The Prediction of 28-Day Mortality in Crush Syndrome by Evaluating Lactate/Albumin Ratio in Patients Presented to the Emergency Department After an Earthquake
Abstract
Introduction: Crush syndrome (CS) is a primary cause of mortality among survivors following earthquakes. Determining discharge outcomes and mortality in cases of CS is critical for guiding management strategies. Biomarkers may be utilized to predict survival and mortality in CS cases early and accurately; however, those currently used are primarily intended for disease diagnosis.
Objectives: Considering that cases associated with impaired vital signs and organ perfusion show alterations in lactate, albumin, and the lactate/albumin (L/A) ratio, it was hypothesized that the L/A ratio could serve as a prognostic and mortality predictor in CS cases.
Methods: Following the February 2023 Kahramanmaraş earthquake, 1145 trauma patients presenting to the hospital emergency department were evaluated. Among these, 62 patients meeting the inclusion criteria were diagnosed with CS. Patient records were retrieved from archives and the hospital management information system. Anamnesis, physical examination findings, laboratory results, consultations, and discharge summaries were retrospectively analyzed.
Results: A total of 62 CS cases meeting the inclusion criteria were included in the study. Upon evaluating the patients’ initial lactate, albumin, and L/A ratio levels, lactate and L/A ratio levels were significantly higher in the deceased group compared to the survivors, while albumin levels were significantly lower (p = 0.018, p = 0.003, and p = 0.007, respectively). To predict 28-day mortality, a cutoff value of 4.35 was determined for lactate with 73.3% sensitivity and 66% specificity (AUC: 0.735). For the L/A ratio, a cutoff value of 1.2 was identified with 86.7% sensitivity and 70.2% specificity (AUC: 0.811). For albumin, a cutoff value of 3.35 was established with 66% sensitivity and 60% specificity (AUC: 0.721). K, lactate, and albumin showed low correlation with mortality, whereas the L/A ratio demonstrated a moderate correlation with mortality.
Conclusion: The serum L/A ratio can serve as a guide in diagnostic decision making for the prediction of CS in patients, and the blood L/A ratio has been found to be a biomarker that can be used to predict 28-day mortality in patients with CS.
1. Introduction
The increasing frequency of natural disasters due to global warming is a growing concern worldwide. Among these, earthquakes are primarily driven by rapid population growth in developing regions, the decline of rural living, and uncontrolled urbanization. This uncontrolled urbanization has led to greater losses during earthquakes, subsequent forced migration, and irreparable economic losses for affected countries [1]. The world has experienced major earthquake disasters at various times. In the most recent natural disaster, the 2023 Maraş-Hatay earthquake, 47,000 people lost their lives [2].
Injuries resulting from disasters can be critically important both during and after the event. The first aspect is health-related problems: these include conditions requiring immediate intervention at the time of the earthquake and treatment protocols that involve close monitoring afterward. Severe conditions develop in survivors trapped under collapsed buildings and immobilized for extended periods, one example being crush syndrome (CS). CS is a set of metabolic alterations caused by skeletal muscle damage severe enough to compromise cellular integrity and result in the leakage of cellular contents into the bloodstream [3]. CS is characterized as the systemic manifestation of significant, acute muscle injury [2]. It was first described by Bywaters and Beall in 1941. Nowadays, this condition is defined as crush injury and CS if there are systemic findings [4]. Complications such as acute kidney injury (AKI), which can be life-threatening, pose significant medical challenges for disaster victims. CS arises from direct physical trauma and compression of the human body, predominantly impacting the lower extremities. Asphyxia can result in severe orthopedic injury, compartment syndrome, hypotension, and organ failures like AKI [2]. The reported incidence of CS among earthquake survivors ranges from 2% to 15%, with mortality rates as high as 48%. CS patients may develop heart failure, renal dysfunction, shock, systemic inflammation, and sepsis [5]. For this reason, prehospital healthcare workers and emergency clinicians play a critical role in identifying CS. CS is not easy to diagnose and is challenging to treat. Particularly in disaster scenarios with mass casualties, such as earthquakes, the management of CS poses a significant problem.
It is known that cases with impaired vital signs and organ perfusion exhibit changes in lactate, albumin, and the lactate/albumin (L/A) ratio. These parameters can be used to predict survival and mortality in CS cases early and accurately; however, currently, they are primarily used for diagnostic purposes. It has been hypothesized that the L/A ratio may serve as a prognostic and mortality predictor in cases of CS.
2. Materials and Methods
2.1. Study Design and Setting
In this study, patients over the age of 18 who presented to the Emergency Department of Malatya Turgut Özal University Medical Center Training and Research Hospital due to earthquake-related injuries between February 6, 2023, and February 16, 2023, were retrospectively evaluated. This study commenced after obtaining local ethics committee approval on November 8, 2024 (Decision Number: 2024/160), and adhered to the principles of the Declaration of Helsinki.
2.2. Participants
A total of 19,348 admissions were recorded following the earthquake. After excluding cases meeting exclusion criteria, 1145 patients were evaluated. Of these, 62 were diagnosed with CS, 17 of whom were deceased, while 45 were discharged following treatment and follow-up. Patients younger than 18 years, those in cardiac arrest at the time of presentation, patients with incomplete hospital records, those with inaccessible identification information, and those admitted for nontrauma-related reasons were excluded from the study.
2.3. Data Collection
Patient files from the archives and the hospital management information system were retrospectively reviewed for trauma-related emergency department admissions. Anamnesis, physical examination findings, laboratory results, consultations, and discharge summaries were analyzed. Demographic data, injury sites, routine laboratory analyses (Abbott Architect c16000 analyzers (Abbott Diagnostics Inc., Lake Forest, IL, USA)), blood gas analysis (ABL 800 Flex® (Radiometer) blood gas analyzer), hospital admissions, clinical outcomes, treatments administered, and 28-day mortality data were recorded. Initial lactate and albumin levels of the cases included in the study were documented. The L/A ratio was calculated for CS cases, and its relationship with mortality was examined.
2.4. Statistical Analysis
Statistical analyses were performed using SPSS Version 26 (IBM, Armonk, New York, USA). The distribution of variables was assessed using visual methods (histograms and probability plots) and analytical methods (Kolmogorov–Smirnov/Shapiro–Wilk test). Numerical variables with a normal distribution were expressed as mean ± standard deviation, while those without a normal distribution were expressed as median (25th–75th percentile). Categorical variables were expressed as frequencies and percentages. For comparisons of numerical variables between independent groups, the Mann–Whitney U test was applied for nonparametric data, and Student’s t-test was applied for parametric data. For comparisons of categorical variables between independent groups, the chi-square test or Fisher’s exact test was used. ROC analysis was performed to predict mortality using lactate and L/A ratio. The area under the curve (AUC) and cutoff values for each parameter were calculated. Sensitivity and specificity values were determined to evaluate the diagnostic performance of each parameter. Bivariate correlations were analyzed using Spearman’s correlation analysis. A p value < 0.05 was considered statistically significant in all analyses.
3. Results
A total of 62 CS cases meeting the inclusion criteria were included in the study. Among these, 15 patients were deceased, while 47 survived.
Table 1 shows the relationship between the demographic, clinical, and laboratory findings of CS cases and 28-day mortality. The mean age of the alive group was 44.98 ± 22.66 years, whereas the mean age of the deceased group was 64.8 ± 16.6 years, with a statistically significant difference between the groups (p = 0.023). The Glasgow Coma Scale (GCS) score was 10.47 ± 4.03 in the deceased group and 13.72 ± 1.7 in the alive group, with a statistically significant difference (p < 0.001). Upon evaluating the patients’ initial lactate, albumin, and L/A ratio levels, lactate and L/A ratio levels were significantly higher in the deceased group compared to the survivors, while albumin levels were significantly lower (p = 0.018, p = 0.003, and p = 0.007, respectively). No statistically significant difference was observed in hemoglobin (Hb) or platelet levels between the groups (p > 0.05 for both); however, blood gas pH levels were found to be 7.21 (7.08–7.32) in the deceased group and 7.35 (7.3–7.39) in the alive group, with a statistically significant difference (p < 0.001). Additionally, potassium (K), aspartate transaminase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were significantly higher in the deceased group compared to the alive group (p = 0.002, p = 0.031, p = 0.021, and p = 0.041, respectively).
| Variables | Crush syndrome | ||
|---|---|---|---|
| Alive (47) | Deceased (15) | p value | |
| Age (year) | 44.98 ± 22.66 | 64.8 ± 16.6 | 0.023µ |
| Gender (F/M) | 27/20 | 8/7 | 0.78∗ |
| GCS | 13.72 ± 1.7 | 10.47 ± 4.03 | <0.001µ |
| Lactate | 3.91 ± 0.2.34 | 6.36 ± 3.39 | 0.018µ |
| Albumin (g/dL) | 3.64 ± 0.65 | 3.13 ± 0.5 | 0.007µ |
| CRP (mg/dL) | 5.46 (2.02–10.85) | 7.18 (1.93–14.86) | 0.17α |
| Creatinine (mg/dL) | 1.4 (0.86–2.24) | 2.11 (1.41–3.81) | 0.06α |
| Hemoglobin (g/dL) | 13.98 ± 3.48 | 13.49 ± 2.4 | 0.385µ |
| Platelet (× 103/mm3) | 259.28 ± 84.18 | 235.8 ± 113.18 | 0.279µ |
| Sodium (mmol/L) | 138.68 ± 4.32 | 140.33 ± 3.98 | 0.7µ |
| Potassium (mmol/L) | 4.64 ± 0.85 | 5.49 ± 1.07 | 0.002µ |
| pH (mmol/L) | 7.35 (7.3–7.39) | 7.21 (7.08–7.32) | <0.001α |
| AST (U/L) | 108 (46–274) | 250 (134–467) | 0.031α |
| ALT (U/L) | 51 (34–114) | 137 (67–236) | 0.021α |
| LDH (U/L) | 4.6 (4.1–5.2) | 4.3 (4.05–4.7) | 0.041α |
| L/A ratio | 1.07 ± 0.62 | 2.0 ± 1.0 | 0.003µ |
- Note: ALT = alanine aminotransferase; AST = aspartate transaminase; LDH = lactate dehydrogenase. Statistically significant values are in bold.
- Abbreviation: CRP = C-reactive protein.
- μStudent t-test was used for normally distributed data, and results are presented as mean ± SD.
- αMann–Whitney U test was used for nonnormally distributed data, and results are presented as median (25–75 percentile).
- ∗Gender variable was analyzed by the chi-square test.
To predict 28-day mortality, ROC analysis was performed for lactate and the L/A ratio in all patients. The ROC curve analyses of lactate and the L/A ratio in CS patients are presented in Table 2. To predict 28-day mortality, a cutoff value of 4.35 was determined for lactate with 73.3% sensitivity and 66% specificity (AUC: 0.735). For the L/A ratio, a cutoff value of 1.2 was identified with 86.7% sensitivity and 70.2% specificity (AUC: 0.811). For albumin, a cutoff value of 3.35 was determined with 66% sensitivity and 60% specificity (AUC: 0.721) (Figure 1).
| ROC curve analyses | |||||
|---|---|---|---|---|---|
| Risk factor | AUC (95%) | Cutoff | p | Sensitivity (%) | Specificity (%) |
| Lactate | 0.735 (0.584–0.887) | 4.35 | 0.006 | 73.3 | 66 |
| Albumin | 0.721 (0.591–0.85) | 3.35 | 0.011 | 66 | 60 |
| L/A ratio | 0.811 (0.686–0.936) | 1.2 | ≤ 0.001 | 86.7 | 70.2 |
- Abbreviation: L/A ratio = lactate/albumin ratio.
The correlation between biochemical values and mortality is presented in Table 3. Potassium (K), lactate, and the L/A ratio showed a positive correlation with mortality, while albumin demonstrated a negative correlation (r = 0.382, p = 0.002; r = 0.375, p = 0.003; r = 0.485, p ≤ 0.001; r = −0.337, p = 0.007, respectively). K, lactate, and albumin showed low correlation with mortality, whereas the L/A ratio demonstrated a moderate correlation with mortality.
| Mortality | ||
|---|---|---|
| K | r | 0.382 |
| p | 0.002 | |
| Ast | R | 0.103 |
| P | 0.423 | |
| Alt | r | 0.178 |
| p | 0.163 | |
| LDH | r | 0.022 |
| p | 0.863 | |
| Lactate | r | 0.375 |
| p | 0.003 | |
| Albumin | r | −0.337 |
| p | 0.007 | |
| L/A ratio | r | 0.485 |
| p | ≤ 0.001 | |
- Note: K, potassium; Ast = aspartate transaminase; Alt = alanine aminotransferase; LDH = lactate dehydrogenase.
Trauma mechanisms and treatment in CS cases are given in Table 4.
| Alive n (%) | Deceased n (%) | |
|---|---|---|
| Trauma | ||
| Head trauma | 2 (50) | 2 (50) |
| Thoracic trauma | 18 (78.3) | 5 (21.7) |
| Spinal trauma | 4 (80) | 1 (20) |
| Pelvic trauma | 2 (50) | 2 (50) |
| Other | 18 (81.8) | 4 (18.2) |
| Treatment | ||
| Intubation | 0 (0) | 5 (100) |
| Tube thoracostomy | 3 (75) | 1 (25) |
| Fracture reduction | 5 (100) | 0 (0) |
| Fasciotomy | 9 (75) | 3 (25) |
| Cast-splint | 12 (80) | 3 (20) |
| Central venous catheter | 3 (50) | 3 (50) |
| Thoracotomy | 0 (0) | 1 (100) |
| Craniotomy | 1 (100) | 0 (0) |
| Laparotomy | 1 (100) | 0 (0) |
| Hemodialysis | 11 (73.3) | 4 (26.7) |
| Other | 21 (91.3) | 2 (8.7) |
4. Discussion
A disaster is defined as any natural event causing physical, economic, and social losses for individuals, disrupting normal life, and being unmanageable with local resources. An increase in natural disasters (floods, earthquakes, wildfires, landslides, etc.) has been observed globally in recent years. One of the most devastating and deadly events in recent times was the earthquake that occurred in Türkiye in February 2023. The earthquake caused the deaths of approximately 47,000 people, impacted 11 cities, and led to the collapse of thousands of buildings. Among the survivors trapped under the rubble, one of the leading causes of subsequent death is CS. Patients diagnosed with CS brought to a tertiary hospital in Malatya following the February 6, 2023 Kahramanmaraş earthquake, one of the most destructive in recent history, were evaluated. This study demonstrated that the L/A ratio is valuable in determining prognosis and mortality in CS.
Although the earthquake caused widespread destruction, the accompanying health problems created a significant burden for healthcare providers. Various injuries and patients presented to hospitals after the earthquake. Brain and spinal cord injuries frequently result in high mortality rates at the scene. Deaths due to internal organ, injuries including liver or spleen rupture, subdural hematoma, and pelvic fractures typically occur within the first few hours following the event. Rapid and effective treatment of these injuries can significantly reduce mortality rates. In-hospital deaths generally occur a few days to weeks later and are often due to CS, sepsis, disseminated intravascular coagulation (DIC), and multiorgan failure [6]. The incidence of CS among earthquake survivors has been reported as 2%–15%, with mortality rates reaching up to 48% [5]. Bywaters originally described CS while identifying trauma survivors who later died from renal failure [7]. CS is a clinical condition caused by prolonged compression of the limbs or torso, leading to ischemic necrosis of muscle tissue and electrolyte imbalances. The primary systemic manifestations result from traumatic rhabdomyolysis and the subsequent release of potentially toxic muscle cell components and electrolytes into the bloodstream, overloading the kidneys [8]. Several factors, including climate, poor construction materials, duration of entrapment, rescue team experience, and distance to medical treatment, influence the clinical course of CS.
Early death in CS typically results from cardiac arrhythmia caused by hypovolemia, metabolic acidosis, or hyperkalemia [9]. Additionally, death may occur from renal failure, acute respiratory distress syndrome (ARDS), DIC, sepsis, or electrolyte imbalances. Understanding the pathophysiology underlying CS is vital for appropriately managing affected individuals [10]. Reperfusion-induced rhabdomyolysis forms the basis of CS pathophysiology. Swelling and muscle necrosis can develop in the affected areas, followed by the release of myoglobin and potassium. These processes can lead to kidney damage, resulting in hyperkalemia and potential cardiac arrhythmias. All these processes exhibit significant clinical variability, depending on the size of the affected area and the duration of entrapment [11]. The diagnosis of CS can be made, particularly in crushed limbs, through repeated examinations and serial measurements of compartment pressure using a needle. A difference of < 20 mmHg between compartment pressure and diastolic blood pressure is considered the threshold value [12]. CS is the systemic expression of rhabdomyolysis caused by extended and continuous pressure on muscle tissue. It can lead to hypovolemic shock, acute kidney failure, compartment syndrome, hyperkalemia, hypocalcemia, and metabolic acidosis [13].
In CS patients, anaerobic glycolysis occurs due to reduced peripheral oxygenation, leading to lactate production. Elevated lactate levels have been associated with tissue hypoxia [14]. In current clinical practice, lactate levels are commonly used to detect tissue hypoxia; however, elevated lactate reflects more than just this characteristic. Numerous studies have proven that lactate levels are reliable parameters for diagnosing circulatory shock, assessing treatment, and predicting prognosis [15–17]. In CS cases, in addition to elevated lactate levels, creatine kinase (CK), LDH, AST, ALT, potassium, phosphorus, uric acid, and myoglobin levels are also elevated. However, these parameters have not been shown to have a prognostic value [18]. As a negative acute-phase protein, albumin levels indicate the intensity of inflammation. Studies indicate that albumin could act as an alternative indicator for mortality and prognosis [19]. It is particularly known that poor nutrition can result in decreased albumin levels [20]. In our study, instead of focusing on diagnostic parameters, we investigated the relationship between the L/A ratio and mortality and prognosis in CS cases. K and lactate showed low correlation with mortality, and L/A ratio showed moderate correlation with mortality. Furthermore, increased lactate and decreased albumin levels were correlated with 28-day mortality. Studies have demonstrated that the L/A ratio has better prognostic value compared to lactate alone [21]. Moreover, it was found that L/A ratios above 1.2 were valuable in predicting mortality, with 86.7% sensitivity and 70.2% specificity. Albumin demonstrated a low negative correlation with mortality, whereas the L/A ratio showed a moderate correlation.
Considering the significant disruption to patients’ physical integrity, along with the intense stress experienced due to being trapped under rubble or facing harsh living conditions post-earthquake, we believe that tracking stress parameters in these patients may impact their prognosis. For this reason, we deemed the examination of lactate and albumin appropriate. Studies have shown that the L/A ratio has superior predictive value compared to lactate or albumin alone, particularly in predicting mortality and hospital stay duration (discharge) in sepsis patients, with a sensitivity of 100% and specificity of 88% [22]. In our study, we found a significant difference in the L/A ratio between deceased patients and those who were discharged. Deceased patients were proportionally older. Additionally, creatinine and CRP levels were higher in deceased patients compared to those discharged. Deceased patients also had lower pH values in blood gas analyses and GCS scores.
Following the Marmara earthquake, the mortality rate due to acute kidney failure in CS cases was reported to be 15.2%. Approximately half of these cases were reported to require fasciotomy [23]. In our study, mortality was observed as an expected outcome in intubated CS cases and those requiring dialysis. Half of the deceased patients underwent fasciotomy treatment.
5. Limitations
In our study, 62 patients meeting the criteria were diagnosed with CS among those brought to the hospital due to the earthquake. Despite the high number of patients presenting after the earthquake, the number of CS diagnoses was relatively low. It is believed that the chaos management during the earthquake led to some patients being referred without a diagnosis, incomplete data entries, and early discharge requests from patients, contributing to the low numbers. As the study was retrospectively designed, CK levels obtained were identified as qualitative values, and thus, they could not be evaluated quantitatively.
6. Conclusion
Earthquakes are considered one of the most significant and inevitable disasters of nature. While it is impossible to prevent them, effective management strategies are vital to mitigate the resulting chaos and reduce loss of life. Laboratory parameters with significant proportional values in treatment could serve as early warning indicators in future disaster monitoring, guiding treatment adjustments and measures to enhance survival. The L/A ratio can be used as a valuable parameter in determining mortality and prognosis.
Conflicts of Interest
The authors declare no conflicts of interest.
Funding
No funding was received for this manuscript.
Open Research
Data Availability Statement
The data supporting the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
