Introduction 68 69 41 72 73 15 55 64 70 26 2 19 58 75 multi-disciplinary 24 25 Based on these observations, we believe that follow-up research of paediatric intensive care survivors and their families is needed to evaluate: (1) physical sequelae and their impact during growth and development; (2) psychological sequelae in patients and their families and their impact on the QoL of patients and family members; and (3) the need for treatment and support after discharge. The aim of this article is to provide an overview of the available literature concerning the different domains of QoL (i.e. physical, psychological and social functioning) in children surviving paediatric intensive care, including the effect on parents, and to suggest directions for future follow-up research. Methods To identify studies eligible for this review, we searched Medline (1966–2006), EMBASE (1974–2006), CINAHL (1982–2006), pre-CINAHL and the Cochrane Library (2006) in March 2006. In the search strategy, all terms mapped to the appropriate MeSH/EMTREE subject headings and “exploded” were used; among them were: paediatric intensive care unit (PICU), septic shock, respiratory insufficiency, meningococcal disease, central venous catheterisation, intubation, physical and psychological sequelae, post-traumatic stress disorder (PTSD), QoL, health status and long-term outcome. Definitions Functional health is defined as an individual’s ability to perform normal daily activities, to fulfil usual roles and to maintain health and well-being. 1 21 Study selection Studies were selected for review if they met two inclusion criteria: (1) study of a representative population of PICU survivors (defined as a population consisting of medical and/or surgical PICU patients <18 years old) and (2) evaluation of physical sequelae, measurement of QoL or functional health >30 days after PICU discharge. Because of the limited number of studies, the measurement tools did not need to be standardised. Studies with a retrospective and prospective design were included. Excluded were: (1) studies in homogeneous PICU populations (e.g. survivors of cardiothoracic surgery and trauma) reporting diagnosis-related outcome in particular but not intensive care treatment as such, and (2) studies evaluating mortality only. Results Eligible studies and quality of the studies 1 2 3 Table 1 Patient characteristics, measurement tools, physical and functional health outcome Reference a n b c d e f Measurement tool n g Interpretation of outcome 23 Meningococcal disease 0.1–15.3 8–12 GMSPS NA Neurological examination 1 spastic quadriplegia Majority of children surviving meningococcal disease neurologically normal. n Median 5 Cognitive tests 5 hearing loss 4 major impairments 35 Cardiopulmonary resuscitation (CPR) 0–16 1 NA NA h 26 normal, 12 mild, 7 moderate, 3 severe disability 60% of survivors of CPR neurological normal. n 37 same as prior to CPR Location, underlying cause and duration of CPR determinants of outcome. 43 CPR 0–17 1 NA NA h 54 normal or mild disability, 6 moderate, 5 severe disability 80% of survivors of CPR neurological normal. n i Location, underlying cause and duration of CPR not determinants of outcome. 53 Acquired brain injury <3 >0.5 GCS<9 NA j GOS: 23 good recovery, 7 moderate, 5 severe disability Majority of children with acquired brain injury dead or disabled. n k BSID-II: 8 normal, 12 cerebral palsy, 11 cognitive delay Neuro-developmental examination 59 CPR 0–18 1 NA PICU h 5 normal, 1 mild, 4 moderate, 1 severe disability, 2 persistent vegetative state 38% of survivors of CPR neurological normal. n Median 5 i Underlying cause and duration of CPR determinants of outcome. 6 ARDS 2–13 5.6±4.3 NA NA Chest radiography 2 ARDS survivors at risk for hypoxaemia during exercise. n Pulmonary function 1 reduced diffusion capacity 14 Meningococcal disease with ARDS 0.3–3.7 0.5–2.1 PRISM 12-53% NA Pulmonary function 1 wheezing for which salbutamol ARDS survivors possibly at risk for mild obstructive lung disease. n 2 obstructive disease 22 ARDS 4.6–15.9 0.9–4.2 NA NA Pulmonary function 3 restrictive or obstructive disease ARDS survivors at risk for restrictive and obstructive lung disease. n Electrocardiography Echocardiography Cardiac function normal in all 30 ARDS 5–14 4.4 NA NA Pulmonary function 1 limitations in activity ARDS survivors at risk for restrictive and obstructive lung disease. n 4 restrictive disease 48 Meningococcal septic shock 1.6–15.4 2.2–4.9 NA NA Pulmonary function 18 normal lung function Meningococcal septic shock survivors at risk for hypoxaemia during exercise. n 2 74 ARDS 0.5–16 0.3–5.5 PRISM 18±14% NA Chest radiography 7 (11) restrictive or obstructive disease ARDS survivors at risk for restrictive and obstructive lung disease. n Pulse oximetry 4 (7) decreased diffusion capacity Pulmonary function Electrocardiography Echocardiography 62 Meningococcal sepsis with renal replacement therapy 0.5–15 2.7–7.1 NA PICU Glomerular filtration rate (GFR) 2 decreased GFR, proteinuria, hypertension Children surviving acute renal failure due to septic shock at risk for long-term renal dysfunction. n Median 12 Serum creatinine 1 parenchymal defect Protein excretion in urine 1 proteinuria DMSA scan 9 Near drowning admitted to PICU 0.7–14 ≥0.5 PRISM 71% NA Functional health: 8 severe neurological impairment Majority of near-drowning survivors lead a normal life. n GCS≤5 Contact primary physician or examination by study facility 17 normal or mildly impaired 12 PICU 0–18 2.5–3 NA PICU Functional health: 7% moderate or severe handicap Majority of PICU survivors seem to lead a normal life. n Mean 2.8 Written questionnaire or telephone contact with the specialist physician or parents 12% mild handicap 91% will lead independent life 44 Bacterial meningitis with respiratory insufficiency 0–12 0.6–6.4 PRISM NA Functional health: 12 normal Half of children surviving severe bacterial meningitis seem to lead a normal life. n Mean 22% Telephone interview 1 independent Range 1–47% 2 partially dependent 6 dependent a b n c d e f g n h i j k Table 2 Patient characteristics, measurement tools and psychological and quality of life (QoL) outcome Reference a n b c d e f Measurement tool n g Interpretation of outcome 40 PICU children and mothers 2.1–15.9 0.3–1 PRISM 0.4–76% PICU 1–30 Psychological outcome: Children: Behaviour high 3 (8), SDQ high 3 (21), IES PTSD 3 (29) PICU survivors and their mothers at risk for psychological distress and PTSD. n h i Mothers: GHQ high 11 (26), IES high 13 (27) j i 50 PICU 5–18 Median 0.6 Parent rating 10 Hospital 4–14 Psychological outcome: Children: PTSD 4 (19) PICU, 0 (27) ward IES high 4 (21) PICU, 2 (17) ward PICU survivors and their parents at risk for psychological distress and PTSD. n k h i l Parents: PTSD 9(33) PICU, 2 (29) ward General ward j i n Children and parents 51 PICU 11.3±3.2 0.5 PRISM 25±23% Hospital 13.0 Psychological outcome: IES and CMFS dependent on invasive procedures, CMFS and CHLOC on age Stress symptoms in children possibly dependent on number of invasive procedures. n i m n General ward n 52 PICU Mean 0.5 PRISM NA Psychological outcome: IES higher in high risk, not decreasing over time, IES related with invasive procedures Stress symptoms possibly dependent on invasive procedures. Stress symptoms not decreasing over time. n Low risk 11.5 Low risk<34% i m n High risk 11.1 High risk≥34% 61 Meningococcal disease PICU and ward Median 6.8 0.3 GMSPS 6.9±3.3 PICU LOS 0–62 Psychological outcome: Child: PTSD 4 (26) PICU survivors and their parents at risk for psychological distress and PTSD. Children and parents Parent rating median 7 Hospital LOS 2–87 h i Mothers: PTSD 22 (58) n j i Fathers: PTSD 8 (43) 4 PICU parents 25% <1, 25% 1–4, 25% 5–11, 25% >11 0.2–0.9 PRISM 0–26% PICU 1–200 Psychological outcome: ASD 87 Parents of PICU survivors with ASD more at risk for PTSD. n Parent rating 1–9 Parents: Acute Stress Disease symptoms PTSD 33 k 8 PICU 1.2±1.3 <0.5 PRISM 12±7% PICU 10.5±11.5 Psychological outcome mothers: Mothers PICU more stress. Stress decreases over time in all groups Mothers of PICU survivors at risk for psychological distress; families at risk for dysfunctioning. n Parent rating 8.3±1.9 o All families dysfunctioning General ward p n q ER n 20 Meningococcal Disease Parents 1–18 0.25–7 NA NA Psychological outcome parents: High psychological distress in mothers and fathers, not decreasing over time Mothers and fathers of PICU survivors at risk for psychological distress. 102 mothers, 90 fathers j 27 PICU 4.6 1 PRISM NA r 106 equal to before PICU 50% of PICU survivors seem to have the same QoL as before admission; 10% normal QoL. n n 58 improved n 62 deteriorated 26 normal 38 PICU 5.7±3.6 1 PRISM PICU 5.7±5.5 r 52 improved 50% of PICU survivors seem to have good QoL. n n 29 deteriorated n 65 normal after PICU 47 PICU Median 2.3 0.3–2 PRISM NA s 256 normal QoL 60% of PICU survivors seem to have normal QoL. n Mean 5.5% 140 fair QoL 9 poor QoL 65 PICU 0–29.3 2.3–6 PRISM PICU 0–57.4 t u HSUI (727): 608 normal, 29 (very) poor QoL 70% of PICU survivors seem to have good QoL. n n GOS (727): 515 normal, 137 mild disability, 75 moderate/severe disability 60% seem to have normal functional health. n a b n c d e f g n h i j k l m n o p q r s t u Table 3 Quality assessment of reviewed studies Reference a b c d e 4 yes yes yes yes no 6 no no yes yes no 8 no no yes yes yes 9 no yes yes no no 12 yes yes yes yes no 14 yes yes yes yes no 20 yes yes yes yes no 22 no no no yes no 23 no no yes yes yes 27 yes no yes yes no 30 no no no yes no 35 yes no yes yes no 38 no no yes yes no 40 no yes yes yes no 43 no no yes yes no 44 yes yes yes yes no 47 yes no yes yes no 48 no no yes yes no 50 yes no yes yes yes 51 no yes yes yes yes 52 no yes yes yes yes 53 yes yes yes yes no 59 yes no yes yes no 61 no yes yes yes no 62 yes no yes yes no 65 no no yes yes no 74 yes yes yes yes no a b c d e 1 In 12 studies that included in total 340 patients, aspects of physical and neuro-cognitive sequelae were evaluated. Neurological evaluation 23 35 43 53 59 Pulmonary evaluation 6 14 22 30 48 74 Cardiac evaluation 22 74 Renal evaluation 62 2 Various questionnaires were used. Cut-off points for the diagnosis of PTSD differed between studies but all of them showed high scores for PTSD in children and parents. Psychological evaluation of children 40 50 52 61 52 Psychological evaluation of parents 4 8 20 40 50 61 4 50 61 8 1 2 Evaluation of functional health 9 12 44 Evaluation of QoL 27 38 47 65 Discussion Only 27 studies consisting of 3,444 PICU survivors met our inclusion criteria. The small numbers, heterogeneity of the studied populations and the used measurement tools, the frequent use of non-validated measurement tools and the various aspects of outcomes studied make aggregation of the data and, therefore, strong conclusive statements difficult. Physical sequelae 24 25 11 46 56 49 34 58 10 67 77 5 18 32 33 45 54 57 63 Psychological sequelae and functional health and QoL 17 26 29 31 3 28 7 11 46 27 38 47 65 36 37 39 66 16 Suggestions for future follow-up research 13 42 60 71 76 In conclusion, this review indicates that PICU survivors and their parents may have substantial physical and psychological sequelae interacting with QoL. Because of longer life expectancy, longer follow-up time is warranted, emphasising the consequences for health care in children. We believe that paediatric intensivists and psychologists should be involved as core members of follow-up teams.