ARTICLE Cardiac Function in Pediatric Septic Shock Survivors Hendrika Knoester, MD; Jeanine J. Sol, MD; Pascal Ramsodit, MD; Irene M. Kuipers, MD, PhD; Sally-Ann B. Clur, MBBCh, MSc, FCP(SA)Paed; Albert P. Bos, MD, PhD Objective: To evaluate the long-term effects of septic shock Results: No children had abnormalities when histories on cardiac function in children treated with inotropic and/or were taken or during physical examination that were at- vasoconstrictive agents for 24 hours or longer. tributable to cardiac dysfunction. Six children (6%) had cardiac abnormalities: polymorphic premature ventricu- Design: Cohort study. lar contractions during exercise and 24-hour electrocar- diography registration (2 patients), decreased left ven- Setting: Tertiary pediatric intensive care unit and out- tricular function (2 patients), decreased left ventricular patient follow-up clinic. function and polymorphic premature ventricular con- tractions (1 patient), and decreased right ventricular func- Participants: One hundred eight of 144 eligible chil- tion (1 patient). dren who were admitted to our tertiary pediatric inten- sive care unit with septic shock from 1995 through 2005 Conclusions: In this small and diverse group of pedi- and were alive in 2006 were invited to participate and atric septic shock survivors, we found an excellent re- visit our outpatient follow-up clinic. Fifty-two healthy covery of cardiac performance in most patients. In a lim- controls were included. ited number of patients, we found rhythm disturbances Main Exposure: Septic shock survival. and decreased ventricular function. We believe that, against the background of aging, long-term cardiac fol- Outcome Measures: History, physical examination, low-up of these patients is important. electrocardiogram during rest and exercise, 24-hour electrocardiography registration, and left and right ven- tricular function. Arch Pediatr Adolesc Med. 2008;162(12):1164-1168 EPSIS IS ONE OF THE LEADING ticularly in children, long-term fol- causes of death in children. low-up studies may be important against Mortality ranges from 4% to the background of the development and 20%.1 Septic shock is charac- maturation of organs. Consider, for ex- terized by myocardial dys- ample, respiratory distress syndrome of the Sfunction, loss of vascular tone, and cap- prematurely born infant (idiopathic res- illary leak leading to diminished organ piratory distress syndrome) and acute lung perfusion and the development of mul- injury in older children. Both have long- tiple organ system failure. Myocardial dys- term pulmonary consequences. The pri- function—caused by hypoperfusion, myo- mary insult occurs when the lung is ex- cardial cell death, and/or cardiodepressant posed to a damaging process (idiopathic circulating substances, such as tumor ne- respiratory distress syndrome or acute lung crosis factor ␣, IL-1 (interleukin 1), and injury); the secondary insult is caused by nitric oxide—is a key factor in the devel- mechanical ventilation.12,13 In children opment of circulatory failure during septic shock.2-4 Treatment includes ad- treated with inotropic and/or vasocon- strictive agents because of septic shock, the Author Affiliations: Pediatric equate fluid resuscitation and the admin- Intensive Care Unit istration of inotropic and/or vasoconstric- primary insult on the myocardium may be (Drs Knoester, Sol, Ramsodit, tive agents.5,6 the septic shock and the secondary insult and Bos) and Pediatric Mortality due to septic shock has de- may be treatment with these agents. This Cardiology Department creased owing to advances in pediatric in- may result in permanent damage to the de- (Drs Kuipers and Clur), Emma tensive care practices, such as improved veloping heart. The aim of this study was Children’s Hospital, Academic to evaluate the late (Ͼ6 months after pe- Medical Centre, Amsterdam, use of inotropic and vasoconstrictive the Netherlands. Dr Ramsodit is agents and early goal-directed fluid diatric intensive care unit [PICU] dis- 6-8 now with the Twenteborg therapy. Follow-up studies of children charge) effects of septic shock on cardiac Hospital, Almelo, the with septic shock have mainly focused on function in children and to analyze risk fac- Netherlands. mortality and short-term morbidity.9-11 Par- tors for cardiac abnormalities. (REPRINTED) ARCH PEDIATR ADOLESC MED/ VOL 162 (NO. 12), DEC 2008 WWW.ARCHPEDIATRICS.COM 1164 ©2008 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/03/2021 METHODS trocardiogram recordings were performed only when rhythm disturbances were suspected. Echocardiography to evaluate sys- tolic function of the right ventricle was not performed. The study was performed in the PICU of the Emma Children’s Hospital/Academic Medical Center Amsterdam. This is a ter- STATISTICAL ANALYSIS tiary multidisciplinary PICU with 14 beds serving the greater Amsterdam area. Data analysis was performed using SPSS (SPSS Inc, Chicago, Illinois). Mann-Whitney and ␹2 tests were done to compare par- PARTICIPANTS ticipants with nonparticipants and the control group with the patient group with regard to patient characteristics. The worst Patients were included if they had been admitted to the PICU shortening fraction during admission was compared with short- for septic shock between 1995 and 2005, had received inotro- ening fraction at follow-up using paired t tests. Shortening frac- pic and/or vasoconstrictive agents for 24 hours or longer (dopa- tion less than 30% and less than 28% during PICU admission mine, dobutamine, epinephrine, and/or norepinephrine), were and at follow-up were compared by using the Fisher exact test. alive in 2006, and had been followed up for longer than 6 months A significance level of PϽ.05 was used in all tests. after PICU discharge. Exclusion criteria were preexisting car- To analyze risk factors for cardiac abnormalities, patients diac disorders and serious psychomotor retardation. The hos- with cardiac abnormalities (rhythm disturbances, decreased left pital’s institutional review board approved the study protocol, ventricular function, and/or decreased right ventricular func- and written consent was obtained for all included patients and/or tion) were clustered because of the small number of patients. their parents. Mann-Whitney and ␹2 tests were used to compare character- istics of patients with and without cardiac abnormalities, such STUDY DESIGN as sex, age at PICU admission, age at follow-up, follow-up time, risk of mortality (Pediatric Index of Mortality 2), length of ven- Cardiac function was evaluated in our outpatient follow-up clinic tilation, and length of PICU stay. Furthermore, nonparamet- by patient history, physical examination, and electrocardio- ric correlations were performed to test the association be- gram (ECG) recorded during rest. Electrocardiogram record- tween cardiac abnormalities and the use of different inotropic ing during exercise was performed when the child was older and/or vasoconstrictive agents, and the dosage and duration of than 7 years at follow-up. Twenty-four-hour ECG recording treatment with these agents. A significance level of PϽ.001 was and echocardiography were performed as well. used in these tests to compensate for multiple testing. A structured checklist was used for history taking and the physical examination. Special attention was paid to syncope, RESULTS chest pain, skipped beats and heart palpitations, peripheral pul- sations, liver size, edema, and heart murmurs. Exercise test- ing was performed in children aged 7 years and older, as sum- One hundred forty-four patients who were admitted to marized in the Bruce protocol (younger children cannot perform our PICU for septic shock from 1995 through 2005 and this test owing to their size and lack of adequate concentration).14 survived fulfilled the inclusion criteria. Eleven patients Echocardiography was performed to evaluate systolic func- refused to participate and 25 patients could not be lo- tion of the left and right ventricles. Systolic function of the left cated. One hundred eight of 144 eligible patients (75%) ventricle was determined by measuring left ventricular end- were evaluated. No statistically significant differences were diastolic diameter (LVEDD) and shortening fraction. Shorten- found between participants and nonparticipants, ex- ing fraction is the percentage of change in the left ventricular cept for sex (Table 1). The age of PICU patients ranged cavity dimension during systole ([(LVEDD−left ventricular end- Ͼ systolic dimension)/LVEDD]ϫ100). In many studies, left ven- from newborns (with a birth weight 2 kg) to 18 years. tricular function is measured by the ejection fraction. In nor- Median follow-up time was 6.3 years (range, 0.8-12.7 mally shaped left ventricles, shortening fraction and ejection years). fraction are comparable. We chose to report shortening frac- The exercise test was performed in 87 of 108 patients tion. In pediatric literature, normal values for systolic func- (81%) aged 7 years or older. Twenty-four-hour ECG re- tion of the left ventricle differ from shortening fraction by more cording was successfully performed in 86 of 108 pa- 15-18 than 28% or more than 30%. Systolic function of the right tients (80%). Evaluations of systolic function of the left ventricle was determined by measuring tricuspid annular plane and right ventricles were successfully performed in 105 systolic excursion (TAPSE). There are no known reference data of 108 patients (97%) and 86 of 108