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A Cardiopulmonary Bypass Technique to 

Physiologically Abate the Deleterious 

Effects of Gaseous Microemboli 

Kristina Schmidt, BS 

Carrie Whittaker, MPS, CCP, FFP 

David Holt, MA, CCT 

University of Nebraska Medical Center, Omaha, NE

University of Nebraska Medical Center 

Objectives 

• Background 

• Hypothesis 

• Materials 

• Methods 

• Results 

• Conclusion 

• Study Limitations 

• References


Introduction 

• Neurocognitive impairment is a serious complication of bypass and can be caused by 

gaseous or particulate emboli (1). 

• Possible neurologic complications include stroke, coma, seizures, and memory 

impairment (2). 

• There are a plethera of ways for air to be introduced into the blood as it circulates 

through the perfusion circuit. Several include excessive suction, cavitation at turbulent 

regions of the circuit, mechanical jarring, and direct injection of gas by drug 

administration or other methods (3). 

• GME behavior within the extracorporeal circuit is multi-factorial. There is a complex 

interrelationship between such factors as flow, gaseous partial pressure, volume, 

solubility, buoyancy, perfusate, temperature, fluid viscosity, and ECC circuit design (19).


http://static.howstuffworks.com/gif/define-pulmonary-embolism-1.jpg 

http://www.sciencedaily.com/images/2006/07/060721195718.jpg


Introduction 

• Hyperoxia refers to using supraphysiologic levels of oxygen (21). 

• One of the reasons that perfusionists use hyperoxia is to prevent against the 

delivery of insoluble nitrogen bubbles to the body from the bypass circuit to 

the patient (5). 

• Running higher FiO 2 levels during cardiopulmonary bypass (CPB) increases 

the partial pressure of oxygen in the blood, in turn reducing the partial 

pressure of nitrogen. 

• Alteration of the composition of gaseous microbubbles through the use of 

hyperoxia can help to prevent the delivery of nitrogenous bubbles to the 

patient.


Henry’s Law 

At a constant temperature, the amount of a given gas 

dissolved in a given type and volume of liquid is directly 

proportional to the partial pressure of that gas in equilibrium 

with that liquid (13).


Hypothesis 

The purpose of the study is to demonstrate that hyperoxia 

can be a protective mechanism during CPB, due to the 

saturation of GME with easily absorbed and more soluble 

oxygen, by varying FiO 2 delivery to affect the solution’s 

partial pressures of oxygen and subsequently nitrogen.


Materials 

• 250 cc 0.9% sodium chloride injection 

• Cincinnati Sub-Zero Hemotherm cooler/heater, Model 400MR 

• BioMedicus centrifugal pump, Model 540 

• Terumo Capiox SX25 Hollow Fiber Oxygenator 

• ½ inch tubing 

• BioMedicus centrifugal pump, Model 540 

• BioMedicus BioProbe transducer Model TXOP 

• BioMedicus centrifugal cone 

• Medtronic Minimax bag reservoir 

• Sechrist air-oxygen mixer 

• Tubing clamps 

• Monoject 3ml syringes 

• Temperature monitor and probe on a Stockert III heart lung machine 

• Bayer Rapid Point Blood-Gas Analysis

University of Nebraska Medical Center



Methods 

• Assembled and primed circuit with 250 cc NaCl. 

• Turned heater/cooler to 37 degrees C and attached temperature probe to 

oxygenator. 

• Set flow and sweep on a 1:1 ratio of 2 L/min. 

• Testing points were randomized for the following FiO 2 s: 21, 50, 60, 70, 80, 

90, and 100%. 

• After 20 minutes of recirculating at the desired FiO 2 , 1.5cc of fluid was 

withdrawn from the luer port on the top of the venous bag. 

• Blood-gas analysis to obtain the PO 2 of the sample. 

• Mathematical derivation of PN 2 and solubility of both gases.


Sample Size 

• The data for this experiment was collected via a series of 21 separate runs 

using 7 different levels of FiO 2 with 3 runs at each level. 

• Conducting three tests at each level of FiO 2 was sufficient. The positive 

association seen in the initial pilot trial was strong and doing 3 tests at each 

level helped to provide an estimate of test variability at each level and 

helped to minimize Type II errors. 

• The order of the runs was randomized to minimize any random interference 

that could be related to the ordering (see next slide).


Randomized numbering 

1st time through - 0.9 0.7 0.6 1.0 0.21 0.8 0.5 

2nd time through - 0.5 0.6 0.7 1.0 0.9 0.21 0.8 

3rd time through - 0.5 0.9 0.8 0.7 0.21 0.6 1.0


Calculating Solubility 

• Air: 78% N 2 , 21% O 2 

• At 37 degrees C and 1atm (14)… 

N 2 solubility= .015 ml/mmHg/L 

O 2 solubility= .030 ml/mmHg/L 

http://www.bbc.co.uk/schools/gcsebitesize/science/im 

ages/50_composition_of_the_earth.gif



Calculating Solubility 

• The solubility of O 2 (in ml/L) was calculated with the following 

equation: 

= (PO 2 mmHg)(.03 ml/mmHg/L) 

• The solubility of N 2 (in ml/L) was calculated with the following 

equation: 

=(740 mmHg - PO 2 mmHg)(.015 ml/mmHg/L) 

…where 740 mmHg was the atmospheric pressure in Kansas City 

on the day of the experiment.


Assumptions 

• It was assumed that the resulting partial pressure of oxygen would increase 

linearly as the level of FiO 2 used in the hyperoxia process was increased. 

• A linear increase was also assumed for the solubility of oxygen while a linear 

decrease was assumed for the solubility of nitrogen. 

• As the solubility of oxygen and nitrogen are linear functions of the partial 

pressure of oxygen for a given temperature and atmospheric pressure, if any 

one of these three assumptions is correct, then all must be correct.


Table 1 

FiO 2 

Baseline 0.21 0.5 0.6 0.7 0.8 0.9 1.0 

PO 2 (mmHg) 

Trial 1 174.3 243.0 303.8 374.4 396.9 422.5 569.5 675.8 

Trial 2 170.2 253.7 300.5 377.2 411.8 432.8 583.6 659.0 

Trial 3 173.2 237.0 289.7 365.4 399.2 439.2 579.9 661.6 

Mean (sd) 172.6 (2.1) 244.6 (8.5) 298 (7.4) 372.3 (6.2) 402.6 (8) 431.5 (8.4) 577.7 (7.3) 665.5 (9) 

Solubility O 2 (ml/L) 

Trial 1 5.23 7.29 9.11 11.23 11.91 12.68 17.09 20.27 

Trial 2 5.11 7.61 9.02 11.32 12.35 12.98 17.51 19.77 

Trial 3 5.20 7.11 8.69 10.96 11.98 13.18 17.40 19.85 

Mean (sd) 5.18 (0.06) 7.34 (0.25) 8.94 (0.22) 11.17 (0.18) 12.08 (0.24) 12.95 (0.25) 17.33 (0.22) 19.96 (0.27) 

Solubility N 2 (ml/L) 

Trial 1 8.49 7.46 6.54 5.48 5.15 4.76 2.56 0.96 

Trial 2 8.55 7.29 6.59 5.44 4.92 4.61 2.35 1.22 

Trial 3 8.50 7.55 6.75 5.62 5.11 4.51 2.40 1.18 

Mean (sd) 8.51 (0.03) 7.43 (0.13) 6.63 (0.11) 5.52 (0.09) 5.06 (0.12) 4.63 (0.13) 2.44 (0.11) 1.12 (0.14)


Results 

• The measured PO 2 values increased proportionally to the FiO 2 values, and 

were used to calculate the solubility of both nitrogen and oxygen in the fluid. 

• The results demonstrated that the calculated solubility of oxygen increased 

from an FiO 2 of 21 to 100% (an average of 5.177 ml/L to 19.964 ml/L, 

respectively.) 

• In turn, the calculated solubility of nitrogen decreased with an increase in 

FiO 2 (8.5115 ml/L and 1.118 ml/L, respectively.)


Measured Results: FiO 2 vs. PO 2 

700 

600 

500 

PO 2 

400 

300 

200 

100 

0 

Trial 1 

Trial 2 

Trial 3 

0 0.2 0.4 0.6 0.8 1 1.2 

FiO 2

Solubility O 2 (ml/L) 


Calculated Results: FiO 2 vs. Solubility of O 2 

25 

20 

15 

10 

5 

0 

Trial 1 

Trial 2 

Trial 3 

0 0.2 0.4 0.6 0.8 1 1.2 

FiO 2

Solubility N 2 (ml/L) 


Calculated Results: FiO 2 vs. Solubility of N 2 

8 

7 

6 

5 

4 

3 

2 

1 

0 

Trial 1 

Trial 2 

Trial 3 

0 0.2 0.4 0.6 0.8 1 1.2 

FiO 2


Statistical Analysis 

• An Ordinary Least Squares Regression (OLS Regression) was performed to 

test for an association between the FiO 2 level and the partial pressure of 

oxygen, solubility of oxygen, and solubility of nitrogen. 

• This regression results allow t-test analysis to determine if the coefficients in 

the model are significantly different from zero. 

• In each of the three regression models, the coefficient for the slope of the 

linear association between the FiO 2 level and each of the three outcomes 

was significantly different from zero, suggesting that there is a relationship 

between the FiO 2 level and each of the three outcomes.


Table 2: Linear Regression Results (N=21) 

Coefficient 

Estimates 

PO 2 (mmHg) 

Intercept 

(se) 

74.6 

(32.4) 

p-value 

0.03 

FiO 2 

(se) 

524.5 

(45.2) 

p-value 


Discussion 

• This research experiment reinforced the accepted theory that PO 2 

will increase as FiO 2 increases. 

• The calculated data also showed a correlation that perhaps many 

perfusionists do not think of- the affect that FiO 2 has on the solubility 

of gases and GME. 

• Amidst the controversy of hyperoxia, the author of this study aimed 

to show how a high oxygen tension can be beneficial to patients in 

which GME are suspected.


Discussion 

• The authors do, however, recognize there are certain instances where 100% FiO 2 s 

should not be used. 

• Reperfusion injury occurs when antioxidants are deactivated during cellular acidosis 

from ischemia followed by capillary reperfusion with warm, oxygenated blood (16). 

• Many hospitals have changed their protocols to normoxic perfusion because of studies 

suggesting increased myocardial injury by free radicals during and after hyperoxia (8). 

• A high PO 2 after cross- clamp removal could result in increased generation of 

deleterious free radical species, but oxygen loading before any period of ischemia might 

negate that risk (21).


Discussion 

• Another argument against the use of hyperoxia during surgery is that it may 

exacerbate retrolental fibroplasia. 

• This is caused by long-term exposure to elevated PaO 2 . It is typically due to 

prolonged ventilatory requirements of premature neonates and is not 

generally a concern in the time length of CPB. 

• In reality, a change to 100% FiO 2 will not drastically increase the amount of 

oxygen the patient receives. 

• The amount of oxygen available to the tissues that can cause reperfusion 

injury is much more dependent on the hemoglobin concentration than the 

sweep FiO 2 (6).


Study Limitations 

• A non-blood prime was used. 

• In blood, bubbles become coated with protein, and this affects how 

bubbles move through solution. 

• In the future, a similar experiment should be done using blood to 

avoid any possible data corruption.


Study Limitations 

• Originally, the authors of this study had planned to conduct the 

experiment differently. 

• The initial methods involved injecting a bolus of room air, which is 

primarily composed of nitrogen, into the venous bag reservoir. 

• The idea was to draw up the bubble into an oxygen analyzer to see 

if the bubble had changed its composition during hyperoxic 

circulation. 

http://www.fetamed.com/images/MiniOx_Oxygen_Analyzer.gif


Conclusion 

• While many perfusionists and surgeons consistently use a certain 

oxygenation strategy regardless of patient parameters, a high FiO 2 

may be beneficial when it comes to fighting air emboli. 

• This study focused on hyperoxia and its direct effect on preventing 

the harmful consequences of GME. Further research is needed to 

study hyperoxia’s effects on this topic, as well as the other benefits 

or possible deleterious effects this gas strategy may have.


References 

1. Gaseous Micro Emboli: Concepts and Considerations. Butler, BD. 2006, JECT, Vol. 38, pp. 271-279. 

2. An In Vitro Study of the Effectiveness of Carbon Dioxide Flushing of Arterial Line Filters. Beckman, R., Gisner, C., 

Evans, E. JECT, Vol. 41, pp. 161-165. 

3. Attenuation of Neurologic Injury During Cardiac Surgery. Murkin, JM. 2001, Annals of Thoracic Surgery, Vol. 72, pp. 

1838-34. 

4. Clinically silent cerebral ischemic events after cardiac surgery: their incidence, regional vascular occurrence, and 

procedural dependence. Floyd TF, Shah PN, Price CC, et al. The Annals of Thoracic Surgery, Vol. 81, pp. 

2160-6. 

5. Gas embolism: pathophysiology and treatment. Van Hulst RA, Klein J, Lachmann B. 2003, Clin Physiol Funct 

Imaging, pp. 26-237. 

6. Gaseous Microemboli and Hyperoxia. Grist, G. 2006, JECT, pp. 367-369. 

7. Solubility. Bookrags. [Online] 2005. [Cited: December 6, 2009.] http://www.bookrags.com/research/solubility-woc/. 

8. Oxygenation Strategy and Neurologic Damage After Deep Hypothermic Circulatory Arrest. II. Hypoxic Versus Free 

Radical Injury. Nollert, G., et al. 1999, The Journal of Thoracic and Cardiovascular Surgery, pp. 1172-1179. 

9. Whittaker, C. Email correspondence. 2008. 

10. Gaseous Microemboli and the Influence of Microporous Membrane Oxygenators. Weitkemper, H., Oppermann, B., 

Spilker, A., Knobl, H., Reiner, K. 2005, JECT, pp. 256-264.


11. The Theoretical Prediction of Safe Deep Hypothermic Circulatory Arrest (DHCA) Time Using Estimated Tissue 

Oxygen Loading. Whittaker, C., Grist, G. 2008, Progess in Pediatric Cardiology, pp. 117-122. 

12. Postoperative Management of Cerebral Air Embolism: Gas Physiology For Surgeons. Tovar EA., Del Campo C., 

Borsari A., et al. 1995, Annals of Thoracic Surgery, pp. 1138-1142. 

13. Pauling, Linus. General Chemistry. s.l. : Dover Publications, 1988. 

14. Durrant, Philip John. General and Inorganic Chemistry. 1939, p. 168. 

15. Commerce, U.S. Department of. National Oceanic and Atmospheric Administration. National Weather Service. 

[Online] October 5, 2009. http://www.nws.noaa.gov. 

16. Myocardial Reperfusion Injury: Etiology, Mechanisms, and Therapies. Hoffman Jr JW., Gilbert TB., Poston RS., 

Silldorff EP. 2004, JECT, pp. 391-411. 

17. Normoxia vs. Hyperoxia: Impact of Oxygen Tension Strategies on Outcomes for Patients Receiving Cardiopulmonary 

Bypass for Routine Cardiac Surgical Repair. Brown, M., Holt, D., Edwards, J., Burnett, R. 2006, JECT, pp. 

241-248. 

18. Wallace, O. What is Retrolental Fibroplasia. Wise Geek. [Online] 2009. [Cited: March 30, 2009.] 

http://www.wisegeek.com/what-is-retrolental-fibroplasia.htm. 

19. Emboli Generation by the Medtronic Maxima Hardshell Adult Venous Reservoir in Cardiopulmonary Bypass Circuits: 

A Preliminary Report. Mitchell, S. J., Wilcox, T., McDougal, C., Gorman, D. F. 1996, Perfusion, Vol. 11, pp. 

145-155. 

20. Air Solubility in Water. Engineering Tool Box. [Online] 2005. [Cited: December 6, 2009.] 

http://www.engineeringtoolbox.com/gases-solubility-water-d_1148.html. 

21. Effects of Hyperoxia on Neonatal Myocardial Energy Status and Response to Global Ischemia. Wittnich, C., Torrance, S., Carlyle, 

C. 2000, The Society of Thoracic Surgeons, pp. 2125-31.

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