At rest, the body normally extracts only 25% of the total amount of oxygen delivered. In a healthy steady state, DO 2 is luxurious when compared to oxygen demands with approximately 75% of the oxygen delivered remaining unused. Oxygen extraction varies across organ beds with some organs being high extractors (i.e. brain and myocardium) and other organs being low extractors (i.e. skin and kidneys). A true mixed venous saturation (SmvO 2 ) allows for a global assessment of the body’s oxygen extraction. The measurement must occur after venous return from all organ beds is “mixed” to avoid having the SmvO 2 be refl ective of a single organ’s bed oxygen extraction. Using a pulmonary artery catheter, the SmvO 2 is obtained in the pulmonary artery. Without a pulmonary artery catheter in place, the pulmonary artery SmvO 2 can be closely approximated by sampling venous blood from a central catheter with its tip at the SVC – RA junction. When a venous blood saturation is determined from the SVC-RA junction or other central site it is referred to as a central venous saturation (ScvO 2 ) or right atrial saturation. The normal oxygen saturation of central venous blood returning to the right heart (ScvO 2 ) is between 65% and 80%. Central venous oxygen saturation values below 60% indicate increased oxygen extraction by the tissues. This may be due to either a decrease in oxygen delivery or an increase in tissue oxygen demands. Common causes of decreased oxygen delivery include reduced cardiac output, anemia, and/or low arterial oxy- gen saturation (hypoxia). Alternatively, a low ScvO 2 may be refl ective of increased tissue oxygen demands in the setting of increased work of breathing, fever, seizures, shivering, pain, physical activity or catheter migration to the coronary sinus. Low ScvO 2 values below 60%
are often accompanied by acidosis due to a shift to anaerobic metabolism (see lactate below).
A normal or high ScvO 2 may also be associated with tissue hypoxia. An elevated ScvO 2 may occur with appropriate or even supranormal DO 2 in the setting of impaired cellular and or mitochondrial oxygen uptake. This may lead to cellular hypoxia and may be observed in the setting of severe vasodilatory sepsis or mitochondrial poisoning (i.e. cyanide toxicity).
Pulse contour waveform analysis evaluates the AUC of the systolic portion of the arterial wave form and equates it to stroke volume.
The estimation of the stroke volume from pulse contour analysis during heart rate monitoring allows for beat-to- beat CO assessment. The compliance of the arterial tree must be considered when using pulse contour analysis.
Due to the dynamic nature of arterial compliance, the use of pulse contour analysis requires serial calibration with another method of CO determination such as transpulmonary
thermodilution.
It is important to note, that although a good surrogate for SmvO 2 , ScvO 2 may vary based on catheter position, disease state and even age of the child. In the healthy state, the superior vena cava (SVC) has a slightly lower venous saturation than the inferior vena cava (IVC) in part due to high cerebral oxygen extraction and low renal oxygen extraction. This is espe- cially true in small children where the relatively large growing brain is a major oxygen extractor. Therefore, the SmvO 2 is greater than ScvO 2 by about 2-3%. The relationship between the SVC and IVC saturation may reverse in the setting of shock. (Figure 5-26 ).
During cardiogenic or hypovolemic shock, mesenteric and renal blood fl ow decrease and oxygen extraction increases causing the IVC saturation to become lower than the SVC.
Therefore, during certain shock states, the ScvO 2 may become greater than SmvO 2 . Despite these important differences, most authors believe that changes in ScvO 2 closely refl ect changes in SmvO 2 and therefore remains a good marker of tissue perfusion.
In summary, a decreased ScvO 2 is associated with decrements in cardiac output, hemoglo- bin concentration and arterial saturation and it varies inversely with oxygen consumption. It is an extremely useful marker for tissue hypoperfusion and can be followed serially to deter- mine the impact of therapeutic maneuvers such as fl uid resuscitation, blood transfusion and inotropic support (Table 5-9 ). Achievement of ScvO 2 ³ 70% is a therapeutic endpoint in the resuscitation from sepsis and septic shock as articulated in the Surviving Sepsis Campaign sponsored by the Society of Critical Care Medicine.
Lactate
Lactate metabolism is complex and its production is highly dependent upon physiological conditions at the cellular level. Although lactic acidosis is often used as a marker of cellular hypoxia, it may be elevated in non-hypoxemic environments. A biochemical review of lactate production is helpful in understanding hyperlactatemia during critical illness.
LOW SCVO 2 HIGH SCVO 2
• Anemia • High cardiac output states
• Low cardiac output states • Defect in oxygen extraction
• Hypoxia • Decreased metabolic rate
• Increased metabolic rate • Supranormal oxygen delivery
TABLE 5-9
TROUBLESHOOTING
ABNORMALITIES IN MIXED OR CENTRAL VENOUS SATURATIONS
Low SvO 2 is associated with decreased cardiac output anemia, arterial desaturation or with states of high oxygen consump- tion. It is an extremely useful marker for tissue hypoperfusion and can be followed serially to determine the impact of thera- peutic maneuvers such as fl uid resuscitation, and inotropic support.
SVC SVC
74%
ScvO2 64%
RA
RA
78% 54%
IVC IVC
RV
RV 76%
60%
PA PA
CS CS
40% 38%
SmvO2
SmvO2 ScvO2
FIGURE 5-26
Relationship between central venous saturation (ScvO 2 ) and mixed venous saturation (SmvO 2 ) during health (left) and cardiogenic or hypovolemic shock (right).
Normally, the SmvO 2 will be slightly higher than the ScvO 2 , whereas shock states may produce a reversal of this relationship. SVC -superior vena cava, IVC - inferior vena cava, RA - right atrium CS - coronary sinus, RV - right ventricle
Cellular respiration is the process by which glucose is utilized to produce cellular energy in the form of adenosine triphosphate (ATP) (Fig. 5-27 ). The cytosolic component of the process does not require oxygen and consists of glycolysis whereas the mitochondrial por- tion is highly dependent on oxygen and consists of the tricarboxylic acid (TCA) cycle (also known as citric acid cycle or Krebs cycle) and oxidative phosphorylation (also referred to as mitochondrial membrane electron transport). During glycolysis, glucose is converted to pyruvate with the net production of 2 molecules of ATP. The majority of energy production occurs in the mitochondria during the tricarboxylic acid cycle (2 ATP) and oxidative phos- phorylation (32 ATP). A small amount of lactate is normally produced during glycolysis, but it is rapidly metabolized by the liver and excreted by the kidney. Thus, normal serum lactate levels remain less than 2 mmol/L. Lactate production is increased dramatically during hypoxia. Due to low oxygen tension, pyruvate can no longer undergo aerobic metabolism in the mitochondria and is shunted toward lactate production. Hypoxia is also known to decrease the activity of pyruvate dehydrogenase which converts pyruvate to acetyl CoA. The contin- ued shunting of pyruvate towards lactate production results in an elevated serum lactate and an elevation in the lactate to pyruvate ratio (normal 10:1).
Lactic acidosis due to hypoperfusion has been traditionally referred to as type A lactic acidosis and is associated with an elevated lactate to pyruvate ratio. Elevated lactate in the setting of acidosis has been use as marker of tissue hypoperfusion and anaerobic metabolism.
Multiple studies have correlated rising lactate levels and mortality in patients with a variety of critical illnesses. However, studies utilizing lactate as a resuscitation endpoint to improve sur- vival have been inconclusive. An explanation for the diffi culty in using lactate as a sole marker of successful resuscitation is that lactate production occurs due to non-hypoxemic stimuli.
Hyperlactatemia in critical illness is often not solely due to cellular hypoxia. Described as nonhypoxemic or type B lactic acidosis, elevations of serum lactate may occur during normal perfusion or after hypoperfusion has been corrected. Lactate production may be increased during states of “hyperglycolysis”. Excessive catecholamine states have been found to stimu- late glycolysis at a rate that exceeds the oxidative capacity of the mitochondria and lead to type b lactic acidosis. Increased skeletal muscle and hepatic glycolysis results in increases in bolth pyruvate and lactate production thus maintaining the lactate to pyruvate ratio. The resul- tant increased pyruvate is then metabolized to lactate at a much higher than normal rate.
Hyperadrenergic states are common in the pediatric ICU and include exogenous administra- tion of catecholamines and disorders associated with a vigorous systemic infl ammatory response (e.g. acute lung injury, trauma, sepsis, burns). Type A or type B lactic acidosis may be further accentuated in the setting of decreased hepatic metabolism and/or renal clearance.
Serum lactate is increased during low oxygen conditions as pyruvate can no longer undergo aerobic metabolism in the mitochondria and is shunted toward lactate production.
FIGURE 5-27
Overview of cellular respiration and lactate production
Acetyl CoA NAD
NADH 2 ATP
Aerobic conditions Anaerobic
conditions Lactate
Glucose Glucose
Pyruvate
34 ATP Oxidative Phosphorylation Glycolysis
REVIEW QUESTIONS
1. Which statement accurately refl ects the utility of the physical assessment of the cardiovascular status of a child?
A. Capillary refi ll time is independent of ambient temperature.
B. Pulse pressure will be decreased in conditions characterized by low systemic vascular resistance.
C. Tachycardia, in and of itself, is a sensitive and specifi c sign of hemodynamic instability.
D. The peripheral skin to ambient temperature gradient (dTp-a) decreases during states of high systemic vascular resistance.
E. Urine output is infl uenced by many factors and therefore should not serve as a proxy for distal tissue perfusion.
2. In the following illustration of an arterial waveform, which number identifi es the incisura or dicrotic notch?
A 2
3
1
4 5
Hyperlactatemia may also occur due to drug or toxin effects. Any drug that interferes with the TCA cycle or oxidative phosphorylation may lead to excessive lactate production.
These medications includes metformin, salicylates, HMG CoA reductase inhibitors, cya- nide, iron and propofol. Inborn errors of metabolism may also present with profound eleva- tions in the serum lactate. Examples of inborn errors of metabolism that may present with lactic acidosis include pyruvate dehydrogenase defi ciency, pyruvate decarboxylase defi - ciency, glucose-6-phosphatase defi ciency, fructose-1,6-diphosphatase defi ciency and mito- chondrial disorders. In addition, certain malignancies may be associated with hyperlactemia.
Finally, hyperlactatemia may be caused by elevation in the D -isomer of lactate. This is usu- ally observed in states of intestinal bacterial overgrowth as occurs in short gut syndrome.