The burden of paediatric adverse medical events.

Ahmed AM ，Thompson LA 《-》

Trends in adverse effects of medical treatment in Paediatric populations in the United States: A global burden of disease study, 2000-2019.

Adverse effects of medical treatment (AEMT) pose significant risks to paediatric patients. However, the mortality trends associated with AEMT in this population have been unclear. We aimed to clarify the trends in the incidence, disability-adjusted life years (DALYs) and mortality rates of AEMT for children in the US from 2000 to 2019. Data were retrieved from the Global Burden of Disease study 2019. We estimated age-standardized incidence, DALYs and mortality rates of paediatric AEMT per 100,000 children in the US using a Bayesian meta-regression model. We also analysed incidence, DALYs and mortality in different age groups, and employed Joinpoint regression models to assess the age- and sex-specific trends. The number of deaths due to AEMT in children, the number of cases, and DALYs were 105.1, 551,076 and 145,555 in 2019, decreased by 37.5%, 6% and 28% from those in 2000, respectively. Age-standardized mortality rates decreased across all age groups, while the incidence increased across all age groups with an average annual percentage change (AAPC) of 2.2% in those children <1 year and 4.5% in 5-9 years of age. The increases in DALYs over time was higher in children aged 1-4 years (AAPC: 0.51, 95% CI: 0.47, 0.62) and 5-9 years (AAPC: 0.33, 95% CI: 0.15, 0.50), with the 1-4 year age group being the highest. The study reveals declining AEMT mortality but rising incidence and DALYs, emphasizing a disproportionate burden in <1, 1-4 and 5-9 years. To develop effective mitigation strategies, future research is warranted to identify the causes of increased AEMT in children, especially young males.

Fujiwara S ，Leibovitch E ，Harada K ，Nishimura Y ，Woo R ，Otsuka F ，Bhagavathula AS ... -  《-》

Effect of introduction of a rapid response system and increasing Medical Emergency Team (MET) activity on mortality over a 20-year period in a paediatric specialist hospital.

Rapid Response Systems are hospital-wide patient-focused systems aiming to improve recognition of acute deterioration in patients and trigger a rapid response aimed at preventing potentially avoidable adverse events such as cardiac arrest and death. In 1994, the Royal Children's Hospital in Brisbane, Australia, was one of the first institutions to adopt a paediatric rapid response system (RRS). The purpose of this study was to investigate the impacts of both introduction of a paediatric RRS and increasing RRS activations (MET dose) on hospital mortality. Prospectively collected data from institutional databases at a specialist paediatric hospital was used to determine hospital mortality rate pre- and post- implementation of the RRS. An interrupted time series model using segmented regression was utilised to assess the pre-intervention trend, as well as immediate and sustained effects of RRS implementation on hospital mortality. Univariate linear regression examined potential effects of MET dose on mortality. Hospital mortality rate did not change significantly over 15 years before RRS implementation. In the first year after implementation, mortality rate fell significantly (-1.4; 95 %CI -2.27 to -0.52; p = 0.0027). For each year that passed after the intervention, there was no significant change in hospital mortality rate (Estimate: -0.08; 95 %CI -0.17 to 0.02; p = 0.11). Univariate linear regression modelling showed that with every unit increase in MET Dose, hospital mortality rate decreased by -0.13 (95 % CI: -0.27 to 0; p = 0.05). Utilising data from one of the earliest and longest duration single-centre cohort of paediatric MET events, this study reaffirms the association between implementation of a paediatric RRS and decreased hospital mortality. The study also provides novel evidence of the impact of MET dose on patient outcome in the paediatric population. It is recommended that factors influencing the benefit of rapid response systems in paediatric populations are further identified so that this life saving initiative can be optimised.

Acworth J ，Ryan C ，Acworth E ，Farah Zahir S ... -  《-》

Inotropes for the prevention of low cardiac output syndrome and mortality for paediatric patients undergoing surgery for congenital heart disease: a network meta-analysis.

Paediatric patients undergoing surgery for congenital heart disease (CHD) are at risk for postoperative low cardiac output syndrome (LCOS) and mortality. LCOS affects up to 25% of children after heart surgery. It consists of reduced myocardial function and increases postoperative morbidity, prolongs mechanical ventilation, and lengthens the duration of intensive care unit (ICU) stay. Pharmacological prophylaxis involves inotropes, including catecholamines, phosphodiesterase III inhibitors, or calcium sensitisers, to enhance myocardial contractility. It is unclear whether they are effective in preventing LCOS or death in this vulnerable population. 1. To evaluate the relative benefits and harms of inotropes for the prevention of LCOS and mortality in paediatric patients undergoing surgery for CHD. 2. To generate a clinically useful ranking of prophylactic inotropes for the prevention of LCOS and mortality in paediatric patients undergoing surgery for CHD according to benefits and harms. We searched CENTRAL, MEDLINE, Embase, Web of Science, and clinical trial registries, most recently in December 2023 and April 2024. We also checked reference lists from identified studies and review articles. We did not apply any language restrictions. We included randomised controlled trials comparing inotropes from one drug class (catecholamines, phosphodiesterase type III inhibitors, calcium sensitisers) to another (either alone or in combination) or placebo, in paediatric patients (birth to 18 years of age) undergoing surgery for CHD. Two review authors independently selected studies, extracted data, assessed risk of bias, and rated the certainty of evidence using the CINeMA framework. We performed random-effects network and pairwise meta-analyses comparing the relative effects of each possible pair of medications with each other or placebo. Where meta-analysis was not possible, we provided a narrative description of the results. We ranked the prophylactic medications according to their effects relative to each other. The primary outcomes were all-cause mortality within 30 days, time to death, and LCOS incidence; secondary outcomes were length of ICU stay, length of hospital stay, duration of mechanical ventilation, inotrope score, mechanical circulatory support, and adverse events. We included 13 studies with 937 participants. All except two multicentre studies were conducted at single tertiary care hospitals. Participants comprised children from birth to 14 years of age undergoing surgery for different types of CHD on cardiopulmonary bypass. Five studies compared levosimendan versus milrinone; two compared levosimendan versus placebo; two compared milrinone versus placebo (one comparing two different doses); one compared levosimendan versus dobutamine, another milrinone versus dobutamine. Two studies used combinations of inotropes. Study duration was between less than one year and 5.3 years, with follow-up mostly during ICU or hospital stay. Funding sources included governmental bodies and hospital departments, but also drug manufacturers. We downgraded the certainty of evidence for high risk of bias at study level, or imprecision at comparison level. Primary outcomes Compared to placebo, levosimendan likely results in a large reduction in mortality (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.15 to 2.13) and milrinone likely results in no difference (RR 0.97, 95% CI 0.11 to 8.49), whereas for dobutamine, no effect was estimable; all moderate-certainty evidence (9 studies, 557 participants, 14 events). LCOS was largely reduced with levosimendan (RR 0.45, 95% CI 0.24 to 0.83; high-certainty evidence), likely largely reduced with milrinone (RR 0.46, 95% CI 0.24 to 0.89; moderate-certainty evidence), and may be reduced with low-dose milrinone (RR 0.7, 95% CI 0.39 to 1.28; low-certainty evidence), compared with placebo (5 studies, 513 participants, 85 events). Secondary outcomes The length of ICU stay may be no different with levosimendan (ratio of means (ROM) 1.12, 95% CI 0.77 to 1.63; low-certainty evidence), and is likely no different with milrinone (ROM 1.13, 95% CI 0.75 to 1.69) or with dobutamine (ROM 1.11, 95% CI 0.66 to 1.86), compared with placebo (9 studies, 577 participants); both moderate-certainty evidence. The length of hospital stay, compared with placebo, is likely no different with levosimendan (ROM 1.03, 95% CI 0.84 to 1.27) or with milrinone (ROM 1, 95% CI 0.78 to 1.3), but is likely reduced with dobutamine (ROM 0.68, 95% CI 0.37 to 1.26); all moderate-certainty evidence (7 studies, 297 participants). The duration of mechanical ventilation, compared with placebo, is likely increased with levosimendan (ROM 1.17, 95% CI 0.65 to 2.12) or with milrinone (ROM 1.25, 5% CI 0.67 to 2.36) and is likely no different with dobutamine (ROM 1.04, 95% CI 0.45 to 2.38); all moderate-certainty evidence (9 studies, 577 participants). There is moderate-certainty evidence that adverse events are likely increased with levosimendan (incidence rate ratio (IRR) 1.23, 95% CI 0.78 to 1.96) or dobutamine (IRR 1.24, 95% CI 0.75 to 2.03) and low-certainty evidence that they may be increased with milrinone (IRR 1.31, 95% CI 0.96 to 1.79) and decreased with low-dose milrinone (IRR 0.84, 95% CI 0.47 to 1.5), compared with placebo (8 studies, 706 participants, 380 events). Levosimendan likely results in a large reduction in mortality compared to placebo in paediatric patients undergoing surgery for congenital heart disease, whereas milrinone likely results in no difference, and the effect of dobutamine is unknown. Low cardiac output syndrome (LCOS) is largely reduced with levosimendan, likely largely reduced with milrinone, and may be reduced with low-dose milrinone, compared to placebo. The length of ICU stay may be no different with levosimendan and is likely no different with milrinone or with dobutamine, compared to placebo. The length of hospital stay is likely no different with levosimendan or with milrinone, but is likely reduced with dobutamine, compared to placebo. The duration of mechanical ventilation is likely increased with levosimendan or with milrinone and is likely no different with dobutamine, compared to placebo. Adverse events are likely increased with levosimendan or dobutamine, and may be increased with milrinone and decreased with low-dose milrinone, compared to placebo. The evidence is based on few, heterogeneous studies, with small numbers of patients and short follow-up periods. Future research should include large numbers of patients, consistently report all co-interventions, and ensure the longest possible follow-up.

Burkhardt BE ，Hummel J ，Rücker G ，Stiller B ... -  《Cochrane Database of Systematic Reviews》

Epidemiology and outcomes of septic shock in Thai children: a nationwide retrospective study from 2015 to 2022.

Paediatric septic shock is a formidable challenge worldwide that significantly impacts health care systems. This nationwide retrospective study analyses the prevalence and mortality rates of paediatric septic shock across Thailand from 2015 to 2022, focusing on hospital burdens, including mechanical ventilation and renal replacement therapy. The study included paediatric patients ranging from infants to individuals under 18 years of age who were admitted to hospitals due to septic shock across Thailand. Data were retrospectively gathered from the Thai National Health Security Office for the years 2015-2022. The data included demographic data, clinical outcomes, and hospital burden indicators such as mechanical ventilation and renal replacement therapy. From 2015 to 2022, there were 30,718 paediatric admissions for septic shock, with a peak in 2019. The highest incidence was observed in infants, accounting for 44.7% of the cases. The prevalence rate increased from 190 per 100,000 population in 2015 to a peak of 280 per 100,000 population in 2020. Mortality rates decreased from 30.7% in 2015 to 20.2% in 2022, with a peak of 40.5% observed in the central region in 2015. The study highlighted a substantial health care burden, with 34.9% of patients requiring prolonged mechanical ventilation and 23.4% needing renal replacement therapy. Despite a decrease in mortality, paediatric septic shock remains a significant burden on the health care system in Thailand. Urgent improvements in resources and adherence to clinical guidelines, especially in under-resourced areas, are necessary. Addressing disparities in mortality and resource usage across hospital levels is vital for improving outcomes and reducing the health care burden of paediatric patients with septic shock.

Niamsanit S ，Sitthikarnkha P ，Techasatian L ，Saengnipanthkul S ，Uppala R ... -  《CRITICAL CARE》