Ten-Year Retrospective Analysis of Continuous Renal Replacement Therapy in Burn Patients: Impact on Survival and Timing of Initiation

Introduction

Managing burned patients is a multidisciplinary challenge for burn treatment units. Extensive burn injury leads to severe dysfunction of many organs, including the heart, lungs, digestive system, central nervous system, and kidneys, and often causes multiorgan failure (MOF). Studies conducted in Europe reported MOF as the most significant cause of death, triggered primarily by sepsis [1,2]. The mechanism is very complex, including a multifactorial cascade of pathophysiological consequences. According to an American study of MOF in a group of 821 children, those with renal and liver failure had the worst outcomes. The combination of impaired function of 3 or more organs was always fatal, with no therapeutic success. Early detection of MOF and effective intervention are essential to improve burn care [3].

The incidence of acute kidney injury (AKI) in burn patients is 9–50%. Despite recent increases in survival, post-burn AKI is associated with an extremely poor prognosis, with mortality >80% in those with severe disease. The main factors contributing to the occurrence of AKI are systemic inflammation and hemodynamic alterations [4]. Post-burn AKI is also caused by return of spontaneous circulation (ROSC), the massive release of endotoxins from damaged and non-viable tissues, and iatrogenic factors. AKI is simply defined as an abrupt decline in renal function, and over time, more specific criteria for renal homeostasis disruption to be quantified had to be developed, such as the Acute kidney injury (AKI) criteria, Risk, Injury, Failure, Loss and End-stage renal disease (RIFLE) score, Acute Kidney Injury Network (AKIN) criteria, and the Kidney Disease: Improving Global Outcomes (KDIGO) systems.

In 3–5% of burn patients, biochemical parameters of renal damage reach life-threatening values, requiring renal replacement therapy (RRT) [5,6]. Severe burns have become an independent risk factor in developing AKI, which occurs in approximately 30% of patients hospitalized in intensive care units (ICU) in burn treatment centers [7]. Numerous pathophysiological problems can accompany AKI, ranging from a brief increase in the concentration of biological markers of kidney damage to serious metabolic and clinical diseases. Currently, there is no specific treatment for post-burn AKI; therefore, supportive treatment is used, such as maintaining fluid and electrolyte balance, including RRT when indicated [8].

There is a wealth of research available on RRT, but many inconsistencies remain regarding burns. The variability in RRT implementation and lack of consensus on optimal treatment strategies for post-burn ARF are controversial and are a knowledge gap that needs to be filled.

Therefore, this study aimed to compile a 10-year summary of CRRT experience at a single burn center, including patient outcomes, effectiveness, and potential complications in the context of severe burns.

Material and Methods

ETHICAL STATEMENT:

This retrospective study adhered to the principles outlined in the Declaration of Helsinki. The Medical University of Lublin Ethics Committee accepted both the study’s protocol and the subject’s participation (reference number: KE: 0254-245/11/2023). Patient confidentiality was strictly maintained by anonymizing all data before analysis. Due to the retrospective nature of the study, the requirement for informed consent was waived by the Ethics Committee in accordance with local regulations.

PATIENT AND STUDY DESIGN:

The study included 723 patients admitted to the East Centre of Burns Treatment and Reconstructive Surgery’s Intensive Care Unit (ICU) from January 2010 to January 2021. Exclusion criteria included minor burns not requiring ICU care and specific dermatological disorders such as toxic epidermal necrolysis (TEN) and Lyell’s syndrome. We conducted a retrospective analysis of clinical data from 300 patients who required continuous renal replacement therapy (CRRT) (Figure 1).

Data collected at admission included age, sex, burn percentage and depth, and the mechanism of burn trauma. The predominant cause of the burn was determined based on medical history, while the Lund and Browder chart was used to estimate the size of the burn area. The diagnosis of inhalation injury was confirmed by direct examination of the airways (bronchoscopy) in each case. The Baux rule and SOFA score were used to assess burn severity and overall condition, respectively.

Sepsis was confirmed with documented infection (at least 2 sets of blood cultures were obtained, drawn from 2 separate venipuncture sites approximately 15 minutes apart). The diagnosis was based on American Burn Association sepsis criteria [9]. SIRS was defined when any 2 of the components were met: temperature above 38°C or below 36°C, heart rate >90 beats per minute (bpm), respiratory rate >20/min or maintenance of Paco2 <32 mmHg, white blood cells count >12 000/mm3 or <4000/mm3, or left shift defined as >10% bands [10]. All data were retrieved from the medical records database at the Burn Center.

Acute kidney injury (AKI) was diagnosed according to KDIGO criteria, defined as an increase in serum creatinine by ≥0.3 mg/dl within 48 hours, or ≥1.5 times baseline in the last 7 days, or urine output <0.5 ml/kg/h for 6 hours. AKI severity was categorized into 3 stages based on KDIGO criteria (Table 1). Additionally, renal compromise was classified according to RIFLE criteria into Risk, Injury, Failure, Loss, and End-Stage Renal Disease using either estimated glomerular filtration rate (eGFR) and serum creatinine (SCr) levels or urine output (UO) criteria (Table 2) [11,12].

CONTINUOUS RENAL REPLACEMENT THERAPY (CRRT):

CRRT was indicated for oliguria (urine output <0.5 ml/kg/h), acidosis (pH <7.15), hyperkalemia (potassium level >6 mEq/L), hyperlactatemia (lactate levels >2 mmol/l), azotemia (BUN >40 mg/dl), volume overload, and septic shock.

Before 2017, CRRT was performed using Ultraflux® AV1000S (Fresenius® Medical Care), and after 2017, Prismaflex® (Baxter®). Regional citrate anticoagulation (RCA) was used in all procedures, which were conducted in continuous veno-venous hemodialysis (CVVHD), hemodiafiltration (CVVHDF), or hemofiltration (CVVH) modes with a blood flow rate of 150 ml/min. Septic patients were treated with the Ultraflux® EMiC®2 filter (Figure 2).

Patients were categorized into early CRRT (initiated within 7 days of burn injury) and late (CRRT initiated more than 7 days post-injury) groups, following established protocols for identifying early and late AKI [13]. This division facilitated the comparison of outcomes based on the timing of CRRT initiation [14].

STATISTICAL ANALYSIS:

Statistical analysis was conducted using Statistica StatSoft Polska version 13.1. A P value of <0.05 was considered statistically significant. Descriptive statistics included mean, standard deviation, range, and percentages. The Shapiro-Wilk test assessed the normality of quantitative variables, and homogeneity of variance was evaluated using Levene’s and Brown-Forsythe tests. For normally distributed variables with homogeneous variance, the t test was employed. The chi-square test and logistic regression analyzed relationships between quantitative variables, while the Mann-Whitney test was used for non-normally distributed variables. Survival analysis was performed using the Cox regression model, and multivariate analysis utilized multiple regression models.

Results

STUDY GROUP CHARACTERISTICS:

The CRRT group accounted for 39% of all burn patients treated in the ICU in 2010–2020. The average age was 54 years, with a predominance of men (77%). Those qualified for CRRT had larger burns (41% vs 39%, OR 0.99; CI 0.96–1.02; P<0.005) and higher Baux scores (96 vs 92, OR 0.96; CI 0.92–0.99; P<0.05). The most common cause of burns was flame (72%) and over half had respiratory injury (56%). The group’s features are displayed in Table 3.

CRRT:

Only 51% of the burned patients had sepsis diagnosed, despite 87% of them presenting SIRS symptoms. AKIN and RIFLE higher scores were associated with sepsis (P<0.001). The laboratory results from the patients’ admission to the burn unit are listed in Table 4. Regarding continuous venovenous hemodialysis, 88% of patients underwent CVVHD and 12% underwent CVVHDF. The total mean dose of CRRT was 34.9 ml/kg/h. Burn patients who required CVVHDF had higher serum sodium levels (155 mmol/l vs 140 mmol/l, P<0.001) and lower potassium levels (3.78 mmol/l vs 4.29 mmol/l, P<0.001).

PROGNOSIS:

The mean time for survivors to receive CRRT after the burn trauma was 213 hours, compared to 52 hours for non-survivors (OR 1; CI 0.99–1, P<0.05). The type or the daily dose of CRRT did not differ between the survivors and non-survivors. The period of time between the burn and admission had no impact on mortality. The effects of the RIFLE and the AKIN ranks on survival were not proved by the Cox regression analysis. The multivariate logistic regression analysis showed that age (P<0.001; OR 1.48), TBSA (P<0.001; OR 1.22) LOS (P<0.001; OR 0.66), and inhalation injury (P<0.001; OR 1.8) were associated with survival. Table 5 presents other factors that affected mortality.

Early CRRT (initiated within 7 days of burn injury) was associated with a higher risk of death (P<0.005). Although the patients with early CRRT were younger, upon admission to the burn center they had greater burn area and higher Baux and SOFA scores (Table 6). Sepsis was diagnosed more frequently in the late CRRT group (P<0.001).

Discussion

STUDY LIMITATIONS:

Although the results of our study offer valuable insight into the use of continuous renal replacement therapy (CRRT) in burn patients, it is important to acknowledge several limitations that may impact the interpretation and generalization of the results. It is prone to selection bias because it was a single-center, retrospective study. Indications for CRRT were not clearly defined and the final decision was often subjective, made by the attending physician, which increases the risk of selection bias. Patients with CRRT are a highly diverse group. Regardless of the therapy itself, variations in the degree of injury, time needed to get to the burn treatment facility, volume of fluids transfused, need for intubation, early use of catecholamines or antibiotics, and prior medical issues all can have a distinct effect on the course of the patient’s treatment. The ability to apply our findings to the use of CRRT is limited by this constraint.

Conclusions

We report our 10-years’ experience with CRRT among severely burned patients. Age and extent of burn and inhalation injury were found to be significant predictors of survival in multivariate logistic regression analysis. We observed that burned patients requiring CRRT in the early period (up to 7 days after the burn injury) have worse prognosis. This may be due to the severity of the trauma in the early CRRT group (greater burn area and higher Baux and SOFA scores). Late CRRT is most often combined with septic complications, as sepsis was diagnosed more frequently in this group.

Prospective randomized multicenter controlled trials (RCTs) are needed to address a number of shortcomings of our retrospective study.