When kidney failure occurs, patients are at risk for fluid overload states, which can cause pulmonary edema, pleural effusions, and upper airway obstruction. Kidney disease is also associated with impaired respiratory function, as in central sleep apnea or chronic obstructive pulmonary disease. Hence, respiratory and renal diseases are frequently coexisting. Hypoxemia is the terminal pathway of a multitude of respiratory pathologies. The measurement of oxygen saturation (SO2) is a basic and commonly used tool in clinical practice. Both arterial oxygen saturation (SaO2) and central venous oxygen saturation (ScvO2) can be easily obtained in hemodialysis (HD) patients, SaO2 from an arteriovenous access and ScvO2 from a central catheter. Here, we give a brief overview of the anatomy and physiology of the respiratory system, and the different technologies that are currently available to measure oxygen status in dialysis patients. We then focus on literature regarding intradialytic SaO2 and ScvO2. Lastly, we present clinical vignettes of intradialytic drops in SaO2 and ScvO2 in association with different symptoms and clinical scenarios with an emphasis on the pathophysiology of these cases. Given the fact that in the general population hypoxemia is associated with adverse outcomes, including increased mortality, cardiac arrhythmias and cardiovascular events, we posit that intradialytic SO2 may serve as a potential marker to identify HD patients at increased risk for morbidity and mortality.

Patients with chronic kidney disease (CKD) show a vast spectrum of signs and symptoms as a result of damage in different organs. Recently, pulmonary manifestations associated with CKD gained increased attention in clinical practice and research. Studies are focusing on the links between pulmonary function and renal damage, and it has been proposed to classify these clinical manifestations as ‘cardio-pulmonary-renal' syndrome [1].

For the study of respiratory pathologies in hemodialysis (HD) patients, the measurement of the hemoglobin (Hgb) oxygen saturation (SO2) has been shown to be valuable. More than 20 years ago, it has been demonstrated that SaO2 decreases during extracorporeal renal replacement therapy [2], and recently, a comparable observation has been made for ScvO2[3]. The purpose of this review is to provide an overview about intradialytic SaO2 and ScvO2 during HD and its clinical correlates.

Structure of the Respiratory System

Disturbances of oxygenation can occur at any level of the cardio-pulmonary system and evaluation of oxygen status must take a variety of different factors into account. The respiratory system is a complex set of organs with the main purpose of delivering oxygen to the blood and removing carbon dioxide.

On its way to the lungs, air passes through the epipharyx, trachea, and two principal bronchi, which then further divide into lobular, segmental and terminal bronchioles. This portion of the respiratory tract holds approximately 150 ml and is known as ‘anatomic dead space', because there is no gas exchange. The terminal bronchioles then branch off into the respiratory bronchioles, which are the transition zone between the upper and the lower airways. The lower respiratory tract is the air exchange compartment and consists of the respiratory bronchioles and alveolar ducts, which are full of alveolar sacs. This compartment can hold a volume of 2.5-3 liters (fig. 1). The alveolar sacs are complex structures that form the air-blood interface with a surface area of about 75 m2 in healthy adults [4].

Fig. 1

Airway anatomy.

Gas Exchange

Respiration is the result of three principal mechanisms: ventilation, diffusion and perfusion [1]. Ventilation is the transport of air into the lungs, which is driven by respiratory muscles and regulated primarily by the respiratory center in the brain stem [5]. The respiratory center integrates neural, chemical and hormonal signals and controls the rate and depth of respiratory movements of respiratory muscles. Chemoreceptors measure chemical signals such as changes in pH, carbon dioxide and oxygen concentration in the blood. These signals are then relayed to the respiratory center. Additionally, baroreceptors in the chest may affect ventilation patterns [6]. Alterations in ventilation can be due to disturbances at the neural level, of respiratory muscles, of chest bones or of airways [7]. The pulmonary perfusion is in series to the right heart and depends on the cardiac output. The relationship between alveolar ventilation and perfusion is a key determinant of gas exchange, and diffusion is the principal mechanism of gas exchange at the air-gas interface.

Oxygenation

Once oxygen has entered the blood by diffusion across the alveolar membranes it is either reversibly bound to Hgb in the red blood cells or dissolved in the plasma. The amount of dissolved oxygen depends on the oxygen partial pressure (PaO2; also called oxygen tension) and the solubility coefficient of oxygen (0.0031 ml/dl/mm Hg). The fraction of Hgb molecules carrying oxygen (SO2) depends on the partial pressure of oxygen and the Hgb oxygen affinity. The latter is modified by the blood pH (Bohr effect), partial pressure of carbon dioxide (Haldane effect), 2,3-diphosphoglycerate (2,3-DPG) levels inside erythrocytes, and blood temperature. All of those factors may change during dialysis [8,9,10]. The blood oxygen-carrying capacity (CaO2) depends on the concentration of Hgb and its affinity to oxygen [11]. One gram of Hgb is able to carry approximately 1.34 ml of oxygen [12]. At sea level, around 98% of the oxygen in the blood is bound to Hgb and 2% dissolved in the plasma.

CaO2 is calculated as follows:

CaO2 (ml O2/dl blood) = 1.34 (ml/g) × Hgb concentration (g/dl) × SaO2 (%) / 100 + 0.0031 (ml/dl/mm Hg) × PaO2 (mm Hg)

In a healthy subject, a single erythrocyte carries around 250-300 million Hgb molecules, resulting in a Hgb concentration inside the cell of around 330 g/l. This means that at a hematocrit of 45%, the Hgb concentration is 150 g/l [8]. Therefore, in healthy subjects, 100 ml of blood has the capacity to bind approximately 20 ml of oxygen. However, carbon monoxide and methemoglobin render Hgb incapable of binding oxygen, thereby reducing the oxygen-carrying capacity.

Thus, the content of oxygen in the blood depends not only on the aforementioned ventilation, diffusion and perfusion but also on the oxygen-carrying capacity of the blood. The oxygen content of the venous blood depends additionally on the extraction of oxygen at the tissue level. Sufficient delivery of oxygen to tissues depends on a well-regulated interplay between these factors (fig. 2).

Fig. 2

Interactions between ventilation, diffusion, perfusion and oxygen-carrying capacity. All these factors affect the blood oxygen content. CNS = Central nervous system.

Fig. 2

Interactions between ventilation, diffusion, perfusion and oxygen-carrying capacity. All these factors affect the blood oxygen content. CNS = Central nervous system.

Close modal

The normal arterial pH of 7.35-7.45 is carefully maintained by the lungs, kidneys and plasma buffers. The predominant buffering mechanism is the carbonic acid/bicarbonate system [13]. Other major buffers include plasma proteins and phosphate ions [14]. When the hydrogen (H+) content in the blood increases, it combines with bicarbonate (HCO3-) to become carbonic acid (H2CO3-).

HCO3- + H+ ↔ H2CO3 ↔ H2O + CO2

Carbonic acid breaks down into water and carbon dioxide; the carbon dioxide diffuses into the lung alveoli and is exhaled. An increase in CO2 triggers the central and peripheral chemoreceptors and thus stimulates ventilation [15]. Reduced central nervous respiratory drive, impaired gas diffusion, or neuromuscular disorders that affect ventilation may result in respiratory acidosis. Conversely, hyperventilation results in respiratory alkalosis. Dialysis patients often suffer from acidosis, which is corrected during HD by the influx of bicarbonate from the dialysate.

Hypoxia indicates an inadequate tissue oxygen supply. In HD patients, several types of hypoxia can be differentiated. Anemic hypoxia is caused by a decreased concentration of functional Hgb or a reduced number of red blood cells. Hypoxic hypoxia results from impaired pulmonary blood oxygenation, abnormal pulmonary function, airway obstruction, or cardiac right-to-left shunt. Ischemic hypoxia is characterized by tissue oligemia and may be caused by reduced tissue perfusion due to vasculopathies [16].

The 2 primary means to assess oxygen status are the measurement of PaO2 and SaO2. Normal values for PaO2 range from 85 to 100 mm Hg [17]. Values between 60 and 80 mm Hg are considered ‘mild hypoxia', values between 40 and 60 mm Hg ‘moderate hypoxia' and values <40 mm Hg indicate ‘severe hypoxia' [16]. An arterial SaO2 >95% is considered normal at an altitude below 1,000 m [17]. Although there is no universally agreed-upon definition, most sources define hypoxemia as SaO2 ≤90% [18,19,20]. The arterial oxygen status is primarily indicative of the respiratory function, although nonrespiratory pathologies may also play a role.

A number of devices allow clinicians to assess the blood oxygen status (table 1). Blood gas analyzers measure partial pressure (PaO2) of oxygen in blood samples using an electrode to measure the electric currents generated from a set of oxidation-reduction reactions. Once PaO2 is obtained, the analyzer calculates the SO2 using empiric models, which may differ between manufacturers [21]. SO2 can be measured noninvasively by optical methods utilizing the fact that oxygenated and deoxygenated Hgb have different light absorption characteristics. Pulse-oximetry probes are usually attached to a finger to measure SO2 either in a static and continuous fashion [22,23]. Near-infrared spectroscopy is used for the measurement of regional tissue SO2 [24,25]. Of particular relevance to the dialysis field is the measurement of SO2 in the extracorporeal circuit during dialysis (CritLine Monitor™; CLM). This device obtains SO2 using different wavelengths and absorption-based algorithms. Depending on the vascular access type, SaO2 or ScvO2 is measured.

Table 1

Devices for measuring SO2 in HD

Devices for measuring SO2 in HD
Devices for measuring SO2 in HD

In HD patients with arteriovenous vascular access, SaO2 can be determined from measurements in the arterial blood line of the extracorporeal circuit. Nielsen and Jensen [16] reported a high correlation between blood gases in the radial artery and the arterial line of HD patients with a well-functioning fistula. However, a few points deserve consideration when interpreting the arterial oxygen status in a HD patient. Anemia may lead to a reduced arterial oxygen content, which escapes detection when considering SaO2 or PaO2 only. Further, an increase in pH during dialysis causes a left shift of the oxygen disassociation curve, reducing oxygen release in the tissue. Erythrocyte 2,3-DPG levels may decline during dialysis and thus increase the Hgb oxygen affinity [9].

A low arterial oxygen status is the common terminal pathway of multiple functional and structural pathologies; sleep apnea, chronic obstructive pulmonary disease, pulmonary edema, and pulmonary calcification are particularly prevalent in HD patients [26,27,28,29,30]. Munger et al. [31] monitored SO2, arrhythmias and silent ischemia in 10 ESRD males and found that all subjects demonstrated intradialytic hypoxemia. All patients had episodes of cardiac ectopy and 5 subjects had a total of 89 episodes of silent ischemia. They postulated that the hypoxia likely contributed to the incidence of arrhythmias and silent ischemia [31]. Sleep apnea syndromes are associated with ventricular arrhythmias, ventricular tachycardia, atrial fibrillation and bradyarrhythmias [32]. In healthy men who are subjected to acute hypoxia, there is an increase in myocardial oxygen extraction, and increased coronary blood flow [33]. However, the incidence of coronary artery disease is high in the ESRD population, and as previously discussed, the SO2 curve shifts to the left during dialysis, decreasing Hgb oxygen disassociation, potentially affecting adversely the patient's ability to cope with the hemodynamic stress during HD. Recently we assessed intradialytic SaO2 in a large cohort of chronic HD patients [34]. In 8% of patients, the mean intradialytic SaO2 was below 90% and 12% had an intradialytic SaO2 below 90% for more than a third of their treatment time, a condition we labeled ‘prolonged intradialytic hypoxemia'. We found that prolonged intradialytic hypoxemia was associated with an inflammatory phenotype [35]. Longitudinal studies are necessary to examine the long-term effects of intradialytic hypoxia.

Other studies demonstrated a drop of PaO2 as well as SaO2 at the beginning of HD treatments reaching a nadir after 30-60 min and then returning to pre-dialysis levels or even rising slightly above starting values toward the end of HD [36,37]. We were able to corroborate these findings (fig. 3). This phenomenon generated much interest in the early days of dialysis; the causes remain unclear until today and seem to be multifactorial. The magnitude of the PaO2 decline varies depending on the type of dialysis membrane and dialysate composition. A proposed mechanism is a complement-mediated leukostasis in small pulmonary vessels caused by bioincompatible dialysis membranes leading to an alveolar ventilation/perfusion mismatch. Further, bicarbonate influx during HD leads to an increase of pH and subsequent hypoventilation and possibly also hypoxemia [38]. In addition, fluid overload may adversely impact alveolar oxygen diffusion, resulting in reduced blood oxygenation (fig. 4). Approaching dry weight should decrease the diffusion distance and thus improve blood oxygenation. In fact, Anand et al. [39] found a positive relationship between the slope of the relative blood volume (RBV) curve, an indirect marker of volume status, and change in SaO2 indicating a contribution of volume overload to hypoxemia. Clinical Vignette 1 exemplifies this phenomenon.

Fig. 3

Time course of mean SaO2 and 95% CI in chronic HD patients with arteriovenous access.

Fig. 3

Time course of mean SaO2 and 95% CI in chronic HD patients with arteriovenous access.

Close modal
Fig. 4

Causes of hypoxemia.

Fig. 4

Causes of hypoxemia.

Close modal

Most patients sleep at some point during dialysis. Clinical Vignette 2 illustrates intradialytic SaO2 drop while the patient was sleeping. During the sleep hours, the central respiratory control is not as tightly regulated as when awake. In dialysis patients, uremic destabilization of the central respiratory control, as well as fluid status related narrowing of the upper airway may be additional factors contributing to episodes of sleep apnea and low SaO2 during dialysis treatments [40]. The incidence of sleep apnea syndromes is much higher in the dialysis population, compared to the general population [41]. Moreover, age-related changes of the respiratory system, such as a weakening of the neuro-mechanical link between chemosensors, brain stem and respiratory muscles, may lead to a reduced ability to maintain blood gas homeostasis in elderly chronic HD patients [42].

Clinical observations indicate that low SaO2 can be associated with a rapid increase in hematocrit during HD, indicative of a reduced vascular refill (Clinical Vignette 3). However, the underlying pathophysiology is not fully elucidated. The physiological responses to intradialytic blood volume reduction resemble to some extent those seen with hemorrhage. First, the reduction in blood volume leads to a reduction in venous return, resulting in a decrease of cardiac output and mean arterial pressure. This is compensated by an increased heart rate and arterial and venous constriction, resulting in increased total peripheral resistance and enhanced venous return. The arteriolar constriction leads to a reduced blood flow in capillaries and thereby a reduced capillary hydraulic pressure, promoting fluid absorption from the interstitium into the capillaries (vascular refill). However, the reduction of blood flow also results in the reduction of oxygen delivery and accumulation of metabolic waste products such as adenosine and lactic acid, which cause vasodilation of arterioles. This vasodilation restores oxygen delivery and blood flow in the capillaries but also leads to an increase of hydraulic capillary pressure and a decrease in vascular refill [43]. An increase of blood oxygen content, for example, by the administration of supplemental oxygen may have the potential to mitigate a drop in blood volume.

Clinical Vignettes 4 and 5 demonstrate that drops in SaO2 and ScvO2, respectively and may coincide with muscle cramps, a frequent intradialytic morbid event [44]. Again, the pathophysiology underlying these observations is not clear [45]. There is a dearth of studies on the association between hypoxia and muscle cramps. Of note, it has been shown in patients with obstructive sleep apnea that continuous positive airway pressure improved or resolved nocturnal leg cramping [46,47]. Clinical observations made authors of this study indicate that the application of oxygen already at the beginning of the treatment prevents or reduces cramps in many patients who frequently experience cramps during HD.

While little is known about the relationship between intradialytic and interdialytic SaO2, it is interesting to note that hypoxia may continue for hours even after HD is completed. Dhakal et al. [48] studied 10 maintenance HD patients, and continuously monitored their SO2 up to 4 h post-HD. In this study, hypoxic episodes were observed as late as 4 h after dialysis.

ScvO2 represents the SO2 of blood drawn from the superior vena cava. ScvO2 is easily obtained in HD patients with central venous catheters, as the catheter tip is usually located at the cavoatrial junction. ScvO2 is clinically valuable as it is a surrogate of pulmonary artery mixed venous oxygen saturation (SvO2), which reflects cardiac output, tissue oxygen delivery, and tissue oxygen extraction [49]. There has been much debate regarding the use of ScvO2 as a surrogate for SvO2. Animal studies in dogs and pigs have demonstrated a good correlation between ScvO2 and SvO2 [50,51]. Human studies have also shown a linear association; however, SvO2 measurements are consistently lower than ScvO2[52]. This is likely due to the fact that the ScvO2 is mostly a measure of upper body oxygen consumption, while the SvO2 includes deoxygenated blood from the lower body and coronary sinus [53]. In addition, during sepsis or heart failure, ScvO2 tends to be higher than SvO2 because of decreased extraction at peripheral tissue, and increased oxygen delivery to the upper body. While the absolute numbers did not correlate, the changes in SvO2 reflected changes in ScvO2 [53,54].

ScvO2 measurement is currently used in critical care and post-surgery monitoring. Rivers et al. [55] have advocated for early goal directed care in sepsis, with measurement of ScvO2 as one of these measures. Obtaining ScvO2 >70% was associated with improved outcomes. Studies showed benefits of monitoring ScvO2 during high-risk surgery, where ScvO2-guided fluid and volume resuscitation were associated with improvements in length of intensive care unit stay, morbidity and mortality [56,57]. Low ScvO2 or SvO2 indicate inadequate tissue oxygenation, either from decreased cardiac output and oxygen delivery or high extraction of oxygen at the tissue level. Despite a body of literature showing the utility of ScvO2 monitoring, data in the dialysis population are scarce.

Eating is generally discouraged during HD, given the concern for hypotension. In healthy subjects eating increases both splanchnic and hepatic blood flow [58]. There is a drop in systemic vascular resistance, accompanied by an increase in both heart rate and cardiac output to maintain blood pressure [59,60,61]. However, postprandial hypotension is seen particularly in patients with autonomic dysfunction, patients with hypertension, elderly patients, patients with cardiovascular disease, and patients with renal failure on HD [62]. The hypotension seen in this patient population is partially explained by an inadequate sympathetic response; the heart rate, cardiac output, and peripheral vasoconstriction do not increase appropriately to the drop in systemic vascular resistance and splanchnic blood pooling [59,63]. Dialysis further limits the cardiovascular systems' ability to compensate, as it decreases blood volume and right ventricular refill due to ultrafiltration, potentially further decreasing cardiac output. Clinical Vignette 6 highlights these points, as approximately 30 min into the meal, the patient's blood volume drops, cardiac output presumably fails to increase appropriately, as demonstrated by a drop in ScvO2, and hypotension ensues.

Cordtz et al. [64] were the first to evaluate ScvO2 in 20 HD patients who were classified as either hypotension prone (HP) or hypotension resistant (HR). While both patient groups started at the same ScvO2 (HP 52.2 ± 6.7% vs. HR 49.7 ± 6.9%), intradialytic ScvO2 only decreased in the HP group. Harrison et al. [3] further expanded on the topic by examining ScvO2 in 18 prevalent dialysis patients. In their study population, they found a strong inverse correlation between ultrafiltration rate (UFR) and ScvO2 (r = -0.680). Clinical Vignette 7 illustrates these findings. This patient had a low baseline ScvO2, and with increasing ultrafiltration, ScvO2 dropped further; finally, saline was administered because of hypotension. Hypotension on dialysis is a common occurrence and it is linked to decreased blood volume and decreased cardiac output [65]. HD is also associated with decreased myocardial blood flow and an increased incidence of regional wall motion abnormalities (RWMAs), which further decrease cardiac output [66,67]. One study found that increasing UF during HD was associated with increased odds of developing RWMAs [68]. In clinical Clinical Vignette 7, 3 h into HD blood volume had decreased to such an extent that apparent cardio-vascular compensatory mechanisms could no longer maintain cardiac output, as reflected by a decrease in ScvO2. With fluid bolus administration, the blood volume increased, and cardiac output, blood pressure, and ScvO2 improved.

We assessed ScvO2 in 25 patients during 294 HD treatments using CLM. In our population, a majority of patients spent the dialysis treatments with mean ScvO2 between 50 and 60%, lower than 70%, which is generally considered normal [49]. Of note, other studies in HD patients have also shown a mean ScvO2 <70% [3,64]. In our patient cohort, a ScvO2 increase in the first hour was followed by a steady decline to levels well below those at HD start (fig. 5). The etiology of these findings is unclear. However, the incidence of congestive heart failure is high in HD patients, and patients usually start HD sessions fluid overloaded. We speculate that the initial ultrafiltration may improve cardiac contractility, cardiac output and tissue perfusion. However, as more fluid is removed, a decrease in cardiac refill and cardiac output may result in poor tissue perfusion and subsequent ScvO2 decline.

Fig. 5

Time course of mean ScvO2 and 95% CI in 25 chronic HD patients with central venous catheters as access.

Fig. 5

Time course of mean ScvO2 and 95% CI in 25 chronic HD patients with central venous catheters as access.

Close modal

ScvO2 has long been used in critical care settings as a marker of adequate tissue perfusion and appropriate resuscitation. Systematically collected data on ScvO2 and HD are scarce; however, some data suggest the low ScvO2 is associated with intradialytic hypotension (IDH) and high UFR. Both IDH and high UFR are associated with increased incidence of cardiac events [67,68,69]. ScvO2 may be a useful monitoring tool to identify high-risk patients; however, further studies are needed to explore that notion.

Respiratory system integrity and function are susceptible to malfunction in CKD and dialysis patients. In addition to pulmonary edema, pleural effusions, and pulmonary calcifications, respiratory control pathways are frequently affected, such as in sleep apnea syndrome. Hypoxemia is a frequent terminal pathway of respiratory pathologies. Current technologies allow continuous measurement of SO2 during routine HD. Clinical observations suggest that intradialytic hypoxemia is associated with intradialytic morbid events, such as hypotension and cramping. While these are important hypothesis-generating clinical observations, further investigations are necessary to define causal pathways.

We would like to thank Patrick Hill from Hill Studio Design for help with preparation of the clinical vignettes.

P.K. holds stock in Fresenius Medical Care.

1.
Husain-Syed F, McCullough PA, Birk HW, Renker M, Brocca A, Seeger W, Ronco C: Cardio-pulmonary-renal interactions: a multidisciplinary approach. J Am Coll Cardiol 2015;65:2433-2448.
2.
Jones JG, Bembridge JL, Sapsford DJ, Turney JH: Continuous measurements of oxygen saturation during haemodialysis. Nephrol Dial Transplant 1992;7:110-116.
3.
Harrison LE, Selby NM, McIntyre CW: Central venous oxygen saturation: a potential new marker for circulatory stress in haemodialysis patients? Nephron Clin Pract 2014;128:57-60.
4.
West JB: Respiratory Physiology: The Essentials. Philadelphia, Lippincott Williams & Wilkins, 2012.
5.
Mazzone SB, Canning BJ: Central nervous system control of the airways: pharmacological implications. Curr Opin Pharmacol 2002;2:220-228.
6.
Sant'Ambrogio G, Tsubone H, Sant'Ambrogio FB: Sensory information from the upper airway: role in the control of breathing. Respir Physiol 1995;102:1-16.
7.
Roussos C, Macklem PT: The respiratory muscles. N Engl J Med 1982;307:786-797.
8.
Pittman RN: Chapter 4: oxygen transport; in Regulation of Tissue Oxygenation. San Rafael, Morgan & Claypool Life Sciences, 2011.
9.
Chillar RK, Desforges JF: Muscular cramps during maintenance haemodialysis. Lancet 1972;2:285.
10.
De Broe ME, De Backer WA: Pathophysiology of hemodialysis-associated hypoxemia. Adv Nephrol Necker Hosp 1989;18:297-315.
11.
Thom CS, Dickson CF, Gell DA, Weiss MJ: Hemoglobin variants: biochemical properties and clinical correlates. Cold Spring Harb Perspect Med 2013;3:a011858.
12.
Dijkhuizen P, Buursma A, Fongers TM, Gerding AM, Oeseburg B, Zijlstra WG: The oxygen binding capacity of human haemoglobin. Hufner's factor redetermined. Pflugers Arch 1977;369:223-231.
13.
Ayers P, Dixon C, Mays A: Acid-base disorders: learning the basics. Nutr Clin Pract 2015;30:14-20.
14.
Johnson RJ, Feehally J, Floege J: Comprehensive Clinical Nephrology, ed 5.
15.
Lindinger MI, Heigenhauser GJ: Effects of gas exchange on acid-base balance. Compr Physiol 2012;2:2203-2254.
16.
Nielsen AL, Jensen HA: Oxygen status: a standard evaluation in uremic patients? Dial Transplant 1994;23:288-302.
17.
Hasan A: The analysis of blood gases & factors modifying the accuracy of ABG results; in Handbook of Blood Gas/Acid-Base Interpretation. London, Springer, 2009, pp 279-295.
18.
O'Driscoll BR, Howard LS, Davison AG; British Thoracic Society: BTS guideline for emergency oxygen use in adult patients. Thorax 2008;63:vi1-vi68.
19.
Morris RW, Buschman A, Warren DL, Philip JH, Raemer DB: The prevalence of hypoxemia detected by pulse oximetry during recovery from anesthesia. J Clin Monit 1988;4:16-20.
20.
Tyler IL, Tantisira B, Winter PM, Motoyama EK: Continuous monitoring of arterial oxygen saturation with pulse oximetry during transfer to the recovery room. Anesth Analg 1985;64:1108-1112.
21.
Severinghaus JW: Blood gas calculator. J Appl Physiol 1966;21:1108-1116.
22.
Nitzan M, Romem A, Koppel R: Pulse oximetry: fundamentals and technology update. Med Devices (Auckl) 2014;7:231-239.
23.
Jubran A: Pulse oximetry. Crit Care 2015;19:272.
24.
Foo JY, Chua KP, Tan XJ: Clinical applications and issues of oxygen saturation level measurements obtained from peripheral sites. J Med Eng Technol 2013;37:388-395.
25.
Scheeren TW, Schober P, Schwarte LA: Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): background and current applications. J Clin Monit Comput 2012;26:279-287.
26.
Harnett JD, Foley RN, Kent GM, Barre PE, Murray D, Parfrey PS: Congestive heart failure in dialysis patients: prevalence, incidence, prognosis and risk factors. Kidney Int 1995;47:884-890.
27.
Roumelioti ME, Buysse DJ, Sanders MH, Strollo P, Newman AB, Unruh ML: Sleep-disordered breathing and excessive daytime sleepiness in chronic kidney disease and hemodialysis. Clin J Am Soc Nephrol 2011;6:986-994.
28.
Unruh ML, Sanders MH, Redline S, Piraino BM, Umans JG, Hammond TC, Sharief I, Punjabi NM, Newman AB: Sleep apnea in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the Sleep Heart Health Study. J Am Soc Nephrol 2006;17:3503-3509.
29.
Plesner LL, Warming PE, Nielsen TL, Dalsgaard M, Schou M, Host U, Rydahl C, Brandi L, Kober L, Vestbo J, Iversen K: Chronic obstructive pulmonary disease in patients with end-stage kidney disease on hemodialysis. Hemodial Int 2015, Epub ahead of print.
30.
Jarava C, Marti V, Gurpegui ML, Merello JI, Rdez-Quesada B, Palma A: Pulmonary calcification in chronic dialysis patients. Nephrol Dial Transplant 1993;8:673-674.
31.
Munger MA, Ateshkadi A, Cheung AK, Flaharty KK, Stoddard GJ, Marshall EH: Cardiopulmonary events during hemodialysis: effects of dialysis membranes and dialysate buffers. Am J Kidney Dis 2000;36:130-139.
32.
Padeletti M, Zaca V, Mondillo S, Jelic S: Sleep-disordered breathing increases the risk of arrhythmias. J Cardiovasc Med (Hagerstown) 2014;15:411-416.
33.
Kaijser L, Grubbstrom J, Berglund B: Coronary circulation in acute hypoxia. Clin Physiol 1990;10:259-263.
34.
Zhang H, Meyring-Wösten A, Ye X, Fuertinger DH, Kappel F, Artemyev M, Ginsberg N, Thijssen S, Kotanko P: Sp734 intradialytic arterial oxygen saturation in chronic hemodialysis patients - results from a large us population. Nephrol Dial Transplant 2015;30(suppl 3):iii620.
35.
Meyring-Wösten A, Zhang H, Ye X, Fuertinger DH, Kappel F, Artemyev M, Ginsberg N, Thijssen S, Kotanko P: Sp685 clinical associations of prolonged intradialytic hypoxemia in hemodialysis patients: results from a population-based study. Nephrol Dial Transplant 2015;30(suppl 3):iii605.
36.
Alfakir M, Moammar MQ, Ali MI, Alhatem E, Curran RD, Saoud RM, Chandran C, Khan MA, Debari VA: Pulmonary gas exchange during hemodialysis: a comparison of subjects with and without COPD on bicarbonate hemodialysis. Ann Clin Lab Sci 2011;41:315-320.
37.
Yilmaz H, Bozkurt A, Cakmak M, Celik HT, Bilgic MA, Bavbek N, Akcay A: Relationship between late arteriovenous fistula (AVF) stenosis and neutrophil-lymphocyte ratio (NLR) in chronic hemodialysis patients. Ren Fail 2014;36:1390-1394.
38.
Pierson DJ: Respiratory considerations in the patient with renal failure. Respir Care 2006;51:413-422.
39.
Anand S, Sinha AD, Agarwal R: Determinants and short-term reproducibility of relative plasma volume slopes during hemodialysis. Clin J Am Soc Nephrol 2012;7:1996-2001.
40.
Roumelioti ME, Brown LK, Unruh ML: The relationship between volume overload in end-stage renal disease and obstructive sleep apnea. Semin Dial 2015;28:508-513.
41.
Hanly P: Sleep apnea and daytime sleepiness in end-stage renal disease. Semin Dial 2004;17:109-114.
42.
Janssens JP, Pache JC, Nicod LP: Physiological changes in respiratory function associated with ageing. Eur Respir J 1999;13:197-205.
43.
Pittman RN: Chapter 9: exercise and hemorrhage; in Regulation of Tissue Oxygenation. San Rafael, Morgan & Claypool Life Sciences, 2011.
44.
Rocco MV, Burkart JM: Prevalence of missed treatments and early sign-offs in hemodialysis patients. J Am Soc Nephrol 1993;4:1178-1183.
45.
Miller TM, Layzer RB: Muscle cramps. Muscle Nerve 2005;32:431-442.
46.
Reddy PL, Grewal RP: Resolution of muscle cramps and fasciculations with treatment of sleep apnea. J Clin Neuromuscul Dis 2009;11:66-67.
47.
Westwood AJ, Spector AR, Auerbach SH: CPAP treats muscle cramps in patients with obstructive sleep apnea. J Clin Sleep Med 2014;10:691-692.
48.
Dhakal MP, Kallay MC, Talley TE: Hemodialysis associated hypoxia extends into the post-dialysis period. Int J Artif Organs 1997;20:204-207.
49.
Walley KR: Use of central venous oxygen saturation to guide therapy. Am J Respir Crit Care Med 2011;184:514-520.
50.
Reinhart K, Rudolph T, Bredle DL, Hannemann L, Cain SM: Comparison of central-venous to mixed-venous oxygen saturation during changes in oxygen supply/demand. Chest 1989;95:1216-1221.
51.
Schou H, Perez de Sa V, Larsson A: Central and mixed venous blood oxygen correlate well during acute normovolemic hemodilution in anesthetized pigs. Acta Anaesthesiol Scand 1998;42:172-177.
52.
Chawla LS, Zia H, Gutierrez G, Katz NM, Seneff MG, Shah M: Lack of equivalence between central and mixed venous oxygen saturation. Chest 2004;126:1891-1896.
53.
Scheinman MM, Brown MA, Rapaport E: Critical assessment of use of central venous oxygen saturation as a mirror of mixed venous oxygen in severely ill cardiac patients. Circulation 1969;40:165-172.
54.
Grissom CK, Morris AH, Lanken PN, Ancukiewicz M, Orme JF Jr, Schoenfeld DA, Thompson BT; National Institutes of Health/National Heart, Lung and Blood Institute Acute Respiratory Distress: Association of physical examination with pulmonary artery catheter parameters in acute lung injury. Crit Care Med 2009;37:2720-2726.
55.
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-1377.
56.
Collaborative Study Group on Perioperative ScvO2 Monitoring: Multicentre study on peri- and postoperative central venous oxygen saturation in high-risk surgical patients. Crit Care 2006;10:R158.
57.
Pearse R, Dawson D, Fawcett J, Rhodes A, Grounds RM, Bennett ED: Changes in central venous saturation after major surgery, and association with outcome. Crit Care 2005;9:R694-R699.
58.
Brandt JL, Castleman L, Ruskin HD, Greenwald J, Kelly JJ Jr: The effect of oral protein and glucose feeding of splanchnic blood flow and oxygen utilization in normal and cirrhotic subjects. J Clin Invest 1955;34(7, part 1):1017-1025.
59.
Sivalingam M, Banerjee A, Nevett G, Farrington K: Haemodynamic effects of food intake during haemodialysis. Blood Purif 2008;26:157-162.
60.
Fagan TC, Sawyer PR, Gourley LA, Lee JT, Gaffney TE: Postprandial alterations in hemodynamics and blood pressure in normal subjects. Am J Cardiol 1986;58:636-641.
61.
Barakat MM, Nawab ZM, Yu AW, Lau AH, Ing TS, Daugirdas JT: Hemodynamic effects of intradialytic food ingestion and the effects of caffeine. J Am Soc Nephrol 1993;3:1813-1818.
62.
Jansen RW, Lipsitz LA: Postprandial hypotension: epidemiology, pathophysiology, and clinical management. Ann Intern Med 1995;122:286-295.
63.
Kistler BM, Fitschen PJ, Ikizler TA, Wilund KR: Rethinking the restriction on nutrition during hemodialysis treatment. J Ren Nutr 2015;25:81-87.
64.
Cordtz J, Olde B, Solem K, Ladefoged SD: Central venous oxygen saturation and thoracic admittance during dialysis: new approaches to hemodynamic monitoring. Hemodial Int 2008;12:369-377.
65.
Chesterton LJ, Selby NM, Burton JO, Fialova J, Chan C, McIntyre CW: Categorization of the hemodynamic response to hemodialysis: the importance of baroreflex sensitivity. Hemodial Int 2010;14:18-28.
66.
McIntyre CW, Burton JO, Selby NM, Leccisotti L, Korsheed S, Baker CS, Camici PG: Hemodialysis-induced cardiac dysfunction is associated with an acute reduction in global and segmental myocardial blood flow. Clin J Am Soc Nephrol 2008;3:19-26.
67.
McIntyre CW: Haemodialysis-induced myocardial stunning in chronic kidney disease - a new aspect of cardiovascular disease. Blood Purif 2010;29:105-110.
68.
Burton JO, Jefferies HJ, Selby NM, McIntyre CW: Hemodialysis-induced cardiac injury: determinants and associated outcomes. Clin J Am Soc Nephrol 2009;4:914-920.
69.
Parfrey PS, Foley RN, Harnett JD, Kent GM, Murray DC, Barre PE: Outcome and risk factors for left ventricular disorders in chronic uraemia. Nephrol Dial Transplant 1996;11:1277-1285.

Israel Campos and Lili Chan contributed equally.

Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.