Cardiac Arrest in Children: Long-term Health Status and HRQoL
Cardiac Arrest in Children: Long-term Health Status and HRQoL
This medical follow-up study was performed at the ICU of the Erasmus MC-Sophia Children's Hospital, a tertiary care university children's hospital, containing the only specialized PICU in this region. Our hospital provides healthcare to children in the southwest of the Netherlands with a total population of approximately 4.2 million people, which is a representative sample of the Dutch population.
The Erasmus MC Ethical Review Board approved the study protocol.
This study concerned all consecutive surviving patients who were 0–18 years old with CA between January 2002 and December 2011, who were admitted to the ICU of the Erasmus MC-Sophia Children's Hospital.
CA was defined as absent pulse rate or the need for cardiac compressions. Cardiopulmonary resuscitation (CPR) was defined as "basic life support" (BLS), in line with the European Resuscitation Council Guidelines for pediatric life support, and if needed, followed by "advanced pediatric life support" (APLS).
All CA data were retrospectively collected. Data were derived from ambulance registration forms, clinical and electronic medical records, and CA registration forms. We collected 1) basic patient characteristics, 2) CA characteristics (e.g., location, rhythm, and etiology), and 3) outcome (mortality). In addition, medical records were retrospectively analyzed if the health status prior to the CA was related to the cause of the arrest (i.e., cardiac, respiratory, or other).
Eligibilities for this study were as follows: 1) children resuscitated in-hospital (e.g., emergency department, ward, and ICU), 2) children resuscitated in a regional hospital or other university hospital and subsequently admitted to the ICU of our hospital, and 3) children resuscitated out-of-hospital and subsequently admitted to our ICU.
Neonates resuscitated at the hospital's neonatal ICU (NICU) or in another hospital and subsequently admitted to the NICU of our hospital were excluded.
Surviving children and parents were invited to participate 2–11 years after ICU discharge. Informed consent was obtained from parents and children (≥ 12 yr). Participating families were invited to complete online health status and HR-QoL questionnaires. Choice of respondent (mother or father) was left to the parents themselves. Parents also completed assessments. Subsequently, children were invited for a medical interview and physical examination.
Parents and children were interviewed by a medical doctor (L.v.Z.) in a semistructured format using a CPR-specific standardized questionnaire on health consequences and medical care since the CA. It included questions on family characteristics, healthcare consumption, current physical and behavioral functioning, and changes in this functioning since the CA. This allowed us to differentiate between preexisting complaints and physical and behavioral changes due to the CA. Somatic symptoms (such as fatigue, pain, headache, among other) were defined as chronic if they had developed in the first weeks after ICU discharge and were still present at the time of follow-up. Severity of these complaints was scored on a 5-point scale (very mild to very severe).
A general physical examination (including blood pressure [BP]) was performed by the same medical doctor (L.v.Z.). BP was measured with an electronic device three times at 1-minute intervals, with the child in a seated position following 5 minutes of rest. Hypertension was defined as median systolic BP (SBP) or diastolic BP (DBP) above the 95th percentile corrected for age, sex, and height.
Renal function was assessed by measuring serum creatinine (SCr), random urine protein sample, and random urine protein to creatinine ratio. An estimated glomerular filtration rate (eGFR) was calculated with the Schwarz formula eGFR (mL/min/1.73 m) = 36.5 × height (cm)/creatinine (μmol/L) for children younger than 16 years. For children older than 16 years, the modification of diet in renal diseases formula was used: eGFR (mL/min/1.73 m) = 186 × (SCr/88.4) × Age × (0.742 if female). Renal function was staged using the chronic kidney disease (CKD) stages provided by the National Kidney Foundation. The stages were defined as stage 0, glomerular filtration rate (GFR) at least 90 mL/min/1.73 m; stage 1, proteinuria with GFR at least 90 mL/min/1.73 m; stage 2, proteinuria with GFR 60–89 mL/min/1.73 m; stage 3, GFR 30–59 mL/min/1.73 m; stage 4, GFR 15–29 mL/min/1.73 m; and stage 5, GFR less than 15 mL/min/1.73 m. A protein concentration in a randomly collected urine sample of more than 22 mg protein/mmol creatinine was classified as proteinuria.
Generic health status was assessed with validated classification systems, the Health Utilities Index mark 2 and 3 (HUI2 and HUI3), encompassing 6–8 health dimensions. As parent report, the 15-item HUI was used (age range, 4–17 yr). The complete dataset of representative normative data was available (1,435 Dutch schoolchildren aged 5–13 yr).
HR-QoL in children was assessed with the CHQ and in parents with the SF-36. The Child Health Questionnaire-Infant Toddler 97 (CHQ-IT97) (0–3 yr) and Child Health Questionnaire-Parent Form 50 (CHQ-PF50) (4–17 yr) were filled out by parents about their child, and the Child Health Questionnaire-Child Form 87 (CHQ-CF87) (age 12–17) was filled out by children about themselves. Normative data were derived from representative samples of the general Dutch population. For the SF-36, Dutch normative data were available (1,742 participants, 16–94 yr) of which a normative reference group (those aged 41–60 yr) was used.
Socioeconomic status (SES) at time of follow-up was categorized as low (elementary occupations), middle (middle occupations), or high (highest professional occupations). The highest occupation of both parents was used. SES of nonparticipants at time of follow-up was calculated based on a combined status score of the Netherlands Institute for Social Research based on home address. This score consisted of average income in neighborhood, percentage of people with low income, percentage of less educated people, and percentage of people not working. A status score of 0 (± 1.16 SD) was classified middle SES, less than –1.16 was classified low SES, and more than +1.16 was classified high SES.
Univariable comparison of the distribution of patient characteristics and clinical data between survivors and nonsurvivors was performed by independent sample t tests for normally distributed data and Mann-Whitney U test for nonnormally distributed data. Fisher exact test was used for comparison of dichotomous data.
Normality of our data was examined with the Kolmogorov-Smirnov test. If the HUI data were normally distributed, the Welch t test (for unequal variances) was performed to compare data of children with CA with normative data. Mann-Whitney U test was used for nonnormally distributed data. If the HR-QoL data were normally distributed, one-sample t test was performed to compare with normative data. One-sample Wilcoxon signed-rank test was used for nonnormally distributed HR-QoL data. Effect sizes were reported with Cohen d.
Associations between putative predictor variables (age at ICU admission, BLS/APLS, preexisting condition, location, SES) and the HUI and HR-QoL scores were explored with the Spearman correlations for continuous variables, Mann-Whitney U test for dichotomous variables, and Kruskal-Wallis test for ordinal variables.
Statistical significance was considered with two-tailed p value of less than 0.05. All analyses were performed with SPSS 21.0 for Windows (SPSS, Chicago, IL).
Materials and Methods
This medical follow-up study was performed at the ICU of the Erasmus MC-Sophia Children's Hospital, a tertiary care university children's hospital, containing the only specialized PICU in this region. Our hospital provides healthcare to children in the southwest of the Netherlands with a total population of approximately 4.2 million people, which is a representative sample of the Dutch population.
The Erasmus MC Ethical Review Board approved the study protocol.
Patient Selection and Data Collection
This study concerned all consecutive surviving patients who were 0–18 years old with CA between January 2002 and December 2011, who were admitted to the ICU of the Erasmus MC-Sophia Children's Hospital.
CA was defined as absent pulse rate or the need for cardiac compressions. Cardiopulmonary resuscitation (CPR) was defined as "basic life support" (BLS), in line with the European Resuscitation Council Guidelines for pediatric life support, and if needed, followed by "advanced pediatric life support" (APLS).
All CA data were retrospectively collected. Data were derived from ambulance registration forms, clinical and electronic medical records, and CA registration forms. We collected 1) basic patient characteristics, 2) CA characteristics (e.g., location, rhythm, and etiology), and 3) outcome (mortality). In addition, medical records were retrospectively analyzed if the health status prior to the CA was related to the cause of the arrest (i.e., cardiac, respiratory, or other).
Eligibilities for this study were as follows: 1) children resuscitated in-hospital (e.g., emergency department, ward, and ICU), 2) children resuscitated in a regional hospital or other university hospital and subsequently admitted to the ICU of our hospital, and 3) children resuscitated out-of-hospital and subsequently admitted to our ICU.
Neonates resuscitated at the hospital's neonatal ICU (NICU) or in another hospital and subsequently admitted to the NICU of our hospital were excluded.
Surviving children and parents were invited to participate 2–11 years after ICU discharge. Informed consent was obtained from parents and children (≥ 12 yr). Participating families were invited to complete online health status and HR-QoL questionnaires. Choice of respondent (mother or father) was left to the parents themselves. Parents also completed assessments. Subsequently, children were invited for a medical interview and physical examination.
Assessment at Follow-up
Parents and children were interviewed by a medical doctor (L.v.Z.) in a semistructured format using a CPR-specific standardized questionnaire on health consequences and medical care since the CA. It included questions on family characteristics, healthcare consumption, current physical and behavioral functioning, and changes in this functioning since the CA. This allowed us to differentiate between preexisting complaints and physical and behavioral changes due to the CA. Somatic symptoms (such as fatigue, pain, headache, among other) were defined as chronic if they had developed in the first weeks after ICU discharge and were still present at the time of follow-up. Severity of these complaints was scored on a 5-point scale (very mild to very severe).
A general physical examination (including blood pressure [BP]) was performed by the same medical doctor (L.v.Z.). BP was measured with an electronic device three times at 1-minute intervals, with the child in a seated position following 5 minutes of rest. Hypertension was defined as median systolic BP (SBP) or diastolic BP (DBP) above the 95th percentile corrected for age, sex, and height.
Renal function was assessed by measuring serum creatinine (SCr), random urine protein sample, and random urine protein to creatinine ratio. An estimated glomerular filtration rate (eGFR) was calculated with the Schwarz formula eGFR (mL/min/1.73 m) = 36.5 × height (cm)/creatinine (μmol/L) for children younger than 16 years. For children older than 16 years, the modification of diet in renal diseases formula was used: eGFR (mL/min/1.73 m) = 186 × (SCr/88.4) × Age × (0.742 if female). Renal function was staged using the chronic kidney disease (CKD) stages provided by the National Kidney Foundation. The stages were defined as stage 0, glomerular filtration rate (GFR) at least 90 mL/min/1.73 m; stage 1, proteinuria with GFR at least 90 mL/min/1.73 m; stage 2, proteinuria with GFR 60–89 mL/min/1.73 m; stage 3, GFR 30–59 mL/min/1.73 m; stage 4, GFR 15–29 mL/min/1.73 m; and stage 5, GFR less than 15 mL/min/1.73 m. A protein concentration in a randomly collected urine sample of more than 22 mg protein/mmol creatinine was classified as proteinuria.
Questionnaires
Generic health status was assessed with validated classification systems, the Health Utilities Index mark 2 and 3 (HUI2 and HUI3), encompassing 6–8 health dimensions. As parent report, the 15-item HUI was used (age range, 4–17 yr). The complete dataset of representative normative data was available (1,435 Dutch schoolchildren aged 5–13 yr).
HR-QoL in children was assessed with the CHQ and in parents with the SF-36. The Child Health Questionnaire-Infant Toddler 97 (CHQ-IT97) (0–3 yr) and Child Health Questionnaire-Parent Form 50 (CHQ-PF50) (4–17 yr) were filled out by parents about their child, and the Child Health Questionnaire-Child Form 87 (CHQ-CF87) (age 12–17) was filled out by children about themselves. Normative data were derived from representative samples of the general Dutch population. For the SF-36, Dutch normative data were available (1,742 participants, 16–94 yr) of which a normative reference group (those aged 41–60 yr) was used.
Socioeconomic Status
Socioeconomic status (SES) at time of follow-up was categorized as low (elementary occupations), middle (middle occupations), or high (highest professional occupations). The highest occupation of both parents was used. SES of nonparticipants at time of follow-up was calculated based on a combined status score of the Netherlands Institute for Social Research based on home address. This score consisted of average income in neighborhood, percentage of people with low income, percentage of less educated people, and percentage of people not working. A status score of 0 (± 1.16 SD) was classified middle SES, less than –1.16 was classified low SES, and more than +1.16 was classified high SES.
Statistical Analyses
Univariable comparison of the distribution of patient characteristics and clinical data between survivors and nonsurvivors was performed by independent sample t tests for normally distributed data and Mann-Whitney U test for nonnormally distributed data. Fisher exact test was used for comparison of dichotomous data.
Normality of our data was examined with the Kolmogorov-Smirnov test. If the HUI data were normally distributed, the Welch t test (for unequal variances) was performed to compare data of children with CA with normative data. Mann-Whitney U test was used for nonnormally distributed data. If the HR-QoL data were normally distributed, one-sample t test was performed to compare with normative data. One-sample Wilcoxon signed-rank test was used for nonnormally distributed HR-QoL data. Effect sizes were reported with Cohen d.
Associations between putative predictor variables (age at ICU admission, BLS/APLS, preexisting condition, location, SES) and the HUI and HR-QoL scores were explored with the Spearman correlations for continuous variables, Mann-Whitney U test for dichotomous variables, and Kruskal-Wallis test for ordinal variables.
Statistical significance was considered with two-tailed p value of less than 0.05. All analyses were performed with SPSS 21.0 for Windows (SPSS, Chicago, IL).