HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT?

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HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT? P. Stoecklin, Y.A. Que, P. Voirol, H. Engel, M.M. Berger Service de Médecine Intensive Adulte et Centre des Brûlés CHUV - Lausanne

HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT Background Some studies suggest that early administration of high-dose ascorbic acid (AA: 66 mg/kg/h in 24hrs) may decrease fluid requirements during resuscitation in major burns via an antioxidant mechanism, reducing capillary leak and resultant tissue edema, with better oxygenation.(reference: Tanaka H, et al «Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study» Arch Surg. 2000 ; 135(3): 326-331 ) Despite promising preliminary results large study is yet available.

HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT? Methods Design: Retrospective quality control study of the impact of Ascorbic Acid (AA) vs. ne (NO) during the first 48h of 16 patients with massive burns. Unicentric. Data: Prospective collected data (MetaVision ) in the reference burn center ICU (CHUV; Lausanne, Switzerland). Ventilation, oxygenation data and lactate at 12, 24, 36 and 48 hrs Patients: Inclusion criteria: admission within 6 hrs, survival > 48h. 8 massive burns resuscitated guided by the new protocol with AA 8 patients paired historical control matched for TBSA, inhalation, age Ventilator settings were by ICU protocol. Statistics: Wilcoxon tests, 2-way ANOVA

HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT? Methods Fluid resuscitation until 2010: Parkland guided (4ml/kg/TBSA%) in all burns 2011: recommendation to use the lower Parkland range for all patients (2ml/kg/TBSA%) with the addition of AA 66 mg/kg/h in patients with burns >50% TBSA.

HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT? Results (Data as medians) Variable Ascorbic Acid NO N 8 8 Age (years) 37.5 30.5 (ns) Sex ratio (M/F) 7/1 6/2 Weight (Kg) 78.5 73.6 TBSA (%) 71 70 Surgical TBSA (%) 65 62.5 Inhalation injury (n) 6 6 SAPS II 44 35 Length mech vent (d) 26 27 Length ICU (days) 50 78 Outcome (Live/D) 5 / 3 6 / 2 (p=0.12)

HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT? Result Total dosis (mg) of Vit C administrated the first 48hrs 30 25 Delai time to high dose AA 15 12 10 Dose tot (mg) VitC 48h 20 15 10 Délai (min) adm arr Vit C 75 50 25 0 AA 50 0 AA (median 509min) 1 orange = 51 mg AA 150 g 2800 oranges

HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT? Result Fluid resuscitation volume 7.0 9 6.5 6.0 8 24h fluid ml/kg/bsa 5.5 5.0 4.5 4.0 3.5 48h ml/kg/bsa 7 6 5 3.0 4 2.5AA AA Fluid input 0-24h (L) 19 21.8 24h fluid ml/kg/bsa 3.2 4.3 48h fluid input ml/kg/bsa 5.0 6.1 p= 0.0264 p= 0.0318

HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT? Results (Data as medians) Variable Ascorbic Acid NO Urine output (ml/kg/h) 1.0 1.9 (p=0.062) Norephinephrine (mg) tot 48h 73.6 13.9 Lactate (mmol/l) 3.7 2.3

HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT? Result Norephinephrine cumulated doses over first 48 hrs (Trend: p= 0.0792) 15 10 Noradré (mg) tot 48h 50 0 AA

HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT? Result Oxygenation: First 48hrs PaO 2 /FiO 2 ratios n.s impact 7 6 P= 0.0004 lactate 7 6 5 4 3 NO P= 0.0003 5 2 lactate 4 3 1 12 24 36 48 Time 2 1 AA lactate 7 6 5 4 3 AA P= ns 2 1 12 24 36 48 Time

HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT? Results Weight change - % from admission Maximum (day 2) Day 7 NS : +27% AA vs +23% NO Ns: + 11.7% AA vs + 14.5% NO 45 35 40 30 % Prise poids max 35 30 25 20 %prise poids J7 25 20 15 15 10 10AA 5 AA Sodium ascorbate provides 131 mg of sodium per 1 g of ascorbic acid

HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT? CONCLUSIONS: High dose AA was associated with a significant reduction of fluid requirements. There was significant impact on weight gain AA was t associated with major organ failure Higher lactate levels are a concern though: cause uncertain. Indeed 2 major changes in resuscitation protocol were introduced simultaneously the fluid restriction may also have been the cause Larger studies are warranted to determine the efficiency of the treatment.

HIGH-DOSE ASCORBIC ACID AND FLUID RESUSCITATION REQUIREMENTS IN MASSIVE BURN INJURY A REAL IMPACT? Results (Data as medians) Variable Ascorbic Acid NO Delay administration AA (min) 509 - Total of Vit.C at 48h (mg) 129 228 3 572 Fluid input 0-24h (L) 19 21.8 Fluid input 25-48h (L) 8.2 15.9 24h fluid input ml/kg/bsa 3.2 4.3 48h fluid input ml/kg/bsa 5.0 6.1 Norephinephrine (mg) tot 73.6 13.9 48h Urinary output (ml/kg/h) 1.0 1.9 (p=0.062) Lactate (mmol/l) 3.7 2.3