Letters to the Editor Fran Balamuth, MD, PhD, MSCE, Division of Emergency Medicine, Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, and Children's Hospital of Philadelphia, PA; Scott Weiss, MD, MSCE, Department of Anesthesia and Critical Care, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, and Children's Hospital of Philadelphia, PA; Mark Neuman, MD, Department of Pediatrics, Harvard University School of Medicine, Boston, MA; Halden Scott, MD, Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO; Patrick Brady, MD, MSc, Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH; Reid Farris, MD, Department of Anesthesia and Critical Care, Washington University School of Medicine, St. Louis, MO; Richard McClead, MD, Department of Pediatrics, Nationwide Children’s Hospital, Columbus, OH; Katie Hayes, BS, Children’s Hospital of Philadelphia, Philadelphia, PA; Raina Paul, MD, Department of Emergency Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC; Matt Hall, PhD, Children’s Hospital Association, Overland Park, KS; Samir Shah, MD, MSCE, Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH; Elizabeth Alpern, MD, MSCE, Department of Pediatrics, Northwestern Feinberg School of Medicine, Chicago, IL
REFERENCES
1. Souza DC, Barreira ER, Shieh HH, et al: Sepsis Is SEPSIS! It’s High Time to Globalize Pediatric Sepsis. Pediatr Crit Care Med 2015; 16:390–391 2. Balamuth F, Weiss SL, Neuman MI, et al: Pediatric severe sepsis in U.S. children’s hospitals. Pediatr Crit Care Med 2014; 15:798–805 3. Weiss SL, Parker B, Bullock M, et al: Defining pediatric sepsis by different criteria: Discrepancies in populations and implications for clinical practice. Pediatr Crit Care Med 2012; 13:e219–e226 4. Ruth A, McCracken CE, Fortenberry JD, et al: Pediatric severe sepsis: Current trends and outcomes from the Pediatric Health Information Systems database. Pediatr Crit Care Med 2014; 15:828–838 5. Weiss SL, Fitzgerald JC, Faustino EV, et al; Pediatric Acute Lung Injury and Sepsis Investigators Network and Australia and New Zealand Intensive Care Society Investigators: Understanding the global epidemiology of pediatric critical illness: The power, pitfalls, and practicalities of point prevalence studies. Pediatr Crit Care Med 2014; 15:660–666 DOI: 10.1097/PCC.0000000000000394
The authors reply:
W
e thank Souza et al (1) for their comments on our recently published article in this journal (2). Our study sample of 1,530 sepsis and severe sepsis was from 27,836 hospitalized patients admitted in 11 level II and III hospital pediatric departments with emergency and inpatient services (two of which provided pediatric intensive care services), as a part of a regional network serving a population of 5.4 million with more than 843,000 children. During the study period, a universal healthcare insurance system was in effect with a robust transport network; there should have been very few cases of sepsis and severe sepsis not admitted to these hospitals. Thus, the prevalence and mortality rate of this study sample should be most likely representative of a complete regional children’s population
Pediatric Critical Care Medicine
based on our data. We feel confident that these data are suitable to address early identification and treatment of sepsis with regard to facility and resource availability and affordability in China and likely some developing countries and regions. The prevalence and mortality rate of pediatric sepsis were based on the total hospital admissions. Clearly, there would be differences in prevalence and mortality rates depending on the denominator used to characterize the patient population. We considered that infrastructure for children’s health care at community level plays an important role in pediatric sepsis outcome, including socioeconomic conditions, healthcare insurance, and quality and timeliness of care in the pediatric emergency and inpatient wards. On the basis of this approach, we concluded that sepsis confers a tremendous burden and high mortality in children. However, we recognize that such assessment is regional specific, and our data show that approaches to treatment were not standardized or did not follow the recommended international guidelines, especially at early stage of sepsis. Although resource limitations may be an issue in some instances, reduction in morbidity and mortality of pediatric sepsis in developing country should take into consideration not only for technology but also the impact of community healthcare infrastructure, continuing medical education for general practitioners and healthcare insurance coverage, and among others. We are also cognizant of the fact that sepsis has been defined in several ways in different settings. For instance, the use of administrative databases (International Classification of Diseases-9th Edition and 10th Edition) would yield a proportion of sepsis cases that, while overlapping with the research definition, are not totally congruent. In addition, the clinical criteria may yield a higher proportion of cases that may also overlap with the other two groups (3). Thus, to compare the incidence and prevalence and mortality and morbidity outcomes from various regions, we need to be cognizant of the definitions being used to define the sepsis cohort. Efforts are underway to craft a universal definition such that, in the ideal situation, we will be using similar definitions in various parts of the world and various settings (4). Clearly, there is a tremendous amount of work being done to describe the burden of sepsis in many parts of the world. There should also be equal effort expended in trying to come to a uniform definition. Should this not be possible, then we should strive to agree on definitions that may be more appropriate for resource-poor and resource-rich settings. We thank you for your interest and appreciate your comments. The authors have disclosed that they do not have any potential conflicts of interest. Yuanyuan Wang, MD, Bo Sun, MD, Departments of Pediatrics and Pediatric Critical Care, Children’s Hospital of Fudan University, Shanghai, China; Hongni Yue, MD, Department of Pediatrics, Huai’an Maternity and Children’s Hospital, Jiangsu, China; Niranjan Kissoon, MD, Department of Pediatrics, University of British-Columbia and BC Children’s Hospital, Vancouver, British Columbia, Canada www.pccmjournal.org
393
Letters to the Editor
REFERENCES
1. Souza DC, Barreira ER, Shieh HH, et al: Sepsis Is SEPSIS! It’s High Time to Globalize Pediatric Sepsis. Pediatr Crit Care Med 2015; 16:390–391 2. Wang Y, Sun B, Yue H, et al: An epidemiologic survey of pediatric sepsis in regional hospitals in China. Pediatr Crit Care Med 2014; 15:814–820 3. Kissoon N: Sepsis in children: A dark cloud with a silver lining. Pediatr Crit Care Med 2014; 15:899–901 4. Thompson GC, Kissoon N: Sepsis in Canadian children: A national analysis using administrative data. Clin Epidemiol 2014; 6:461–469 DOI: 10.1097/PCC.0000000000000395
Invasive Measurement of Global End-Diastolic Volume: Is It Possible to Add Any Data Besides Clinical Parameters? To the Editor:
H
emodynamic instability is very common in critically ill children, and noninvasive methods have been studied to optimize cardiac output (CO) monitoring with accessible and less influenced by extracardiac factors. In a recent article in Pediatric Critical Care Medicine, de la Oliva et al (1), in a very original study, aimed to characterize cardiac preload responsiveness in pediatric patients with normal cardiovascular function, cardiovascular dysfunction, and dilated cardiomyopathy by using the following group of indicators: global end-diastolic volume (GEDV), stroke volume, CO, and extravascular lung water (EVLW). The Spanish Group (1) made transpulmonary thermodilution measures before and after fluid challenge. This method is incorporated in PiCCO device and has many advantages such as less influence of mechanical ventilation and continuous estimation of the CO and pulmonary edema (2). Despite being considered a minimally invasive method of monitoring, PiCCO is still a device with a good chance of complications due to the insertion of a catheter in the femoral artery (specially in very young children, limited to 3.5 kg or more), imprecision of information in intracardiac shunts and postoperative cardiac surgery, and large variation of the method result in the case of shock and hemorrhage (constant recalibration) (3). The article proposes to set up “normal” values of GEDV index in children, but a limited number of patients in the normal cardiovascular status group, and the heterogeneity sample of patient’s basic diseases in the PICU hospitalization may cause troublesome results. The great variability of diagnoses presented, including those intrinsically related to heart problems, such as Kawasaki disease, was not differentiated in each group and could be responsible for bias. The GEDV is important and can determine in which part of Frank-Starling curve the patient is situated, but recent studies show that fluid management can be more multifactorial than
394
www.pccmjournal.org
the original Starling model. In some diseases where the inflammatory response can increase the pulmonary capillary permeability (4), an elevated EVLW can be found in a patient with normal cardiovascular status. Monnet et al (5) suggest that the ratio of EVLW to GEDV may better discriminate between pulmonary edema caused by abnormal capillary permeability and left heart failure. Especially in patients with diastolic dysfunction, the edge between normovolemia and fluid overload may be very close. Sankar et al (6) showed that diastolic dysfunction evaluated by echocardiography in patients with positive fluid balance was associated to a higher mortality. Although troponin-T was not linked to predict diastolic dysfunction in an early moment (6), other biomarkers, such as brain natriuretic peptide, should be taken in consideration (7). The elaboration of a protocol including biomarkers, echocardiography, and clinical parameters (noninvasive methods) could be useful in the majority of patients, and in very critical condition (persistent unresponsiveness of fluid challenge or higher dosage of vasoactive drugs), the sequential measurement of EVLW/GEDV would be necessary. The precise estimative of diastolic volume and CO has been looking forward in PICU for long time, but adverse effects of invasive monitoring and difficulties related to the methods turned real-time procedures (main clinical data and bedside echocardiography) more realistic. The best association of all relevant parameters is still pending. The authors have disclosed that they do not have any potential conflicts of interest. Natalia Viu Degaspare, MD, Felipe de Oliveira Rezende Caino, MD, Artur Figueiredo Delgado, MD, PhD, Werther Brunow de Carvalho, MD, PhD, Instituto da Criança, Faculdade de Medicina da Universidade de São Paulo–FMUSP, São Paulo, Brazil
REFERENCES
1. de la Oliva P, Menéndez-Suso JJ, Iglesias-Bouzas M: Cardiac Preload Responsiveness in Children With Cardiovascular Dysfunction or Dilated Cardiomyopathy: A Multicenter Observational Study. Pediatr Crit Care Med 2015; 16:45–53 2. Gazit AZ, Cooper DS: Emerging technologies. Pediatr Crit Care Med 2011; 12:S55–S61 3. Brotschi B, Hug MI, Latal B, et al: Incidence and predictors of indwelling arterial catheter-related thrombosis in children. J Thromb Haemost 2011; 9:1157–1162 4. Rodrigues PC, Menezes AM, Carvalho WB, et al: Are children similar to adults when there is fluid overload? Crit Care Med 2013; 41:e48–e49 5. Monnet X, Anguel N, Osman D, et al: Assessing pulmonary permeability by transpulmonary thermodilution allows differentiation of hydrostatic pulmonary edema from ALI/ARDS. Intensive Care Med 2007; 33:448–453 6. Sankar J, Das RR, Jain A, et al: Prevalence and outcome of diastolic dysfunction in children with fluid refractory septic shock— A prospective observational study. Pediatr Crit Care Med 2014; 15:e370–e378 7. Lubien E, DeMaria A: Utility of b-natriuretic peptide in detecting diastolic dysfunction. Circulation 2012; 105:595–601 DOI: 10.1097/PCC.0000000000000377
May 2015 • Volume 16 • Number 4
REFERENCES
1. Souza DC, Barreira ER, Shieh HH, et al: Sepsis Is SEPSIS! It’s High Time to Globalize Pediatric Sepsis. Pediatr Crit Care Med 2015; 16:390–391 2. Balamuth F, Weiss SL, Neuman MI, et al: Pediatric severe sepsis in U.S. children’s hospitals. Pediatr Crit Care Med 2014; 15:798–805 3. Weiss SL, Parker B, Bullock M, et al: Defining pediatric sepsis by different criteria: Discrepancies in populations and implications for clinical practice. Pediatr Crit Care Med 2012; 13:e219–e226 4. Ruth A, McCracken CE, Fortenberry JD, et al: Pediatric severe sepsis: Current trends and outcomes from the Pediatric Health Information Systems database. Pediatr Crit Care Med 2014; 15:828–838 5. Weiss SL, Fitzgerald JC, Faustino EV, et al; Pediatric Acute Lung Injury and Sepsis Investigators Network and Australia and New Zealand Intensive Care Society Investigators: Understanding the global epidemiology of pediatric critical illness: The power, pitfalls, and practicalities of point prevalence studies. Pediatr Crit Care Med 2014; 15:660–666 DOI: 10.1097/PCC.0000000000000394
The authors reply:
W
e thank Souza et al (1) for their comments on our recently published article in this journal (2). Our study sample of 1,530 sepsis and severe sepsis was from 27,836 hospitalized patients admitted in 11 level II and III hospital pediatric departments with emergency and inpatient services (two of which provided pediatric intensive care services), as a part of a regional network serving a population of 5.4 million with more than 843,000 children. During the study period, a universal healthcare insurance system was in effect with a robust transport network; there should have been very few cases of sepsis and severe sepsis not admitted to these hospitals. Thus, the prevalence and mortality rate of this study sample should be most likely representative of a complete regional children’s population
Pediatric Critical Care Medicine
based on our data. We feel confident that these data are suitable to address early identification and treatment of sepsis with regard to facility and resource availability and affordability in China and likely some developing countries and regions. The prevalence and mortality rate of pediatric sepsis were based on the total hospital admissions. Clearly, there would be differences in prevalence and mortality rates depending on the denominator used to characterize the patient population. We considered that infrastructure for children’s health care at community level plays an important role in pediatric sepsis outcome, including socioeconomic conditions, healthcare insurance, and quality and timeliness of care in the pediatric emergency and inpatient wards. On the basis of this approach, we concluded that sepsis confers a tremendous burden and high mortality in children. However, we recognize that such assessment is regional specific, and our data show that approaches to treatment were not standardized or did not follow the recommended international guidelines, especially at early stage of sepsis. Although resource limitations may be an issue in some instances, reduction in morbidity and mortality of pediatric sepsis in developing country should take into consideration not only for technology but also the impact of community healthcare infrastructure, continuing medical education for general practitioners and healthcare insurance coverage, and among others. We are also cognizant of the fact that sepsis has been defined in several ways in different settings. For instance, the use of administrative databases (International Classification of Diseases-9th Edition and 10th Edition) would yield a proportion of sepsis cases that, while overlapping with the research definition, are not totally congruent. In addition, the clinical criteria may yield a higher proportion of cases that may also overlap with the other two groups (3). Thus, to compare the incidence and prevalence and mortality and morbidity outcomes from various regions, we need to be cognizant of the definitions being used to define the sepsis cohort. Efforts are underway to craft a universal definition such that, in the ideal situation, we will be using similar definitions in various parts of the world and various settings (4). Clearly, there is a tremendous amount of work being done to describe the burden of sepsis in many parts of the world. There should also be equal effort expended in trying to come to a uniform definition. Should this not be possible, then we should strive to agree on definitions that may be more appropriate for resource-poor and resource-rich settings. We thank you for your interest and appreciate your comments. The authors have disclosed that they do not have any potential conflicts of interest. Yuanyuan Wang, MD, Bo Sun, MD, Departments of Pediatrics and Pediatric Critical Care, Children’s Hospital of Fudan University, Shanghai, China; Hongni Yue, MD, Department of Pediatrics, Huai’an Maternity and Children’s Hospital, Jiangsu, China; Niranjan Kissoon, MD, Department of Pediatrics, University of British-Columbia and BC Children’s Hospital, Vancouver, British Columbia, Canada www.pccmjournal.org
393
Letters to the Editor
REFERENCES
1. Souza DC, Barreira ER, Shieh HH, et al: Sepsis Is SEPSIS! It’s High Time to Globalize Pediatric Sepsis. Pediatr Crit Care Med 2015; 16:390–391 2. Wang Y, Sun B, Yue H, et al: An epidemiologic survey of pediatric sepsis in regional hospitals in China. Pediatr Crit Care Med 2014; 15:814–820 3. Kissoon N: Sepsis in children: A dark cloud with a silver lining. Pediatr Crit Care Med 2014; 15:899–901 4. Thompson GC, Kissoon N: Sepsis in Canadian children: A national analysis using administrative data. Clin Epidemiol 2014; 6:461–469 DOI: 10.1097/PCC.0000000000000395
Invasive Measurement of Global End-Diastolic Volume: Is It Possible to Add Any Data Besides Clinical Parameters? To the Editor:
H
emodynamic instability is very common in critically ill children, and noninvasive methods have been studied to optimize cardiac output (CO) monitoring with accessible and less influenced by extracardiac factors. In a recent article in Pediatric Critical Care Medicine, de la Oliva et al (1), in a very original study, aimed to characterize cardiac preload responsiveness in pediatric patients with normal cardiovascular function, cardiovascular dysfunction, and dilated cardiomyopathy by using the following group of indicators: global end-diastolic volume (GEDV), stroke volume, CO, and extravascular lung water (EVLW). The Spanish Group (1) made transpulmonary thermodilution measures before and after fluid challenge. This method is incorporated in PiCCO device and has many advantages such as less influence of mechanical ventilation and continuous estimation of the CO and pulmonary edema (2). Despite being considered a minimally invasive method of monitoring, PiCCO is still a device with a good chance of complications due to the insertion of a catheter in the femoral artery (specially in very young children, limited to 3.5 kg or more), imprecision of information in intracardiac shunts and postoperative cardiac surgery, and large variation of the method result in the case of shock and hemorrhage (constant recalibration) (3). The article proposes to set up “normal” values of GEDV index in children, but a limited number of patients in the normal cardiovascular status group, and the heterogeneity sample of patient’s basic diseases in the PICU hospitalization may cause troublesome results. The great variability of diagnoses presented, including those intrinsically related to heart problems, such as Kawasaki disease, was not differentiated in each group and could be responsible for bias. The GEDV is important and can determine in which part of Frank-Starling curve the patient is situated, but recent studies show that fluid management can be more multifactorial than
394
www.pccmjournal.org
the original Starling model. In some diseases where the inflammatory response can increase the pulmonary capillary permeability (4), an elevated EVLW can be found in a patient with normal cardiovascular status. Monnet et al (5) suggest that the ratio of EVLW to GEDV may better discriminate between pulmonary edema caused by abnormal capillary permeability and left heart failure. Especially in patients with diastolic dysfunction, the edge between normovolemia and fluid overload may be very close. Sankar et al (6) showed that diastolic dysfunction evaluated by echocardiography in patients with positive fluid balance was associated to a higher mortality. Although troponin-T was not linked to predict diastolic dysfunction in an early moment (6), other biomarkers, such as brain natriuretic peptide, should be taken in consideration (7). The elaboration of a protocol including biomarkers, echocardiography, and clinical parameters (noninvasive methods) could be useful in the majority of patients, and in very critical condition (persistent unresponsiveness of fluid challenge or higher dosage of vasoactive drugs), the sequential measurement of EVLW/GEDV would be necessary. The precise estimative of diastolic volume and CO has been looking forward in PICU for long time, but adverse effects of invasive monitoring and difficulties related to the methods turned real-time procedures (main clinical data and bedside echocardiography) more realistic. The best association of all relevant parameters is still pending. The authors have disclosed that they do not have any potential conflicts of interest. Natalia Viu Degaspare, MD, Felipe de Oliveira Rezende Caino, MD, Artur Figueiredo Delgado, MD, PhD, Werther Brunow de Carvalho, MD, PhD, Instituto da Criança, Faculdade de Medicina da Universidade de São Paulo–FMUSP, São Paulo, Brazil
REFERENCES
1. de la Oliva P, Menéndez-Suso JJ, Iglesias-Bouzas M: Cardiac Preload Responsiveness in Children With Cardiovascular Dysfunction or Dilated Cardiomyopathy: A Multicenter Observational Study. Pediatr Crit Care Med 2015; 16:45–53 2. Gazit AZ, Cooper DS: Emerging technologies. Pediatr Crit Care Med 2011; 12:S55–S61 3. Brotschi B, Hug MI, Latal B, et al: Incidence and predictors of indwelling arterial catheter-related thrombosis in children. J Thromb Haemost 2011; 9:1157–1162 4. Rodrigues PC, Menezes AM, Carvalho WB, et al: Are children similar to adults when there is fluid overload? Crit Care Med 2013; 41:e48–e49 5. Monnet X, Anguel N, Osman D, et al: Assessing pulmonary permeability by transpulmonary thermodilution allows differentiation of hydrostatic pulmonary edema from ALI/ARDS. Intensive Care Med 2007; 33:448–453 6. Sankar J, Das RR, Jain A, et al: Prevalence and outcome of diastolic dysfunction in children with fluid refractory septic shock— A prospective observational study. Pediatr Crit Care Med 2014; 15:e370–e378 7. Lubien E, DeMaria A: Utility of b-natriuretic peptide in detecting diastolic dysfunction. Circulation 2012; 105:595–601 DOI: 10.1097/PCC.0000000000000377
May 2015 • Volume 16 • Number 4
