Difference in Cerebral and Hepatic Oxygenation in Response to Ultrafiltration in a Hemodialysis Patient With Congestive Heart Failure

Near-infrared spectroscopy has been used to measure regional oxygen saturation (rSO2), and intradialytic tissue rSO2 measurements have been playing an important role in evaluating changes in tissue oxygenation in various clinical settings of hemodialysis (HD) therapy.However, few reports have described changes in hepatic oxygenation associated with body fluid management in overhydrated HD patients. We herein report an HD patient with congestive heart failure (CHF) that had improved systemic and tissue oxygenation, including in the brain and liver, during HD with ultrafiltration. A 73-year-old man undergoing HD was admitted to our hospital with CHF. After admission, HD with ultrafiltration was performed to adequately manage his body fluid excess. Because of deterioration of systemic oxygenation on admission, we monitored his percutaneous arterial oxygen saturation (SpO2) using a pulse oximeter and regional oxygen saturation (rSO2) in the brain and liver using an INVOS 5100c oxygen saturation monitor during HD. At HD initiation, his cerebral and hepatic rSO2 levels were relatively low, at 43.2% and 34.1%, respectively, in addition to the SpO2 of 88%. During HD with ultrafiltration, systemic oxygenation evaluated by SpO2 and tissue oxygenation by cerebral and hepatic rSO2 improved. Interestingly, the hepatic rSO2 ratio, defined as the ratio of rSO2 values at t (min) during HD and the initial rSO2 value before HD, increased larger than the cerebral rSO2 ratio during HD. After the adjustment of body fluid condition under the maintained SpO2 values, we confirmed the hepatic and cerebral SO2 ratio again during HD, and these two values changed nearly in the same manner. Throughout our experience, in this case, we confirmed a remarkable increase in hepatic rSO2 ratio relative to cerebral rSO2 ratio under a CHF status during HD, and these differences disappeared after the adjustment of the body fluid status.


Introduction
Cardiovascular disease is known as one of the major complications in chronic kidney disease (CKD) patients, including those on hemodialysis (HD). Its prevalence has been affected by multiple factors, including body fluid excess, hypertension, anemia, and mineral bone disorder [1]. In addition, heart failure was reportedly the most important cause of death in patients on HD [2]. Therefore, adequate body fluid management is necessary to prevent the onset of cardiovascular disease, including congestive heart failure (CHF), and to improve patient prognosis [3,4].
Near-infrared spectroscopy has been used to measure regional oxygen saturation (rSO2), and intradialytic tissue rSO2 measurements, including those of the brain and liver, have been playing an important role in evaluating changes in tissue oxygenation in various clinical settings of HD therapy. Thus far, it has been reported that cerebral rSO2 is low at the onset of acute CHF and improves throughout the management of body fluid excess during HD with ultrafiltration [5], although cerebral and hepatic rSO2 were maintained during HD without intradialytic hypotension [6,7]. However, few reports have described changes in hepatic oxygenation associated with body fluid management in overhydrated HD patients. In this paper, we report an HD patient with CHF that had improved systemic and tissue oxygenation, including in the brain and liver, during HD. Furthermore, the relative increase in hepatic rSO2 might be larger than that in cerebral rSO2 in response to the improvement of body fluid status induced by ultrafiltration during HD.

Case Presentation
A 73-year-old man undergoing HD was referred to our hospital because of chest discomfort and dyspnea. His medical history included hypertension, diabetes mellitus, and myocardial infarction. At the time of referral, his body weight increased by 4.6 kg, which was nearly equivalent to 10% of his body weight, from the end of the last HD therapy two days ago. Furthermore, his chest radiograph showed perihilar vascular engorgement, and he was diagnosed with acute CHF due to excess body fluid. After admission, HD with ultrafiltration was performed to adequately manage his body fluid excess. Table 1 shows the vital signs, laboratory findings, and systemic oxygenation status before HD.  This patient provided informed consent before evaluation, and we monitored his percutaneous arterial oxygen saturation (SpO2) using a pulse oximeter (PULSOX-Me300; Teijin Pharma, Tokyo, Japan) and rSO2 in the brain and liver using an INVOS 5100c oxygen saturation monitor during HD. At HD initiation, cerebral and hepatic rSO2 levels were 43.2% and 34.1%, respectively, in addition to the SpO2 of 88%, even with the use of noninvasive positive pressure ventilation with oxygen administration. Throughout this HD procedure, systemic oxygenation evaluated by SpO2 and tissue oxygenation by cerebral and hepatic rSO2 improved (Figure 1a), and respiratory management using noninvasive positive pressure ventilation was able to be completed at the end of HD. Interestingly, the hepatic rSO2 ratio, which was defined as the ratio of rSO2 values at t (min) during HD and the initial rSO2 value before HD, increased larger than the cerebral rSO2 ratio during HD (Figure 1a). On the 4th hospital day without his respiratory symptoms under the maintained SpO2 values, we again confirmed the hepatic and cerebral SO2 ratio during HD. Before HD without oxygen inhalation, cerebral and hepatic rSO2 levels were 46.7 % and 36.7%, respectively (Table 1). Furthermore, values in cerebral and hepatic rSO2 were changed nearly in the same manner throughout the HD procedure (Figure 1b), in contrast to changes in those during HD with an overhydrated status.

Discussion
The progression of CKD has been associated with several major complications. Cardiovascular disease, including heart failure, is a major complication induced by excess sodium with fluid retention; its prevalence and severity also increase from early stage CKD to end-stage renal disease [1]. Indeed, heart failure was the most common cause of death (23.5%) in all-cause deaths in dialysis patients [2]. Therefore, in the field of HD therapy, it is important to adequately manage patients' body fluid status to prevent the prevalence of heart failure [3,4]. However, the causes of heart failure are known to be multifactorial [1]; therefore, it may be hard to completely prevent the onset of CHF in the clinical setting of HD therapy. Thus far, reports regarding tissue oxygenation, including the brain and liver, in patients with CHF and on HD have been limited. A review of the data and findings in previous reports of acute phase CHF and changes in tissue oxygenation are summarized in Table 2 [5,8,9]. Tissue oxygenation increased during treatment in CHF patients without future adverse outcomes. However, it was unchanged for those who later died or were readmitted. Lack of tissue oxygenation improvement maybe associated with higher rates of death and readmission.

Room air
Cerebral oxygenation deteriorated with the CHF status but was improved by body-fluid management during HD. [5] Brain 34 45

TABLE 2: Changes in tissue oxygenation throughout the treatment of congestive heart failure
Only three reports were found, which discussed the association between them. Two out of the three reports did not include patients with dialysis therapy [8,9] and only one case report was for an HD patient [5]. Tissue oxygenation was measured at the forehead [5,8] and hypothenar [9] and improved after CHF treatment in all reports. Particularly, ultrafiltration during HD had a positive effect on cerebral oxygenation [5] and lack of tissue oxygenation improvement might be associated with higher rates of death and readmission [9].
In HD patients without intradialytic hypotension, cerebral and hepatic rSO2 at HD initiation were 46.5 ± 1.3% and 52.4 ± 1.7%, respectively [7]. Furthermore, these rSO2 values were relatively constant despite ultrafiltration and cerebral rSO2 values were significantly lower than hepatic rSO2, which might be a specific feature of tissue oxygenation in HD patients without excess body fluid [7]. Recently, in a patient with acute CHF on HD, cerebral rSO2 reportedly increased during HD with ultrafiltration according to the systemic oxygenation increase [5]. This increase in cerebral rSO2 might have originated from the improvement of cerebral microcirculation associated with body fluid adjustment, in addition to the improvement of systemic oxygenation. Therefore, the increase in cerebral rSO2 in response to the improvement in body fluid status, in this case, might be consistent with a previous report [5]. Furthermore, hepatic rSO2 was 34.1%, which was relatively low compared to that in 43.2% of cerebral rSO2 in this case. However, the hepatic rSO2 ratio rapidly increased by ultrafiltration, and the degree of increase in hepatic rSO2 ratio was larger than that in cerebral rSO2 ratio during HD. Therefore, different from the relationship between cerebral and hepatic oxygenation without excess body fluid in HD patients [7], the deterioration in hepatic oxygenation may be larger than that in cerebral oxygenation under overhydrated status. In addition, hepatic oxygenation may be likely to improve compared to cerebral oxygenation according to the body fluid improvement induced by ultrafiltration. In this case, there might be a possibility to increase hepatic rSO2 beyond cerebral rSO2 in response to the further improvement in body fluid status, although hepatic rSO2 value was still low compared to that in cerebral rSO2 at second measurement after the improved CHF.
After his respiratory symptoms disappeared on the fourth hospital day, SpO2 dramatically improved at HD initiation even without oxygen inhalation. However, cerebral and hepatic rSO2 less improved compared to the SpO2 improvements. Previous studies reported no significant association between cerebral rSO2 and SpO2 in HD patients [10][11][12]. Therefore, the improvement of systemic oxygenation in the central circulation might be different from changes in tissue oxygenation in the microcirculation. That is, the improvement of microcirculation in tissues may be delayed compared to that of central circulation throughout the body fluid adjustment in HD patients. However, fluid status in the microcirculation could not be accurately evaluated and we cannot directly comment on these associations. Therefore, further studies are needed to investigate the mechanism of changes in systemic and tissue oxygenation in response to ultrafiltration in acute CHF.

Conclusions
We confirmed a remarkable increase in hepatic rSO2 ratio relative to cerebral rSO2 ratio under a CHF status during HD, and these differences disappeared after the adjustment of the body fluid status.

Additional Information Disclosures
Human subjects: Consent was obtained by all participants in this study. Institutional Review Board of the Saitama Medical Center, Jichi Medical University, Japan issued approval RIN 15-104. This patient provided written informed consent to participate. The study was approved by the Institutional Review Board of the Saitama Medical Center, Jichi Medical University, Japan (RIN 15-104) and conformed to the provisions of the Declaration of Helsinki (as revised in Tokyo in 2004). Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.