
Acid–Base Tests
In critically ill patients, the most common bedside laboratory test is blood–gas analysis
to assess acid–base homeostasis. If we define sepsis as a malignant intravascular
inflammatory reaction, it is easy to see how an uncontrolled release of inflammatory
mediators and complement activation lead to tissue oxygen deficit and consequential
metabolic acidosis through increased oxygen consumption due to altered metabolic autoregulation
and through reduced oxygen availability.[131] The process is only aggravated by microcirculatory and endothelial dysfunction,
and an initially relative, and later absolute, fluid deficit. Testing for pH and base
deficit provides a quick and easy-to-represent picture of the body's metabolic status
and therapeutic efficacy.
Lactate
Tissue lactate assessment is a good indicator of both appropriate tissue supply and
aerobic glucose utilization. Elevated lactate levels are a good predictor of shock
and tissue hypoperfusion even in normotensive patients. In suspicion of septic shock,
it is recommended to test for lactate level at the time of diagnosis because it is
known to be elevated in early stage shock. It is an excellent therapy monitoring marker;
in the presence of elevated levels, therapeutic objectives include restoring a physiological
lactate level.[132]
[133]
[134]
Pediatric evidence is limited, but one study has found that children satisfying SIRS
criteria and having a venous lactate level greater than 4 mmol/L at diagnosis are
more likely to develop organ dysfunction in the first 24 hours of treatment.[135]
Blood Glucose
Blood glucose testing is of fundamental importance in all critically ill children.
Hypoglycemia, especially in infants, can be explained by altered metabolic utilization
and a decline in enteral intake due to a poor general condition. Hypoglycemia, of
course, needs immediate correction to avoid potential harmful neurologic outcomes.
On the other hand, a disturbed glucose homeostasis, peripheral insulin resistance,
and stress hormone release can lead to hyperglycemia as well.[136]
[137] Stress-induced hyperglycemia has been reported in cases of meningococcemia.[138]
[139]
Both hypoglycemia and hyperglycemia have been reported to be associated with higher
mortality in newborns.[140] Since a correlation exists between hypercytokinemia and blood glucose levels in
septic patients, adequate glycemic control is important during therapy. Under tight
control, it is possible to avoid hypoglycemia induced by intensive insulin therapy.[141]
[142]
[143]
Calcium
Intracellular calcium has a major role in maintaining vascular tone and also affects
myocardial function. Its assessment is important in any shock processes including
septic shock. Reduced calcium levels are a frequent symptom in critically ill patients,
most likely due to hormonal milieu alterations, but with a pathophysiology not yet
fully understood.[144]
[145]
[146] In sepsis, reduced calcium levels may contribute to a decreased myocardial function.[147]
[148] Upon detecting a low ionized calcium level (< 1.1 mmol/L) or symptomatic hypocalcemia
(positive Chvostek or Trousseau sign, spasms, prolonged QT interval) during the septic
process, immediate correction of the hypocalcemia is recommended.[45]
[149]
