burns 33 (2007) 973–978
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Base deficit and lactate: Early predictors of morbidity and mortality in patients with burns D. Andel a, L.-P. Kamolz b,*, J. Roka b, W. Schramm a, M. Zimpfer a, M. Frey b, H. Andel a a
Department of Anesthesia and Intensive Care, Medical University Vienna, Vienna, Austria Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
b
article info
abstract
Article history:
Severe burn results in severe and unique physiological changes called burn shock. Histori-
Accepted 29 June 2007
cally, resuscitation has been guided by a combination of basic laboratory values, invasive monitoring and clinical findings, but the optimal guide to the endpoint of resuscitation still
Keywords:
remains controversial. Two hundred and eighty patients, who were admitted to our Burn
Lactate
Unit, were enrolled in this prospective study. Resuscitation of these patients was under-
Base deficit
taken according to the current standard of care. Parkland formula was used as a first
Outcome
approximation of acquired fluid administration rates; final fluid administration was adapted
Morbidity
in order to meet clinical needs. The aim of this study was to evaluate if plasma lactate (PL)
Mortality
and base deficit (BD) are useful early parameters to estimate the severity of a burn. One of the main objectives was to evaluate if BD and its changes due to fluid resuscitation adds additional information in comparison to the evaluation of PL alone. The results of this study indicate that initial PL and BD level (Day 0) are useful parameters to separate survivors from non-survivors. Moreover, an outcome predictor of shock and effective resuscitation could be defined by evaluating the changes of BD on Day 1. Normalization of the BD within 24 h is associated with a better chance of survival. One explanation for this phenomenon might be the fact that many burn patients are still sub-optimally resuscitated; in summary, measuring PL and BD may help to identify critically injured patients either for enhancement of treatment, or selection of therapeutic options. # 2007 Elsevier Ltd and ISBI. All rights reserved.
1.
Introduction
Severe burn results in rapid loss of intravascular volume due to development of a severe capillary leak [1]. Burn shock is initially hypovolemic in nature and is characterized by profound hemodynamic changes including decreased plasma volume, cardiac output, urinary output with consecutively increased systemic vascular resistance resulting in diminished peripheral blood flow [2]. Historically, resuscitation of trauma and surgical critical care patients is guided by a
combination of basic laboratory values, invasive monitoring and clinical findings [3–5]. Increasing resuscitation volume will lead to increased interstitial edema due to the capillary leak, thereby further deteriorating microcirculation [6]. Therefore, the optimal guide to the endpoint of resuscitation still remains controversial. Ideal markers of adequate resuscitation should detect under infusion as well as excessive infusion by monitoring tissue hypoxia; moreover, they should be predictive of patient mortality and outcome. Although not unanimously accepted, abnormal plasma lactate (PL) and
* Corresponding author. E-mail address:
[email protected] (L.-P. Kamolz). 0305-4179/$32.00 # 2007 Elsevier Ltd and ISBI. All rights reserved. doi:10.1016/j.burns.2007.06.016
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burns 33 (2007) 973–978
delayed PL clearance are reported to be precise markers of cellular hypoxia and shock [7–10]. The correlation between PL and clinical outcome has been well accepted in hemorrhagic and septic shock [9]. On the contrary to the existing evidence related to PL the real impact of base deficit (BD) in burned patients is still under discussion [11]. The aim of this study was to evaluate if BD is a useful parameter to assess morbidity and predict the outcome of burned patients. One further objective was to evaluate if BD contributes additional information to PL.
2.
Material and methods
2.1.
Clinical protocol
Two hundred and eighty patients, admitted to our Burn Unit due to burns within the past 2.5 years, were prospectively enrolled in this study. Initiation of the study protocol began immediately after admission. For each measurement, 1 ml of arterial blood was drawn into a heparin-coated syringe. PL and BD were analyzed using the Radiometer Copenhagen ABL 700 Series (Bronshoj, Denmark) at admission and on the following day. Automatically quality check controls were performed by the Auto Check quality control module, which is included in the Radiometer. Moreover to guarantee exact results our lab has implemented and maintains a Quality Management System, which fulfills the requirements of the ISO 9001:2000 standards. For resuscitation of these patients only Ringer’s solution was used according to the current standard of care. Parkland formula based on the burn size and body weight of the patient was applied as a first approximation of required fluid administration rates (6). Thereafter fluid administration was adapted in order to meet clinical needs with a target urinary output of 1 ml/kg bodyweight/h and a target mean arterial pressure of 65 mmHg. The target urinary output was slightly above the current guidelines for burn care (30–50 ml/h) [12] but below the fluid amount used in the study of Cartotto et al. [13] (1.2–1.3 ml/kg bodyweight/h).
2.2.
Data analysis
In order to evaluate the predictive validity of PL and BD at admission for estimating outcome of burned patients, a Binary Logistic Regression Analysis was performed. In order to demonstrate that the initial PL and BD value does not only reflect total body surface area burned (TBSA), the correlation between initial PL-TBSA and BD-TBSA was calculated. To evaluate if BD and PL are really useful for assessing the impact of different factors (e.g. additional inhalation injury) on the severity of a burn trauma, patients were divided into two groups: Group Inhal: patients with additional inhalation injury. Group non-Inhal: patients without additional inhalation injury. In order to demonstrate the effect of early BD changes (Day 0–Day 1), patients were divided into five groups based on their
initial BD value (Day 0) and their group related survival rate was noted and documented.
Group Group Group Group Group
3.
A: patients with a BD from 2 to 2 mmol/l. B: patients with a BD from 6 to 2.1 mmol/l. C: patients with a BD from 10 to 6.1 mmol/l. D: patients with a BD < 10 mmol/l. E: patients with a BD > 2 mmol/l.
Results
The age of the patients ranged from 15 to 95 years with TBSA ranging from 11 to 98%. Demographic data of the abbreviated burn severity index (ABSI) variables are presented in Table 1. The median time from trauma to admission was 96 min (interquartile range: 42–119 min) and there was no difference between survivors and non-survivors concerning this time interval. No patient died directly due to ‘‘burn shock’’. The death of all non-survivors occurred after the initial postburn phase and was caused by sepsis, inhalation injury or complications due to pre-existing diseases. None of the patients enrolled in the study received any kind of blood products during the study period. Within each group (Groups A–E) the patients were divided into two groups depending on their BD values at Day 1 after trauma. Details are presented in Table 2, showing that failure of normalization of BD is associated with worse outcome. We performed a Binary Logistic Regression Analysis to predict the outcome of patients with acute burn injury based on a consecutive series of 280 patients with mild to severe burns. Survivors were coded as 0, non-survivors as 1. The obtained logistic regression function pðdeathÞ ¼ 1= 1 þ eð2:41þ0:16BD0:325PLÞ is the probability of death, depending on the parameters BD and PL. Both parameters BD ( p = 0.0001) as well as first-PL ( p = 0.0001) have significant (Wald-test) influence on mortality. 22.8% of the variance (Cox and Snell) of mortality can be predicted by these two variables. e: 2.72. As an example for a patient with initial BD = 6 mmol/l and PL = 4 mmol/l the probability of death ( p(death)) would be 0.46. The correlation between initial PL-TBSA was 0.54 and between initial BD-TBSA was 0.48 (Table 3). Concerning the factor inhalation injury, patient details and results are presented in Tables 4 and 5, showing that inhalation injury is associated with higher PL, lower BD and worse outcome.
Table 1 – The demographic data of the abbreviated burn severity index (ABSI) variables of 280 patients
Total patients Survivor Non-survivor
F%
III8%
INHAL%
TBSA%
Age
33 31 35
62 52 86
34 24 56
29 23 20 16 48 25
50 21 46 20 59 22
F%: percentage of women; III8%: percentage of patients with full thickness burns; INHAL%: percentage of patients with inhalation trauma; TBSA%: percentage of total body surface area burned; AGE: age in years. Where applicable, data are presented as mean standard deviation.
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Table 2 – Base deficit (BD) on Day 0 (admission) and its changes on Day 1 and its related outcome BD related groups
BD on Day 0 mortality rate in %
Number of patients
Normalized BD on Day 1 mortality rate in %
Number of patients
Not normalized BD on Day 1 mortality rate in %
100 74 29 13 13
1 67 66 54 92
– 50 16 11 0
– 8 36 40 17
100 78 44 19 16
<10 mmol/l 10 to 6 mmol/l 6 to 2 mmol/l 2 to 2 mmol/l >2 mmol/l
Table 3 – Correlation coefficients between plasma lactate (PL), base deficit (BD) and total body surface area burned (TBSA) Correlation coefficient PL-TBSA BD-TBSA
4.
0.45 0.48
Significance NS NS
Discussion
The main finding of this study is that the PL as well as the BD are highly reliable outcome predictors. PL, BD and early BD changes are significant markers of shock and resuscitation. Both parameters add information for assessment of burn severity. They might help to improve therapeutic strategies, because the search for reliable global marker of shock, adequate resuscitation and outcome optimization has not yet ended. It is widely accepted that traditional markers, such as blood pressure and urinary output, are useful but do not sufficiently reflect global perfusion, regional microcirculation nor reversal of shock. Therefore, the importance of finding reliable indicators or parameters of perfusion is obvious, because Husain et al. have postulated that in today’s ICU, most deaths are secondary to multiple-organ failure, as an endstage of systemic inflammatory response syndrome (SIRS). SIRS in itself is most often a result of repeated or unresolved hypoperfusion [7]. It is well recognized that tissue ischemia plays a determining role in the development of systemic inflammation and organ failure. The ‘‘two-hit’’ model of multiple-organ failure recognizes that an initial trauma, such as shock, can ‘‘prime’’ the inflammatory response. Subsequently, a second ‘‘activating’’ hit, such as sepsis, may cause onset of multiple-organ failure [13–15]. Reviewing the literature concerning shock resuscitation beside PL and BD is as well frequently used to predict morbidity and outcome. Waisman et al. have demonstrated in 1993 in an animal investigation [16] that the best indicator
Number of patients 1 59 30 14 75
for quantification of acute blood loss was the change in BD; this value was superior to other 27 measured hemodynamic as well as laboratory values, including PL concentration. Qualitatively the same result was found by Rixen et al. [17]. Based on these findings it was demonstrated in several studies of polytrauma patients that BD at hospital admission is the best predictor for mortality [18–20]. All these data from more than 8000 polytrauma patients, i.e. mortality versus base excess at admission, were summarized by Zander [21]. Furthermore, in trauma patients the change in base excess from hospital admission to the ICU admission was demonstrated as a reliable prognostic indicator for a further change in mortality [21,22]. However, in none of the previous cited studies BD was evaluated as prognostic factor for burned patients. A severe burn puts patients in a very specific pathophysiological situation, not being comparable to patients suffering from severe trauma like for instance hemorrhagic shock [23,24]. Like no other trauma, severe burn leads to a high amount of borderline perfused tissue. Sambol et al. have postulated that many mediators are generated at the site of the burn wound contributing to organ dysfunction [25]. Moreover, the combination of a time-limited capillary leak and the possible development of compartment syndromes are very important co-factors in the development of SIRS [26]. This special situation might be the reason that the impact of BD in severely burned patients is still discussed controversially [14,27,28]. Specially in burned patients high resuscitation volumes are needed—thereby large amounts of chlorine are administered, potentially leading to hyperchloremic acidosis [29]. Therefore uncoupling PL and BD might be more likely in burned patients than in other traumatic shock patients [30]. These findings are in concordance with our results showing a correlation of PL to BD of only 0.57. In the acute phase of severe burn injuries in the majority of patients the mismatch of intravascular volume and intravascular fluid leads despite administration of large amounts of fluids to cellular hypoxia. On the other hand, excessive infusion regimes will not decrease malperfusion due to the resulting excessive edema
Table 4 – Details of 280 patients concerning additional inhalation injury Lactate
Inhal Non-Inhal
4.0 3.6 2.0 1.9
Base deficit
Mortality rate (%)
Day 0
Day 1
5 4.5 2.4 3.9
2.4 4.2 1.9 4.1
Lactate in mmol/l and base deficit in mmol/l. Where applicable, data are presented as mean standard deviation.
45 25
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Table 5 – Bloodgas parameters on Day 0 in patients with and without inhalation trauma Survivor
Inhalation trauma No inhalation trauma
Non-survivor
pH
paCO2
paO2
pH
paCO2
paO2
7.41 0.06 7.38 0.06
48 11 46 9
124 43 120 56
7.24 0.13 7.31 0.08
53 18 49 17
132 84 112 48
Data are presented as mean standard deviation. pH: arterial pH value; paO2: arterial oxygen partial pressure in mmHg; paCO2: arterial CO2 partial pressure in mmHg.
consequently reducing microcirculation and increasing diffusion distance for oxygen. This study examines diagnostic accuracy of PL and BD in reproducible predicting outcome in severe burn injuries a common clinical scenario of shock. In states of global or severe local hypoperfusion, or shock, when everywhere anaerobic metabolism predominates, changes in the PL and BD result. Furthermore, decreased liver perfusion caused by the presence of generally capillary leak potentially aggravated by invasive mechanical ventilation may result in even more pronounced PL increase due to decreased PL metabolism. The results of this study indicate that PL levels and BD levels on admission were able to separate survivors from non-survivors. A significant marker of shock and resuscitation was the change of BD within 24 h. In all patients, who reached normal BD values an increased survival rate was observed (Table 2). This study, to our knowledge, is the largest study performed on burned patients showing that PL and BD, as well as BD changes due to resuscitation, accurately predicts shock and the response to resuscitation. Several burn experts continue to argue that current burn shock resuscitation is adequate and that these abnormalities in PL and BD do not indicate poor resuscitation [11,29–32], but are simply reflecting burn size [11]. In spite of the fact, that the initial PL and BD levels seem to be only marginally influenced by the burn size and trauma severity (correlation: initial PL-TBSA ! 0.58, BDTBSA ! 0.48), BD levels of the following time periods are mainly influenced by reversing shock. As one of the basic requirements in reversing shock is the correction of the initial postburn capillary leak; the inability of normalizing PL and BD levels might simply reflect a persisting capillary leak, e.g. due to an early SIRS. Other reasons for persisting lactate and BD levels include an early posttraumatic liver-failure due to abdominal compartment, invasive ventilation in combination with low circulating volume state or pre-existing liver disease [33]. These postulations are according to Jeng et al. [11], who were not able to find recent studies which support the view that lactate only reflects burn size. However we have to take into account that blood values might not reflect local alterations in lactate or BD [34]. There are several studies published recently that support our hypothesis that burn patients are still sub-optimally resuscitated [11,29–32]. The main strength of this study is the significant degree to which plasma lactate and BD predicted burn mortality. These findings are partly according to Jeng et al. [11], but in contrast to them, more patients with considerable higher mean age were included in this study. Jeng et al. mentioned that the weakness of their study was the relatively small number of patients (49 patients) and the fact that they were not able to include patients over the age of 60 years with very large burns
(median age 40 years) [11]. Our findings indicate that patients in which BD could be normalized within 24 h had a better outcome (Table 2). Correction of the BD during burn shock resuscitation probably affects outcome by diminishing extend of organ dysfunction thereby leading to a lower mortality rate. Although the effects of correcting the BD during burn shock resuscitation are unknown, it is worth speculating how an abnormal BD might be normalized. In burned patients titration fluid resuscitation to normalize PL and BD levels may be a reasonable method to reduce burn mortality [35]. Moreover Cochran et al. stated that resuscitation should not be withheld from burn patients on the basis of any PL or BD value [36]. On the other hand there are preliminary data on ‘‘permissive hypovolemia’’ showing that fluid restriction below the Parkland Formula might lead to reduction of multiple-organ dysfunction by less edema fluid accumulation [37]. In this context the use of ‘‘small volume resuscitation’’ using hyperosmotic solutions in order to minimize tissue edema might be a promising approach [38,39]. However, although less volume is needed [40] the amount of skin-edema does not change significantly [41] and Huang et al. observed a negative effect on outcome [42]. As previously mentioned large amounts of chlorine are administered, potentially leading to hyperchloremic acidosis [29]. By using alternative resuscitation fluids beneficial effects on homeostasis and edema might be achieved [43–45]. Inadequate fluid resuscitation might present the ‘‘second hit’’ for burned patients [7] thereby prolonging the initial capillary leak, leading directly to SIRS and multiple-organ failure. From this point of view early death after burn injury might be considered as resuscitation failure. According to previously published data [46] inhalation injury has significant impact on outcome in severely burned patients. The percentage of non-survivors in patients with inhalation trauma was higher than in patients without additional inhalation injury (Table 4). These results are in accordance to the findings of Traber and coworkers [47–49].
5.
Conclusion
Our results indicate that BD and PL levels plainly predict survival or mortality in patients with burn injury. PL and BD are not equal in evaluation of burn shock. Severely injured patients develop an extreme BD which is rarely related to burn size, but rather seems to be a marker of malperfusion. The consequences of this impaired perfusion are an increased incidence of SIRS, with more frequent severe multiple-organ dysfunction. Although effects of correcting BD during burn shock resuscitation are unknown normalizing BD might lead
burns 33 (2007) 973–978
to better outcome. Therefore titration of burn resuscitation to nearly normalize PL and BD levels may be a reasonable method to reduce burn mortality. As outcome of burned patients is affected by a large number of modulating factors a multicentric prospective study would be necessary to confirm the hypothesis that correction of BD during burn shock resuscitation affects outcome due to less organ dysfunction and might lead to a lower mortality rate.
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