University of Utah Burn Center

Adult Fluid Resuscitation Protocol12

Evaluation of High-dose Ascorbic Acid in Thermal Injury Scott Allen, PharmD1; Ann Marie Prazak, PharmD, BCPS1-2; Giavonni Lewis, MD, FACS1; Amalia Cochran, MD, MA, FACS, FCCM1

1University of Utah Health Care, Salt Lake City, UT; 2University of Utah College of Pharmacy, Salt Lake City, UT

• Burns >20% total body surface area (TBSA) are associated with hypovolemic shock, local tissue edema, and release of inflammatory mediators1-3

• Inflammatory mediators lead to production of reactive oxygen species, which can worsen burn shock by causing lipid peroxidation and increased vascular permeability1, 4-5

• Ascorbic acid is a free radical scavenger that may reduce lipid peroxidation and vascular permeability by inactivating reactive oxygen species6

• Ascorbic acid has been shown in animal models and one human clinical trial to reduce fluid requirements in thermal injury5, 7-10

• Concerns for osmotic diuresis and risk for renal injury have limited widespread use in burn centers1, 11

Background

• The addition of AA to fluid resuscitation with LR + albumin did not reduce 24-hour fluid requirements

• Ascorbic acid did not statistically increase the risk for renal injury • Patients receiving AA may survive longer, but no difference in mortality

versus LR + albumin alone

Analyse the impact of high-dose ascorbic acid in reducing fluid requirement and the risk for renal injury during the first 24 hours of fluid resuscitation

Inclusion Criteria: • Patients 18 years of age • Admission to the University of Utah Burn Trauma ICU (BTICU) from June 1, 2014 to July 1, 2016

• Patients with 15% TBSA thermal injury requiring fluid resuscitation according to BTICU protocol

• High-dose ascorbic acid administration (defined as 66 mg/kg/hr) initiated during first 24 hours of fluid resuscitation

Exclusion Criteria: • Patients who survived fewer than 48 hours • Patients not resuscitated based on compassionate withdrawal of care • Patients presenting ≥ 10 hours from time of thermal injury • Patients with documented renal insufficiency or renal failure (defined as admission creatinine >1.5 mg/dL or ESRD requiring hemodialysis)

• Pregnant or incarcerated patients Statistical Analysis:

• Fisher’s exact test and Student’s T-test will be used for analysis of categorical and continuous data

Methods

Primary Outcomes: • Determine the impact of high-dose ascorbic acid on total fluid

requirements during the first 24 hours of fluid resuscitation • Assess the risk for renal injury following high-dose ascorbic acid

administration Secondary Outcome: • Evaluate the impact of high-dose ascorbic acid administration on all-

cause mortality

Initiate fluid resuscitation with LR at calculated starting rate

Target UOP 30-50 mL/hr

Adjust rate based on UOP until maintenance

rate achieved

Consider adding albumin at 1/3 of hourly LR rate

Consider adding ascorbic acid

UOP at goal for 2 hours and patient is >24 hours post-burn, change fluids to D5W NaCl 0.45% with KCl 20 mEq/L

Fluid resuscitation complete Continue fluids at calculated maintenance rate

References 1. Kramer, George, Chapter 8 - Pathophysiology of burn shock and burn edema, In

Total Burn Care (Fourth Edition), edited by David N. Herndon, W.B. Saunders, London, 2012, Pages 103-113.

2. Haberal M, Sakallioglu Abali AE, Karakayali H. Fluid management in major burn injuries. Indian J Plast Surg. 2010;43:S29-S36.

3. Latenser BA. Critical care of the burn patient: the first 48 hours. Crit Care Med. 2009;37:2819-2826.

4. Friedl HP, Till GO, Trentz O, Ward PA. Roles of histamine, complement and xanthine oxidase in thermal injury of skin. Am J Pathol. 1989;135:203-217.

5. Matsuda T, Tanaka H, Yuasa H, et al. The effects of high-dose vitamin C therapy on postburn lipid peroxidation. Journal of Burn Care & Research. 1993;14:624-629.

6. Oudemans-van Straaten HM, Spoelstra-de Man AM, de Waard MC. Vitamin C revisited. Crit Care. 2014;18:460.

7. Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch Surg. 2000;135:326-331.

8. Matsuda T, Tanaka H, Reyes HM, et al. Antioxidant therapy using high dose vitamin C: reduction of postburn resuscitation fluid volume requirements. World J Surg.

1995;19:287-291 9. Dubick MA, Williams C, Elgjo GI, Kramer GC. High-dose vitamin C infusion reduces

fluid requirements in the resuscitation of burn-injured sheep. Shock. 2005;24:139-144.

10. Sakurai M, Tanaka H, Matsuda T, Goya T, Shimazaki S, Matsuda H. Reduced resuscitation fluid volume for second-degree experimental burns with delayed initiation of vitamin C therapy (beginning 6 h after injury). Journal of Surgical

Research. 1997;73:24-27. 11. Kahn SA, Beers RJ, Lentz CW. Resuscitation after severe burn injury using high-

dose ascorbic acid: a retrospective review. J Burn Care Res. 2011;32:110-117. 12. Cochran A, Morris SE, Edelman LS, Saffle JR. Burn patient characteristics and

outcomes following resuscitation with albumin. Burns. 2007; 33:25-30.

All authors have no relevant conflicts of interest to report

UOP <15 mL/hr for two hours

UOP >30 mL/hr

UOP >30 mL/hr Failing

resuscitation

Adjust rate based on UOP until maintenance

rate achieved

Figure 1

Objectives

Outcomes of Interest

Results

Conclusions

Characteristic AA

(31)

Control

(31)

P-value

24-hr fluid

resuscitation* 5.9 ± 2.9 5.1 ± 2.7 0.16

Renal injury 10 5 0.24

Mortality 8 8 1

* mL/kg/%TBSA