1 Department of Nephrology, stanbul School of Medicine,
stanbul, Turkey,
2 Department of Nephrology, Cerrahpasa School of Medicine,
stanbul, Turkey,
3 Renal Disaster Relief Task Force, Renal Division, University Hospital, Ghent, Belgium,
4 Department of Nephrology, Marmara School of Medicine,
stanbul, Turkey,
5 Department of Nephrology, Uluda
School of Medicine, Bursa, Turkey,
6 Department of Nephrology, Göztepe Social Security Hospital,
stanbul, Turkey,
7 Department of Surgery, Osman Gazi School of Medicine, Eski
ehir, Turkey,
8 Department of Nephrology,
stanbul School of Medicine,
stanbul, Turkey,
9 Department of Nephrology, Ankara Numune Hospital, Ankara, Turkey,
10 Department of Nephrology, Gazi School of Medicine, Ankara, Turkey and
11 Renal Disaster Relief Task Force European Branch, University Hospital, Ghent, Belgium
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Abstract |
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Methods. Within the first week of the disaster, specific questionnaires asking about 63 clinical and laboratory parameters were sent to 35 reference hospitals that were treating the victims. Of the registered 639 victims, 423 were admitted within the first 3 days of the disaster; the admission laboratory data of these 423 patients are the subject of this analysis.
Results. In the 423 patients (233 males, mean age 31.3±14.4 years), time under the rubble was 10.7±10.4 h. Mean values at admission were as follows: serum potassium 5.4±1.3 mEq/l, creatine phosphokinase 58205±77889 IU/l, albumin 2.6±0.7 g/dl, phosphorus 5.2±1.8 mg/dl, haematocrit 35.0±9.3%, leukocyte count 14945±6614/mm3, platelet count 183975±134012/mm3, blood urea nitrogen 55.1±28.9 mg/dl, and creatinine 3.9±2.3 mg/dl. Serum potassium above 6.5 mEq/l was noted in 91 patients (22.7%), an alarming finding for risk of fatal arrhythmias. Non-survivors were characterized by higher figures of serum potassium (P=0.001), as well as lower haematocrit (P=0.028), platelets (P<0.001), and serum albumin (P=0.003). In a multivariate analysis model of admission laboratory parameters, serum creatinine (P<0.001, o.r.=2.19), potassium (P=0.001, o.r.=3.64), and phosphorus (P=0.004, o.r.=1.78) predicted dialysis needs, whereas serum albumin (P=0.028, o.r.=0.23) and creatinine (P=0.039, o.r.=0.60) were related to mortality.
Conclusions. Admission laboratory data may be useful for predicting dialysis needs and survival chance of disaster victims. High incidences of some life-threatening abnormalities dictate the need for empirical therapy even in the field.
Keywords: acute renal failure; crush syndrome; dialysis; hyperkalaemia; laboratory findings; Marmara earthquake
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Introduction |
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Turkish nephrologists were faced with all these problems in August 1999 following a devastating earthquake which registered 7.4 on the Richter scale, and which struck the north-western part of the country. It resulted in 17480 deaths and 43953 injured according to the official statistics [6]; locally estimated mortality was even higher. The disaster also caused serious renal problems in many victims, directly contributing to trauma-related morbidity and mortality. Detailed descriptions of the disaster, including offers of help as well as epidemiological features of the renal patients, have been provided in other publications [7,8].
The present analysis concentrates on the admission biochemical data obtained of the victims who suffered from acute nephrological problems caused by this earthquake. By analysing this data, we aimed to search for the variables that influence morbidity and mortality, and which therefore might be helpful in planning interventions in the case of future disasters.
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Patients and methods |
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In the questionnaires, crush syndrome was defined as crush injury and systemic manifestations such as shock, acidosis, and ARF [9]. The term nephrological problem was defined as at least one of the following criteria at admission: oliguria (urinary output <400 ml/day), elevated levels of BUN (>40 mg/dl), serum creatinine (SCr) (>2.0 mg/dl), uric acid (>8 mg/dl), potassium (K+) (>6 mEq/l), phosphorus (P) (>8 mg/dl), or decreased serum calcium (Ca2+) (<8 mg/dl) in patients with crush syndrome. For hypoalbuminaemic victims, serum calcium levels were corrected. Corrected calcium values were calculated by an increase of 0.8 mg/dl of the measured serum calcium, for each 1.0 g/dl fall in the plasma albumin concentration beyond the normal levels of 3.55.0 g/dl [10]. The number of patients meeting the criteria to be included in the analysis has been described elsewhere [8].
Such a broad definition of nephrological problems, which considered more than SCr, urea, and urinary volume alone, was dictated by our concern to include all victims whose kidneys could not cope with the metabolic derangements of crush injury at that particular time.
Together with the questionnaire, pamphlets, including treatment guidelines (which also described the indications for dialysis), were distributed to the primary and secondary care centres. According to these guidelines, the indications for dialysis were: BUN >100 mg/dl, serum potassium >7 mEq/l, creatinine >8 mg/dl, blood pH <7.1, bicarbonate <10 mEq/l, and/or any clinical symptoms related to uraemia. More liberal indications or even prophylactic dialyses were applied in exceptional (mostly hypercatabolic) cases if this was considered necessary, e.g. when potassium rose very rapidly, even in the absence of hyperkalaemia [11]. All these indications were defined by the local physicians.
Of the registered 639 victims, 423 were admitted within the first 3 days of the disaster, and their admission laboratory data is the subject of this analysis. In the present study, raw and stratified data, statistical comparisons, and correlations will be provided about serum potassium, creatine phosphokinase (CK), albumin, creatinine, BUN, and blood-count parameters, since they are the main vital parameters related to renal function, muscular damage, and inflammatory and nutritional status. Considering other parameters (serum uric acid, calcium, phosphorus, alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase), which are more indirectly related to outcome, only raw data will be given because of space limitations. Detailed analyses, statistics, and discussion of the latter will be the subject of a separate study.
Statistical analysis
Descriptive statistics of all numeric variables including means, standard deviations, and minimum and maximum values, together with the proportions of all categorical variables were calculated. Two independent group means were compared by means of Student's t test for independent groups. If the group variances were not homogeneous as evidenced by Levene's test, P values were adjusted.
Admission laboratory findings were correlated with individual characteristics of the victims (age, time spent under the rubble, lapse between disaster and date of admission to reference hospitals), with clinical findings at admission and hospitalization (24-h urinary volume, mean blood pressure, body temperature, number of traumatized extremities, and duration of oliguria and polyuria), and with therapeutic interventions (numbers of fasciotomized and amputated extremities; blood, fresh frozen plasma (FFP), and human albumin transfusions; haemodialysis sessions, and days for haemodialysis support). Correlations between numeric variables were examined by Pearson simple correlation coefficients. The correlation between all other variables and the number of traumatized extremities, the number of extremity fractures, the number of extremities with fasciotomies and the number of amputated extremities were examined by Spearman non-parametric correlation coefficients. P values were not adjusted when multiple statistical tests were performed.
For the prediction of death and dialysis needs, univariate tests (Student's t test for independent groups for numeric variables) were performed first. Then logistic regression analysis was performed. Admission laboratory parameters (which included blood count, BUN, SCr, uric acid, potassium, corrected calcium, phosphorus, and albumin) were defined as predictors, all in one block (all as numeric variables). To select significant predictors, a forward selection method was used with entry cut-off value for a P value of 0.05 and a removal cut-off value for a P value of 0.10. Statistical significance was assigned to P values less than 0.05.
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Results |
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Overall, the most commonly traumatized parts of the body were the extremities, 790 extremity traumas being noted. Regarding other parts of the body, thoracic and abdominal traumas were noted in 69 and 41 cases respectively. Mortality rates of the patients who suffered from thoracic and abdominal traumas were significantly higher compared to the cases not complicated by these traumas (unpublished data).
Of the 603 victims whose admission data were specified in the questionnaires, 423 (70.1%) were admitted to reference hospitals within the first 3 days of the disaster, and hence became the subject of this analysis.
To summarize the clinical findings in the early-admitted victims at the time of admission, 61.4% were characterized by oliguria, 31.8% by high fever, and 35% by a mean blood pressure lower than 90 mmHg. Non-survivors were admitted with higher body temperature, lower mean blood pressure and lower urinary volume, while dialysed victims were characterized by higher mean blood pressure and lower urinary volume (unpublished data).
Mean age (31.3±14.4 years) and gender distribution (233 male, 190 female) of these early-admitted victims were not significantly different from those victims who were admitted later; however, in this particular group, the time spent under rubble was shorter (10.7±10.4 vs 14.5±21.0 h, P=0.03). In addition, the mortality rate of these first-admitted patients was higher than those who were admitted later (17.7% (75/423) vs 10.0% (18/180), P=0.016). On the other hand, there was no significant difference between the two groups for dialysis needs.
Biochemical parameters at the time of admission
Table 1 provides the means, standard deviations, and ranges of the admission laboratory parameters. Mean serum potassium at admission was 5.4±1.3 (range 2.413.3) mEq/l, and 91 (22.7%) patients were admitted with serum potassium levels above 6.5 mEq/l. The number of patients corresponding to various strata of serum potassium at the time of admission is provided in Figure 1
. Serum potassium level was higher in the victims who needed dialysis support (5.7±1.3, range 2.413.3 mEq/l vs 4.7±0.9, range 2.7±8.9 mEq/l, P<0.001) and in the non-survivors (6.0±1.7, range 313.3 mEq/l vs 5.3±1.2, range 2.48.4 mEq/l, P=0.001). Potassium levels correlated negatively with 24-h urine volume at admission (P<0.001, r=-0.251, n=360), and positively with CK (P<0.001, r=0.432, n=69), the number of traumatized extremities (P=0.004, r=0.142, n=401), fasciotomized extremities (P<0.001, r=0.173, n=401), blood transfusions (P=0.026, r=0.111, n=401), human albumin transfusions (P<0.001, r=0.201, n=401), number of haemodialysis sessions (P<0.001, r=0.243, n=401), and days of haemodialysis support (P<0.001, r=0.236, n=395).
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Of the 400 patients whose haematocrit values were recorded in the questionnaires, 116 (29%) and 25 (6.3%) were admitted with haematocrit levels lower than 30% and equal to or above 50% respectively. Stratified data for admission haematocrit and corresponding numbers of patients are shown in Table 2C.
Considering dialysis needs and final outcome of the patients, leukocyte count was higher (P=0.002) and platelet count was lower (P=0.006) in the dialysed victims, while haematocrit (P=0.028) and platelets (P<0.001) were lower in the non-survivors (Table 3).
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Mean BUN level was 55.1±28.9 (range 9269) mg/dl at admission. Almost half of the patients were admitted with BUN levels between 40 and 70 mg/dl (Table 2D). This parameter was higher in the dialysed (58.6±28.8, range 13269 mg/dl) vs non-dialysed victims (45.4± 26.9, range 9149 mg/dl, P<0.001); no significant difference was observed between survivors and non-survivors. BUN levels correlated negatively with 24-h urinary volume at admission (P<0.001, r=-0.207, n=367) and positively with the time lapse between the disaster and the moment of admission to the reference hospitals (P=0.001, r=0.161, n=411), SCr (P<0.001, r=0.540, n=407), uric acid (P<0.001, r=0.233, n=240), potassium (P<0.001, r=0.204, n=400), and albumin (P=0.038, r=0.124, n=278), while borderline level of significance was observed with mean arterial blood pressure (P=0.051, r=0.098, n=394).
Mean SCr concentrations was equal to or more than 2.0 mg/dl in 334 (81.7%) of the 409 victims (Figure 1). This parameter was higher in the patients who were started on dialysis later during their evolution (4.6±2.2, range 0.516.1 mg/dl vs 2.3±1.5, range 0.37.8 mg/dl, P<0.001); however, no significant difference was noted between survivors and non-survivors. Admission SCr correlated negatively with the time period under the rubble (P=0.003, r=-0.159, n=339) and urinary volume (P<0.001, r=-0.313, n=367), while positive correlations were noted between serum potassium (P=0.001, r=0.168, n=400), phosphorus (P=0.002, r=0.206, n=217), days of oliguria (P<0.001, r=0.308, n=379), the number of haemodialysis sessions (P<0.001, r=0.277, n=409), and days on haemodialysis support (P<0.001, r=0.356, n=395) (Figures 2
and 3
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Discussion |
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In the present series, admission laboratory parameters of the victims who were admitted within the first 3 days of the disaster were analysed with the concern that laboratory parameters (especially the muscle enzymes) might have changed by time, as there were patients admitted to reference hospitals up to 1 month after the disaster. However, it should be stressed that even these results may not represent the exact laboratory profile of a disaster victim who has been just extricated from the rubble, since time lapse between disaster and admission to hospitals can blur the findings and even hours can have an impact on blood test results.
It has been reported that many victims experience dangerous hyperkalaemia at the disaster field [12]. Cardiotoxicity of hyperkalaemia is aggravated by hypocalcaemia, another laboratory abnormality that is also frequently noted in the crush syndrome [1]. Therefore, many casualties with extreme hyperkalaemia might have not been analysed due to pre-hospital fatality, and early prevention and treatment of this complication in the disaster field can save many lives. Data of the present series also support the rationale for initiating empirical therapy for hyperkalaemia with potassium exchange resins even before hyperkalaemia is detected, as has been suggested previously [12,13].
A rise of serum muscle enzymes, especially CK, is the most prominent and earliest laboratory feature of muscle injury. Different threshold values, from 500 to 3000 U/l, have been proposed as indicators of rhabdomyolysis [2,4,14]. Peak values are recorded immediately at admission or within the first 24 h after hospitalization [3,4]. Low values noted in this series may be the result of a steady decrease of serum levels of the enzyme by time.
As can be noted, the number of CK measurements provided in the present analysis was quite low compared to other parameters. The most important reason of this low figure is that only the records of university hospitals were taken into account for statistics, since in many public hospitals serum dilutions were not made during the analysis of serum CK, because of a heavy workload in the aftermath of the disaster.
Both high and low values of admission serum albumin can be expected during disasters. While dehydration at an early stage results in hyperalbuminaemia; malnutrition, inflammation, capillary leak, and fluid overload may cause hypoalbuminaemia at a later stage [11]. Opinions about the prognostic value of serum albumin levels at admission are controversial. Hyperalbuminaemia may be an ominous sign [14], because it indicates haemoconcentration and severe dehydration; on the other hand, since hypoalbuminaemia is related to a low serum 2-globulin, the carrier protein of myoglobin, a decrease of
2-globulin may result in a decreased binding of myoglobin, and hence increased nephrotoxicity [4].
In the present series, low serum albumin reflects a poor prognosis. Hypoalbuminaemia has previously been noted to be a risk factor of mortality in ARF of different aetiologies [15].
In the present series, 29% of the patients had haematocrits lower than 30%, while only 6.2% presented with levels higher than 50%. Low values of haematocrit may indicate either blood loss or haemodilution in the oligoanuric patients if they received large amounts of fluids. The latter mechanism may be a significant contributing factor, since from the second day of the disaster on, pamphlets of the ISN and the Turkish Society of Nephrology were provided to primary-care physicians advising early and energetic volume substitution [7]. In addition, the negative correlation between haematocrit and the time lapse between the disaster and admission may suggest that the patients who were admitted later had received more fluids. On the other hand, haematocrit values higher than 50% may indicate severe dehydration, as has been suggested previously [4,16]. The correlation between haematocrit and serum albumin may also indicate that these two parameters evolved in parallel, as well in dehydrated as in overhydrated states, and further corroborates the above-mentioned suggestion.
In the present series the majority of patients presented with leukocytosis, which might have been the result of rhabdomyolysis per se [13,17] or of accompanying infectious complications. Lower platelet counts were more frequently noted in the non-survivors and dialysed victims; this finding may point to disseminated intravascular coagulation (DIC), which is a possible complication of sepsis and rhabdomyolysis [13,18]. On the other hand, thrombocytopenia without DIC has also been reported in conjunction with rhabdomyolysis [18]. The negative correlation between serum CK levels and platelet count may also point to such a relationship.
The majority of the patients were admitted with elevated levels of BUN and SCr. A higher ratio of SCr/BUN has been suggested in patients with rhabdomyolysis, possibly because of the release of creatinine from damaged muscle cells [1,18,19]; nevertheless, not all authors confirm this hypothesis [14,20]. In the present series the ratio of SCr/BUN was 1/14.1 (3.9/55.1), which fits into the presumed physiological ratio of 1/1015 [10]. Therefore the possibility should be considered that creatinine generation is not increased in rhabdomyolysis. Alternatively, we suggest that in addition to a high production of creatinine, increased urea generation by the liver in these seriously traumatized and highly catabolic patients [10] may contribute to the maintenance of this physiological ratio.
These traumatized, surgical victims who are also (usually) poorly nourished in disaster conditions, represent typical hypercatabolic patients. Hypercatabolism is characterized by abnormal protein breakdown; therefore, by itself it contributes to the complications of rhabdomyolysis, especially hyperkalaemia as well as hyperphosphataemia, metabolic acidosis, and higher levels of nitrogenous waste products. In the present series, most of these features were characterized by higher needs of dialysis and mortality, underlying the importance of very close follow-up in disaster victims, and treatment of the complications as soon as possible; such a policy should be effective in preventing the metabolic consequences of hypercatabolism, and thus improving the final outcome.
To conclude, the Marmara earthquake was one of the most devastating disasters of this century and our experience covered one of the largest databases of simultaneous crush victims in disaster conditions. Since many victims were admitted to reference hospitals with potentially fatal hyperkalaemia, the first concern should be to treat or prevent this complication. The victims with hyperkalaemia, hyperphosphataemia, and high admission SCr are candidates for higher needs of dialysis, while non-survivors were characterized by hypoalbuminaemia and elevated SCr; therefore these patients should be followed up more closely. From the technical point of view, although rare, it was noted that some of the victims transferred from the disaster field received solutions containing potassium; therefore education of the primary care physicians for the treatment of crush syndrome is of vital importance. It is hoped that these data may be helpful in planning interventions in the case of any future disasters.
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Notes |
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References |
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