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Matched Retrospective Cohort Study of Thiamine to Treat Persistent Hyperlactatemia in Pediatric Septic Shock

Weiss, Scott L. MD, MSCE1–3; Blowey, Bridget PharmD4; Keele, Luke PhD5; Ganetzky, Rebecca MD6; Murali, Chaya N. MD6; Fitzgerald, Julie C. MD, PhD, MSCE1,2; Sutton, Robert M. MD, MSCE1; Berg, Robert A. MD1

Pediatric Critical Care Medicine: July 3, 2019 - Volume Online First - Issue - p
doi: 10.1097/PCC.0000000000002074
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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.

1Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

2Pediatric Sepsis Program at the Children’s Hospital of Philadelphia, Philadelphia, PA.

3Center for Mitochondrial and Epigenomic Medicine at the Children’s Hospital of Philadelphia, Philadelphia, PA.

4Department of Pharmacy, Children’s Hospital of Philadelphia, Philadelphia, PA.

5Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

6Division of Human Genetics, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

Supported, in part, by grant from the National Institute of General Medical Sciences K23GM110496 (to Dr. Weiss) and the Department of Anesthesiology and Critical Care at the Children’s Hospital of Philadelphia.

Drs. Weiss’s and Blowey’s institutions received funding from National Institute of General Medical Sciences K23GM110496. Drs. Weiss, Blowey, and Ganetzky received support for article research from the National Institutes of Health (NIH). Dr. Ganetzky received funding from the NIH. Dr. Sutton’s institution received funding from NIH National Heart, Lung, and Blood Institute R01; he received funding from Zoll Medical (speaking honoraria); and he disclosed he is a writing group member of the Pediatric Advanced Life Support Guidelines and Chair of the American Heart Association’s Get With the Guidelines-Resuscitation Pediatric Research Task Force. The remaining authors have disclosed that they do not have any potential conflicts of interest.

This study was performed at the Children’s Hospital of Philadelphia.

Address requests for reprints to: Scott L. Weiss, MD, MSCE, FCCM, Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, 3401 Civic Center Blvd, Wood Building 6th Floor, Suite 6026A, Philadelphia, PA 19104. E-mail: WeissS@email.chop.edu

©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies