|Year : 2020 | Volume
| Issue : 2 | Page : 38-43
Positive cumulative fluid balance in the first 72 h is associated with adverse outcomes following heat stroke
Xiaoxue Yin, Gang Ye
Emergency Intensive Care Unit, Beijing Lu He Hospital, Capital Medical University, Beijing, China
|Date of Submission||10-Feb-2020|
|Date of Decision||07-Apr-2020|
|Date of Acceptance||02-Jun-2020|
|Date of Web Publication||06-Jul-2020|
Dr. Gang Ye
Beijing Lu He Hospital, Capital Medical University, Beijing
Source of Support: None, Conflict of Interest: None
Objective: The objective of the study was to determine the association between positive cumulative fluid balance following heat stroke (HS) and its impact on patient outcomes.
Methods: A retrospective chart review of HS patients admitted to the emergent intensive care unit (ICU), Beijing Lu He Hospital, Capital Medical University, from 2015 to 2018 was conducted.
Results: Forty-nine surviving HS patients met the inclusion criteria. Patients were divided into two groups based on the median duration of mechanical ventilation (MV). Patients with MV for more than 6 days were placed in the longer length of the MV group. Patients with MV for <6 days were placed in the shorter MV group. There were significant differences between the two groups regarding the fluid balance on day 2 (3040 ml vs. −533 ml, P = 0.017) and persistent cumulative fluid overload in the first 72 h (6112 ml vs. −46 ml, P = 0.04). Patients with a higher cumulative fluid overload in the first 72 h were more likely to receive a longer duration of MV (10.7 days vs. 3.2 days, P < 0.001) and ICU length of stay (22.5 days vs. 6.2 days, P < 0.001). Spearman analysis of fluid overload in the first 72 h and MV time showed that the correlation coefficient was 0.662. Binary logistic regression analysis showed that the positive cumulative fluid balance in the first 72 h (odds ratio [OR] = 1, 95% confidence interval [95% CI] = 0.99–1.01] and alanine aminotransferase (OR = 0.978, 95% CI = 0.95–0.99) were both independent risk factors for prolonged MV in patients with HS (P = 0.025, P = 0.026). There were also differences between groups regarding creatine kinase-MB (P = 0.01) and Glasgow Coma Scale scores (P = 0.033). The patients with a higher cumulative fluid overload in the first 72 h had larger sequential organ failure assessment cores. Based on the receiver operating characteristic analysis, the cumulative fluid overload in the first 72 h predicted the need for invasive MV with the area under the curve of 0.869 (P < 0.0001, 95% CI: 0.779–0.958) at a cutoff value >1685 ml (sensitivity: 86%; specificity: 78%).
Conclusions: Fluid overload in the first 72 h was a predictor of prolonged MV and ICU length of stay in surviving HS patients. Maintaining cautious about fluid resuscitation for HS patients may be critical for improving patient outcomes.
Keywords: 72 h, heat stroke, mechanical ventilation, persistent cumulative fluid overload
|How to cite this article:|
Yin X, Ye G. Positive cumulative fluid balance in the first 72 h is associated with adverse outcomes following heat stroke. Environ Dis 2020;5:38-43
| Introduction|| |
Heat stroke (HS) is a life-threatening condition characterized by a body core temperature (Tc) of more than 40° or with central nervous system (CNS) dysfunction. Two types of HS have been identified: one occurs with exposure to a high environmental Tc and is called nonexertional HS and the other results from strenuous exercise and is termed exertional HS. Thermoregulatory failure and an exaggerated acute-phase response may lead to disseminated intravascular coagulation (DIC) and multiple organ dysfunction syndrome (MODS). Mortality ranges from 10% to 64% and increases with delays in patient cooling.,
Currently, no effective well-defined treatment measures are available to curb the deteriorating condition of HS patients. HS patients may suffer from severe electrolyte losses, thus timely and effective fluid resuscitation is essential. Rapid and effective cooling is the basis of treatment unless the patient requires cardiopulmonary resuscitation., The usual practice is to control the target temperature from 38.5°C to 38.0°C to reduce the risk of clinical deterioration. Early investigations regarding the standard treatment of HS included surface cooling methods combined with rapid intravenous infusion of 3–4 L of crystalloids., Hongjun et al. reported that aggressive fluid resuscitation needs to be performed on HS patients enrolled in the intensive care unit (ICU). Conversely, some researchers have put forward the concept of more moderate fluid resuscitation in the early stage of HS, and the study suggested that during acute cooling treatment, caution should be exercised when providing intravenous fluids of more than 1 L to HS patients. They thought that rehydrating patients with high central venous pressure heavily may allow them to develop acute heart failure and pulmonary edema.
As such, we designed the study to investigate the relationship between different fluid resuscitation strategies in HS survivors and their prognosis. Specifically, we investigated whether liquid overload was associated with a longer duration of mechanical ventilation (MV) and additional complications.
| Methods|| |
Setting and study population
The study was conducted at the emergent ICU (EICU), Beijing LuHe Hospital, Capital Medical University. Eighty-two cases of patients with severe heat stoke admitted in our department from July 2015 to July 2018 were included, 33 patients were excluded, 27 patients dead, 3 transferred, 1 giving up treatment, and 2 nonintubated. HS survival patients were divided into two groups based on the median duration of MV. Patients with MV for more than 6 days were placed in the longer length of MV (LLMV) group. Patients with MV for no more than 6 days were placed in the shorter MV (SMV) group. Forty-nine mechanically ventilated HS patients were divided into the LLMV group (17 cases) and the SMV group (32 cases). Schematic of patient selection is shown in [Figure 1].
After admission to the ICU, all patients were equipped with sterile thermometer catheters to monitor their bladder temperature. Cooling by alcohol sponge bath, carpet and ice compress bag, or continuous renal replacement therapy was started. The cooling was stopped when the Tc of the patient dropped to 38°C. The initial fluid resuscitation goal was to achieve a mean arterial pressure of 65 mmHg or higher or to decrease lactate levels. Recovery after 24 h was not standard. Any further resuscitation was performed by an experienced clinician.
Statistical analysis was performed on the data of all patients during hospitalization. The gender, age, body weight, body Tc, duration of hyperthermia, and EICU length of stay were recorded. The worst clinical biochemical indexes were extracted from patient records within 24 h of EICU admission. The fluid overload (fluid overload = daily input − daily output (milliliters) on day 1, day 2, day 3, and in the first 72 h was determined for both study cohorts and the sequential organ failure assessment (SOFA) scores. We derived an optimum threshold of cumulative fluid overload for predicting longer MV. The optimum threshold was defined by receiver operator characteristic (ROC) curve analysis followed by Youden's J statistic, which simultaneously maximizes the sensitivity and specificity of the categorization.
SPSS 22.0 statistical software (SPSS 22.0; IBM, Chicago, IL, USA) was used for the statistical analysis. Data were expressed as the frequency and percentage for categorical variables and the mean ± standard deviation for continuous variables. Continuous variables were indicated as median (25%–75%) and compared through Mann–Whitney U-test. Categorical variables were indicated as number (%) and compared through Fischer's exact test. All statistical tests were two-sided and significance was defined as P < 0.05. Baseline correlations were assessed by Pearson or Spearman correlation coefficients. Receiver operating characteristic (ROC) analysis was performed to detect the sensitivity and specificity of the test.
| Results|| |
A total of 49 HS patients from the original 82 patients were included in the study [Figure 1]. Patients' demographic data and clinical data were recorded and analyzed [Table 1]. Forty-five patients were building workers, and baseline patient characteristics were similar. MV duration and EICU length were statistically significant between the two groups (all P < 0.001). Glasgow Coma Scale (GCS) score was statistically significant between the LLMV and SMV groups (P = 0.033). In addition, a statistically significant relationship between the two groups was also observed in alanine aminotransferase (ALT) and creatine kinase-creatine phosphokinase isoenzyme (CK-MB) levels (P = 0.013, P = 0.01). No statistically significant relationship between the two groups regarding other clinical biochemical indexes was identified. (all P > 0.05). A statistically significant trend was evident in fluid overload on day 2 and persistent cumulative fluid overload in the first 72 h between the two groups (P = 0.017, P = 0.04). No statistically significant trend was evident in fluid overload on day 1 and day 3 [Table 1] and [Figure 2]. Spearman analysis of fluid overload in the first 72 h and MV time showed that the correlation coefficient was 0.662, the correlation coefficient between CK-MB and MV time was 0.643, and between ALT and MV time was 0.491. Binary logistic regression analysis showed that the positive cumulative fluid balance in the first 72 h (odds ratio [OR] = 1, 95% confidence interval [95% CI] = 0.99–1.01) and ALT (OR = 0.978, 95% CI = 0.95–0.99) were both independent risk factors for prolonged MV in patients with HS (P = 0.025, P = 0.026). In a post hoc analysis, all SOFA measurements during the first 72 h between two groups were taken into account. No statistical significance was observed on day 1. SOFA scores were statistically significant between the LLMV and SMV groups on day 2 (P = 0.021) and day 3 (P = 0.002) [Table 2]. It has been found that fluid overload was notably higher among patients in the LLMV group in the first 72 h. The 72 h cumulative fluid overload values were used as a potential risk factor to predict weaning from ventilation. Based on the ROC analysis, the optimum threshold of cumulative fluid overload was predictive of invasive MV with an area under the curve of 0.869 (P < 0.0001, 95% CI: 0.779–0.958) at a cutoff value >1685 ml (sensitivity: 86%; specificity: 78%) [Figure 3].
|Table 1: Comparison of clinical biochemical indexes and clinical data affecting patients' duration of mechanical ventilation|
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|Figure 2: Mean cumulative fluid overload over the first 5 days of emergent intensive care unit stay (longer length of mechanical ventilator group vs. shorter mechanical ventilator group). X-axis represents the days 1–5 for patients admitted to the hospital. The y-axis is the mean cumulative fluid overload per day in each group in the first 5 days of emergent intensive care unit stay. Mean cumulative fluid overload of longer length of mechanical ventilator group becomes significantly higher than those of shorter mechanical ventilator group on day 2|
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|Table 2: Comparison of sequential organ failure assessment scores for the 1st 3 days between the two groups|
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|Figure 3: Receiver operating characteristic for the optimum threshold of cumulative fluid overload in predicting invasive mechanical ventilation need. AUC = 0.869 (P < 0.0001, 95% CI: 0.779–0.958) at cutoff value > 1685 ml (sensitivity: 86%; specificity: 78%). AUC: Area under the curve, CI: Confidence interval, IMV: Invasive mechanical ventilator, ROC: Receiver operating characteristic|
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| Discussion|| |
HS is an acute medical emergency and sometimes maybe fatal; thus, it is paramount to begin treatment immediately, such as cooling measures and fluid resuscitation to avoid progression to tissue damage and death. Dehydration and electrolyte loss can lead to a decrease in cardiac output and can lead to low blood pressure. Thus, patients are commonly subjected to rapid infusion with large volumes of fluids. The inflammatory response associated with HS is similar to the systemic inflammatory response syndrome (SIRS);, SIRS can lead to DIC, multiple organ failure, and death. In one study of exertional HS patients, 84% met the diagnostic criteria for SIRS, and the length of hospital stay was prolonged. The hemodynamic characteristics of most patients are high cardiac index, low systemic vascular resistance, and normal low filling pressure, and shock is distributed. Myocardial failure and a hypodynamic state may occur in the elderly.
Few studies have been conducted regarding resuscitation strategies in HS patients. There was a literature reported that the fluid resuscitation volume was about 9 ml/kg/h in the first 6 h, and the fluid overload in the first 48 h reached 6 L. With resuscitation, more than 77% of patients experienced increased extravascular lung water. It has been found that fluid overload on day 2 and fluid overload in the first 72 h were independent predictors of prolonged MV [Table 1]. The fluid balance in the first 72 h was 6112 ml and −46 mL in the LLMV and SMV groups, respectively. Obviously, the fluid balance in the SMV groups was far below LLMV. A previous study indicated that caution should be exercised when administering intravenous fluids of more than 1 L to HS patients during the cooling period. Most patients had normal blood pressure, blood volume, and cardiac output, and some even had increased cardiac output., For surviving HS patients, it was concluded that the LLMV group patients' positive cumulative fluid balance may cause pulmonary edema, which leads to prolonged MV. During the study, it has been observed that with the decrease in body temperature in survival patients, the urine volume showed the tendency to increase. For HS patients, providing invasive hemodynamic monitoring (e.g., Pulse-indicated continuous cardiac output (PICCO)) in the process of rehydration may avoid the liquid overload. However, for patients without invasive monitoring further fluid resuscitation needs to be taken with caution as soon as there is an increase in urine volume and a decrease in lactic acid during the process of rehydration.
When comparing and analyzing clinical biochemical indexes and clinical data, CK-MB and GCS scores showed statistically significant difference between the two groups. Patients with elevated serum CK-MB often suffer from cardiac insufficiency. Although N-terminal pro-brain natriuretic peptide (NT-proBNP) showed no statistically significant difference, this level was elevated in both the groups at 1353 ng/ml and 1586 ng/ml in the LLMV and SMV groups, respectively. The plasma level of NT-proBNP was significantly increased in the two groups, which indicated that HS patients had already undergone heart dysfunction. Echocardiographic findings and myocardial marker levels for HS patients have also been reported., The pathophysiology of HS includes major cardiovascular involvement, which has been well-documented for decades., Myocardial ischemia has been reported in HS patients, and the increased oxygen demand due to high fever, tachycardia, and a significantly high cardiac output state, or hypotension, were considered to be causative factors. One previous investigation using a rat model of HS reported that troponin I (cTnI) showed a 40-fold increase over control animals, which was consistent with cardiorenal failure. cTNI generally reaches the peak level at 6–18 h, in HS patients suffering from myocardial injury. The markers of myocardial injury in the LLMV group were higher than those in the SMV group, suggesting that the myocardial injury was more severe in the LLMV group. Thus, fluid overload may further exacerbate cardiac dysfunction in HS patients. Animal experiments have revealed that an increase in cerebral temperature of even 1°C above the normal 37°C for 60 min can cause neurologic deterioration and measurable histopathological lesions. Research has also confirmed that brain temperature is 0.5°C–2°C warmer than Tc., Cooling therapies seem to play a more significant role in HS patient outcomes when the body Tc is dropped to 38.0°C within 2 h after HS onset. It has been reported that the average GCS score at admission for the survival HS patients was 6 points, which is consistent with the observed results in this study. GCS score was statistically significant between the LLMV and SMV groups. Patients with higher GCS scores may have experienced longer duration of hyperthermia than those of low GCS scores. The brain is so extremely sensitive to heat treatment that the CNS disorders are inevitable in HS patients. People with severe exertional HS may develop seizures and sphincter incontinence. In the early stage, the CNS injury caused by HS may be multifactors. HS itself can cause brain cell toxicity, and heat stress can increase brain metabolism, and heat release from the skin, as well as quickly, reduces blood flow to the brain. Heat stress can also directly inhibit the heart tissue, resulting in a decline in cardiac output. In addition, diseases such as inflammation, dehydration, and low blood pressure can also lead to cerebral ischemia and hypoxia, thus resulting in brain injury.
By analyzing, patients in the LLMV group had higher SOFA scores. MV was required more frequently in the LLMV group. Although the total fluid balance was not statistically significant between the two groups on day 1, MODS may peak within 24–48 h in exertional HS patients. If patients got treated promptly, their clinical symptoms became mild in most cases and subsided within a few days. If HS patients were admitted with unstable hemodynamics, aggressive fluid treatment was necessary. When patients' condition improved after timely treatment, excessive fluid resuscitation might contribute to edema of organs, which was unfavorable for patient recovery. The data on HS patients collected by our group show that HS occurs suddenly and sometimes without prodrome, so fluid depletion in these patients should not always be considered. Thus, fluid administration should be based on the fluid responsiveness status of each patient during the intervention period.
This study has several limitations, including its retrospective nature and small sample size. In addition, it did not control for differences in resuscitation protocols. Furthermore, the volume of fluid resuscitation given to patients with HS prior to admission to the ICU was not counted, which may lead to an underestimation of the volume of fluid resuscitation during the study. Last but not least, although we have shown a link between positive cumulative fluid balance and adverse outcomes, invasive monitoring data were of absence in the study. The findings suggest an association between cumulative fluid overload in the first 72 h and adverse outcomes for HS patients. This association warrants further study in HS patients.
| Conclusions|| |
In this study, we found that fluid overload in the first 72 h may be an independent predictor of prolonged MV usage and duration of EICU stay in HS patients. The results revealed that maintaining cautious about fluid resuscitation may be critical for improving HS patient recovery and minimizing the impact of fluid overload on clinical outcomes following HS.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]