Post hospital admission blood lactate measurements are associated with mortality but not neurologic morbidity in children with cerebral malaria.

BACKGROUND: In children with cerebral malaria (CM) admission blood lactate has previously guided intravenous fluid therapy and been validated as a prognostic biomarker associated with death. The usefulness of post-admission measurements of blood lactate in children with CM is less clear. The strength of association between blood lactate and neurological sequelae in CM survivors, as well as the optimal duration of post-admission measurements of blood lactate to identify children at higher risk of adverse outcomes is unknown. METHODS: A retrospective cohort study of 1674 Malawian children with CM hospitalized from 2000 to 2018 who had blood lactate measurements every 6 h for the first 24 h after admission was performed. The strength of association between admission lactate or values measured at any time point in the first 24 h post-admission and outcomes (mortality and neurological morbidity in survivors) was estimated. The duration of time after admission that lactate remained a valid prognostic biomarker was assessed. RESULTS: When lactate is analysed as a continuous variable, children with CM who have higher values at admission have a 1.05-fold higher odds (95% CI 0.99-1.11) of death compared to those with lower lactate values. Children with higher blood lactate at 6 h have 1.16-fold higher odds (95% CI 1.09-1.23) of death, compared to those with lower values. If lactate levels are dichotomized into hyperlactataemic (lactate > 5.0 mmol/L) or not, the strength of association between admission lactate and mortality increases (OR = 2.49, 95% CI 1.47-4.22). Blood lactate levels obtained after 18 h post-admission are not associated with outcomes. Similarly, the change in lactate concentrations through time during the first 24 h of hospital admission is not associated with outcomes. Blood lactate during hospitalization is not associated with adverse neurologic outcomes in CM survivors. CONCLUSIONS: In children with CM, blood lactate is associated with death but not neurologic morbidity in survivors. To comprehensively estimate prognosis, blood lactate in children with CM should be assessed at admission and for 18 h afterwards.

Loss to Hospital Follow-Up in Pediatric Cerebral Malaria Survivors: A Case-Control Study.

Children surviving central nervous system (CNS) infections are at high risk of neurological, behavioral, and cognitive sequalae. Early identification, characterization, and treatment of these sequelae may improve child and family health. In Africa, it is unclear if there are demographic or clinical factors that increase the risk of post-hospital loss to follow-up in children with CNS infections. If these factors exist, targeted educational efforts to increase rates of post-hospital retention could be focused on families at highest risk. We performed a case-control study of Malawian children with cerebral malaria, a locally common CNS infection, previously admitted to a specialized research unit in Blantyre, Malawi. Routine survivor post-hospital follow-up was scheduled for 1 month, 6 months, and 12 months. We compared demographic and clinical characteristics between 84 children who missed one or more of these post-hospital visits with 120 children who attended all visits. There were no statistically significant differences in demographic or clinical characteristics between children whose families returned for all follow-up visits and those who did not. Specifically, when comparing these groups, we found no differences in age (P = 00.646), sex (P = 0.789), duration of hospitalization (P = 0.903), distance from home to hospital (P = 0.355), type or severity of neurological sequelae (P = 0.837), guardian literacy (P = 0.057), or number of discharge medications (P = 0.464). No factors assessed in this study were associated with higher risk of loss to follow-up in Malawian child survivors of CNS infections. During hospitalization, educational efforts to increase post-hospital retention should focus on all families.

Temporal Trends of Blood Glucose in Children with Cerebral Malaria.

Hypoglycemia, defined as a blood glucose < 2.2 mmol/L, is associated with death in pediatric cerebral malaria (CM). The optimal duration of glucose monitoring in CM is unknown. We collected data from 1,674 hospitalized Malawian children with CM to evaluate the association between hypoglycemia and death or neurologic disability in survivors. We assessed the optimal duration of routine periodic measurements of blood glucose. Children with hypoglycemia at admission had a 2.87-fold higher odds (95% CI: 1.35-6.09) of death and, if they survived, a 3.21-fold greater odds (95% CI: 1.51-6.86) of sequelae at hospital discharge. If hypoglycemia was detected at 6 hours but not at admission, there was a 7.27-fold higher odds of death (95% CI: 1.85-8.56). The presence of newly developed hypoglycemia after admission was not independently associated with neurological sequelae in CM survivors. Among all new episodes of blood sugar below a treatment threshold of 3.0 mmol/L, 94.7% occurred within 24 hours of admission. In those with blood sugar below 3.0 mmol/L in the first 24 hours, low blood sugar persisted or recurred for up to 42 hours. Hypoglycemia at admission or 6 hours afterward is strongly associated with mortality in CM. Children with CM should have 24 hours of post-admission blood glucose measurements. If a blood glucose less than the treatment threshold of 3.0 mmol/L is not detected, routine assessments may cease. Children who have blood sugar values below the treatment threshold detected within the first 24 hours should continue to have periodic glucose measurements for 48 hours post-admission.