Cerebral Tissue Regional Oxygen Saturation as a Valuable Monitoring Parameter in Pediatric Patients Undergoing Extracorporeal Membrane Oxygenation

Objective: Brain function monitoring technology for extracorporeal membrane oxygenation (ECMO) support has been developing quite slowly. Our objective was to explore the data distribution, variation trend, and variability of cerebral tissue regional oxygen saturation (CrSO₂) in pediatric patients undergoing ECMO.

Methods: Eight patients who received venoarterial ECMO (V-A ECMO) were included in our study. All of them accepted continuous CrSO₂ monitoring by near-infrared spectroscopy (NIRS) within 12 h of ECMO initiation until ECMO wean. Differences in the CrSO₂ distribution characteristic, the variation trend of daily CrSO₂, and the variability of CrSO₂ for the first 5 days following ECMO initiation were compared between survivors and non-survivors according to pediatric intensive care unit (PICU) mortality.

Results: The percentage of time of CrSO₂ <60% against the whole monitoring time was significantly lower in survivors in both hemispheres {right: 4.34% [interquartile range (IQR) = 0.39–8.55%] vs. 47.45% [IQR = 36.03–64.52%], p = 0.036; left: 0.40% [IQR = 0.01–1.15%] vs. 30.9% [IQR = 26.92–49.62%], p = 0.036}. Survivors had significantly higher CrSO₂ on the first 4 days. Root mean of successive squared differences (RMSSD), the variability variable of CrSO₂, was significantly lower in survivors (right: 3.29 ± 0.79 vs. 6.16 ± 0.67, p = 0.002; left: 3.56 ± 1.20 vs. 6.04 ± 1.44, p = 0.039).

Conclusion: Lower CrSO₂, CrSO₂ <60% over a longer period of time, and higher fluctuation of CrSO₂ are likely associated with PICU mortality in pediatric patients undergoing V-A ECMO.

Clinical Trial Registry: URL: http://www.chictr.org.cn/showproj.aspx?proj=46639, trial registry number: ChiCTR1900028021.

Introduction

Extracorporeal membrane oxygenation (ECMO) is an extracorporeal life support technology used for patients with cardiopulmonary failure as a severe refractory to conventional treatment measure (1–3). With the development of ECMO, it has been widely applied to the clinical (4–6); however, monitoring technology for ECMO support, particularly the brain function monitoring, has been developing quite slowly.

Near-infrared spectroscopy (NIRS) can provide useful data on cerebral tissue regional oxygen saturation (CrSO₂). Because of its characteristics, such as non-invasiveness, continuousness, and being performed in real time and at the bedside (7–10), NIRS has been suggested as one of the regular monitoring technologies during ECMO support by the Extracorporeal Life Support Organization (ELSO) (11). Although NIRS is extensively used in various fields, there have been only a few studies on NIRS in the pediatric patients with ECMO. Consequently, the aim of this study was to explore the data distribution, variation trend, and variability of CrSO₂ in pediatric patients undergoing ECMO so as to provide a relevant reference.

Methods

Patients

This prospective observational study was conducted between May 24, 2019, and January 18, 2020 in the 32-bed pediatric intensive care unit (PICU) of the Children's Hospital of Chongqing Medical University, China. All patients aged from 28 days to 18 years needing venoarterial ECMO (V-A ECMO) support were included in this study. Exclusion criteria included the following: with open heart surgery or cardiac catheterization procedure; with ECMO support <24 h; with validated cerebral injury before ECMO, including cerebral hemorrhage and ischemia; with serum total bilirubin >7 mg/dL before ECMO (12); with forehead skin damage not fit for NIRS monitoring.

Assessments of neurologic status were mainly based on the medical history and clinical symptoms and signs before ECMO. Patients suspected of having brain injury were examined with brain computed tomography (CT) or magnetic resonance imaging (MRI). Those patients without suspected brain injury and without abnormal neurologic imaging findings were all considered as without brain injury.

This study has been approved by the Institutional Review Board of Children's Hospital of Chongqing Medical University (2019-237) and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards and has been registered in Chinese Clinical Trial Registry (ChiCTR1900028021). Written informed consent for participation was obtained from children's parents or legal guardians.

Data Collection

Baseline information before ECMO initiation was recorded and included: age, gender, weight, diagnosis, the interval of hospital admission to ECMO initiation, the interval of PICU admission to ECMO initiation, the interval of invasive mechanical ventilation begun to ECMO initiation, the use of vasoactive drugs before ECMO, PaO₂/FiO₂ ratio, and arterial blood gas parameters (pH, PaCO₂, PaO₂, SaO₂, lactate) before ECMO.

Follow-up variables included ECMO duration, ECMO parameters, treatment measures during ECMO, hemodynamic parameters during ECMO, duration of the invasive mechanical ventilation after ECMO wean, length of PICU and hospital stays, and PICU mortality.

ECMO Management

All patients receiving ECMO support were managed by our ECMO team. We chose the mode of ECMO support in pediatric respiratory failure according to the patient's hemodynamic status and weight. We have to choose V-A ECMO in infants and low-weight toddlers with respiratory failure purely for a lack of double-lumen venovenous (V-V) cannulas in China. Venoarterial ECMO was surgically implanted using heparin-coated cannulation (Bio-Medicus, Medtronic Inc., Minneapolis, MN, USA) via the right internal jugular vein and the right common carotid artery. The centrifugal pump (Deltastream DP3, Medos, Stolberg, Germany) and membrane oxygenator (Hilite 800 LT, Hilite 2400 LT, or Hilite 7000 LT, Medos, Stolberg, Germany) were used. ECMO-related parameters and hemodynamic parameters were recorded every 2 h during ECMO support.

Cerebral Tissue Regional Oxygen Saturation Monitoring

Monitoring of CrSO₂ began within 12 h of ECMO initiation and continued until the weaning of ECMO using NIRS (FORE-SIGHT P/N01-06-2030C, CAS Medical Systems Inc., Branford, CT, USA). Cerebral tissue regional oxygen saturation data were gathered every 2 s and recorded on the device's memory. Our ECMO team did not adjust therapies following CrSO₂ data. The daily median CrSO₂ values were calculated for the first 5 days following ECMO initiation in both hemispheres and were then used to analyze the variation trend of CrSO₂. At the same time, the median CrSO₂ values over 4-h time intervals were calculated for the first 5 days and plotted as a time series. The variability of CrSO₂ was evaluated using the standard deviation (SD), coefficient of variation (CV), and root mean of successive squared differences (RMSSD).

$\begin{array}{l}RMSSD=\sqrt{\frac{{\displaystyle {\sum }_{i=2}^n}{(x_i-x_{i-1})}^2}{n}}\end{array}$

where x_i is the median CrSO₂ at interval i (13). The differences of different CrSO₂ variables were compared between survivors and non-survivors.

Outcome

The primary outcome was PICU mortality. All patients weaned off ECMO successfully had accepted brain CT or MRI as soon as the patients' condition relatively stabilized.

Statistical Analysis

Statistical analysis was performed with SPSS version 26 (IBM Corp., Armonk, NY, USA). Continuous variables were confirmed for normal distribution using the Shapiro–Wilk test and are presented either as means ± SD for data with a normal distribution or as median (IQR) for non-normal data. The differences between groups were tested with Student t-test, Satterthwaite t-test, or Mann–Whitney U-test, as appropriate. Categorical variables are presented as counts (percentages). Repeated measurement data were analyzed using the generalized estimating equation. p < 0.05 was considered as statistically significant.

Results

Study Population

Thirteen patients accepted ECMO support during the study period. Five of them were excluded from the analysis: two had V-V ECMO for respiratory failure, one died within 24 h of ECMO initiation, and two accepted V-A ECMO following open heart surgery. Finally, eight patients undergoing V-A ECMO were included in the study. Patients' demographics and clinical characteristics are summarized in Table 1. Six patients weaned off ECMO successfully, whereas one of them could not detach from the ventilator after ECMO and died of respiratory failure. Two patients had no improvement and died after decannulation. Two patients had abnormal neurologic imaging findings. Patient 4 had intracranial hemorrhage, and patient 8 had cerebral infarction, whereas both of them survived to PICU discharge. For all eight included patients, the PICU length of stay was 20 ± 7 days, and the hospital length of stay was 45 ± 24 days. Arterial blood gas parameters before ECMO were pH 7.40 ± 0.10, PaCO₂ = 44.4 ± 7.5 mm Hg, PaO₂ = 47.4 ± 13.0 mm Hg, SaO₂ = 79.6 ± 12.5%, and lactate = 1.6 ± 0.9 mmol/L. PaO₂/FiO₂ ratio before ECMO was 48 ± 14.

TABLE 1

Table 1. Patients' demographics and clinical characteristics.

ECMO Management

The centrifugal pump rotating speed was 5,468 ± 347 r/min, and the ECMO flow was 70 ± 10 mL/kg/min for the first 5 days following ECMO initiation. Patients' mean arterial pressure (MAP) was 71 ± 12 mm Hg, SvO₂ was 66 ± 3%, and hematocrit was 35 ± 2%. All patients accepted vasoactive drugs during ECMO support, and the duration of vasoactive drugs use was 1.5 days (IQR = 1–3 days). The maximum vasoactive–inotropic score (14, 15) was 17.85 (IQR = 5.36–31.38). Three (37.5%) patients received continuous renal replacement therapy during ECMO support, and all of them suffered PICU mortality.

Cerebral Tissue Regional Oxygen Saturation Variables

The duration of CrSO₂ monitoring was 79.0 ± 17.0% of the time on the first 5 days of ECMO. The distribution of CrSO₂ data for the first 5 days in both hemispheres is shown in Figure 1. The percentage of time of CrSO₂ <60% against the whole monitoring time was significantly lower in survivors in both hemispheres [right: 4.34% (IQR = 0.39–8.55%) vs. 47.45% (IQR = 36.03–64.52%), p = 0.036; left: 0.40% (IQR = 0.01–1.15%) vs. 30.9% (IQR = 26.92–49.62%), p = 0.036)].

FIGURE 1

Figure 1. Right–left split violin plot of CrSO₂ for the first 5 days following ECMO initiation. According to PICU mortality, patients 5, 6, and 7 suffered death; others survived. Results of the Mann–Whitney U-test indicate that the percentage of time of CrSO₂ <60% against the whole monitoring time was significantly lower in survivors in both hemispheres (both p < 0.05).

Table 2 and Figure 2 show CrSO₂ variation trends for the first 5 days in both hemispheres. Because of the risk of developing pressure sores, we did not gather CrSO₂ signals in the fifth day for patient 1. While the duration of ECMO support was only 41 h for patient 8; thus, the patient did not contribute data to the third, fourth, and fifth day. Survivors had significantly higher CrSO₂ for each of the first 4 days in both hemispheres (all p < 0.05), but there were no significant differences between survivors and non-survivors on the fifth day in both hemispheres (right: Wald χ² = 3.402, p = 0.065, left: Wald χ² = 1.216, p = 0.270).

TABLE 2

Table 2. CrSO₂ for the first 5 days following ECMO initiation according to PICU mortality.

FIGURE 2

Figure 2. Daily CrSO₂ for the first 5 days following ECMO initiation according to PICU mortality. Results of the generalized estimating equation (GEE) indicate significant differences between survivors and non-survivors for each of the first 4 days following ECMO initiation in both hemispheres. *p < 0.05.

The indicators of CrSO₂ variability between survivors and non-survivors for the first 5 days following ECMO initiation are shown in Figure 3. Root mean of successive squared differences (RMSSDs) were significantly lower in survivors in both hemispheres (right: 3.29 ± 0.79 vs. 6.16 ± 0.67, p = 0.002; left: 3.56 ± 1.20 vs. 6.04 ± 1.44, p = 0.039). Coefficient of variation was significantly lower in survivors only in the left hemisphere (right: 4.54 ± 0.89 vs. 11.50 ± 3.85, p = 0.084; left: 5.36 ± 1.36 vs. 9.71 ± 2.47, p = 0.016). Standard deviation was seemingly lower in survivors in both hemispheres, but there were no significant differences (right: 3.27 ± 0.47 vs. 6.50 ± 1.83, p = 0.087; left: 3.92 ± 1.03 vs. 5.91 ± 1.71, p = 0.081).

FIGURE 3

Figure 3. CrSO₂ variability for the first 5 days following ECMO initiation according to PICU mortality. Indicators of CrSO₂ variability are RMSSD, root mean of successive squared differences; CV, coefficient of variation; SD, standard deviation. Results of the Student t-test indicate significant differences between survivors and non-survivors for right RMSSD, left RMSSD, and left CV, respectively. *p < 0.05.

Discussion

Monitoring technology has not been developed along with ECMO-related technologies, and monitoring of the central nervous system is particularly challenging. The head ultrasound was used in patients undergoing ECMO with several limitations (16, 17), for example, this approach could not capture the neurologic imaging in pediatric patients with closed cranial fontanels and adult patients (8). Besides, it cannot be used for continuous monitoring. As for electroencephalography, amplitude-integrated electroencephalography, and somatosensory-evoked potentials, a few studies have tested their roles in ECMO support (8, 18). Although head CT and MRI can clearly detect the cerebral hemorrhage or ischemia, the hospital transfer may have potential risks (8). Different from all these monitoring methods, cerebral NIRS can provide a continuous value of CrSO₂. Because of its non-invasiveness, continuousness, and being performed in real time and at the bedside (7–10), ELSO suggests regular application of NIRS to patients undergoing ECMO support (11). Nonetheless, there was not a certain method to use NIRS. In our study, we explored the CrSO₂ distribution characteristic, the variation trend of daily CrSO₂, and the variability of CrSO₂ for the first 5 days following ECMO initiation.

In the present study, survivors had higher CrSO₂ for the first 4 days following ECMO initiation in both hemispheres, and the percentage of time of CrSO₂ <60% against the whole monitoring time was lower in survivors. Previous studies also revealed that survivors had higher CrSO₂ than non-survivors (19, 20). And the occurrence of cerebral desaturation, which is defined as CrSO₂ <60% for >5% of the entire monitoring period, was independently associated with hospital mortality (21). Wong et al. (22) adjusted therapy measures that could affect the cerebral oxygen balance to improve CrSO₂ values. They also found that unilateral or bilateral CrSO₂ decreasing persistently was associated with worse outcome. We have similar findings and consider that lower CrSO₂ and the longer time of CrSO₂ <60% reduce the possibility of survival. However, there was no significant difference for the median CrSO₂ of the fifth day among survivors and non-survivors. We guess volume overload may play a role in this phenomenon, because all deceased patients in our study accepted continuous renal replace therapy in the later days of ECMO support. Studies suggested cerebral autoregulation impairment during ECMO was associated with worse outcome (20, 23). Excessive blood would stream into brain circulation without the regulation of cerebral autoregulation, so that the CrSO₂ signal gets higher.

Besides, for the indicators of CrSO₂ variability, bilateral RMSSD and left CV were significantly higher in non-survivors; meanwhile, bilateral SD and right CV also showed the trend to be higher in non-survivors. Therefore, we speculate that greater fluctuation of CrSO₂ is associated with a worse prognosis. Absolute CrSO₂ values can be different between different types of NIRS devices, because of different algorithms (24). Different from using absolute CrSO₂ value directly, indicators of CrSO₂ variability can reduce the error caused by different types of NIRS devices. Using RMSSD to describe the variability of CrSO₂ had been studied in perioperative period of cardiac surgery. Spaeder et al. (13) found that lower RMSSD was associated with poor neurodevelopmental outcomes in neonatal survivors of congenital heart disease. Meanwhile, Flechet et al. (25) found that pediatric patients with lower RMSSD had larger probability of developing acute kidney injury after cardiac surgery. This is the first study to explore the CrSO₂ variability using RMSSD in patients with ECMO support. However, different from those findings that came from the perioperative period of cardiac surgery, survivors had a lower RMSSD in our study. We consider that there are several potential factors that may cause this difference. First, patients with open heart surgery were excluded in our study, whereas those two previous studies had focused on the perioperative period of cardiac surgery. Second, conclusion of those two previous studies came from CrSO₂ data gathered from postoperative period. Cerebral blood flow is pulsatile for most patients in this period, whereas cerebral blood flow in V-A ECMO is non-pulsatile or partial pulsatile, which is associated with endothelial dysfunction, decreased microvascular perfusion, and increased vascular resistance (26). Third, the total monitoring duration is longer in our study. Meanwhile, those two previous studies averaged CrSO₂ over 1-min intervals to calculate RMSSD. But we calculated RMSSD using the median CrSO₂ over 4-h intervals, because missing data cannot be avoided in such long a time in clinical. We have checked CrSO₂ signal every 4–6 h, so that we have enough data in every 4-h intervals. Further studies are needed to confirm our findings and explore underlying mechanisms.

There are some limitations to our study. First, our findings came from a small sample size and single-center study, and most patients in our study had a similar diagnosis of human adenovirus pneumonia. Those make it cautious to interpret the results of our study. Second, only patients receiving V-A ECMO were included in our study; thus, conclusions obtained from the current study may not be extrapolated to those with V-V ECMO. However, Clair et al. (19) reported the mean CrSO₂ for the whole time of ECMO support, the duration of CrSO₂ below the threshold of 20% from baseline, and the duration of CrSO₂ <50% were not different in patients with V-V ECMO compared to V-A ECMO. Third, we only compared CrSO₂ values between survivors and non-survivors, as the small sample size is a limitation in adjusting for suspected confounding factors. The relationships between CrSO₂ values and hemodynamic parameters were not discussed. At the same time, we did not explore the correlation between CrSO₂ and neurologic complications. Studies found that lower CrSO₂ and more frequently occurrence of cerebral desaturation in patients with ECMO were more likely related to brain injury (19, 27, 28). However, different studies had different definitions of cerebral desaturation and brain injury. Tian et al. (29) assessed the dynamic relationship between the MAP and CrSO₂ fluctuations and found that patients with significant in-phase MAP to CrSO₂ coherence always had abnormal neurologic imaging findings. Finally, there are limitations in CrSO₂ monitoring. CrSO₂ mainly represents the regional oxygen saturation of the forehead. Thus, it may be hard to evaluate the deeper part or other region of the brain. Meanwhile, CrSO₂ can be affected by serum bilirubin, skin surface temperature, or scalp blood flow (12, 21, 28).

Conclusion

Cerebral tissue regional oxygen saturation can be used as a regular monitoring parameter for pediatric patients undergoing ECMO. Lower CrSO₂, CrSO₂ <60% over a longer period of time, and higher fluctuation of CrSO₂ are likely associated with PICU mortality in pediatric patients undergoing V-A ECMO. Future multicenter and large-scale studies are needed to mitigate confounding factors and verify our findings and explore the correlation between neurologic complications and CrSO₂ variables in our study.

Data Availability Statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics Statement

The studies involving human participants were reviewed and approved by Institutional Review Board of Children's Hospital of Chongqing Medical University. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.

Author Contributions

SC is the principal author and contributed to data collection, data analysis and interpretation, and drafted the manuscript. SC and FX contributed to the study conception and design. FF, WL, CL, and FX contributed to data analysis and interpretation and revised the manuscript critically for important intellectual content. All authors contributed to the article and approved the submitted version.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

We thank all the medical and nursing staff in our ECMO team. We thank Hui Dong (MD, Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, PR China) for his contributions to language instruction.

Abbreviations

ECMO, extracorporeal membrane oxygenation; V-A ECMO, venoarterial ECMO; V-V ECMO, venovenous ECMO; PICU, pediatric intensive care unit; NIRS, near-infrared spectroscopy; CrSO₂, cerebral tissue regional oxygen saturation; SD, standard deviation; CV, coefficient of variation; RMSSD, root mean of successive squared differences; GEE, the generalized estimating equation.

References

1. White A, Fan E. What is ECMO? Am J Respir Crit Care Med. (2016) 193:9–10. doi: 10.1164/rccm.1936P9

PubMed Abstract | CrossRef Full Text>

2. Nasr DM, Rabinstein AA. Neurologic complications of extracorporeal membrane oxygenation. J Clin Neurol. (2015) 11:383–9. doi: 10.3988/jcn.2015.11.4.383

PubMed Abstract | CrossRef Full Text | Google Scholar

3. Hervey-Jumper SL, Annich GM, Yancon AR, Garton HJL, Muraszko KM, Maher CO. Neurological complications of extracorporeal membrane oxygenation in children. J Neurosurg Pediatr. (2011) 7:338–44. doi: 10.3171/2011.1.Peds10443

PubMed Abstract | CrossRef Full Text | Google Scholar

4. Combes A, Hajage D, Capellier G, Demoule A, Lavoue S, Guervilly C, et al. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med. (2018) 378:1965–75. doi: 10.1056/NEJMoa1800385

PubMed Abstract | CrossRef Full Text | Google Scholar

5. Lorusso R, Barili F, Di Mauro M, Gelsomino S, Parise O, Rycus PT, et al. In-hospital neurologic complications in adult patients undergoing venoarterial extracorporea l membrane oxygenation: results from the extracorporeal life support organization registry. Crit Care Med. (2016) 44:e964–72. doi: 10.1097/ccm.0000000000001865

PubMed Abstract | CrossRef Full Text | Google Scholar

6. Lin JC. Extracorporeal membrane oxygenation for severe pediatric respiratory failure. Respir Care. (2017) 62:732–50. doi: 10.4187/respcare.05338

PubMed Abstract | CrossRef Full Text | Google Scholar

7. Hirsch JC, Charpie JR, Ohye RG, Gurney JG. Near-infrared spectroscopy: what we know and what we need to know-a systematic review of the congenital heart disease literature. J Thorac Cardiovasc Surg. (2009) 137:154–9; 159e1–12. doi: 10.1016/j.jtcvs.2008.08.005

PubMed Abstract | CrossRef Full Text | Google Scholar

8. Lin N, Flibotte J, Licht DJ. Neuromonitoring in the neonatal ECMO patient. Semin Perinatol. (2018) 42:111–21. doi: 10.1053/j.semperi.2017.12.007

PubMed Abstract | CrossRef Full Text | Google Scholar

9. Krishnan S, Schmidt GA. Hemodynamic monitoring in the extracorporeal membrane oxygenation patient. Curr Opin Crit Care. (2019) 25:285–91. doi: 10.1097/mcc.0000000000000602

PubMed Abstract | CrossRef Full Text | Google Scholar

10. Ostadal P, Kruger A, Vondrakova D, Janotka M, Psotova H, Neuzil P. Noninvasive assessment of hemodynamic variables using near-infrared spectroscopy in patients experiencing cardiogenic shock and individuals undergoing venoarterial extracorporeal membrane oxygenation. J Crit Care. (2014) 29:690.e11–5. doi: 10.1016/j.jcrc.2014.02.003

PubMed Abstract | CrossRef Full Text | Google Scholar

11. Maratta C, Potera RM, van Leeuwen G, Castillo Moya A, Raman L, Annich GM. Extracorporeal Life Support Organization (ELSO): 2020 pediatric respiratory ELSO guideline. ASAIO J. (2020) 66:975–9. doi: 10.1097/mat.0000000000001223

PubMed Abstract | CrossRef Full Text | Google Scholar

12. Song J-G, Jeong S-M, Shin W-J, Jun I-G, Shin K, Huh I-Y, et al. Laboratory variables associated with low near-infrared cerebral oxygen saturation in icteric patients before liver transplantation surgery. Anesth Analg. (2011) 112:1347–52. doi: 10.1213/ANE.0b013e318214b2b0

PubMed Abstract | CrossRef Full Text | Google Scholar

13. Spaeder MC, Klugman D, Skurow-Todd K, Glass P, Jonas RA, Donofrio MT. Perioperative near-infrared spectroscopy monitoring in neonates with congenital heart disease: relationship of cerebral tissue oxygenation index variability with neurodevelopmental outcome. Pediatr Crit Care Med. (2017) 18:213–8. doi: 10.1097/pcc.0000000000001056

PubMed Abstract | CrossRef Full Text | Google Scholar

14. Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye RG, et al. Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med. (2010) 11:234–8. doi: 10.1097/PCC.0b013e3181b806fc

PubMed Abstract | CrossRef Full Text | Google Scholar

15. Musick MA, Loftis LL, Kennedy CE. Comparing vasoactive-inotropic score reporting strategies in the picu relative to mortality risk. Pediatr Crit Care Med. (2018) 19:1130–6. doi: 10.1097/pcc.0000000000001738

PubMed Abstract | CrossRef Full Text | Google Scholar

16. O'Brien NF, Buttram SDW, Maa T, Lovett ME, Reuter-Rice K, LaRovere KL, et al. Cerebrovascular physiology during pediatric extracorporeal membrane oxygenation: a multicenter study using transcranial Doppler ultrasonography. Pediatr Crit Care Med. (2019) 20:178–86. doi: 10.1097/PCC.0000000000001778

PubMed Abstract | CrossRef Full Text | Google Scholar

17. Zamora CA, Oshmyansky A, Bembea M, Berkowitz I, Alqahtani E, Liu S, et al. Resistive index variability in anterior cerebral artery measurements during daily transcranial duplex sonography a predictor of cerebrovascular complications in infants undergoing extracorporeal membrane oxygenation? J Ultrasound Med. (2016) 35:2459–65. doi: 10.7863/ultra.15.09046

PubMed Abstract | CrossRef Full Text | Google Scholar

18. Bembea MM, Felling R, Anton B, Salorio CF, Johnston MV. Neuromonitoring during extracorporeal membrane oxygenation: a systematic review of the literature. Pediatr Crit Care Med. (2015) 16:558–64. doi: 10.1097/pcc.0000000000000415

PubMed Abstract | CrossRef Full Text | Google Scholar

19. Clair MP, Rambaud J, Flahault A, Guedj R, Guilbert J, Guellec I, et al. Prognostic value of cerebral tissue oxygen saturation during neonatal extracorporeal membrane oxygenation. PLoS ONE. (2017) 12:e0172991. doi: 10.1371/journal.pone.0172991

PubMed Abstract | CrossRef Full Text | Google Scholar

20. Kim HS, Ha SO, Yu KH, Oh MS, Park S, Lee SH, et al. Cerebral oxygenation as a monitoring parameter for mortality during venoarterial extracorporeal membrane oxygenation. ASAIO J. (2019) 65:342–8. doi: 10.1097/MAT.0000000000000827

PubMed Abstract | CrossRef Full Text | Google Scholar

21. Pozzebon S, Ortiz AB, Franchi F, Cristallini S, Belliato M, Lheureux O, et al. Cerebral near-infrared spectroscopy in adult patients undergoing veno-arterial extracorporeal membrane oxygenation. Neurocrit Care. (2018) 29:94–104. doi: 10.1007/s12028-018-0512-1

PubMed Abstract | CrossRef Full Text | Google Scholar

22. Wong JK, Smith TN, Pitcher HT, Hirose H, Cavarocchi NC. Cerebral and lower limb near-infrared spectroscopy in adults on extracorporeal membrane oxygenation. Artif Organs. (2012) 36:659–67. doi: 10.1111/j.1525-1594.2012.01496.x

PubMed Abstract | CrossRef Full Text | Google Scholar

23. Caicedo A, Papademetriou MD, Elwell CE, Hoskote A, Elliott MJ, Van Huffel S, et al. Canonical correlation analysis in the study of cerebral and peripheral haemodynamics interrelations with systemic variables in neonates supported on ECMO. Adv Exp Med Biol. (2013) 765:23–9. doi: 10.1007/978-1-4614-4989-8_4

PubMed Abstract | CrossRef Full Text | Google Scholar

24. Greenberg S, Murphy G, Shear T, Patel A, Simpson A, Szokol J, et al. Extracranial contamination in the INVOS 5100C versus the FORE-SIGHT ELITE cerebral oximeter: a prospective observational crossover study in volunteers. Can J Anaesth. (2016) 63:24–30. doi: 10.1007/s12630-015-0451-7

PubMed Abstract | CrossRef Full Text | Google Scholar

25. Flechet M, Guiza F, Scharlaeken I, Vlasselaers D, Desmet L, Van den Berghe G, et al. Near-infrared-based cerebral oximetry for prediction of severe acute kidney injury in critically ill children after cardiac surgery. Crit Care Explor. (2019) 1:e0063. doi: 10.1097/cce.0000000000000063

PubMed Abstract | CrossRef Full Text | Google Scholar

26. Veraar CM, Rinoesl H, Kuehn K, Skhirtladze-Dworschak K, Felli A, Mouhieddine M, et al. Non-pulsatile blood flow is associated with enhanced cerebrovascular carbon dioxide reactivity and an attenuated relationship between cerebral blood flow and regional brain oxygenation. Crit Care. (2019) 23:426. doi: 10.1186/s13054-019-2671-7

PubMed Abstract | CrossRef Full Text | Google Scholar

27. Tsou P-Y, Garcia AV, Yiu A, Vaidya DM, Bembea MM. Association of cerebral oximetry with outcomes after extracorporeal membrane oxygenation. Neurocrit Care. (2020) 33:429–37. doi: 10.1007/s12028-019-00892-4

PubMed Abstract | CrossRef Full Text | Google Scholar

28. Khan I, Rehan M, Parikh G, Zammit C, Badjatia N, Herr D, et al. Regional cerebral oximetry as an indicator of acute brain injury in adults undergoing veno-arterial extracorporeal membrane oxygenation-a prospective pilot study. Front Neurol. (2018) 9:993. doi: 10.3389/fneur.2018.00993

PubMed Abstract | CrossRef Full Text | Google Scholar

29. Tian F, Morriss MC, Chalak L, Venkataraman R, Ahn C, Liu H, et al. Impairment of cerebral autoregulation in pediatric extracorporeal membrane oxygenation associated with neuroimaging abnormalities. Neurophotonics. (2017) 4:041410. doi: 10.1117/1.NPh.4.4.041410

PubMed Abstract | CrossRef Full Text | Google Scholar