Elsevier

Journal of Critical Care

Volume 36, December 2016, Pages 200-206
Journal of Critical Care

Clinical Potpourri
Effect and mechanism of hydrocortisone on organ function in patients with severe burns

https://doi.org/10.1016/j.jcrc.2016.06.007Get rights and content

Abstract

Introduction

In patients with severe burns, resuscitation with large volumes of fluid is needed, partly because of an increase in capillary leakage. Corticosteroids might be beneficial by diminishing capillary leakage. This study aimed to assess in severely burned nonseptic patients whether hydrocortisone (HC) improved outcome and diminished capillary leakage.

Methods

Retrospective analyses of a prospectively collected database were performed, including 39 patients (age 52 [35-62] years, 72% male). Patients were divided based on HC therapy. First, in patients in whom HC was started late, that is when deteriorating (late; 5-12 days postburn) data before and after start of HC were compared. Second, patients in whom HC was started day 0 or 1 postburn (upfront; within 48 hours) were compared with patients who did not receive HC (control). Outcome was assessed as organ dysfunction by Denver Multiple Organ Failure (MOF) score and Sequential Organ Failure Assessment (SOFA) score. As markers for capillary leakage and hydration state, proteinuria, B-type natriuretic peptide (BNP), and fluid administration were assessed. Follow-up was 20 days postburn. Possible adverse effects including mortality were recorded. Repeated measurement regression analyses were performed using MLwiN.

Results

In the late group, Denver MOF and SOFA scores significantly decreased after HC (P < .001). Proteinuria tended to decrease (P = .13), BNP increased on the days HC was used (P < .001), and amounts of fluids diminished (P < .001). In the upfront vs control group, Denver MOF and SOFA scores (P < .001) decreased more quickly. Proteinuria (P = .006) and administered fluids decreased more rapidly (P < .001).

Mortality rate, numbers of positive blood cultures, incidence of pneumonia, and graft loss were similar in all groups.

Conclusions

Hydrocortisone treatment in severe burned patients without sepsis might improve organ dysfunction possibly because of a reduction in capillary leakage, as reflected by a decrease of proteinuria, an increase of BNP, and diminished fluid resuscitation volumes.

Introduction

In clinical practice, resuscitation of patients with severe burns remains difficult because of an increased capillary leakage on the one hand, and the drawbacks of fluid overload on the other hand. An important feature of burn trauma is massive loss of plasma from the intravascular to the extravascular space because of systemic microvascular leakage, triggered by inflammatory mediators [1]. Because of this capillary leakage in combination with vasodilatation and alterations in cardiac function, resuscitation with large volumes is necessary, but too large volumes of fluid may have negative consequences, including compartment syndromes, conversion of superficial into deep burns, and worsening of burn edema [1], [2]. Therefore, an intervention that can reduce capillary leakage is of great importance in burn care. Although controversial, in septic nonburn intensive care patients, treatment with corticosteroids reduces vasopressor dependency and may improve morbidity and mortality [3]. Two studies assessed corticosteroid treatment in septic burn patients [4], [5]. Their results suggested that corticosteroids may improve hemodynamics in septic burn patients who were catecholamine-dependent. However, only 1 study was available describing the results of treatment with corticosteroids in nonseptic burn patients [6], until very recently, another randomized controlled trial (RCT) was published evaluating the use of glucocorticoid treatment in patients with burns more than 70% of their total body surface area [7]. This last study demonstrated a decrease of levels of proinflammatory cytokines and a decrease in the incidence of pulmonary infection and stress ulcer, resulting in a shorter length of hospital stay. Unfortunately, no further data are available on outcome measures or on possible mechanisms of this potentially beneficial effect of corticosteroids in burn patients. One of the proposed mechanisms is decrease of capillary leakage [8]. Proteinuria and especially microalbuminuria have been described as markers of endothelial dysfunction c.q. systemic capillary leakage [9], [10]. B-type natriuretic peptide (BNP) is emerging as a potential marker of hydration state and has been suggested to increase if capillary leakage diminishes [11], [12], [13], [14]. Furthermore, we and others showed that BNP levels increase with fluid resuscitation [11], [13], [15]. In several studies, high levels of BNP predict poor prognosis and this thus may be related to excessive resuscitation. In contrast, we found that patients with burns high levels of BNP were associated with better outcome if combined with low proteinuria and lower volumes of fluid resuscitation [11]. These data together thus suggest that lowering capillary leakage can be a favorable mechanism to be used to optimize fluid resuscitation: increasing volume when necessary, but preventing excessive volume administration.

Based on these data, we hypothesized that in severely burned nonseptic patients treatment with hydrocortisone (HC) improves outcome (ie, organ failure) as a result of less capillary leakage, as reflected by a decrease in proteinuria and an increase in BNP, and thereby diminished amounts of administered fluids.

Section snippets

Patients and methods

This study involved patients admitted to the burn center of the Martini Hospital between January 2002 and October 2009. Eligible were patients with severe burns, that is with a total body surface area (TBSA) burned of more than 20% or a TBSA of more than 15% and inhalation injury. Excluded were patients younger than 18 years of age, with a life expectancy of less than 24 hours or a history of renal disease (to exclude proteinuria from other causes).

We distinguished 3 groups of patients based on

Results

Characteristics of the 3 different groups at time of admission are shown in Table 1. In the late group, HC was started when patients deteriorated, that is from day 5 to 12 (median 7) days postburn. Although these patients in the late group were considered stable at first and were only deteriorating 1 or 2 days before the start of HC, to analyze changes in time, data after the start of HC were compared with those of the 5 days before start of HC, as this was the longest period available in the

Discussion

In this retrospective study, we investigated the effects of HC in patients with severe burns without sepsis. The data support our hypothesis that HC may have a beneficial effect on organ function because of a decrease of capillary leakage.

Only 4 studies thus far have assessed the efficacy of corticosteroid treatment in burn patients [4], [5], [6], [7]. In 2 of these studies, septic burn patients who were catecholamine-dependent were analyzed. Fuchs et al [4] included 10 patients who received HC

Conclusion

Our data support the hypothesis that hydrocortisone in a setting of damage control strategy could be beneficial in patients with severe burns, even when no septic shock is present, as demonstrated by lower Denver MOF and SOFA scores.

Our data suggest a decrease in capillary leakage as possible mechanism for the beneficial effect of hydrocortisone, as hydrocortisone induced a decrease of proteinuria and increase of BNP, resulting in a diminished need for fluid resuscitation.

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgments

We thank Dr MAJ van Duijn, Associate Professor of Statistics in the Department of Sociology, Faculty of Behavioral and Social Sciences, University of Groningen, Groningen, The Netherlands for analyzing our data with MLwiN.

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