Treatment of the critically ill child in low-resource settings : Essential paediatric emergency and critical care
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Introduction: In 2019 approximately 5.2 million children died before the age of 5 years. Around 2.2 million children and young people died between the age of 5‐24 years. A large number of these deaths are attributable to severe infections associated with respiratory failure or haemodynamic instability and other organ dysfunctions. While social determinants and public health interventions have a major impact on child health, access to essential emergency and critical care on different levels of referral pathways has the potential to contribute to a reduction of preventable mortality and morbidity of critically ill children treated in resource‐limited settings. Aim: The aim of this thesis is to evaluate essential elements of respiratory support (both non‐invasive and invasive), as well as fluid resuscitation in critically children treated in sub‐Saharan Africa. Methods: Paper 1 describes an observational study conducted between February and April 2014, in a busy paediatric department in Malawi. The use of bubble continuous positive airways pressure (bCPAP) in the treatment of critically ill children (0‐59 months) with acute respiratory dysfunction was evaluated. Paper 2 describes the analysis of a database which prospectively collected data on the outcomes of patients suffering from snake‐bites admitted to the intensive care unit of a rural hospital in Northern‐Uganda between 2006 and 2017. Particular attention was drawn to patients with acute respiratory failure following neuro‐toxic snake envenomation. Paper 3 describes a re‐analysis of data from a large randomised controlled trial conducted between 2009 and 2011 in three East‐African countries (the FEAST‐study), in a setting with no availability of advanced intensive care treatment. In order to better understand impact of intravenous fluid resuscitation on vital organ functions in critically ill children, “organ‐function scores” were developed using data from the FEAST‐study. These scores describe respiratory, cardiovascular, and neurological function and were compared with four other patient cohorts of critically ill patients treated in South Africa, Malawi and the UK. Odds of adverse outcome were assessed using logistic regression for each cohort. Among participants of the FEAST‐trial the organ function scores were used to identify differences between children treated with fluid bolus (n=2097) as compared to critically ill children receiving maintenance fluids (n=1044). Using FEASTstudy data, further analysis were conducted, including evaluation of the impact of fluid resuscitation on Hb levels and plasma biochemistry in conjunction with changes of organ‐function scores. Statistical models were used to identify subgroups of patients with certain “clinical phenotypes” differing in response to fluid bolus administration. Results: In the Malawian study (Paper 1), 117 children (median age: 7 months) with signs of respiratory failure were treated with bubble CPAP. Overall survival was 79/117 (68%); survival was 54/62 (87%) in children with very severe pneumonia but without further organ‐dysfunction. Among 19 children with very severe pneumonia (single‐organ failure) and negative HIV tests, all children survived. Survival rates were lower in children with respiratory dysfunction associated with further organ failure (e.g., shock) (45%) as well as in children with severe acute malnutrition (SAM) (36%) and HIV infection or exposure (45%). In the study evaluating treatment and clinical outcomes among critically ill snake‐bite victims in northern Uganda (Paper 2) 67 patients (38.5%) were children (<18 years). 60 patients (36.5%) developed acute respiratory failure requiring invasive mechanical ventilation. Despite limitations in data‐collection, study results suggest that neurotoxic envenomation was the most common cause of respiratory failure among study patients requiring mechanical ventilation. Antivenom (at low and probably inadequate doses) was administered to 12.6% of study patients. The median ICU length of stay was 3 days (interquartile range, 2‐5) and mortality was 8%. ICU mortality of patients with ARF, requiring mechanical ventilation was 16.7%. In Paper 3 increasing respiratory, neurological and cardiovascular scores were associated with death among FEAST study patients, and with adverse outcomes for specific scores in the four other cohorts. In FEAST‐participants, IV fluid bolus increased respiratory and neurological scores and decreased cardiovascular score at 1 h after the start of IV fluid boluses. Fluid bolus recipients had mean 0∙33 g/dL (95% CI 0∙20–0∙46) reduction in Hb levels after 8 h (p<0∙0001), and at 24 h had a decrease of 1∙41 mEq/L (95% CI 0∙76–2∙06; p=0∙0002) in mean base excess and increase of 1∙65 mmol/L (0∙47–2∙8; p=0∙0070) in mean chloride, and a decrease of 0∙96 mmol/L (0∙45 to 1∙47; p=0∙0003) in bicarbonate. There were similar effects of fluid bolus administration in three patient subgroups, identified on the basis of their baseline clinical characteristics. Conclusions: Paper 1 suggests that bubble CPAP can be used efficiently in the treatment of acute respiratory dysfunction in paediatric units in malaria‐endemic, resource‐limited contexts. The role of non‐invasive respiratory support as part of a care package for critically ill children with multiorgan dysfunction needs further evaluation, while children with malnutrition or human immunodeficiency virus infection need particular attention. Provision of basic intensive care, including mechanical ventilation, was a feasible treatment option for snakebite victims presenting with acute respiratory failure in a rural hospital in sub‐Saharan Africa. Acute respiratory failure in this context was associated with neuro‐toxic snakeenvenomation, without severe acute lung injury and no other associated severe organdysfunctions. Fluid resuscitation using “unbuffered” intra‐venous solutions can be associated with severe adverse events: respiratory and neurological dysfunction, hyperchloraemic acidosis as well as reduction of haemoglobin‐levels. Using smaller volumes of electrolyte balanced resuscitation fluids may be beneficial in the treatment of critically ill patients with haemodynamic instability, while careful monitoring of haemoglobin‐levels and other vital organ functions is required. Future pragmatic research needs to be directed to optimize a “comprehensive paediatric critical care package” adapted to resource‐limited contexts.
Has partsPaper 1: Myers S, Dinga P, Anderson M, Schubert C, Mlotha R, Phiri A, Colbourn T, McCollum ED, Mwansambo C, Kazembe P, Lang H-J. Use of bubble continuous positive airway pressure (bCPAP) in the management of critically ill children in a Malawian paediatric unit: an observational study. BMJ Open Respiratory Research 2019; 6: e000280. The article is available in the thesis file. The article is also available at: http://dx.doi.org/10.1136/bmjresp-2018-000280
Paper 2: Lang HJ, Amito J, Dünser MW, Giera R, Towey R. Intensive-care management of snakebite victims in rural sub-Saharan Africa: An experience from Uganda. Southern African Journal of Critical Care (Online) 2020; 36: 39-45. The article is available in the main thesis. The article is also available at: https://doi.org/10.7196/SAJCC.2020.v36i1.404
Paper 3: Levin M, Cunnington AJ, Wilson C, Nadel S, Lang HJ, Ninis N, McCulloch M, Argent A, Buys H, Moxon CA, Best A, Nijman RG, Hoggart CJ. Effects of saline or albumin fluid bolus in resuscitation: evidence from re-analysis of the FEAST trial. The Lancet Respiratory Medicine 2019 Jul;7(7):581-593. The article is available in the thesis file. The article is also available at: http://dx.doi.org/10.1016/S2213-2600(19)30114-6