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- J Emerg Trauma Shock
- v.17(1); Jan-Mar 2024
- PMC11045001
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J Emerg Trauma Shock. 2024 Jan-Mar; 17(1): 20–24.
Published online 2023 Oct 24. doi:10.4103/jets.jets_72_23
PMCID: PMC11045001
Neurinda Permata Kusumastuti,1,2 Teddy Ontoseno,2 and Anang Endaryanto
2
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Abstract
Introduction:
Septic shock, the most severe form of sepsis, has high morbidity and mortality rates among children. In patients with septic shock, impaired microcirculatory perfusion is associated with the severity of organ failure and the likelihood of death. Because near-infrared spectroscopy (NIRS) can assess microcirculation status and peripheral tissue oxygenation directly and noninvasively, provides real-time results, and can be performed at the patient's bedside. This study aimed to determine the prognostic value of renal oxygen saturation (rRSO2) measured by NIRS in septic shock among children.
Methods:
This prospective observational study enrolled children aged 1 month to 18 years with septic shock who were treated in a pediatric intensive care unit from August 2020 to January 2021. NIRS was used to measure rRSO2 in patients diagnosed with septic shock according to the Third International Consensus Definition of Sepsis and Septic Shock. The baseline rRSO2 value (%) formed a receiver operating characteristic curve and was used to calculate the optimal cutoff value, sensitivity, specificity, and odds ratio (OR).
Results:
We enrolled 24 patients, 13 nonsurvivors and 11 survivors, whose mean baseline rRSO2 values were 67.27 ± 12.95 versus 48.69 ± 16.17, respectively (P = 0.006). The optimal cutoff value for baseline rRSO2 was <60.5%, with a sensitivity of 76.9%, a specificity of 81.8%, and an area under curve 0.804 (95% confidence interval [CI]: 59.2%–98.1%, P = 0.012; OR = 15; 95 CI: 2.04–111.74).
Conclusion:
Measured by NIRS, rRSO2 values are a good predictor of mortality among children with septic shock.
Keywords: Children, near-infrared spectroscopy, renal oxygen saturarion, septic shock
INTRODUCTION
Sepsis is a dysregulated host response to infection that tends to be not only dangerous but, in causing organ dysfunction, destructive as well. Among children, septic shock is the most severe form of sepsis and is often associated with high morbidity and mortality rates.
Sepsis results in impaired microcirculation, characterized by decreased vascular density, and a significant number of nonperfused vessels.[1,2,3] The degrees of organ failure and mortality among patients with septic shock in particular relate to impaired microcirculatory perfusion, whereas organ dysfunction that results from systemic or regional alterations may be influenced by tissue perfusion.[1,2]
Improvement in macrohemodynamic parameters as the goal of therapy in sepsis guidelines, does not always correlate with improvement in microcirculation, the restoration of organ function, or a better prognosis. That discrepancy implies that the ideal macrohemodynamic objectives for enhancing arterial perfusion and microcirculation differ for each patient and their vascular condition.[1,2,4] As a result, several macrohemodynamic markers, including cardiac output, blood pressure, and other systemic cardiovascular variables, are not reliable predictors of changes in septic shock.[5] By contrast, measuring oxygen release to peripheral tissues can provide a relatively accurate picture of microcirculatory status. Even so, many factors influence peripheral oxygenation, including capillary blood flow, regional blood flow around the organ, hemoglobin level, and partial pressure of oxygen.[6]
Pediatric septic shock can rely on prognostic markers to improve its clinical management by directing attention to the ultimate goal of therapy – that is, improved micro-and macrocirculation and patient stratification. The current prognostic markers for septic shock are ineffective because they require knowledge of when to measure and how to analyze them. To date, most studies using serum lactate as an indicator of tissue hypoxia have been conducted among adults.[7]
In such work, Bakker et al. discovered that serial blood lactate levels were a better predictor of death because the duration of lactic acidosis was more significant than the initial lactate value.[7,8] Although several pediatric studies have shown that higher initial serum lactate levels among children with septic shock are associated with a higher mortality rate, other studies have revealed that increased lactate levels were not solely due to cellular hypoxia.[7]
Near-infrared spectroscopy (NIRS) has been proposed as a tool for measuring microvascular dysfunction among patients with sepsis,[9] chiefly because it can assess microcirculation status and peripheral tissue oxygenation directly and noninvasively, provides real-time results, and can be performed at the patient's bedside. Studies on adults with sepsis have shown that using NIRS in the brachioradialis muscle can help to evaluate microvascular changes that have prognostic implications.[1,10] To the best of our knowledge, despite studies on using NIRS among patients with septic shock, the prognostic value of renal oxygen saturation (rRSO2) among children with septic shock remains unknown. Therefore, this study was conducted to determine the prognostic value of rRSO2 in septic shock among children measured by NIRS. Due to the high specificity and reliability of rRSO2 in septic shock, it is prudent to consider its number as a reliable prognostic criteria for septic shock fatality rate in children aged 1–18 years old.
METHODS
Patient population and methods
In this prospective observational study using a cross-sectional study design, children with septic shock were enrolled from 1 month to 18 years of age who were cared to the pediatric intensive care unit (PICU) of Dr. Soetomo General Hospital in Surabaya, Indonesia. The data were collected from August 2020 to January 2021 after obtaining consent from parents and/or guardians. Patients with cyanotic congenital heart disease or chronic kidney disease were excluded from the study. Parents and/or guardians of all participating children were fully informed of the purpose of the study. According to statistical calculations, this study requires at least 15 patients. This sample size was calculated using the following formula for a two-tailed unpaired t-test:
where the 95% confidence interval (CI) for Z1–α/2 is 1.96, the power for Z–β is 0.84, and σ is the pooled variance from the Creteur et al., 2007[2] study. Mean μ1–μ2 was used to estimate the difference in her NIRS mean values between surviving and nonsurviving patients with septic shock.
Data collection and methods of measurement
After obtaining consent from each patient's family, we gathered the identification and chief diagnosis of all patients in critical condition diagnosed with septic shock who were admitted to the PICU. Next, their vital signs were measured noninvasively using the GE40 monitor, their stroke volume (SV) was measured by pediatric cardiology using the GE Vivid-q echocardiograph, and their urine production and medication as well as the amount and type of fluid administered during measurement were determined. The basis for the diagnosis of septic shock is the Third International Consensus Definition of Sepsis and Septic Shock (i.e., Sepsis-3).
The Invos 5000 (Somanetics Corporation, Troy, MI, USA), was used to measure rSO2 in the patients' kidneys. Blood was collected from a central venous catheter inserted at the same time as NIRS monitoring to gauge lactate levels, complete peripheral blood count, liver function, and kidney function. We also performed a blood gas analysis using an inserted arterial catheter.
Lactate was collected within the 1st h and 6 h after diagnosis and the initiation of the treatment, and NIRS and other hemodynamic parameters were monitored until all procedures were completed. Each patient obtains a Paediatric Logistic Organ Dysfunction 2 (PELOD-2) score within 24 h of admission to the PICU to detect any organ failure and assess the severity of the disease. The research flow is shown in Figure 1.
Figure 1
Flow and study design of renal oxygen saturation in septic shock children research. PICU: Pediatric intensive care unit, NIRS: Near-infrared spectroscopy, rRSO2: Renal oxygen saturation, PELOD-2: Pediatric Logistic Organ Dysfunction-2
Near-infrared spectroscopy
With each child on their back in the supine position, a nonsterile, nonreusable disposable probe appropriate for the patients' weight (i.e., for infants and children weighing 5–40 kg) was attached to the skin's surface above the right waist. Once the probe was confirmed to be securely attached to the skin, the NIRS monitor was activated, and after the probe's signal appeared in full on the monitor, the monitor recorded rRO2 from the kidneys.
Measuring stroke volume using echocardiography
To measure SV using echocardiography, we measured the area of the left ventricular outflow tract and the amount of blood flowing there. After the echocardiograph calculated SV, we calculated the SV index (SVI), and cardiac index using the calculator (https://www.omnicalculator.com/health/stroke-volume).
Data analysis
The collected data were analyzed using the Statistical Package for the Social Sciences version 20.0 (IBM, Armonk, NY, USA). Narration, tables, and images are used to present the data. The Kolmogorov–Smirnov test was used to determine the normality of demographic and clinical data, as well as the numerical data of all studied variables. If the data were normally distributed, then they are presented as mean ± standard deviation; otherwise, they are presented as medians and ranges. If the mean values of the two unpaired groups were normally distributed, then the independent sample t-test was used to analyze them. By contrast, data not normally distributed were tested using the Mann–Whitney U-test. Predicted values of rRSO2 were calculated using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) was calculated. The ROC curve values were subsequently used to determine the rRSO2 cutoff value for future use as a new cutoff value for predictors of outcomes in patients with septic shock, and its sensitivity and specificity were calculated. Based on the existing cutoff value, the odds ratio (OR) was calculated to determine the risk of death.
RESULTS
Of the 24 pediatric patients with septic shock admitted into Dr. Soetomo General Hospital's PICU between August 2020 and January 2021, 13 (54.16%) did not survive. The patients' major characteristics are shown in Tables 1 and and22.
Table 1
Baseline characteristics of pediatric patients with septic shock
| Characteristics | Survivor (n=11) | Nonsurvivor (n=13) | Septic shock (n=24) | P |
|---|---|---|---|---|
| Age (mean±SD) | 95.36±72.09 | 130.77±64.01 | 114.54±68.717 | 0.052 |
| Sex (boy), n (%) | 7 (50) | 7 (50) | 14 | 0.697 |
| Nutritional status, n (%) | ||||
| Malnourished | 4 | 7 | 11 (45.8) | 0.506 |
| Obesity | 2 | 3 | 5 (20.8) | |
| Site of infection, n (%) | ||||
| Respiratory | 4 | 4 | 8 (33.3) | 0.614 |
| Abdominal | 2 | 5 | 7 (29.2) | |
| Urinary | 3 | 2 | 5 (21) | |
| Other | 2 | 2 | 4 | |
| Hemoglobin (g/dL) (mean±SD) | 9.6±2.1 | 9.1±1.9 | 9.3±1.9 | 0.200 |
| Temperature (°C) (mean±SD) | 37.63±1.16 | 38.36±0.88 | 38.02±1.06 | 0.149 |
| GCS (>13), n (%) | 4 | 6 | 10 (41.7) | 0.770 |
| Mechanichal ventilation, n (%) | 5 (41.67) | 7 (58.33) | 12 (50) | 1.000 |
| HR (bpm) (mean±SD) | 153±16.50 | 148.62±24.93 | 150.63±21.16 | 0.200 |
| CRT (>2 s), n (%) | 8 (47.06) | 9 (52.94) | 17 (70.8) | 1.000 |
| Diuresis (<1 mL/kg BW/h), n (%) | 2 (18.18) | 9 (81.82) | 11 (45.8) | 0.019 |
| Serum creatinine (mg/dL) (mean±SD) | 0.91±0.63 | 0.66±0.21 | 0.77±0.09 | 0.08 |
| Glomerular filtration rate (mL/min/1.73 m2) (mean±SD) | 94.69±71.37 | 122.68±54.62 | 109.85±63.04 | 0.087 |
| Lactate (mmol/L) (mean±SD) | 4.51±1.28 | 4.91±2.25 | 4.72±1.84 | 0.052 |
| PELOD-2 score (mean±SD) | 6.73±1.68 | 10.38±1.85 | 8.71±2.55 | 0.051 |
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GCS: Glasgow Coma Scale, HR: Heart rate, CRT: Capillary refill time, SD: Standard deviation, PELOD-2: Pediatric Logistic Organ Dysfunction-2
Table 2
Basic hemodynamic characteristics of pediatric patients with septic shock
| Characteristics | Mean±SD | P | ||
|---|---|---|---|---|
| Survivor (n=11) | Nonsurvivor (n=13) | All patients (n=24) | ||
| MAP (mmHg) | 54.50±9.54 | 60.64±12.94 | 57.83±11.69 | 0.207 |
| Cardiac index (L/min/m2) | 5.63±2.85 | 3.84±1.57 | 4.81±2.48 | 0.077 |
| SVI (mL/m2) | 36.04±10.33 | 43.84±17.99 | 40.27±15.19 | 0.217 |
| DO2 (mL/min) | 696.23±392.86 | 903.23±588.04 | 808.35±508.55 | 0.331 |
| SVRI (dyn×s/cm5) | 898.45±367.82 | 772.15±242.54 | 830.04±306.02 | 0.325 |
| ScVO2 (%) | 63.09±10.62 | 63.92±19.57 | 63.54±15.78 | 0.901 |
| SaO2 (%) | 98.45±1.69 | 96.23±5.79 | 97.25±4.47 | 0.208 |
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MAP: Mean arterial pressure, SVI: Stroke volume index, DO2: Delivery oxygen, SVRI: Systemic vascular resistance index, ScVO2: Central venous oxygen saturation, SaO2: Arterial oxygen saturation, SD: Standard deviation
The results of the rRSO2 examination with NIRS from the time of diagnosis until treatment are shown in Table 3.
Table 3
Renal oxygen saturation values in surviving and nonsurviving pediatric patients with septic shock
| NIRS | Mean±SD | P | |
|---|---|---|---|
| Survivor | Nonsurvival | ||
| rRSO2 baseline | 67.27±12.95 | 48.69±16.17 | 0.006 |
| rRSO2 minimum | 57.82±17.17 | 38.38±17.89 | 0.013 |
| rRSO2 maximum | 81.00±6.89 | 65.77±13.83 | 0.003 |
| rRSO2 delta | 23.00±16.61 | 27.31±17.46 | 0.544 |
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rRSO2: Renal oxygen saturation, SD: Standard deviation, NIRS: Near-infrared spectroscopy
Meanwhile, the results of our evaluation of hemodynamic parameters 6 h after fluid therapy and vasoactive agents are shown in Table 4.
Table 4
Evaluation of patient's hemodynamics after 6 h of therapy
| NIRS | Mean±SD | P | |
|---|---|---|---|
| Survivor | Nonsurvival | ||
| MAP (mmHg) | 67.55±10.36 | 47.38±17.78 | 0.003 |
| Cardiac index (L/min/m2) | 4.90±1.45 | 5.26±2.35 | 0.661 |
| SVI (mL/m2) | 35.24±13.94 | 43.81±19.89 | 0.234 |
| DO2 (mL/min) | 678.49±468.81 | 870.10±612.83 | 0.406 |
| SVRI (dyn×s/cm5) | 1497.36±682.49 | 928.69±350.62 | 0.015 |
| Lactate (mmol/L) | 2.36±0.35 | 4.27±2.91 | 0.037 |
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MAP: Mean arterial pressure, SVI: Stroke volume index, DO2: Delivery oxygen, SVRI: Systemic vascular resistance index, SD: Standard deviation, NIRS: Near-infrared spectroscopy
The AUC was 80.4% (range: 59.2%–98.1%, P = 0.012) based on the value of the ROC, which confirmed that the baseline rRSO2 was significantly associated with mortality [Figure 2]. A cutoff value of 60.5% for rRSO2 had a sensitivity of 76.9% and a specificity of 81.8%. Despite applying to the same severity disease, this cutoff value represented a 15-fold increase in the risk of death (OR = 15.0; 95% CI: 2.04–111.74).
Figure 2
Receiving operating curve for renal oxygen saturation baseline. ROC: receiver operating characteristic curve
Aside from its relationship with mortality, the baseline rRSO2 value had a statistically significant inverse relationship with the PELOD-2 score (r = −0.512, P = 0.010).
DISCUSSION
The results of our continuous, noninvasive examination of baseline rRSO2 indicate values that differed significantly between surviving and nonsurviving pediatric patients with septic shock and that, as such, can predict death. In patients with septic shock, a baseline rRSO2 value of <60.5% significantly increased the risk of death. Thus, our study has demonstrated that monitoring microcirculation with NIRS is a simple, direct method of assessing the risk of death in patients with septic shock. As a result, finding a way to correct the patient condition before the rRSO2 value drops to the cutoff is critical.
Our results align with previous findings presented by Marín-Corral et al. (2016) among adult patients with septic shock. In their sample, oxygen saturation was measured in the thenar muscles, which is rSO2 baseline had a prognostic value at a cutoff of 60% with a sensitivity of 83% in nonsurviving patients.[1] Even so, our findings differ from the results of Shapiro et al., who found that the initial StO2 value in adult patients with septic shock did not significantly differ between survivors and nonsurvivors when a value of 80% was used to classify StO2.[11] That disparity in results could be attributed to the very high NIRS saturation cutoff value used in Shapiro et al. Research which was not accompanied by the identification of a clinically useful cutoff value.
Directly and continuously assessing the presence of microcirculatory dysfunction at the patient's bedside is challenging. In our study, commonly performed clinical assessments using capillary refill time and laboratory testing, namely lactate level examination, did not show a significant difference between surviving and nonsurviving patients, because the diagnostic criteria for our sample were the same as the initial conditions. In theory, the lactate level rises in septic conditions because microcirculation disorders or shunting can result in a lack of oxygen delivered to cell tissue or hypoxia in patients with sepsis.[12] Based on the Sepsis-3 guidelines, serum lactate levels exceeding 2 mmol/L indicate septic shock,[13] which is consistent with our study's initial mean lactate value of 4.72 mmol/L. However, the results of our examination of lactate levels 6 h after therapy revealed a significant difference in levels between surviving and nonsurviving patients. That difference suggests that repeated measurements of lactate levels after therapy among patients with septic shock may have better prognostic value than measuring lactate levels only once when the patients are first diagnosed with septic shock. Previous research has shown that lactate clearance of 10% or higher predicts survival in patients with septic shock, thereby implying that effective resuscitation can prevent the worsening of tissue oxygenation and anaerobic metabolism.[14]
Meanwhile, our macrohemodynamic examination, which was expected to describe the condition of microcirculation in terms of cardiac index, mean arterial pressure (MAP), SVI, oxygen delivery index, and systemic vascular resistance index (SVRI) at baseline, did not allow us to distinguish survivors from nonsurvivors. Microcirculatory disorders in the heart are found in patients with sepsis due to endothelial dysfunction and the maldistribution of blood flow at the capillary level, which results in regional ischemia but does not affect macrocirculation.[12] Nevertheless, the MAP value increased among surviving patients and differed significantly between them and nonsurvivors. Arguably, postresuscitation MAP values that match the Sepsis-3 guideline's postresuscitation MAP targets can improve the patient's prognosis.[13] Moreover, survivors had significantly higher SVRI values than nonsurvivors. Our findings are thus consistent with those of Groeneveld et al. who discovered that the lower the SVRI, the worse the outcome.[15]
Our study not only showed that the rRSO2 value can be used to assess the prognosis of patients with sepsis, but also that the lower the rRSO2 value, the higher the PELOD-2 score, implying that the rRSO2 value further indicates the severity of organ dysfunction in patients with sepsis. Consistent with previous studies in adult patients with septic shock undergoing vascular occlusion testing, initial StO2 measured by NIRS in the first 24 h was significantly associated with the Sequential Organ Failure Assessment Score (r = −0.18, P = 0.04).[11]
Among our study's limitations, we examined only one rRSO2 value without considering its dynamic conditions instead of following changes in rRSO2 values over time. Moreover, many rRSO2 values were not evaluated during measurement.
CONCLUSION
Our findings suggest that a NIRS-derived baseline rRSO2 value is a good predictor of outcomes among pediatric patients with septic shock.
Research quality and ethics statement
This study was approved by the Institutional Ethics Committee (Ref. No. 0104/LOE/301.4.2/VIII/2020). The authors followed applicable EQUATOR Network (https://www.equator-network.org/) guidelines during the conduct of this research project.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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