Department of Paediatrics and Child Health

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Browsing Department of Paediatrics and Child Health by Author "Akech, Samuel O."

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    Mortality after Fluid Bolus in African Children with Severe Infection
    (New England Journal of Medicine, 2011) Maitland, Kathryn; Kiguli, Sarah; Opoka, Robert O.; Engoru, Charles; Olupot-Olupot, Peter; Akech, Samuel O.; Nyeko, Richard; Mtove, George; Reyburn, Hugh; Lang, Trudie; Brent, Bernadette; Evans, Jennifer A.; Tibenderana, James K.; Crawley, Jane; Russell, Elizabeth C.; Levin, Michael; Babiker, Abdel G.; Gibb, Diana M.
    Background The role of fluid resuscitation in the treatment of children with shock and lifethreatening infections who live in resource-limited settings is not established. Methods We randomly assigned children with severe febrile illness and impaired perfusion to receive boluses of 20 to 40 ml of 5% albumin solution (albumin-bolus group) or 0.9% saline solution (saline-bolus group) per kilogram of body weight or no bolus (control group) at the time of admission to a hospital in Uganda, Kenya, or Tanzania (stratum A); children with severe hypotension were randomly assigned to one of the bolus groups only (stratum B). All children received appropriate antimicrobial treatment, intravenous maintenance fluids, and supportive care, according to guidelines. Children with malnutrition or gastroenteritis were excluded. The primary end point was 48-hour mortality; secondary end points included pulmonary edema, increased intracranial pressure, and mortality or neurologic sequelae at 4 weeks. Results The data and safety monitoring committee recommended halting recruitment after 3141 of the projected 3600 children in stratum A were enrolled. Malaria status (57% overall) and clinical severity were similar across groups. The 48-hour mortality was 10.6% (111 of 1050 children), 10.5% (110 of 1047 children), and 7.3% (76 of 1044 children) in the albumin-bolus, saline-bolus, and control groups, respectively (relative risk for saline bolus vs. control, 1.44; 95% confidence interval [CI], 1.09 to 1.90; P = 0.01; relative risk for albumin bolus vs. saline bolus, 1.01; 95% CI, 0.78 to 1.29; P = 0.96; and relative risk for any bolus vs. control, 1.45; 95% CI, 1.13 to 1.86; P = 0.003). The 4-week mortality was 12.2%, 12.0%, and 8.7% in the three groups, respectively (P = 0.004 for the comparison of bolus with control). Neurologic sequelae occurred in 2.2%, 1.9%, and 2.0% of the children in the respective groups (P = 0.92), and pulmonary edema or increased intracranial pressure occurred in 2.6%, 2.2%, and 1.7% (P = 0.17), respectively. In stratum B, 69% of the children (9 of 13) in the albuminbolus group and 56% (9 of 16) in the saline-bolus group died (P = 0.45). The results were consistent across centers and across subgroups according to the severity of shock and status with respect to malaria, coma, sepsis, acidosis, and severe anemia. Conclusions Fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these resource-limited settings in Africa. (Funded by the Medical Research Council, United Kingdom; FEAST Current Controlled Trials number, ISRCTN69856593.)
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    Mortality risk over time after early fluid resuscitation in African children
    (Clinical care, 2019) George, Elizabeth C.; Kiguli, Sarah; Olupot Olupot, Peter; Opoka, Robert O.; Engoru, Charles; Akech, Samuel O.; Nyeko, Richard; Mtove, George; Mpoya, Ayub; Thomason, Margaret J.; Crawley, Jane; Evans, Jennifer A.; Gibb, Diana M.; Babiker, Abdel G.; Maitland, Kathryn; Walker, A. Sarah
    Background: African children hospitalised with severe febrile illness have a high risk of mortality. The Fluid Expansion As Supportive Therapy (FEAST) trial (ISCRTN 69856593) demonstrated increased mortality risk associated with fluid boluses, but the temporal relationship to bolus therapy and underlying mechanism remains unclear. Methods: In a post hoc retrospective analysis, flexible parametric models were used to compare change in mortality risk post-randomisation in children allocated to bolus therapy with 20–40 ml/kg 5% albumin or 0.9% saline over 1–2 h or no bolus (control, 4 ml/kg/hour maintenance), overall and for different terminal clinical events (cardiogenic, neurological, respiratory, or unknown/other). Results: Two thousand ninety-seven and 1041 children were randomised to bolus vs no bolus, of whom 254 (12%) and 91 (9%) respectively died within 28 days. Median (IQR) bolus fluid in the bolus groups received by 4 h was 20 (20, 40) ml/kg and was the same at 8 h; total fluids received in bolus groups at 4 h and 8 h were 38 (28, 43) ml/kg and 40 (30, 50) ml/kg, respectively. Total fluid volumes received in the control group by 4 h and 8 h were median (IQR) 10 (6, 15) ml/kg and 10 (10, 26) ml/kg, respectively. Mortality risk was greatest 30 min post-randomisation in both groups, declining sharply to 4 h and then more slowly to 28 days. Maximum mortality risk was similar in bolus and no bolus groups; however, the risk declined more slowly in the bolus group, with significantly higher mortality risk compared to the no bolus group from 1.6 to 101 h (4 days) post-randomisation. The delay in decline in mortality risk in the bolus groups was most pronounced for cardiogenic modes of death. Conclusions: The increased risk from bolus therapy was not due to a mechanism occurring immediately after bolus administration. Excess mortality risk in the bolus group resulted from slower decrease in mortality risk over the ensuing 4 days. Thus, administration of modest bolus volumes appeared to prevent mortality risk declining at the same rate that it would have done without a bolus, rather than harm associated with bolus resulting from a concurrent increased risk of death peri-bolus administration.
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    Predicting mortality in sick African children: the FEAST Paediatric Emergency Triage (PET) Score
    (BMC Medicine, 2015) George, Elizabeth C.; Walker, A. Sarah; Kiguli, Sarah; Olupot-Olupo, Peter; Opoka, Robert O.; Engoru, Charles; Akech, Samuel O.; Nyeko, Richard; Mtove, George; Reyburn, Hugh; Berkley, James A.; Mpoya, Ayub; Levin, Michael; Crawley, Jane; Gibb, Diana M.; Maitland, Kathryn; Babiker, Abdel G.
    Background: Mortality in paediatric emergency care units in Africa often occurs within the first 24 h of admission and remains high. Alongside effective triage systems, a practical clinical bedside risk score to identify those at greatest risk could contribute to reducing mortality. Methods: Data collected during the Fluid As Expansive Supportive Therapy (FEAST) trial, a multi-centre trial involving 3,170 severely ill African children, were analysed to identify clinical and laboratory prognostic factors for mortality. Multivariable Cox regression was used to build a model in this derivation dataset based on clinical parameters that could be quickly and easily assessed at the bedside. A score developed from the model coefficients was externally validated in two admissions datasets from Kilifi District Hospital, Kenya, and compared to published risk scores using Area Under the Receiver Operating Curve (AUROC) and Hosmer-Lemeshow tests. The Net Reclassification Index (NRI) was used to identify additional laboratory prognostic factors. Results: A risk score using 8 clinical variables (temperature, heart rate, capillary refill time, conscious level, severe pallor, respiratory distress, lung crepitations, and weak pulse volume) was developed. The score ranged from 0–10 and had an AUROC of 0.82 (95 % CI, 0.77–0.87) in the FEAST trial derivation set. In the independent validation datasets, the score had an AUROC of 0.77 (95 % CI, 0.72–0.82) amongst admissions to a paediatric high dependency ward and 0.86 (95 % CI, 0.82–0.89) amongst general paediatric admissions. This discriminative ability was similar to, or better than other risk scores in the validation datasets. NRI identified lactate, blood urea nitrogen, and pH to be important prognostic laboratory variables that could add information to the clinical score. Conclusions: Eight clinical prognostic factors that could be rapidly assessed by healthcare staff for triage were combined to create the FEAST Paediatric Emergency Triage (PET) score and externally validated. The score discriminated those at highest risk of fatal outcome at the point of hospital admission and compared well to other published risk scores. Further laboratory tests were also identified as prognostic factors which could be added if resources were available or as indices of severity for comparison between centres in future research studies.