Myocardial Dysfunction in Pediatric Septic Shock

Shashi Raj, MD1, James S. Killinger, MD1, Jennifer A. Gonzalez, RDCS2, and Leo Lopez, MD, FASE2

Objective To evaluate the prevalence and significance of myocardial dysfunction in children with septic shock.
Study design Thirty patients with septic shock were evaluated by transthoracic echocardiography within 24 hours
of admission to a pediatric critical care unit. Transthoracic echocardiography evaluation included left ventricular
(LV) size and function, mitral valve inflow velocities in early and late diastole, mitral valve annular velocities in systole
and early and late diastole, and LV myocardial performance index. LV systolic dysfunction was defined as an ejec-
tion fraction or shortening fraction z-score < 2, and LV diastolic dysfunction was defined as a mitral valve inflow
velocity/annular velocity in early diastole ratio z-score >2. Secondary outcomes included troponin I concentration,
acute kidney injury, and 28-day mechanical ventilation–free duration.
Results Mortality for the 30 patients (mean age, 9.5  7 years) was 7%. The prevalence of LV systolic and/or dia-
stolic dysfunction was 53% (16 of 30). Eleven patients (37%) had systolic dysfunction, 10 (33%) had diastolic
dysfunction, and 5 (17%) had both. Systolic and/or diastolic dysfunction was significantly associated with troponin
I level (P = .007) and acute kidney injury (P = .02), but not with ventilation-free duration (P = .12). Kaplan-Meier
analyses for pediatric critical care unit and hospital length of stay identified no differences between patients with
and those without myocardial dysfunction.
Conclusion Myocardial dysfunction occurs frequently in children with septic shock but might not affect hospital
length of stay. (J Pediatr 2014;164:72-7).

S
eptic shock is defined as sepsis with cardiovascular organ dysfunction or sepsis-induced hypotension that persists
despite adequate fluid resuscitation.1 Important components of the clinical progression from systemic inflammation
to death in these patients are circulatory instability and myocardial dysfunction. Mortality is higher in adults with septic
shock and myocardial dysfunction compared with those without myocardial dysfunction.2,3 Recent studies of septic shock,
mostly in adults, have used echocardiography to evaluate myocardial function in both systole and diastole.4-6 Unlike adults
in septic shock, who are more likely to have vasomotor dysfunction and to require vasopressor therapy, children in septic shock
frequently respond to both inotropic and vasodilating agents, suggesting that myocardial dysfunction may play a more signif-
icant role in children than in adults.3
Quantitative assessment of myocardial function in pediatric septic shock can be quite challenging, given the confound-
ing effects of loading conditions and rapid heart rates on functional indices. Studies in children with septic shock have
shown reversible impairment of left ventricular (LV) contractility, an inverse correlation of ejection fraction (EF) and
fractional shortening with admission troponin I concentration, and myocardial wall motion abnormalities.7-9 Although
mortality from septic shock has declined significantly since the advent of goal-directed therapy, there remains a paucity
of comprehensive data on myocardial function in children, especially during the early phase when acoustic interference
from the lungs during mechanical ventilation often precludes accurate echocardiographic quantification of myocardial
function.
In this prospective cohort study, we examined the prevalence and pattern of LV systolic and diastolic dysfunction in pediatric
septic shock. In addition, we used several measures of clinical status in the pediatric critical care unit (PCCU) to evaluate the
association between echocardiographic functional measures and morbidity in children with septic shock, including the Pedi-
atric Logistic Organ Dysfunction (PELOD) score, which has been used previously to quantify multiorgan dysfunction in the
PCCU setting.10

A Mitral valve inflow velocity in late LV Left ventricular

diastole MPI Myocardial performance index


a Mitral valve annular velocity in late PCCU Pediatric critical care unit
diastole PELOD Pediatric Logistic Organ
E Mitral valve inflow velocity in early Dysfunction
diastole pRIFLE Pediatric Risk, Injury, Failure, Loss, From the Divisions of 1Pediatric Critical Care Medicine


e Mitral valve annular velocity in early and End-Stage Kidney Disease and 2Pediatric Cardiology, Department of Pediatrics, The
diastole
s Mitral valve annular velocity during Children‘s Hospital at Montefiore, Albert Einstein College
of Medicine of Yeshiva University, Bronx, NY
EF Ejection fraction systole
The authors declare no conflicts of interest.
IVA Mitral valve annular acceleration RV Right ventricular
during isovolumic contraction TTE Transthoracic echocardiography 0022-3476/$ - see front matter. Copyright ª 2014 Mosby Inc.
All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2013.09.027

72
 Vol. 164, No. 1  January 2014

morphometric and Doppler evaluation were used as

Methods
described previously.12 All Doppler measurements were aver-
aged over 3 consecutive cardiac cycles to account for respira-
This prospective cohort study, approved by the Institutional
tory variation, especially because most of the patients were
Review Board of Montefiore Medical Center, was conducted
supported with mechanical ventilation. One patient treated
in the PCCU of The Children’s Hospital at Montefiore be-
with high-frequency oscillatory ventilation had poor echo-
tween July 2011 and September 2012. Fluid-refractory septic
cardiographic windows, and TTE was performed on the
shock was defined as shock persisting despite $60 mL/kg of
day after the onset of septic shock when he was changed to
fluid resuscitation (when appropriate) using the American
conventional mechanical ventilation.
College of Critical Care Medicine’s definition, and standard
All offline measurements were performed independently
noninvasive and invasive monitoring and laboratory testing
by 2 investigators under the supervision of the Medical Di-
techniques were used in all patients.1 Patients aged 1 month
rector of the Pediatric Echocardiography Laboratory at The
to 21 years with suspected sepsis and fluid-refractory shock
Children’s Hospital at Montefiore who were blinded to the
were eligible for study participation on admission to the
clinical data and management for each patient. Interobserver
PCCU after informed consent was obtained. Exclusion
variability was assessed as the percent variance of individual
criteria included primary conditions associated with myocar-
variables from the mean of 2 measurements. Statistical ana-
dial ischemia or cell injury (eg, myocarditis, cardiomyopa-
lyses were performed using SPSS version 17.0 (SPSS Inc,
thy), cardiothoracic surgery or trauma within the previous
Chicago, Illinois). Descriptive analysis was applied for demo-
14 days, pregnancy, Kawasaki disease, congenital heart dis-
graphic and clinical variables, such as age, sex, and source of
ease, and cardiopulmonary resuscitation (cardioversion and
sepsis. All variables were evaluated for normality and equal
defibrillation) within the previous 14 days. All patients who
variance. To account for the effects of body size and age, all
met the inclusion criteria and who did not have any exclusion
TTE data were expressed as z-scores based on available
criteria were enrolled regardless of race, ethnicity, sex, or
normal values in children.13 The median and IQR of normal
socioeconomic status.
values from resting children were used for the analysis of
Overall morbidity in the setting of septic shock was evalu-
IVA.14 The association between mitral valve
s and MPI in
ated using the PELOD scores at the time of admission and
the setting of systolic and diastolic dysfunction was analyzed
daily during the entire PCCU stay; 28-day mechanical venti-
using the Pearson c2 test or Fisher exact test. For data
lation–free duration; pediatric Risk, Injury, Failure, Loss, and
showing a non-Gaussian distribution, comparisons were
End-Stage Kidney Disease (pRIFLE) score to assess acute
made using the Mann-Whitney U test, with a significance
kidney injury11; troponin I level; and PCCU and hospital
level of P = .05 (2-tailed). Correlations between myocardial
length of stay.
dysfunction and secondary outcome measures were calcu-
Transthoracic echocardiography (TTE) was performed
lated using the 2-tailed Spearman coefficient for nonpara-
with the Philips IE33 system (Philips, Andover, Massachu-
metric correlations. Multiple binary logistic regression was
setts) in all eligible patients within 24 hours of admission
used to calculate the effect of multiple predictor variables
for septic shock or within 24 hours of development of septic
(eg, PELOD, pRIFLE) on the dichotomous outcome of pres-
shock during hospitalization. All TTE studies included
ence or absence of myocardial dysfunction. Kaplan-Meier
2-dimensional and M-mode echocardiography, as well as
analysis was used to evaluate the influence of myocardial
blood flow and tissue Doppler analysis. Images were stored
dysfunction on time-to-event data, including 28-day PCCU
digitally for offline review and analysis. Evaluation of systolic
stay and 60-day hospital stay.
function included measures of LV size and function as well as
tissue Doppler evaluation of medial and lateral mitral valve
annular velocities in systole (
s) and mitral valve annular ac- Results
celeration during isovolumic contraction (IVA). Evaluation
of LV diastolic function included mitral valve inflow veloc- Thirty patients were eligible for inclusion into the study
ities by blood flow Doppler analysis in early (E) and late (Figure 1; available at www.jpeds.com). The demographic
(A) diastole and mitral valve annular velocities by tissue and clinical characteristics of the study cohort are
Doppler analysis in early (
e) and late (
a) diastole. The LV presented in Table I. The mean patient age was 9.5  7
myocardial performance index (MPI) for assessing combined years (range, 1 month to 21 years); 6 patients were aged <1
systolic and diastolic function was calculated as the sum of year and 24 were aged >1 year. Two of the 30 patients died
isovolumic contraction and relaxation times divided by ejec- (6.7%).
tion time as assessed by tissue Doppler evaluation. Positive bacterial cultures from blood, urine, trachea, and/
LV systolic dysfunction was defined as an EF or shortening or other soft tissues were documented within the first 72
fraction z-score < 2. LV diastolic dysfunction was defined as hours of admission in 22 patients (73%). In these 22 patients
a mitral valve medial E/
e z-score or lateral E/
e z-score >2. with septic shock and a positive bacterial source, methicillin-
Myocardial dysfunction was considered present when the pa- resistant Staphylococcus aureus (n = 6) and Klebsiella pneumo-
tient had LV systolic dysfunction, LV diastolic dysfunction, niae (n = 5) were the most common organisms detected.
or both. Optimization techniques for imaging as well as Other organisms identified included Pseudomonas aeruginosa

73
THE JOURNAL OF PEDIATRICS  www.jpeds.com Vol. 164, No. 1

therapy. Data on secondary outcomes (including PELOD

Table I. Demographic and clinical characteristics of the and pRIFLE scores and mechanical ventilation–free dura-
study patients tion) are summarized in Table II. Vasoactive and inotropic
Characteristic Value medications used in patients with septic shock in the
Age <1 y, n (%) 6 (20) PCCU included dopamine, epinephrine, norepinephrine,
Age >1 y, n (%) 24 (80) vasopressin, and milrinone; 12 patients (40%) required 2
Males:females, n 15:15
Ethnicity, n or more of these medications.
Multiracial 10 Systolic measurements were available in all 30 patients,
Unknown 8 whereas diastolic measurements were available in only 28.
African American 7
Caucasian 5 Fusion of mitral valve E and A waves with blood flow
Primary diagnosis of septic shock, n 30 Doppler interrogation occurred in 6 patients (20%). The
Previously healthy before admission, n (%) 9 (30) overall prevalence of myocardial dysfunction (systolic and/
Chronic illness, n (%) 21 (70)
Hospital mortality, n (%) 2 (6.7) or diastolic dysfunction) was 53% (16 of 30; 95% CI, 34%-
PCCU length of stay, d, mean  SD 14  10 72%), including 37% (n = 11) with systolic dysfunction,
Hospital length of stay, d, mean  SD 29  19 33% (n = 10) with diastolic dysfunction, and 17% (n = 5)
Source of sepsis, n (%)
Bloodstream infection 15 (50) with both systolic and diastolic dysfunction. Fourteen pa-
Urosepsis 2 (6) tients (47%) had normal myocardial function. The hemody-
Tracheitis 1 (3) namic and echocardiographic characteristics of the patients
Soft tissue infection 2 (6)
Pharyngitis/toxic shock syndrome 2 (6) with and those without myocardial dysfunction are summa-
Culture negative 8 (27) rized in Table III. Systolic dysfunction was significantly
associated with mitral valve lateral
s z-score < 2 (P =
.005), mitral valve IVA (P = .05), and MPI z-score >2 (P =
(n = 2), methicillin-sensitive S aureus (n = 1), Acinetobacter .03). There was no association between diastolic
baumannii (n = 1), Escherichia coli (n = 1), group A (n = dysfunction and MPI (P = .28). The median troponin I
1) and group B (n = 1) streptococci, Citrobacter freundii (n level was normal (<0.1 ng/mL), although an elevated
= 1), and Mycoplasma pneumoniae (n = 1). Streptococcal an- troponin I level ($0.1 ng/mL) was present in 10 patients
tigen was isolated from the throat in 2 patients with toxic (33%) and was significantly associated with myocardial
shock syndrome. There was no significant difference in the dysfunction (P = .04; area under the receiver operating
prevalence of systolic dysfunction (P = .34) and/or diastolic characteristic curve = 0.78) (Figure 2; available at www.
dysfunction (P = .24) between patients with and those jpeds.com). Kaplan-Meier survival analysis of 28-day
without a positive bacterial source; however, patients with PCCU length of stay (Figure 3; available at www.jpeds.
septic shock and methicillin-resistant S aureus bacteremia com) and 60-day hospital length of stay (Figure 4)
demonstrated a trend toward systolic dysfunction compared demonstrated no differences between patients with and
with culture-negative patients (P = .14; OR, 8; 95% CI, 0.58- those without myocardial dysfunction. Myocardial
110). Twenty-two patients (73%) required mechanical venti- dysfunction was significantly associated with pRIFLE score
lation, and 2 patients (7%) underwent renal replacement (P = .02), but not with 28-day mechanical ventilation–free

Table II. Morbidity patterns of the study patients

Variable Patients with myocardial dysfunction Patients without myocardial dysfunction P value
Admission PELOD score, median (IQR) 13 (11-24) 13 (12-22) .77
PCCU PELOD score, median (IQR) 14 (11-32) 14 (12-22) .68
Mechanical ventilation, n 13 9 .42
28-day mechanical ventilation–free duration, days, median (IQR) 18 (2-21) 21 (12-28) .12
P:F, mm Hg.% 1, median (IQR) 202 (108-419) 336 (167-456) .12
Days of vasoactive medication use, median (IQR) 2 (1-4) 2 (1-3) .36
Vasoactive inotropic medications, n
Dopamine 11 8
Norepinephrine 8 5
Epinephrine 7 2
Vasopressin 5 0
Milrinone 2 1
Troponin I, ng$mL 1, median (IQR) 0.1 (0.02-0.2) 0.01 (0.01-0.0.04) .007
Lactate, mmol$L 1, median (IQR) 3.6 (1.6-5.5) 2 (0.9-5.8) .29
Acute kidney injury at 24 hr, n
pRIFLE Scr 14 7 .04
pRIFLE U 4 2 .68
Acute kidney injury during PCCU stay, n
pRIFLE SCr 16 9 .02
pRIFLE U 2 4 .38

P:F, ratio of partial pressure of oxygen in arterial blood to fractional oxygen content of inspired gas; pRIFLE SCr, pRIFLE for serum creatinine; pRIFLE U, pRIFLE for urine output.

74 Raj et al
January 2014 ORIGINAL ARTICLES

Table III. Hemodynamic and echocardiographic characteristics of the study patients

Variable Patients with myocardial dysfunction Patients without myocardial dysfunction P value
Heart rate, beats$min 1
164  26 157  27 .49
Arterial systolic blood pressure, mm Hg 72  15 74  14 .59
EF z-score 2.6  2.1 0.5  1.4 .00
Shortening fraction z-score 2.4  3.1 0.3  1.4 .02
Mitral valve medial
s wave z-score 0.6  1.3 0.8  2.2 .06
Mitral valve lateral
s wave z-score 0.9  1.3 0.1  1 .07
Septal IVA, msec 2, median (IQR) 1.77 (1.38-1.87) 1.31 (1.24-1.67) .05
MPI z-score 1.3  1.6 0.8  0.7 .30
Mitral valve E/A z-score 0.7  0.6 0.3  1 .18
Mitral valve medial E/
e z-score 2.2  1.7 0.8  0.7 .007
Mitral valve lateral E/
e z-score 2.2  1.9 0.7  0.9 .01
Mitral valve A wave z-score 2.5  0.9 1.7  0.9 .06

All values are mean  SD unless specified otherwise.

duration (P = .12). The interobserver variance was higher for
MPI, E:A, and IVA compared with that for mitral valve
medial
s, mitral valve lateral
s, mitral valve medial E:
e, and
mitral valve lateral E:
e (Table IV; available at www.jpeds.
com).
Discussion
Myocardial dysfunction in severe sepsis and septic shock is
well recognized but incompletely understood. Septic patients
with persistent hypotension after adequate fluid resuscitation
may have a low, normal, or high cardiac output state.3 Mea-
surements of cardiac output and performance are paramount
when caring for children with septic shock, especially those
with catecholamine-resistant septic shock.1 In a study of chil-
dren with septic shock, Ceneviva et al3 demonstrated the het-
Figure 4. Kaplan-Meier plot of hospital stay and myocardial
dysfunction in pediatric septic shock.
Myocardial Dysfunction in Pediatric Septic Shock
erogeneous hemodynamic states of cardiac output and
systemic vascular resistance and their evolution over time
in relation to inotropic and vasopressor therapy. The choice
of inotropic agents (eg, epinephrine, dopamine) and/or vaso-
active agents (eg, norepinephrine, vasopressin) to support
cardiovascular function in pediatric septic shock is guided
by the assessment of warm or cold shock states in relation
to blood pressure, although vasoactive therapy (eg, norepi-
nephrine) remains the first-line treatment in adult septic
shock.15
The 6.7% mortality rate in our septic shock cohort is
consistent with the literature.1,15 Overall morbidity as re-
flected by the PELOD score and the need for mechanical
ventilation did not differ between the patients with and those
without myocardial dysfunction; however, this result may be
confounded by our relatively small sample size.
Elevated cardiac troponin I level, although a fairly sen-
sitive and specific marker of myocardial cell injury, is
seen in several disease states, such as septic shock and
renal insufficency, in the absence of coronary artery dis-
ease.16 In a large prospective randomized study of adult
patients with septic shock, elevated troponin I level was
not associated with increased mortality, but its prognostic
role in predicting the severity of illness in septic shock was
unclear given the variation in assay technique and
timing.17 Our finding of an elevated troponin I level in
33% of our patients with septic shock concurs with previ-
ous reports.5,8
Acute kidney injury in septic shock is not well under-
stood but is thought to result from hemodynamic factors
(eg, hypoperfusion), as well as several nonhemodynamic
factors (eg, microvascular thrombosis, apoptosis), and is
associated with high morbidity in the pediatric popula-
tion.18 Our finding of acute kidney injury in 70% of our
patients at 24 hours is also consistent with the reported
incidence of acute kidney injury in children with sepsis
and septic shock.19 Cardiorenal syndrome, defined as
concomitant renal and cardiovascular dysfunction, is a
well described but poorly understood phenomenon in sep-
tic shock.20 In the present study, the incidence of acute kid-
ney injury was significantly higher in the patients with
myocardial dysfunction.
75
THE JOURNAL OF PEDIATRICS  www.jpeds.com
A recent study of neonates with sepsis (n = 20) used tissue
Doppler analysis to evaluate myocardial dysfunction,
although systolic dysfunction and diastolic dysfunction
were not defined.21 A large prospective study of adults with
septic shock found myocardial dysfunction in 64%, including
LV diastolic dysfunction in 37%, LV systolic dysfunction in
27%, and right ventricular (RV) dysfunction in 31%,6
compared with the 53% prevalence of myocardial dysfunc-
tion in our pediatric cohort.
In an effort to account for the effects of body size on mea-
sures of ventricular function, we used z-scores based on a
normal population of children across the range of body sizes
encountered in pediatric practice. Following standard prac-
tice, we defined LV systolic dysfunction as an EF z-score or
fractional shortening z-score < 2. We also used nongeomet-
ric measures of systolic function through blood flow and tis-
sue Doppler analyses, understanding that the variable loading
conditions and increased heart rate frequently seen in septic
shock have a significant effect on all of these measures. As ex-
pected, systolic tissue Doppler indices (
s and IVA) correlated
with the geometric measures; however, the addition of non-
geometric measures did not improve the ability to detect LV
systolic dysfunction. Interestingly, a recent study reported
isolated LV systolic dysfunction in only 8% of adults with
septic shock,6 significantly lower than the 20% rate of isolated
LV systolic dysfunction seen in our cohort.
The importance of LV diastolic function, especially in the
setting of a dynamic cardiovascular response to fluid resusci-
tation in the early phase of septic shock, cannot be overem-
phasized. Even though there is no standard definition of
LV diastolic dysfunction in children, the velocity ratio of
blood flow Doppler-derived mitral valve inflow E wave to
the tissue Doppler-derived mitral valve
e wave (E:
e) has
been used to estimate LV filling pressures in adults.22,23 Pulse
wave Doppler-derived variables (such as the E:A) represent
flow toward the transducer rather than true flow across the
mitral valve. An abnormal E:A (ie, E:A z-score >2) usually re-
flects significant diastolic dysfunction and is usually preceded
by an abnormal mitral valve E:
e, and thus is less useful in the
scenario of pediatric septic shock. Despite its limitations in
discerning ventricular vs myocardial diastolic dysfunction,
E:
e is considered a reasonable surrogate for diastolic func-
tion, and thus we defined LV diastolic dysfunction as either
a medial or lateral annular mitral valve E:
e z-score >2.24
Although E:
e has been shown to independently predict mor-
tality in adults with septic shock,5,24 our study population
likely is too small to allow an evaluation of this relationship.
Our finding of isolated diastolic dysfunction in 16% of our
patients with septic shock does highlight the role of echocar-
diography in detecting this problem, particularly in terms of
predicting LV filling pressures in these patients. Echocardio-
graphic evaluation of myocardial function, especially in crit-
ically ill children, is user-dependent, and we observed
substantial interobserver variability in several echocardio-
graphic measures; however, this was similar to the variability
in echocardiographic measures recently reported in a large
study involving 8 pediatric clinical centers.25
76
Vol. 164, No. 1
The present study has some limitations. First, we did not
assess the potential direct and indirect interactions between
diastolic dysfunction and mechanical ventilation in children
with septic shock. Second, we did not assess RV function in
our patients, particularly in terms of its role in the relationship
between venous capacitance and systemic vascular resistance.
However, RV dysfunction in septic shock has not been evalu-
ated in children, especially as it relates to factors such as me-
chanical ventilation, pulmonary vascular resistance,
hypoxemia, and medications.6 Tricuspid annular plane sys-
tolic excursion is a measure of RV systolic function that corre-
lates well with EF in adults and may be useful in children in
future studies. Third, systolic and diastolic function may be
associated not only with septic shock, but also with other dis-
ease states, such as pulmonary disease requiring mechanical
ventilation, with its consequent effects on cardiac loading con-
ditions. In other words, the role of cardiopulmonary interac-
tions in these patients cannot be overemphasized. Finally,
although our data suggest a tendency toward longer hospital
length of stay in patients with septic shock and myocardial
dysfunction, our sample size of 30 patients may be insufficient
to allow detection of significant differences among the patients
with regard to secondary outcomes, such as mechanical venti-
lation, or an association of myocardial dysfunction with spe-
cific bacterial organisms, such as methicillin-resistant S aureus.
The clinical utility of the echocardiographic findings in
children with septic shock and their potential implications
for the choice of vasoactive inotropic medications have not
yet been evaluated. Considering the heterogeneous patho-
physiology and etiology of sepsis in children, we still do not
fully understand the relationship between hemodynamics
and the child’s clinical status and course of sepsis; echocardio-
graphic evaluation of myocardial dysfunction provides only a
“snapshot” assessment at the time of the study. n
Authors want to thank all the cardiac sonographers from the Division
of Pediatric Cardiology who helped in the acquisition of TTE data.
Submitted for publication Mar 29, 2013; last revision received Aug 29, 2013;
accepted Sep 12, 2013.
Reprint requests: Shashi Raj, MD, University of Miami/Jackson Health System,
1611 NW 12th Ave, Pediatric Cardiology, North Wing Room 109, Miami,
FL 33136. E-mail: drshashiraj@gmail.com
References
1. Brierley J, Carcillo JA, Choong K, Cornell T, Decaen A, Deymann A, et al.
Clinical practice parameters for hemodynamic support of pediatric and
neonatal septic shock: 2007 update from the American College of Critical
Care Medicine. Crit Care Med 2009;37:666-88.
2. Parrillo JE, Parker MM, Natanson C, Suffredini AF, Danner RL,
Cunnion RE, et al. Septic shock in humans: advances in the understand-
ing of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern
Med 1990;113:227-42.
3. Ceneviva G, Paschall JA, Maffei F, Carcillo JA. Hemodynamic support in
fluid refractory pediatric septic shock. Pediatrics 1998;102:e19.
4. Bouhemad B, Nicolas-Robin A, Arbelot C, Arthaud M, F
eger F,
Rouby JJ. Isolated and reversible impairment of ventricular
relaxation in patients with septic shock. Crit Care Med 2008;
36:766-74.
Raj et al
January 2014
5. Sturgess DJ, Marwick TH, Joyce C, Jenkins C, Jones M, Masci P, et al.
Prediction of hospital outcome in septic shock: a prospective compari-
son of tissue Doppler and cardiac biomarkers. Crit Care 2010;14:R44.
6. Pulido JN, Afessa B, Masaki M, Yuasa T, Gillespie S, Herasevich V, et al.
Clinical spectrum, frequency, and significance of myocardial dysfunc-
tion in severe sepsis and septic shock. Mayo Clin Proc 2012;87:620-8.
7. Feltes TF, Pignatelli R, Kleinert S, Mariscalco MM. Quantitated left ven-
tricular systolic mechanics in children with septic shock utilizing nonin-
vasive wall stress analysis. Crit Care Med 1994;22:1647-59.
8. Fenton KE, Sable CA, Bell MJ, Patel KM, Berger JT. Increases in serum
levels of troponin I are associated with cardiac dysfunction and disease
severity in pediatric patients with septic shock. Pediatr Crit Care Med
2004;5:533-6.
9. Basu S, Frank LH, Fenton KE, Patel KM, Berger JT. Two-dimensional
speckle tracking imaging detects impaired myocardial performance in
children with septic shock, not recognized by conventional echocardiog-
raphy. Pediatr Crit Care Med 2012;13:259-64.
10. Leteurtre S, Martinot A, Duhamel A, Proulx F, Grandbastien B,
Cotting J, et al. Validation of the paediatric logistic organ dysfunction
(PELOD) score: prospective, observational, multicentre study. Lancet
2003;362:192-7.
11. Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS,
Goldstein SL. Modified RIFLE criteria in critically ill children with acute
kidney injury. Kidney Int 2007;71:1028-35.
12. Lopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK,
et al. Recommendations for quantification methods during the perfor-
mance of a pediatric echocardiogram: a report from the Pediatric Mea-
surements Writing Group of the American Society of Echocardiography
Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr
2010;23:465-95.
13. Eidem BW, McMahon CJ, Cohen RR, Wu J, Finkelshteyn I, Kovalchin JP,
et al. Impact of cardiac growth on Doppler tissue imaging velocities: a
study in healthy children. J Am Soc Echocardiogr 2004;17:212-21.
14. Roche SL, Vogel M, Pitk€anen O, Grant B, Slorach C, Fackoury C, et al.
Isovolumic acceleration at rest and during exercise in children normal
values for the left ventricle and first noninvasive demonstration of
exercise-induced force-frequency relationships. J Am Coll Cardiol
2011;57:1100-7.
Myocardial Dysfunction in Pediatric Septic Shock
ORIGINAL ARTICLES
15. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al.
Surviving Sepsis Campaign: international guidelines for management of
severe sepsis and septic shock, 2012. Crit Care Med 2013;41:580-637.
16. Mehta S, Granton J, Gordon AC, Cook DJ, Lapinsky S, Newton G, et al.
Cardiac ischemia in patients with septic shock randomized to vaso-
pressin or norepinephrine. Crit Care 2013;17:R117.
17. Basu RK, Standage SW, Cvijanovich NZ, Allen GL, Thomas NJ,
Freishtat RJ, et al. Identification of candidate serum biomarkers for se-
vere septic shock–associated kidney injury via microarray. Crit Care
2011;15:R273.
18. Basu RK, Devarajan P, Wong H, Wheeler DS. An update and review of
acute kidney injury in pediatrics. Pediatr Crit Care Med 2011;12:339-47.
19. Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal
syndrome. J Am Coll Cardiol 2008;52:1527-39.
20. Abdel-Hady HE, Matter MK, El-Arman MM. Myocardial dysfunction in
neonatal sepsis: a tissue Doppler imaging study. Pediatr Crit Care Med
2012;13:318-23.
21. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Qui~ nones MA.
Doppler tissue imaging: a noninvasive technique for evaluation of left
ventricular relaxation and estimation of filling pressures. J Am Coll Car-
diol 1997;30:1527-33.
22. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK,
Redfield MM, et al. Clinical utility of Doppler echocardiography and tis-
sue Doppler imaging in the estimation of left ventricular filling pres-
sures: a comparative simultaneous Doppler-catheterization study.
Circulation 2000;102:1788-94.
23. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA,
et al. Recommendations for the evaluation of left ventricular diastolic
function by echocardiography. J Am Soc Echocardiogr 2009;22:107-33.
24. Furian T, Aguiar C, Prado K, Ribeiro RV, Becker L, Martinelli N, et al. Ven-
tricular dysfunction and dilation in severe sepsis and septic shock: relation
to endothelial function and mortality. J Crit Care 2012;27:319.e9-e15.
25. Colan SD, Shirali G, Margossian R, Gallagher D, Altmann K, Canter C,
et al. The ventricular volume variability study of the Pediatric Heart
Network: study design and impact of beat averaging and variable type
on the reproducibility of echocardiographic measurements in children
with chronic dilated cardiomyopathy. J Am Soc Echocardiogr 2012;25:
842-54.
77
THE JOURNAL OF PEDIATRICS  www.jpeds.com Vol. 164, No. 1

Table IV. Interobserver variability in

echocardiographic parameters
Variability, %
Parameter Mean ± SD Range
Mitral valve medial
s wave 1.9  5.9 0-29
Mitral valve lateral
s wave 2.9  9 0-40
Mitral valve IVA 24.7  18.2 0-81
MPI 9.8  6.3 1.6-24
Mitral valve E:A 14.1  13.5 0-30
Mitral valve medial E:
e 1.4  4.1 0-17
Mitral valve lateral E:
e 0.5  2.4 0-12

Figure 1. Profile of patient enrollment for septic shock.

77.e1 Raj et al
January 2014 ORIGINAL ARTICLES

Figure 2. Receiver operating characteristic curve comparing

troponin I level and myocardial dysfunction in pediatric septic
shock.

Figure 3. Kaplan-Meier plot of PCCU length of stay and

myocardial dysfunction in pediatric septic shock.

Myocardial Dysfunction in Pediatric Septic Shock 77.e2