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Crit Care. 2015 Nov 27;19:418. doi: 10.1186/s13054-015-1131-2.

Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock?

Author information

1
Department of Pathology, University of Otago, Christchurch, PO Box 4345, Christchurch, 8140, New Zealand. anitra.carr@otago.ac.nz.
2
Department of Intensive Care Medicine, Christchurch Hospital, Private Bag 4710, Christchurch, 8011, New Zealand. geoff.shaw@cdhb.health.nz.
3
Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Box 980050, Richmond, VA, 23298, USA. alpha.fowler@vcuhealth.org.
4
Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Box 980050, Richmond, VA, 23298, USA. ramesh.natarajan@vcuhealth.org.

Abstract

Severe systemic inflammatory response to infection results in severe sepsis and septic shock, which are the leading causes of death in critically ill patients. Septic shock is characterised by refractory hypotension and is typically managed by fluid resuscitation and administration of catecholamine vasopressors such as norepinephrine. Vasopressin can also be administered to raise mean arterial pressure or decrease the norepinephrine dose. Endogenous norepinephrine and vasopressin are synthesised by the copper-containing enzymes dopamine β-hydroxylase and peptidylglycine α-amidating monooxygenase, respectively. Both of these enzymes require ascorbate as a cofactor for optimal activity. Patients with severe sepsis present with hypovitaminosis C, and pre-clinical and clinical studies have indicated that administration of high-dose ascorbate decreases the levels of pro-inflammatory biomarkers, attenuates organ dysfunction and improves haemodynamic parameters. It is conceivable that administration of ascorbate to septic patients with hypovitaminosis C could improve endogenous vasopressor synthesis and thus ameliorate the requirement for exogenously administered vasopressors. Ascorbate-dependent vasopressor synthesis represents a currently underexplored biochemical mechanism by which ascorbate could act as an adjuvant therapy for severe sepsis and septic shock.

PMID:
26612352
PMCID:
PMC4661979
DOI:
10.1186/s13054-015-1131-2
[Indexed for MEDLINE]
Free PMC Article

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