Pediatric Emergency Care for Children and Adolescents with Cancer: Causes of Consultation and Factors Associated with Hospitalization
Atendimento de Emergência Pediátrica a Crianças e Adolescentes com Câncer: Causas de Consultas e Fatores associados à Internação
Atención de Emergencia Pediátrica al Niño y Adolescente con Cáncer: Causas de Consultas y Factores Asociados a la Hospitalización
https://doi.org/10.32635/2176-9745.RBC.2023v69n4.4076
Maria Ourinda Mesquita da Cunha1; Fernanda Ferreira da Silva Lima2; Marilia Fornaciari Grabois3; André Ricardo Araújo da Silva4; Sima Ferman5
1-3,5Instituto Nacional de Câncer (INCA), Departamento de Oncologia Pediátrica. Rio de Janeiro (RJ), Brazil. E-mails: maria.cunha@inca.gov.br; fernanda.lima@inca.gov.br; mgrabois@inca.gov.br; sferman@inca.gov.br. Orcid iD: https://orcid.org/0000-0002-5863-5477; Orcid iD: https://orcid.org/0000-0002-6658-3101; Orcid iD: https://orcid.org/0000-0002-9368-1030; Orcid iD: https://orcid.org/0000-0002-7076-6779
4Universidade Federal Fluminense (UFF), Departamento de Saúde Maternal e Infantil. Niterói (RJ), Brazil. E-mail: aricardo@id.uff.br. Orcid iD: https://orcid.org/0000-0002-3896-9226
Corresponding author: Sima Ferman. Departamento de Oncologia Pediátrica do INCA. Praça Cruz Vermelha 23, 5º andar – Centro. Rio de Janeiro (RJ), Brazil. CEP 20230-130. E-mail: sferman@inca.gov.br
ABSTRACT
Introduction: Pediatric emergency care is essential for adequate medical treatment of pediatric cancer-associated complications and for increasing the chances of cure. Objective: This study aimed to describe pediatric cancer-associated emergencies and outcomes, and to analyze the factors associated with hospitalization. Method: A retrospective observational cohort study was conducted including patients aged ≤19 years who attended the pediatric emergency of a general cancer hospital from April 17 to October 17, 2019. The variables analyzed were demographics, socioeconomic status, disease and treatment factors, reasons for seeking emergency care, and associated outcomes. Results: This study included 309 patients who required 994 emergency consultations, with a total of 766 reasons for seeking care. The median age was 4.86 years; 50.8% were female and 51.5% were white. The patients had solid tumors (49.8%), central nervous system tumors (27.5%), and hematological neoplasms (15.5%). Most of the patients were home discharged (72.2%) or to support houses (6.7%). Fever was the most frequent symptom (30.8%) and the most common reason for admission. 19.2% of the patients were admitted to the ward and 2.0% to the pediatric intensive care unit (2.0%). Only two of the 309 patients (0.6%) seeking care in the pediatric emergency died in the emergency room, and these patients were in end-of-life care. Conclusion: The availability of a pediatric emergency room with skilled professionals in supportive care of pediatric patients with cancer was essential for the management of disease and treatment-related complications.
Key words: febrile neutropenia; medical oncology; emergency medical services; children; adolescent.
RESUMO
Introdução: O atendimento de emergência pediátrica é essencial para o tratamento adequado das complicações associadas ao câncer pediátrico e para aumentar as chances de cura. Objetivo: Descrever as emergências associadas ao câncer pediátrico e seus desfechos, e analisar os fatores associados à hospitalização. Método: Estudo de coorte observacional retrospectivo incluindo pacientes com idade ≤ 19 anos que foram atendidos na emergência pediátrica de um hospital oncológico geral no período de 17 de abril a 17 de outubro de 2019. As variáveis analisadas foram demográficas, socioeconômicas, fatores relacionados à doença e ao tratamento, razões para procurar atendimento de emergência e resultados associados. Resultados: Foram incluídos 309 pacientes que necessitaram de 994 consultas de emergência, totalizando 766 causas de atendimento. A idade mediana foi de 4,86 anos; 50,8% eram do sexo feminino e 51,5% afirmaram ser da raça branca. Os pacientes apresentavam tumores sólidos (49,8%), tumores do sistema nervoso central (27,5%) e neoplasias hematológicas (15,5%). A maioria dos pacientes foi liberada para a residência (72,2%) ou casa de apoio (6,7%). A febre foi o sintoma mais frequente (30,8%) e o motivo mais comum de admissão. Os pacientes foram internados em enfermaria (19,2%), ou em unidade de terapia intensiva pediátrica (2,0%). Somente dois dos 309 (0,6%) pacientes atendidos na emergência pediátrica morreram nesse setor, estando estes em cuidados de fim de vida. Conclusão: A disponibilidade de um departamento de emergência pediátrica com profissionais especializados e treinados em cuidados de suporte a pacientes pediátricos com câncer foi essencial para o manejo das complicações relacionadas à doença e ao tratamento.
Palavras-chave: neutropenia febril; oncologia; serviços médicos de emergência; criança; adolescente.
RESUMEN
Introducción: La atención de emergencias pediátricas es fundamental para el adecuado tratamiento médico de las complicaciones asociadas al cáncer pediátrico y para aumentar las posibilidades de cura. Objetivo: Describir las emergencias asociadas al cáncer pediátrico y sus desenlaces, y analizar los factores asociados a la hospitalización. Método: Estudio de cohorte observacional retrospectivo que incluyó pacientes con edad ≤ 19 años que fueron atendidos en el servicio de emergencias pediátricas de un hospital general de oncología del 17 de abril al 17 de octubre de 2019. Las variables analizadas fueron demográficas, socioeconómicas, factores relacionados con la enfermedad y tratamiento, razones para buscar atención de emergencia y resultados asociados. Resultados: Se incluyeron 309 pacientes que requirieron 994 consultas de urgencia, totalizando 766 causas de atención. La mediana de edad fue de 4,86 años; el 50,8% eran mujeres y el 51,5% eran personas blancas. Los pacientes tenían tumores sólidos (49,8%), tumores del sistema nervioso central (27,5%) y neoplasias hematológicas (15,5%). La mayoría de los pacientes fueron dados de alta a su hogar (72,2%) o casa de apoyo (6,7%). La fiebre fue el síntoma más frecuente (30,8%) y el motivo de ingreso más frecuente. Los pacientes fueron admitidos en una sala (19,2%) o en una unidad de cuidados intensivos pediátricos (2,0%). Solo 2 de 309 (0,6%) pacientes atendidos en el servicio de emergencias pediátricas fallecieron en este sector, estando estos en cuidados al final de la vida. Conclusión: La disponibilidad de un servicio de emergencias pediátricas con profesionales especializados y capacitados en el cuidado de apoyo al paciente oncológico pediátrico fue fundamental para el manejo de las complicaciones relacionadas con la enfermedad y el tratamiento.
Palabras clave: neutropenia febril; oncología médica; servicios médicos de emergencia; niño; adolescente.
INTRODUCTION
Estimates indicate that 7,930 cases of childhood and adolescent cancer will be diagnosed in Brazil1 in 2023. Cancer is the second most common cause of death for this population2. The disease and therapies used for patients with cancer can pose life-threatening risks to them. The reasons for emergency care include disease and treatment-related complications, as infections and non-infectious toxicities3,4. Immediate recognition and management of emergencies is essential to reduce morbidity and mortality in these patients5. Pediatric emergency (PE) care is essential for adequate medical treatment of pediatric cancer-associated complications and to increase the chances of cure5,6.
Neutropenia is a common complication of chemotherapy and radiation therapy; fever can be an alarming sign of a serious bacterial infection7,8. The risk of febrile neutropenia in patients undergoing cancer treatment depends on several factors, including the patient´s age, tumor type, and the chemotherapy protocols utilized. The immediate use of broad-spectrum empirical antibiotic therapy, regardless of prior microbial isolation, has successfully reduced the mortality rate associated with febrile neutropenia9. Moreover, access to PE care facilitates the early use of antibiotic therapies5.
Determining the reasons for needing care in the PE and the outcomes is essential for assessing the quality of the service and patient care with effective strategies to anticipate, prevent and manage complications to improve the outcomes of cancer treatment3,6. However, studies addressing emergency care in pediatric oncology are scarce4,10.
This study aimed to evaluate the main pediatric cancer-associated complaints in PE of a major cancer hospital in an upper middle-income country and the associated outcomes, as well as risk factors for hospital admission.
METHOD
Retrospective observational cohort study of pediatric patients with solid tumors and malignant hematological diseases admitted to the PE from April 17 to October 17, 2019. The inclusion criteria were patients with malignant and benign solid tumors who received cancer treatment. Patients treated at other institutions but admitted for imaging exams, invasive procedures, or exclusive radiotherapy treatments were excluded. Data from physical and electronic medical records were collected. The Institutional Review Board of INCA (CAAE (submission for ethical review) 94086318.0.0000.5274) approved the study, report number 3,815,145, in compliance with Resolution 466/201211 of the National Health Council. The informed consent form was waived because of the study design.
This study was conducted at the Pediatric Oncology of the National Cancer Institute – INCA. This institution is a reference center for the diagnosis and treatment of pediatric patients with solid tumors and hematological malignancies, as part of the services offered by the Brazilian National Health System (SUS)12,13. Approximately 250 pediatric patients with cancer are registered annually. The INCA’s PE performs around 2,500 consultations per year and is responsible for the emergency care of the patients at diagnosis and during treatment, long-term follow-up, and palliative care. Patient care at the PE is provided by a specialized multidisciplinary team to assist pediatric patients with cancer 24 hours a day, 7 days a week.
The treatment approach is multidisciplinary and includes socioeconomic support and prevention of treatment abandonment14. Patients who live far from the hospital are eligible for accommodation free of charge15.
The demographic and socioeconomic variables analyzed included age at diagnosis, age at PE consultation, sex, race, distance from the hospital (≤ 80 km or > 80 km), monthly family income per capita, and maternal and paternal ages.
Disease and treatment-associated factors analyzed were diagnosis of hematological, central nervous system (CNS) tumors and other solid and benign tumors, in addition to metastasis at diagnosis (staging), time since diagnosis up to consultation (≥ 1 year or < 1 year), diagnostic investigations, first-line treatment, second-or later-line treatment, follow-up after treatment and end-of-life care (oncological status) and type of treatment (chemotherapy, radiotherapy, surgery, and bone marrow transplantation). The types of cancers were classified according to the International Classification of Childhood Cancer (CICI)16.
The reasons for emergency care were: febrile neutropenia with axillary temperature ≥ 38.3°C in a single measurement or a peak of 38°C sustained for more than one continuous hour in a patient with absolute neutrophil count of < 500 cells/mL or an expected drop to < 500 neutrophils/mm3 within 48h9,17. Any other symptoms related to disease or treatment were recorded. The reviews of the emergency causes per patient were also measured. Patients were categorized as frequent PE users if they had > 2 visits in 6 months18.
The outcomes were home or support house discharge, hospitalization at the ward, emergency room, or Pediatric Intensive Care Unit (PICU) and death at the emergency room or within 30 days of emergency care.
A descriptive analysis of the study population was performed by estimating measures of central tendency and dispersion for continuous variables, and percentage values for categorical variables. The Kolmogorov-Smirnov test was performed to assess the normality of the continuous variables. The chi-square hypothesis or Fisher's exact test was calculated when the absolute counts were lower than five observations to detect possible differences between categorical independent variables and outcomes. The Mann–Whitney U test was used to detect differences between the variables and outcomes, since the distribution was non-parametric.
The odds ratio was calculated using logistic regression to assess the association between the exposures and outcomes. Variables with p < 0.25 or theoretical relevance with the theme were selected for the multiple regression model using the Enter method (stepwise forward) to control the confounding factors.
After entering the variables into the multiple regression model, variables with p < 0.05 were considered statistically significant and were kept in the final model. The quality of the model fit was determined using Hosmer-Lemeshow test values. IBM SPSS Statistics for Windows, version 24.0 (IBM Corp., Armonk, N.Y., USA) was used for the analyses.
RESULTS
This study included all 309 consecutive patients who met the eligibility criteria and were treated at the PE from April 17 to October 17, 2019, for 766 different causes, requiring 994 consultations, including 228 appointments to review patients when necessary.
The median age at cancer diagnosis was 4.86 years (interquartile range 2.02–11.40). The 0–4-year-old age group (46.6%) was most frequently enrolled, followed by the 5–9-year-old age group (22.7%), 50.8% were females who claimed there were White (51.1%). The median per capita family monthly income was US$ 59.71 (range: 00.00-599.45), which means 0.25 times the national minimum wage (range 0–2.5 times the minimum wage), 86.4% lived ≤ 80 km far from the treatment center (Table 1). The mean age at the emergency consultation was 9.50 years (range: 1-31) (Table 2).
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Table 1. Sociodemographic and clinical characteristics of pediatric patients who attended INCA’s PE from April to October 2019 (n = 309) |
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Captions: IQR = interquartile range; CICI = International Classification of Childhood Cancer; CNS = central nervous system; BMT = bone marrow transplant; PE = pediatric emergency. (*) Brown/Black/Yellow. (**) Others: Intra-arterial chemotherapy for retinoblastoma among others National Minimum Wage in 2019: US$ 239,33 |
A total of 766 reasons for emergency care were identified, resulting in 994 visits, with an average of 2.49 visits per reason (range 1–13). The mean age of patients was 9.50 (SD ± 6.35) and 49.9% of the consultations occurred in less than one year since registration. At the institution, 49.6% of the consultations were for solid tumors.
Fever was reported as reason for seeking emergency care in 30.8% of the PE visits. The most frequent reasons for emergency consultations were fever without neutropenia (21.4%), pain (16.7%), upper airway infection (14.4%), viral or bacterial infection (7.4%), nausea and vomiting (6.9%), and fever with neutropenia (5.6%). There were 43 episodes of febrile neutropenia in 34 patients. Microbiologically confirmed infections occurred in six of the 34 (17.6%) patients; three (8.8%) required PICU admission, but no deaths occurred.
In 603 (78.8%) consultations, patients were home-discharged (72.1%) or to support houses (6.7%). Hospitalization was required in 162 (21.2%) cases, of which 147 (19.2%) were to the ward and 15 (2.0%) to the PICU (Table 2).
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Table 2. Characteristics of consultations provided at the PE and outcomes, from April to October 2019 (n = 766) |
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A significant difference was found among patients who were hospitalized and those who were treated and discharged, in terms of the following variables: fever as a reason for consultation, time from enrollment, metastasis at diagnosis, necessity of surgical intervention, and oncological status at the time of consultation (Table 3).
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Table 3. Clinical and treatment characteristics of patients according to admission versus discharge after care at the PE, from April to October 2019 (n = 766) |
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In the univariate analysis, the following variables showed significant differences: fever as a reason for PE care (p = 0.009); patients within 1 year of enrollment (p < 0.001); metastatic disease at diagnosis (p = 0.031), and patients undergoing diagnostic investigations (p < 0.001), first-line treatment (p < 0.001), second- or later-line treatment (p = 0.001), and exclusive palliative care (p < 0.001). Patients with hematological malignancies also tended to be hospitalized after emergency care (p = 0.075) (Table 4).
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Table 4. Crude odds ratios between the clinical characteristics of patients and the outcome hospitalization versus discharge after the cause of care at the PE, from April to October 2019 |
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In the multiple regression model, patients with fever were 1.78 times more likely to be hospitalized than patients without fever. Patients receiving exclusive palliative care were 4.28 times more likely to be hospitalized than patients whose cancers were being followed up after cancer treatment. An increased likelihood of hospitalization was also observed in patients undergoing diagnostic investigations (3.89 times), first-line treatment (2.30 times), and second- or later-line treatment (2.68 times) (Table 5).
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Table 5. Factors associated with the hospitalization outcome after the causes of care at the PE, from April to October 2019 |
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Only two of the 309 patients (0.6%) seeking care at the PE died. Six patients (1.9%) died within 30 days from care. In all, eight patients died due to disease progression (2.5%).
DISCUSSION
There is scarce literature on emergency care for pediatric patients with solid tumors and hematologic malignancies, especially by institutions which provide services to treat these patients exclusively. This study assessed 309 children at a pediatric cancer referral center along the cancer care continuum. Retrospective studies investigated a database with 45 Emergency Departments of Pediatric Hospitals in the United States4,8,18. Another retrospective report studied the main complaints of children with cancer in a general PE, but restricted to patients undergoing active cancer treatment19. In a study from Turkey, 88 patients admitted to the Department of Pediatric Oncology who presented with oncological emergencies were prospectively analyzed20. To the best of the current knowledge, no studies have addressed specific PE care in a cancer hospital.
The most frequent neoplasms in pediatric patients who attended the institution’s PE were CNS tumors (27.5% of cases). These findings differ from those of another study, where 25.9% of the cases were due to acute lymphoblastic leukemia (ALL), which was the most frequent neoplasm20. Similarly, in other publication the authors found that 41.3% of children consulted at the PE had ALL19. One explanation for this finding is that the PE care is provided to patients enrolled at INCA, which is the largest referral center in the city for the treatment of solid tumors, whereas hematological neoplasms, such as leukemias, are treated at several local institutions.
Another objective was to investigate patients’ main reasons for requiring PE care of which fever was the most frequent reason. This finding concurs with previous studies8,19. In a study of patients undergoing active treatment who were consulted at the emergency, 61.2% had fever, which was the most frequently reported symptom. However, the number of cases of fever with neutropenia was unspecified19.
Febrile neutropenia occurred in 5.6% of the patients and was the sixth most frequent reason for emergency consultation in this cohort, while it was the second most frequent reason in other reports4,18. Febrile neutropenia is one of the most life-threatening complications experienced by patients undergoing cancer treatment. Its prompt recognition and treatment has reportedly led to a decrease in mortality and morbidity21. Standard operating procedures for cases of febrile neutropenia have been established at the institution. The entire team is trained to promptly attend to the patient, collect specimen for tests, and initiate antibiotic therapy within less than one hour of the patient's arrival. In this cohort, microbiologically confirmed infections occurred in 17.6% of the patients, while 8.8% required PICU admission and no deaths occurred. Another study evaluated 199 episodes of febrile neutropenia in 119 patients. Similar to these results, microbiologically confirmed infections occurred in 22.6% of the cases, while eight (4%) patients required PICU admission and one patient died (0.8%)22. Nausea and vomiting were frequent complaints, accounting for 6.9% of the visits to the PE. An explanation for the high incidence of nausea and vomiting could be that many patients were receiving highly emetogenic chemotherapy treatment on an outpatient basis. These patients were followed up in the outpatient clinics and day hospitals for clinical and symptom control and hydration when necessary, avoiding evolution to dehydration. In another study nausea or vomiting was present in only 2.3% of the PE visits in pediatric patients with cancer4. Patients were home or support houses discharged in 78.8% of the cases as the investigation of the outcomes of the emergency consultations revealed. Hospitalization was required in only 21.1% of cases. Independent risk factors associated with hospital admission were fever, diagnostic investigations, active treatment, and exclusive palliative care. Patients receiving palliative care rarely presented to the emergency room for care, but the risk of hospitalization for these patients was higher than that for patients in other oncologic situations when treated at the PE. In another study, approximately 50% of children with cancer consulted at the PE were hospitalized8. The same authors found a similar admission rate (50.8%) in another study conducted the following year8,18. However, they did not analyze the relation between oncological situation and hospitalization. A study with pediatric patients with cancer treated at the PE of a pediatric hospital enrolled only patients receiving active treatment18. Patients undergoing diagnostic investigations and those who were newly diagnosed or relapsed were excluded. Hospitalization and discharge were the outcomes considered. The authors found similar reasons for seeking care of those identified in the current investigation, such as fever, pain, nausea and vomiting, and laboratory result abnormalities. Unlike these results, bleeding was among the top five reasons for seeking care, perhaps because the cohort investigated was on active treatment, and a higher frequency of acute leukemias was observed. Of the total visits, 56.5% resulted in hospitalization. The risk factors for hospitalization were fever and hospitalization in the previous four weeks19. Death at the institution’s PE was very rare, occurring in only 0.6% of cases, and 1.9% of all deaths occurred within 30 days of care. In this study, patients who died at the PE, or up to 30 days after care, were receiving exclusive palliative care. Other studies confirmed these findings: one study was on pediatric patients receiving palliative care who were consulted at the PE22. Of those, 39.4% had cancer and were generally ill with dyspnea, fever, pain, and seizures. Many were terminally ill, but none died at the PE, although 38.3% died after admission and 19% within 72 hours of admission23. Other researchers found that death at the emergency room was rare, at a rate of one death for every 15,000 visits in the United States24. These studies highlight the importance of a structured health service for immediate treatment of complications, with a specialized team trained in supportive care to reduce mortality and morbidity.
The study limitations are the retrospective design with data obtained from charts not designed for research data collection. Nevertheless, collection bias was minimized by the fact that a single researcher performed the data search. Additionally, considering the heterogeneity of the population in terms of age, underlying pathologies, and chemotherapy protocols, studies over a longer period may establish better performance indicators.
CONCLUSION
The availability of a PE with skilled professionals trained in supportive care of pediatric patients, as well as standard operating procedures for most life-threatening complications with cancer enabled safe and effective oncologic treatment. Fever was the most frequent cause of PE consultations and in this cohort no death occurred due to fever neutropenia. Most patients consulted at the PE were discharged. Factors associated with increased odds of admission included main complaint of fever and oncological status of diagnostic investigations, treatment, and end-of-life care. This knowledge is important to plan treatment and improve safe and effective care of children with cancer.
CONTRIBUTIONS
All the authors contributed to the study design, data acquisition, interpretation, analysis and wording. They approved the final version for publication.
DECLARATION OF CONFLICT OF INTEREST
There is no conflict of interests to declare.
FUNDING SOURCES
None.
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Recebido em 27/6/2023
Aprovado em 18/9/2023
Scientific-Editor: Anke Bergmann. Orcid iD: https://orcid.org/0000-0002-1972-8777
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