Annals of Burns and Fire Disasters - vol. IX - n. 2 - June 1996

EFFECTS OF HYPERTONIC SODIUM LACTATE DEXTRAN 70 RESUSCITATION IN SEVERELY BURNED DOGS

Ge S.D., Xhu S.H., Liu S.K., Chen Y.L.

Burn Institute, Shanghai Hospital, Shanghai, People s Republic of China

SUMMARY. The present comparative study was performed to evaluate the effects of resuscitation with hypertonic sodium lactate dextran (HLD) 70 solution (HLD, Na+ 250 mmol/l, 6% dextran 70) and with lactated Ringer s (LR) solution on the volune OfIltlid illfused, Seruill Na+ and alburnin, crystalloid osmolarity, plasma lipid peroxide, and SOD activity. Twelve adult dogs were dividcd randomly into two equal groups. A 35% TBSA third-degree burn was created on the back. One hour post-burn the six animals in the HLD group received HLD (19.6 mI/kg/3 hours) intravenously in bolus injection, followed by LR solution (6 ml/kg/% TBSA). The six aninials in the LR group received only LR solution for resuscitation (8 ml/kg/% TBSA). Infusion of LR solution in both groups was adjusted by maintaining urinary output at 0.5-1 ml/kg/h. The volume of fluid infused in the HLD group (5.05 ± 1.11 ml/kg/% TBSA) was much les, than lhat ill the IR group (10.03 ± 1.30 ml/kg/% TBSA) (p<0.01). There was no significant difference between the two group serumNa+ andalburnin, and plasma crystalloid. Theplasmalevel of NIDA decreased after resuscitation with HI,I), which was nitich lowor (0.81 ± 0.20 mmol/g Hb) than that in the LIZ group (1.39 ± 0.44 inmol/g Hb) four hours post-burn (p<0.05). Plas nia Sol) activity (722) t 0.68 p/g Hb) in the HLD group was much higher than that in the LIZ group (4.86 ± 0.53 p/g Hb) four hours pos(-bnrn (1)<0.05), It is concill ded that HLD resuscitation could significantly reduce the required amount of fluid infused during resuscitation coinpared with LR  ,olulion, and attenuate post-burn damage to tissue induced by lipid peroxide by elevating plasma SOD activity. Hypertonic solutions have been reported to restore systemic haemodynamics during resuscitation after circulatory shock more effectively and more rapidly than isotonic solutions. , , . In particular, hypertonic saline dextran (7.5% NaCI/6% dextran 70) (HSD) has been used as a rapid expander of intravascular volume in hypovolaemic shock` and burn injury, ,  although the improvement seems to be transient and the total fluid requirements and oedema formation remain unchanged in burns. There are however some controversial issues in HSD resuscitation .7 The volume of fluid infused in burn shock resuscitation varies. ,  In the present study, hypertonic sodium lactate dextran 70 (Na+ 250 mmol/1, 6% dextran 70) (HLD) was used in burn resuscitation. We compared the effects of HLD and lactated Ringer s (LR) solution on the volume of fluid infused, serum Na+ alburnin and crystalloid osmolarity. We also investigated the level of NIDA and SOD activity in plasma 24 hours post-burn. This presented lipid peroxidation indirectly, which plays an important role in the post-burn phase.

Material and methods

Experimental design
Twelve dogs were randomly distributed in two groups. The HLD group (N  = 6) received a 35% total body surface area (TBSA) third-degree flame burn under anaesthesia with intravenous injection of pentobarbital sodium (30 mg/kg). One hour post-burn the animals received FILD (19.6 mIlkg/3 hours) intravenously in bolus, followed by LR solution (6 ml/lkg/% TBSA). The LR group (N received only LR solution (8113SA). liall of llic total amount of fluid infused was given Ill the fii,;1 eighi hours post-burn and the remainder Ill the nexl 10 houis, Infusion of LR solution in both groups wit,,,, bv maintaining haemodynamic stability and urillary oullm, al 05-1 ml/kg/h.

Burn injury
A 35% third-degree burn was created with intravenous injection of pentobarbital sodium by radiation using a hroc mine tungsten lamp (5000 W) for 25 ,se(...oi)(.1,., at 75 cut focus length. We confirmed the leslon ofilw burned skin by histological evaluation oil itiiol),,,,y. Measurements of serum Na+ albunfin, cr , o,vllola rity and the plasma level qfMDA alid,N 01) acin-itv Serum Na+ and alburnin were inew,,urod by nw;in,; of an ASTRA-8 biochemical autoanalysis iw,,tiunwitt (Beckman company, USA). Serun) crysl,,illoid osinoLuNy was measured by means of an osmolmily analysis ins(in ment (Shanghai First Medical (Inivcrsily Instiunicill Factory, Shanghai). MDA was measured occordinp, to the TBA-fluorometic method.  SOD aclivity was, measuied according to Chen et al. s modified polaroriaphic analvscs method.

Statistical analysis
Data are presented as the mean -i- ShM lind 1,tiizilyse(f as a two-factorial experiment willi repealed ineasures.
Comparative statistics of time effects were analysed using Dunnett s test after ANOVA by comparing the values between time intervals with baseline values within each group. Between groups, data at each time point were compared by using Student s impaired t test. Statistical significance was accepted at p < 0.05.

The volume of fluid infused in the HLD group (5.05 1.11 ml/kg/% TBSA) was much less than that in the LR group (10.03 ± 1.30 ml/kg/% TBSA) (p < 0.01). There were no significant differences in urinary output between the HLD group (0.89 ± 0.27 ml/kg/h) and the LR group (0.54 ± 0.11 ml/kg/h) (Figs. 1,2).

Fig. 1 - Fluid volume infuse first 24 hours post-burn (** p<0.01) Fig. 2 - Urinary output during first 24 hours post-burn

Serum Na+, alburnin and crystalloid osmolarity
Serum Na+ decreased post-burn and increased after resuscitation in both groups. The maximum serum sodium concentration was 146.2 ± 5.2 mmol/l in the HLD group and 140.8 ± 11.4 mmol/l in the LR group two hours postburn. The maximum serum crystalloid osmolarity was 308.4 1 ± 12.8 mOsm/l in the HLD group and 300.6 ± 18.6 mOsm/1 in the LR group two hours post-burn. Serum alburnin concentration decreased gradually after resuscitation in both groups. No significant difference was demonstrated between the HLD group and the LR group as regards serum sodium concentration, and serum crystalloid osmolarity (Table 1).

Plasma level of MDA and SOD activity
The plasma level of NIDA increased post-burn from pre-burn levels of 1.10 ± 0.45 i-niiiol/- Hb in the HLD group) and 1.07 ± 0.21 mi-nol/g Hb in LR group) to 1.25 0.38 mmol/g Hb and 1.37 ± 0.04 niniol/g Hb, respectively. The plasma level of NIDA decreased after resuscitation. The level of MDA in the HLD oroup (0.8 1 ± 0.20 minol/g Hb) was much lower than iiiti in the LI\  group (1J9 ± 0.44 mmol/g Hb) four hours post-burn (p < 0.05) (Fig. 3). Plasma SOD activity decreased from pre-burn values of 4.27 ± 0.83 p/g Hb (HLD group) and 5.87 ± 2.24 M1g Hb (LR group) to 4.15 ± 2.72 p/g Hb and 4.77 ± 0.83 p/g Hb, respectively, 0.5 hours post-burn. SOD activity increased after resuscitation in both groups. SOD activity in the HLD group (7.07 ± 4.09 plg Hb) was much higher than that in the LR group (3.89 ± 1.33 plg Hb) eight hours postburn (p < 0.05) (Fig. 4).

Fig. 3 - Changes of plasma levels of MDA Fig. 4 - Changes of plasma SOD activity during first 24 hours post-burn (* p<0.05)

Hypertonic sodium combined with dextran (HSU)), are very c[ leenve in res ns citating animals subjected to li ici)ioj-ilia,,,ic shock, even when given in volumes as srnall as 4 in]/kg body weight.   This kind of solution was also used in btlrll shock WSMSCi tation in animals. Although several reports have denion strated that HSD resuscitation can improve cardiac func: tion and reduce the volume offluid versial issues still remain. Onarlicirn Ct  lf., Llsiiig an anacs thetized sheep model of thermal injury, demonstrated that in two minutes an HSD (4 ml/kg) bolus improved cardiovascular function compared to an equal volume of 0.9% saline following thermal injury.

The improvements were only transient. Recent work by Tokyay et al.  using a pig model of burns showed that HSD (10 ml/kg HS13, followed by 4 ml/kg/% burn) can be beneficial in improving post-burn microcirculation. In the present study, we did not give animals a constant LR volume, as previously reported. After administration of an equal volume of HI-D or LR solution in the HLD and LR groups, respectively, the infusion of LR solution was adjusted by maintaining urinary output at 0.5-1 m]/kg/h and stable haemodynarnics in both groups. The results of our experiment indicated that the Parkland formula is unable to maintain stable haemodynamics in severely burned dogs, in which the volume of LR solution was twice the amount calculated by the Parkland formula and even more. On the basis of urinary output maintained at 05-1 ml/kg/h, our experiment showed that HI-D can reduce the volume of fluid infusion during the first 24 hours postburn by nearly 50%, which is consistent with reports by Schenk et al.  Onarheim  believes Iliat HSD resuscitation could cause a rise of serum sodium concentration and crystalloid osmolarity. Walsh and Kramer    reported that resuscitation with dextran could increase the loss of  alburnin. Our experimental results showed (hat there was no significant difference between the two ,roups, a s regards this parameter, which suoocsts Ilial HH) rcstiscitation does not significantly increase dic conccnlralioil ol  sodium and crystalloid osinolarity wlicii (lit, niodk  of infusion is that of our study.
There is ample evidence in the hwi;ilmc ihai oxN/pt-ii derived free radicals may be prodticcd Atei lheiiwil injiny and that they may play an important role In 11w stibso(Iticiii tissue damage  ,  Although the rnechanisin undcilyinti posi iscluicmic injury is not completely undermood mid alihou ,  dl oxidant-induced darnage may ciwoinp i, s many ccil components, peroxidative deconiposihon of inombiam lipids has been considered to I)L- Hic basis, of ccll injury.    Walsh and Kramer  conl ii in(,([ di;it I IS[) i   beneficial in reducing the post-hurn rel)eifusion injury seen with LR resuscitation, while Behrinan believe that the reduced reperfusion injury with LISD resuscitation might be the result of dextran s oxygen free-radical scavenging and anti-neutrophil plugging properties. Our findings indicate that HLD can decrease plasma N1DA level and increase SOD activity, which might reduce the damage of lipid peroxidation to issue and cells.
In conclusion, HLD resuscitation cart significantly reduce the volume of fluid infused compared with LR resuscitation. Our findings also indicate that HL,D resuscitation can be beneficial in attenuating post-burn oxidant-induced lipid peroxidation not only by its   oxygen free-radical scavenger

RESUME. Les auteurs, dans cette étude comparative, évaluent les effets de la réanimation avec une solution ile laciale (le sodium dextran 70 (HLD) (HLD, Na+ 250 mmol/l, 6% dextran 70) et avec la solution de lactate de Ringer (LR) mu le voluine du liquide infusé, le Na+ et l alburnine sérique, l osmolarité cristalloïde, le peroxyde du ipide plasmatique et l activité SOI). Douze chiens adultes ont été divisés au hasard en deux groupes égaux. Une brûlure de troisième degré en 35% de la surface corporelle (SC) totale a été créée sur le dos. Une heure après la lésion les six animaux du groupe HLD ont reçu HLD (19,6 ml/kg/3 heures) par voie intraveineuse avec injection de bol, et ensuite la solution LR (6 ml/kg/% SC suivi par la solution LR (6 ml/kg/% SC). Lex six animaux du groupe LR ont reçu seule ment la solution LR pour la réanimation (8 ml/kg/% SC). L infusion de la solution LR dans tous les deux groupes a été réglée en mainte nant la production urinaire à 0,5-1 ml/kg/h. Le volume du liquide infusé dans le groupe HLD (5,05 ± 1,11 ml/kg/lY,  SC) était notamment inférieur au volume infusé dans le groupe LR (10.03 ± 1,30 ml/kg/% SC) (p < 0,01). Les auteurs n ont pas observé aucune différence significative entre les deux groupes pour ce qui concerne la production urinaire, le Na+ et l alburnine sérique, et le cri stalloïde plasmatique. Le niveau plasmatique du MDA diminuait après la réanimation avec HLD, qui était notamment inférieur (0,81 ± 0,20 mmol/g Hb) à celui du groupe LR (1,39 ± 0,44 mmol/g Hb) quatre heures après la brûlure (p<0.05). L activité plasmatique du SOD (7,22 ± 0,68 p1g Hb) dans le groupe HLD était largement supérieure à celle du groupe LR (4,86 ± 0,53 p/g Hb) quatre heures après la brûlure (p<0,05). Les auteurs concluent que la réanimation avec HLD pourrait réduire en manière significative la quantité nécessaire du fluide infusé pendant la réanima tion par rapport à la solution LR, et atténuer les dommages tissulaires après la brûlure causés par le peroxyde lipidique CI) élevant l activité du SOD plasmatique.

BIBLIOGRAPHY

1. Bitterman H., Triolo J., Jefer A.M.: Use of hypertonic saline in the treatment of hemorrhagic shock. C. Shock, 21: 271, 1987.
2. Gunn M.L., Hansbrough J.F., Davis JW. et a].: Prospective, randomized trial of hypertonic sodium lactate versus lactated Ringer s solution for burn shock resuscitation. J. Trauma, 29: 1261, 1989.
3. Sondeen J.L., Gonzaludo G.A., Loveday J.A et at.: Hypertonic salme dextran improves renal function after hemorrhagic shock in conscious swine. Resuscitation, 20: 231, 1990.
4. Hannon J.P., Wade C.E., Bossone C.A. et al.: Blood gas and acidbase status of conscious pigs subjected to fixed-volume hemorrhage and resuscitation with hypertonic saline dextran. C. Shock, 32: 19, 1990.
5. Hannon J.P., Wade C.E., Bossone C.A. et al.: Oxygen delivery and demand in conscious pigs subjected to fixed-volume hemorrhage and resuscitation with 7.5% NaCl in 6% dextran. C. Shock, 29: 205, 1989.
6. Horton J.W., White D.J., Baxter C.R.: Hypertonic saline dextran resuscitation of thermal injury. Ann. Surg., 211: 301, 1990.
7. Onarheim H., Missavage A.E., Kramer G.C. et a[.: Effectiveness of  hypertonic saline dextran 70 for initial fluid resuscitation of major burns. J. Trauma, 30: 597, 1990.
8. Tokyay R.T., Zerigler S.T., Kramer G.C. et al.: Effects of hypertonic saline dextran resuscitation on oxygen delivery, oxygen consumption and lipid peroxidation after burn injury. J. Trauma, 32: 704, 1992.
9. Yagi K.: A simple fluorometric assay for lipoperoxide in blood plasma. Bioch. Med., 15: 212, 1976.
10. Chen K.M., Liao M.Y., Wna F.: The measurement of SOD activity of plasma in severely injured iats. Acad. 1. Milit. Med. Univ., 16:23,1985.
11. Maningas P.A., De Guzman L.R., Tillman FJ. et a].: Sniall-volunic infusion of 7.5% NaCl in 6% dextran 70 tor the treatment of severe hemorrhagic shock in swine. Ann. Ernerg. Med., 15: 113, 1986.
12. Schenk W.G.: Experimental inhalation injury with concomitant surface burn: dextran rescuscitation improves lung water and oxygenation. J. Trauma, 30: 813, t990.
13. Walsh J.C., Kramer G.C.: Resuscitation of hypovoleinic sheep with hypertonic saline/dextran: the role of  dextran. C. Shock, 34: 336, 1991.
14. Till G.O., Hatberill J.R., Tourtellotte W.W. et a].: Lipid peroxidation and acute-lung injury after thermal tratuna to skin. Evidence of a role for the hydroxyl radical. Ain. J. Pathol., 119: 376, 1985.
15. Demling R.H., Lalonde C.: Systernic lipid peroxidation and inflammation induced by thermal injury persists into the post-resuscitation period. J. Trauma, 30: 69, 1990.
16. McCord J.M.: Oxygen-derived free radical in post ischeinic issue injury. N. Eng]. J. Med., 312: 159, 1985.
17. Behrman S.W., Fabian T.C., Kud.,, k et al.: Microuirculnory flow after initial resuscitation of  hemordinpic shock widi 7.51X, saline/6%dexti-an 70. J. Traunia, 3 1: 581, 1991