Patients and methods

The study comprised 40 burn patients admitted to the Burn Unit of Tanta University Hospital (Egypt) with burns exceeding 15% total body surface area (TBSA); an acute fluid resuscitation regimen was started.

Exclusion criteria

1. Burns in less than 15% TBSA

2. Patients with electrical or chemical burns

3. Patients with inhalation injuries

4. Patients with serum creatinine above 2 mg/dl

Fluid regimens

Group 1 (LR group) - patients in group 1 received LR solution, according to the Parkland formula5 (4 ml/kg/% BSA burned), aiming at a urinary output of 0.5-1 ml/kg/h.

Group II (Haes group) - patients in group II received Haes-Steril 10%, with a maximum daily dose of 20 ml/kg body weight, until a urinary output of 0.5-1 ml/kg/h was achieved.

Adequacy of resuscitation

All patients included in the study were subjected to the following procedures in order to guide fluid resuscitation:

1. Clinical assessment to ensure patency of airways. The TBSA burned was calculated using the rule of nine.6 A central venous catheter and an indwelling urinary catheter were applied.

2. Estimation of central venous pressure (CVP).

3. Using the estimated CVP, cardiac output (COP) was determined using COP curves.

4. The cardiac index (CI) was calculated by the following formulae:

TBSA (m²) = weight0.425 x height0.725 x 0.00718
CI (l/min/m²) = COP/TBSA

5. VO2 was determined using curves illustrating the relationship between CI and VO2.

6. Estimation of endothelin-1 (ET-1)8 and serum lactate9 levels.

7. Estimation of serum urea,10 and creatinine and creatinine clearance rate.11

The studied variables were evaluated on admission of the patients, and were considered the pre-infusion values. Thereafter these variables were re-evaluated 6, 12, and 24 h after initiation of fluid therapy.

Statistical analysis

Data were presented as means + SD. The statistical analysis of demographic data (age, sex distribution, TBSA, percentage burned TBSA) was performed using one-factor analysis of variance. Both groups were compared for changes occurring in the studied variables using the two-tailed t-test. Pearson’s correlation coefficient (r) was used to correlate some of the studied variables. The level of significance was set at a p value <0.05.12 Computations were performed using the statistical software package SPSS 7 for Windows (SPSS Inc., Chicago, Illinois, USA).

Results

The study comprised 40 patients with burns in more than 15% TBSA. These were allocated to two study groups: the first group received LR solution according to the Parkland formula, while the second group received Haes-Steril 10% as acute resuscitation therapy aimed at producing a urine output of 0.5-1 ml/kg/h.

An analysis of the demographic data revealed a non-significant (p > 0.05) difference between the two groups with regard to age, sex distribution, TBSA, and percentage of burned BSA (Table I).

Data LR group Haes group p Age (yr) 38.4 ± 12.8 (19-62) 37.8 ± 13.1 (18-59) > 0.05 TBSA (%) 1.87 ± 0.155 1.83 ± 0.152 > 0.05 % burned BSA 29 ± 8.4 (16-45) 29.5 ± 8.2 (17-47) > 0.05 Sex (m:f) 9.11 6.14 > 0.05 Values are mean ± SD, with ranges in parentheses p > 0. 05 = statistically nonsignificant difference   Table I- Demographic data patients in the groups studied  

During the study period, heart rate (HR) decreased by 18.5% in the LR-group and by 19.8% in patients in the Haes group; however, HR showed a non-significant difference (p > 0.05) between the two groups. The mean arterial blood pressure (mABP) increased by 6.7% in patients in the LR-group and by 9.9% in patients in the Haes group. The percentage increase in mABP in patients in the LR group showed a non-significant difference (p > 0.05) compared with that in Haes-group patients. CVP increased in LR-group patients by 25% and in the Haes group by 42.3%; there was a significant increase (p <0.05) in CVP values in the Haes group compared with values in the LR group (Fig. 1). A comparison of CVP measurements in the two groups showed a significant increase (p <0.05) in values in the Haes group compared with those in the LR group 6 and 24 h after initiation of fluid therapy. COP showed an 11% increase during the study period in LR patients, while in Haes-group patients COP increased by 23%. A comparison of the changes in COP in the two groups showed a significant increase (p < 0.05) in Haes-group patients (Fig. 2). However, COP showed a significant increase (p < 0.05) in the Haes-group only 12 h after initiation of fluid therapy. With regard to CI, this increased by 13% in LR-group patients and by 23% in Haes-group patients (Fig. 3). An analysis of the differences in CI showed a significant increase (p < 0.05) in CI in Haes-group patients compared with that in LR-group patients 6 and 24 h post-infusion. Oxygen consumption (VO2) increased by 35.9% in LR patients and by 41.1% in Haes-group patients 24 h after initiation of fluid therapy (Fig. 4). During the study period there was a significant increase (p < 0.05) in VO2 in Haes-group patients compared with VO2 in the LR group (Table II).

Fig. 1 - Changes in central venous pressure (mm/Hg) in groups studied (pre- and post-infusion).  

Fig. 2 - Changes in cardiac output (1/min) in groups studied (pre- and post-infusion).  

Fig. 3 - Changes in cardiac index (1/min/m2) in groups studied (pre- and post-infusion).  

Fig. 4 - Changes in oxygen consumption in groups studied (pre- and post-infusion).  

Parameter Pre-infusion 6 h post-infusion 12 h post-infusion 24 h post-infusion Percentage change HR (beat/min) LR group 121.5 ± 7.1 111.8 ± 7.1 106.3 ± 8.4 103.5 ± 11.3 18.05 Haes group 123.3 ± 6.3 114.5 ± 6 104.8 ± 7.3 95.0 ± 5.8 19.08 mABP (mmHg) LR group 81.1 ± 7.2 85.7 ± 3.5 85.8 ± 3.8 85.8 ± 4.5 6.07 Haes group 78.9 ± 5.3 80.5 ± 4.1 84.3 ± 3.9 86.4 ± 4 9.09 CVP (mmhg) LR group 5.6 ± 0.9 6.97 ± 1.11 5.9 ± 0.9 8.1 ± 1.29 25.00.00 Haes group 5.7 ± 0.8 8.23 ± 1.16S 6.5 ± 0.92 9.5 ± 1.33S 42.3S COP (l/min) LR group 5.8 ± 0.47 5.86 ± 0.5 6.28 ± 0.86 7.39 ± 0.82 13.00 Haes group 5.6 ± 0.5 5.73 ± 0.5 6.83 ± 0.98 8.1 ± 0.97S 23.00 CI (l/min/m2) LR group 3.09 ± 0.05 3.37 ± 0.4 3.14 ± 0.06 3.96 ± 0.3 13.00 Haes group 3.06 ± 0.13 3.72 ± 0.42S 3.13 ± 0.06 4.2 ± 0.41S 23.0S VO2 (l/min) LR group 0.73 ± 0.03 0.78 ± 0.03 0.82 ± 0.05 1.0 ± 0.4 35.09.00 Haes group 0.74 ± 0.03 0.82 ± 0.05S 0.88 ± 0.06S 1.04 ± 0.09S 41.01.00 S = statistically significant difference   Table II- Changes in heart rate (HR), mean arterial blood pressure (mABC), central venous pressure (CVP), cardiac output (COP), and cardiac index (CI) in patients according to group  

The plasma ET-1 level decreased by 39.6% in LR patients and by 44.5% in Haes-group patients, with a non-significant decrease (p > 0.05) in the plasma ET-1 level in the Haes group compared with its level in the LR group (Fig. 5). The plasma ET-1 level showed a non-significant difference (p > 0.05) between the two groups during the study period, except at 12 h after initiation of infusion therapy, when the difference was significant (p <0.05). The plasma ET-1 level showed a negative significant correlation with CI in both groups (r="-0.65" and 0.652, p="0.002," respectively). Estimation of the serum lactate level showed a 34.2% decrease in patients receiving LR solution and a 32.3% decrease in patients receiving Haes-Steril. Comparing treatment with serum lactate prior to initiation of infusion therapy, however, there was a non-significant difference (p> 0.05) in serum lactate levels, throughout the study period, between the groups (Fig. 6). There was a negative significant correlation between serum lactate and both CI and VO2 in both the LR group (r = -0.52 and -0.683, p = 0.019 and 0.001, respectively) and in the Haes group (r = -0.505 and -0.612, p = 0.023 and 0.004, respectively). Serum urea decreased by 19.4% in LR patients and by 23.1% in Haes patients; however, there was a non-significant difference (p > 0.05) between the two groups as regards serum urea. Serum creatinine showed a significant decrease (p <0.05) during the study period in Haes-group patients compared with levels in the LR group (Table III). The creatinine clearance rate significantly increased (p < 0.05) in Haes-group patients (mean, 122.16 ± 36.06; range, 62.3-186.5 ml/min) compared with that in the LR group (mean, 101 ± 27.4; range, 49.3-129 ml/min) (Table IV). A positive significant correlation was found between CI and the creatinine clearance rate in the two groups (r="0.518" and 0.571, p="0.019" and 0.011).

Fig. 5 - Changes in plasma endothelin-1 (ng/ml) levels in groups studied (pre- and post-infusion).  

Parameter Pre-infusion 6 h post-infusion 12 h post-infusion 24 h post-infusion Percentage change Plasma ET-1 (ng/dl) LR group 17.6 ± 3.8 12.95 ± 1.88 9.95 ± 2.04 10.1 ± 1.74 -39.6 Haes group 16.6 ± 3.9 12.6 ± 3.5 10.65 ± 2.5 8.7 ± 1.45S -44.5 S. lactate (mg/dl) LR group 16.3 ± 4.4 14 ± 3 11.7 ± 1.98 9.8 ± 2.4 -34.2 Haes group 16.4 ± 3.95 14.4 ± 2.8 12.1 ± 2.34 10.6 ± 2.44 -32.3 S. urea (mg/dl) LR group 34 ± 4.2 31 ± 4.5 26 ± 3.7 24.4 ± 2.8 -19.4 Haes group 38 ± 5.3 34.5 ± 5 26.5 ± 3.7 26 ± 3.5 -23.1 S. creatinine (mg/dl) LR group 1.2 ± 0.21 1.1 ± 0.2 1 ± 0.2 0.9 ± 0.11 -15.9 Haes group 1.1 ± 0.12S 1 ± 0.13S 0.9 ± 0.1S 0.8 ± 0.11S -15.5 S = statistically significant difference   Table III- Changes in plasma endothelin-1, serum lactate, serum urea, and serum creatinine occurring in patients in patients according to group  

Fig. 6 - Changes in serum lactate (mg/dl) in groups studied (pre- and post-infusion).  

Urine output in Haes-group patients showed a significant increase (p <0.05) as total output both per 24 h (mean, 1865 ± 281 ml/24 h; range, 1400-2300 ml/24 h) and per min (mean, 1.04 ± 0.16 ml/kg/h; range, 0.7-1.31 ml/kg/h) compared with that of LR patients per 24 h (mean, 1650 ± 303 ml/24 h; range, 1070-2200 ml/24 h) and as output in ml/kg/h (mean, 0.91 ± 0.22 ml/kg/h; range, 0.6-1.32 ml/kg/h) (Fig. 7). During the first six hours after initiation of fluid therapy, urine output significantly increased (p <0.05) in the Haes group compared with that in the LR group. However, during the remaining study period, the difference in outputs by patients in the two groups was non-significant (p> 0.05) (Table IV).

Fig. 7 - Urine output (ml/kg/h) of patients in groups studied.  

Parameter / Group LR group Haes group ml/period ml/kg/h ml/period ml/kg/h Urine Output 6 h Post infusion 413.8 ± 69.4 (300-500) 0.91 ± 0.22 (0.54-1.4) 497.8 ± 88S (350-700) 1.11 ± 0.19S (0.84-1.5) 12 h Post infusion 521 ± 109 (300-500) 1.15 ± 0.28 (0.67-1.7) 587 ± 116 (400-750) 1.31 ± 0.27 (0.84-1.8) 24 h Post infusion 712.4 ± 133 (500-950) 0.79 ± 0.2 (0.48-1.2) 780 ± 121.2 (600-1050) 0.87 ± 0.15 (0.6-1.16) Total amount/24 h 1650 ± 303 (1070-2200) 0.91 ± 0.22 (0.6-1.32) 1865 ± 281S (1400-2300) 1.04 ± 0.16S (0.7-1.31) Creatinine clearance rate (ml/min) 101 ± 27.4 (49.3-129) 122.16 ± 36.06S (62.3-186.5) S = statistically significant difference   Table IV- Changes in urine output and creatinine clearance rate in patients according to group  

Discussion

Thermal injury disrupts normal haemostasis and sets off a cascade of events. Cellular alterations and the release of inflammatory mediators cause hypovolaemic shock. Accurate burn size estimation, correct choice of type of fluid, and appropriate subsequent fluid administration are mandatory for the improvement of survival of patients with extensive burn injuries.11

Hydroxyethyl starches are derivatives of amylopectin, which is widely used for plasma volume expansion in patients with shock, sepsis, burns, or trauma. These solutions, especially when used at a concentration of 10%, may be retained better in the circulation in capillary leak syndromes, and may reduce reperfusion injury.14 Additional advantages of Haes solutions are the low incidence of anaphylactic reactions and their efficiency in preventing venous thrombosis, both of which make them a better choice than dextran or gelatin. The effects of the early administration of Haes solutions on coagulation mechanisms have caused some concern, but they do not appear to have deleterious consequences.15

Our data suggested that the use of standard vital signs such as blood pressure, pulse rate, and urine output failed to give early warning of the inadequacy of fluid replacement in burn patients, since there was a non-significant (p > 0.05) difference between the two groups with regard to blood pressure and HR. This result was consistent with that of Holm et al.,2 who concluded that standard vital signs may be invalid as an outcome related to resuscitation goals and are too insensitive to ensure appropriate fluid replacement.

With regard to urine output, there was a significant increase (p <0.05) in the total amount of urine output in Haes-group patients compared with that in LR patients. However, during the study period, urine output in Haes-group patients increased significantly (p < 0.05) compared with output in LR patients only during the first 6 h of infusion therapy. These results are consistent with those of Nagy et al.,16 who reported that urinary output showed a significant increase within 2 h of infusion of 500 ml of Haes-Steril.

There was a significant increase (p <0.05) in COP (13% and 23%) and in CI (13% and 23%) in the LR and Haes groups, respectively. CVP increased significantly (p < 0.05) in Haes-group patients (42.3%) compared with values in LR patients (25%). These results were consistent with those of Waxman et al.17 and Hankelin et al.,18 who found that Haes-Steril 10% produced a significant increase in CI, CVP, and left and right ventricular stroke work index, but that LR solution improved CVP and did not significantly improve other haemodynamic variables.

The study revealed a significant increase (p <0.05) in VO2 in Haes-group patients compared with that in patients in the LR group. This result is consistent with those of Waxman et al.17 and Hankelin et al.,18 who reported that haemodynamic and oxygen transport variables were improved in colloid trials, whereas LR solution did not improve the patients’ cardiopulmonary conditions, and that while all colloids produced an improvement in the patients’ haemodynamics and oxygen transport conditions, a statistically significant improvement could be demonstrated only during infusion of Haes 10%.

The data obtained show a decreased serum lactate level in the two groups studied (34.2% reduced in the LR group and 32.3% in the Haes group). Serum lactate level showed a non-significant decrease (p > 0.05) in the Haes group compared with the LR group throughout the study period. There was a negative significant correlation between serum lactate and CI in both groups (r = -0.52 and -0.505, p <0.019 and 0.023, respectively). Also, there was a negative significant correlation between serum lactate and VO2 (r="-0.683" and 0.612, p="0.001" and 0.004) in both the LR and the Haes group, respectively. These results were consistent with those of Holm et al.,2 who reported that initial serum lactate levels as well as the ability to clear elevated lactate were found to be significantly associated with a higher CI and oxygen delivery rate.

The study showed a significant decrease (p <0.05) in the plasma ET-1 level at the end of the period. The plasma ET-1 level decreased by 39.6% in LR patients and by 44.5% in the Haes group. There was a significant decrease (p < 0.05) in plasma ET-1 in Haes-group patients compared with the level in LR patients, 12 h after initiation of fluid therapy. A negative significant correlation was found between plasma ET-1 levels and CI in both groups (r="-0.65" and 0.652, p="0.002," respectively). The results obtained were consistent with those of Youn et al.20 and Huribal et al.,21 who reported that ET-1 was usually detected in high concentrations a few hours post-burn and started to decline after initiation of fluid replacement therapy.

Serum urea decreased non-significantly (p > 0.05) in both the LR and the Haes groups during the study period. However, serum creatinine showed a significant decrease (p <0.05) in Haes-group patients during the study period compared with the level in patients in the LR group. The decrease in serum creatinine in patients in the study groups was manifested as a significant increase (p < 0.05) in the creatinine clearance rate in both groups; however, the creatinine clearance rate increased significantly (p < 0.05) in Haes-group patients compared with the rate detected in LR patients. The creatinine clearance rate showed a positive significant correlation with CI in both groups (r="0.518" and 0.571, p="0.019" and 0.011). These results were consistent with those of Köhler et al.,22 who reported that an infusion of 500 ml of Haes-Steril 10% increased the creatinine clearance rate within afew hours.

On the basis of the above results, we can conclude that Haes-Steril, a colloidal plasma volume substitute, can increase cardiac output and oxygen transport values and improve organ function and the overall haemodynamic situation in patients with hypovolaemic burn shock. We can also conclude that the serum lactate level correlates well with the improvement of haemodynamic parameters and can be used as a predictive parameter for such improvement.

RESUME. Les lésions thermales provoquent beaucoup de complications et de décès. La plupart des patients brûlés présentent une réduction du volume plasmatique et une augmentation du fluide interstitiel. On emploie le Haes-Steril dans la thérapie expansive pour la substitution de volume à moyen terme afin d’obtenir une amélioration plus rapide et plus profonde des variables hémodynamiques. Dans cette étude les Auteurs ont confronté les effets de la fluidothérapie aiguë avec l’emploi de la solution de Ringer lactatée (RL) et le Haes-Steril 10% sur les variables hémodynamiques, le volume d’oxygène consommé et la fonction rénale des patients brûlés. L’étude comprenait 40 patients atteints de brûlures dans plus de 15% de la superficie corporelle totale divisés en deux groupes qui ont reçu ou la solution RL ou le Haes-Steril 10%. La comparaison des résultats des deux groupes étudiés indiquait une différence non significative (p > 0.05) dans le rythme cardiaque et la tension artérielle moyenne et montrait aussi une augmentation significative (p <0.05) de la pression veineuse centrale, du débit cardiaque, de l’indice cardiaque et du VO2 dans les patients du groupe Haes par rapport aux patients du groupe RL. Ces niveaux du lactate sérique et d’endothéline plasmatique-I étaient réduits dans les deux groupes à la fin du période de l’étude et étaient corrélés en manière significative avec un indice cardiaque augmenté. La créatinine sérique diminuait en manière significative et le taux de la clearance de la créatinine augmentait dans les patients inclus dans le groupe Haes par rapport aux patients du groupe RL. Les Auteurs concluent que le Haes-Steril peut améliorer la situation complessive hémodynamique des patients atteints de brûlures et que la créatinine sérique peut être utilisée comme facteur de prédiction de l’amélioration.

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