A Clinical and Physiological Prospective Observational Study on the Management of Pediatric Shock in the Post-Fluid Expansion as Supportive Therapy Trial Era

Abstract

Objectives: Fluid bolus resuscitation in African children is harmful. Little research has evaluated physiologic effects of maintenance-only fluid strategy.

Design: We describe the efficacy of fluid-conservative resuscitation of septic shock using case-fatality, hemodynamic, and myocardial function endpoints.

Setting: Pediatric wards of Mbale Regional Referral Hospital, Uganda, and Kilifi County Hospital, Kenya, conducted between October 2013 and July 2015. Data were analysed from August 2016 to July 2019.

Patients: Children (≥ 60 d to ≤ 12 yr) with severe febrile illness and clinical signs of impaired perfusion.

Interventions: IV maintenance fluid (4 mL/kg/hr) unless children had World Health Organization (WHO) defined shock (≥ 3 signs) where they received two fluid boluses (20 mL/kg) and transfusion if shock persisted. Clinical, electrocardiographic, echocardiographic, and laboratory data were collected at presentation, during resuscitation and on day 28. Outcome measures were 48-hour mortality, normalization of hemodynamics, and cardiac biomarkers.

Measurement and main results: Thirty children (70% males) were recruited, six had WHO shock, all of whom died (6/6) versus three of 24 deaths in the non-WHO shock. Median fluid volume received by survivors and nonsurvivors were similar (13 [interquartile range (IQR), 9-32] vs 30 mL/kg [28-61 mL/kg], z = 1.62, p = 0.23). By 24 hours, we observed increases in median (IQR) stroke volume index (39 mL/m 2 [32-42 mL/m 2 ] to 47 mL/m 2 [41-49 mL/m 2 ]) and a measure of systolic function: fractional shortening from 30 (27-33) to 34 (31-38) from baseline including children managed with no-bolus. Children with WHO shock had a higher mean level of cardiac troponin ( t = 3.58; 95% CI, 1.24-1.43; p = 0.02) and alpha-atrial natriuretic peptide ( t = 16.5; 95% CI, 2.80-67.5; p < 0.01) at admission compared with non-WHO shock. Elevated troponin (> 0.1 μg/mL) and hyperlactatemia (> 4 mmol/L) were putative makers predicting outcome.

Conclusions: Maintenance-only fluid therapy normalized clinical and myocardial perturbations in shock without compromising cardiac or hemodynamic function whereas fluid-bolus management of WHO shock resulted in high fatality. Troponin and lactate biomarkers of cardiac dysfunction could be promising outcome predictors in pediatric septic shock in resource-limited settings.

Figure 1

Echocardiographic variables at admission, post resuscitation, and at 24 hr. Box (displaying the data distribution through their upper and lower quartiles) and whiskers plots (outliers) of ejection fraction (EF), cardiac index (CI), systemic vascular resistance index (SVRI), global radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain (GLS) comparing survivors versus fatalities. The horizontal lines indicate published pediatric reference values.

Figure 2

Biomarker profiles at admission, post resuscitation, and at 24 hr. Box and whisker plots of cardiac troponin I (cTnI), alpha-atrial natriuretic peptide (ANP), beta-brain natriuretic peptide (BNP), and hyaluronan comparing survivors versus fatalities. The horizontal lines indicate published reference values.