Scott L Weiss, Bridget Blowey1, Luke Keele2, Rebecca Ganetzky3, Chaya N Murali3, Julie C Fitzgerald4,5, Robert M Sutton4, Robert A Berg4. 1. Department of Pharmacy, Children's Hospital of Philadelphia, Philadelphia, PA. 2. Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 3. Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 4. Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 5. Pediatric Sepsis Program at the Children's Hospital of Philadelphia, Philadelphia, PA.
Abstract
OBJECTIVES: Thiamine deficiency may propagate lactate production by limiting pyruvate dehydrogenase activity, and studies suggest benefit for thiamine administration in septic adults. We studied the effect of thiamine on physiologic and clinical outcomes for children with septic shock and hyperlactatemia. DESIGN: Retrospective matched cohort study. SETTING: Single academic PICU. PATIENTS: Six thiamine-treated cases and nine matched controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was change in blood lactate from prethiamine (T0, cases) or maximum (T0, controls) lactate through 24 hours later (T24). Secondary outcomes were change in lactate over 48 hours (T48) and 72 hours (T72), time to lactate normalization, changes in vasoactive-inotrope score, organ dysfunction severity (daily Pediatric Logistic Organ Dysfunction 2 score), and creatinine, PICU length of stay, and hospital mortality. Lactate was greater than 5 mmol/L for a median of 39 hours (range, 16.1-64.3 hr) prior to thiamine administration for cases compared with 3.4 hours (range, 0-22.9 hr) prior to maximum lactate for controls (p = 0.002). There was no difference in median (interquartile range) change in lactate from T0 to T24 between thiamine-treated cases and controls (-9.0, -17.0 to -5.0 vs -7.2, -9.0 to -5.3 mmol/L, p = 0.78), with both groups exhibiting a rapid decrease in lactate. There were also no differences in secondary outcomes between groups. CONCLUSIONS: Treatment of pediatric septic shock with thiamine was followed by rapid improvement in physiologic and clinical outcomes after prolonged hyperlactatemia. Although we are not able to infer that thiamine provided benefit over usual care, the rapid decline in lactate after thiamine despite a prolonged period of hyperlactatemia raises the possibility that thiamine helped to reverse lactate production.
OBJECTIVES:Thiamine deficiency may propagate lactate production by limiting pyruvate dehydrogenase activity, and studies suggest benefit for thiamine administration in septic adults. We studied the effect of thiamine on physiologic and clinical outcomes for children with septic shock and hyperlactatemia. DESIGN: Retrospective matched cohort study. SETTING: Single academic PICU. PATIENTS: Six thiamine-treated cases and nine matched controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was change in blood lactate from prethiamine (T0, cases) or maximum (T0, controls) lactate through 24 hours later (T24). Secondary outcomes were change in lactate over 48 hours (T48) and 72 hours (T72), time to lactate normalization, changes in vasoactive-inotrope score, organ dysfunction severity (daily Pediatric Logistic Organ Dysfunction 2 score), and creatinine, PICU length of stay, and hospital mortality. Lactate was greater than 5 mmol/L for a median of 39 hours (range, 16.1-64.3 hr) prior to thiamine administration for cases compared with 3.4 hours (range, 0-22.9 hr) prior to maximum lactate for controls (p = 0.002). There was no difference in median (interquartile range) change in lactate from T0 to T24 between thiamine-treated cases and controls (-9.0, -17.0 to -5.0 vs -7.2, -9.0 to -5.3 mmol/L, p = 0.78), with both groups exhibiting a rapid decrease in lactate. There were also no differences in secondary outcomes between groups. CONCLUSIONS: Treatment of pediatric septic shock with thiamine was followed by rapid improvement in physiologic and clinical outcomes after prolonged hyperlactatemia. Although we are not able to infer that thiamine provided benefit over usual care, the rapid decline in lactate after thiamine despite a prolonged period of hyperlactatemia raises the possibility that thiamine helped to reverse lactate production.
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