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Ann Thorac Surg 2002;74:2132-2137
© 2002 The Society of Thoracic Surgeons


Original article: cardiovascular

Does vacuum-assisted venous drainage increase gaseous microemboli during cardiopulmonary bypass?

Timothy J. Jones, FRCSa,b, Dwight D. Deal, BSa,b, Jason C. Vernon, BSa,b, Noel Blackburn, CCPa,b, David A. Stump, PhDa,b*

a Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
b Department of Department of Perfusion, Cleveland Clinic, Cleveland, Ohio, USA

Accepted for publication July 22, 2002.

* Address reprint requests to Dr Stump, Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1009, USA.
e-mail: dstump{at}wfubmc


    Abstract
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: Vacuum-assisted venous drainage enables adequate drainage through small-diameter cannulas but concerns are that it results in more gaseous microemboli delivered to the patient.

METHODS: Five identical embolus detectors monitored the propagation of entrained air through a cardiopulmonary bypass (CPB) model. The ability of the CPB circuit to remove gaseous microemboli was studied with vacuum-assisted venous drainage and gravity siphon venous drainage using different pump speeds and rates of gaseous microemboli delivery.

RESULTS: Under all conditions entrained venous air resulted in the detection of gaseous microemboli in the perfusate after the arterial filter. In blood-primed circuits, increased flow rates and higher levels of vacuum-assisted venous drainage were independently associated with increased gaseous microemboli counts in the arterial line. Vacuum-assisted venous drainage at -40 mm Hg did not significantly increase gaseous microemboli activity when compared with gravity siphon venous drainage at 4 L/min flow rate.

CONCLUSIONS: Vacuum-assisted venous drainage at -40 mm Hg does not statistically reduce the ability of the CPB circuit to remove gaseous microemboli at lower pump rates. High levels of vacuum and increased pump flow rates should be avoided. Air should not be introduced into the venous line.


    Introduction
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Cardiac surgery and the use of cardiopulmonary bypass (CPB) are associated with damage to end organs. Brain injury during surgery is relatively common with 6.1% of patients suffering a major neurologic event [1]. Two thirds of patients experience brain dysfunction after surgery which persists in as many as 20% of patients at 3 months [2]. Perioperative renal impairment of varying severity occurs in 7.7% of patients with the development of severe renal dysfunction requiring supportive therapy resulting in an increase in mortality to more than 60% [3]. Lung injury and damage to the splanchnic viscera [4] during CPB are well documented and similarly increase morbidity and mortality.

The etiology of the above injuries is varied and probably multifactorial [5]. There is substantive evidence, however, particularly with regard to brain injury [6] implicating emboli as a cause of organ damage during CPB. Emboli may be gaseous, liquid, or particulate and they may originate in the circulation or be introduced into the circulation. Gaseous microemboli (GME) may either be entrained into the CPB circuit [7] or they may be generated by the circuit components such as the oxygenator [8], venous reservoir, or roller occlusive pump [9]. Circuit design and CPB technique are directed toward eliminating the generation of GME. The risk of inadvertent air embolism will always be present and the circuit components should be able to significantly reduce and preferably stop any GME from reaching the patient.

With the advent of minimally invasive cardiac surgery and the progression of congenital heart surgery there is a desire to reduce the diameter of the venous cannula to improve surgical access, decrease pump priming volumes, and enable cannulation of vessels remote from the heart. Unfortunately, decreasing cannula diameter increases resistance and reduces the adequacy of gravity siphon venous drainage (GSVD). Vacuum-assisted venous drainage (VAVD) is a method of active venous drainage dependent upon maintaining a negative pressure in the venous reservoir to ensure adequate venous drainage through small diameter cannula and tubing. Although the advantages of VAVD have been detailed, it has been suggested that the technique decreases the ability of the CPB circuit to remove GME thereby subjecting the patient to increased numbers of emboli [10].

The present study uses five identical embolus detectors to simultaneously monitor the propagation of venous entrained air through circuit components in an experimental model of adult CPB. Using reproducible volumes of entrained air we studied the influence of VAVD and GSVD on the ability of the CPB circuit to remove GME. In addition the influence of variations in pump flow and rate of GME delivery on GME behavior were studied.


    Material and methods
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Circuit design
A standardized in vitro model of an adult CPB circuit (see Fig 1) was used for all experiments. The circuit contained a Bentley BMR-4500S GOLD Filtered Venous Reservoir (Baxter Healthcare, Irvine, CA), Bentley SpiralOxy Hollow Fiber Oxygenator (Baxter Healthcare), and a Bentley AF-1040D Duraflo II 40 µm arterial filter (Baxter Healthcare). A new circuit was constructed for each experiment from single-use, sterile items with no component being reused. Standardized lengths of 1/2 inch and 3/8 inch clinical bypass tubing (Baxter Healthcare) were used to complete the circuit. Flow was generated by a properly occluded and calibrated roller occlusive pump (model 5000; Sarns, Ann Arbor, MI). The heat exchanger of the oxygenator was connected to an external heater-cooler unit (Sarns). VAVD was regulated using a Bentley Vacuum pack connected to the hard-shell venous reservoir (Baxter Healthcare).



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Fig 1. Schematic of model cardiopulmonary bypass circuit demonstrating detector location and air introduction. (EDAC = embolus detection and classification systems.)

 
An 8 L polycarbonate carboy (Nalgene, Rochester, NY) served as the "patient." A two-stage, 29/29F venous cannula was connected to the carboy outflow for VAVD experiments and a 34/46F cannula for GSVD experiments. In all cases arterial inflow was through a 24F curved tip, single lumen aortic cannula placed in the top of the carboy with the tip submerged and directed away from the venous outflow. A thermistor connected to a calibrated temperature meter was also placed in the carboy.

All circuits were flushed with carbon dioxide for 5 minutes before priming and deairing according to clinical standards. The circuits were primed with fresh, anticoagulated bovine blood (Sierra Medical, Santa Fe Springs, CA) corrected to a hematocrit of 24% ± 1% using isotonic saline.

Air introduction
A Luer lock connector was cut into the venous line midway between the venous cannula and the venous reservoir to enable the introduction of air. A 60 ml quantity of air was introduced either rapidly as a bolus to replicate a sudden catastrophic event or as a steady stream to replicate a nonocclusive atrial purse string or leaking connector. The volume of air delivered was standardized by displacement of a 60 ml column of air by water either introduced rapidly from a pressurized (300 mm Hg) intravenous giving set or slowly by a Harvard Apparatus syringe pump. The rapid or bolus introduction lasted 12 seconds and the slower or stream method lasted 120 seconds.

Experimental conditions
All circuits were maintained at 37°C. The venous reservoir level was maintained at 800 ± 25 mL through a variably occlusive Hoffman Clamp placed on the venous line.

A perfusate pO2 of 200 ± 50 mm Hg was achieved using 95% air and 5% CO2, adjusting gas flow rates to match pump flow rates. The arterial line pressure was measured from the top of the arterial filter and maintained at 200 ± 10 mm Hg using a second Hoffman Clamp located on the arterial line proximal to the aortic cannula. For VAVD experiments the level of suction was set through the vacuum controller, and the corresponding negative pressure was recorded through a transducer located on the top of the venous reservoir.

Embolus detection and validation
Embolic activity was monitored simultaneously at five locations using five identical embolus detection and classification (EDAC) systems. The five transducers were attached to modified Bentley Oxysat Optical Transmission Cells (Baxter Healthcare) cut into the tubing in the venous line, after the venous reservoir, after the roller pump, postoxygenator, and postarterial filter. Preliminary studies demonstrated this method of transducer attachment to be associated with the least variation in counts arising from variations in probe orientation.

The EDAC system was developed jointly by Orincon Corporation and Embolus Incorporated, funded by National Institutes of Health and National Medical Technology Testbed. Each EDAC system consists of a 5 mHz "active sonar" transducer connected to a Pentium personal computer operating on a Windows-based system. Signal analysis and processing enables rejection of motion artifacts, radio frequency interference, and other such causes of false alarms. The system is able to count GME as small as 40 micron. Figure 2, taken during validation work, demonstrates synchronized acoustic signal collection and image capture of GME using a camera interfaced with the EDAC system.



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Fig 2. The embolus detection and classification (EDAC) system was validated by interfacing with a camera for synchronized image and signal capture. (GME= gaseous microemboli.)

 
Before each experiment the five EDAC systems were compared with each other on a circulating closed-loop circuit. One milliliter of air was injected into the circuit and repeated counts were taken over a 10-minute period to ensure intersystem and intrasystem reliability.

Conduct of study
Three identical circuits were perfused with blood (hematocrit of 24% ± 1%). During each experiment the circuit was studied using GSVD, VAVD (-40 mm Hg), and VAVD (-65 mm Hg). Each type of venous drainage was studied at 4 L/min and 6 L/min pump flow rates. After achievement of steady-state and for all conditions, 60 mL air was introduced into the venous line either as a bolus or as a stream. Emboli were counted over the next 2 minutes. Each trial was repeated three times and between trials a steady-state was reestablished. The combination of circuit, method of venous drainage, flow rate, and air delivery was determined by a randomization schedule.

An additional three identical circuits were primed with deionized water and the experimental sequence was repeated. Deionized water was used as a protein deficient, clear perfusate to enable comparison of results with other investigators who have published their studies of the behavior of GME using non blood primes. The clear prime also enabled visualization and recording of the flow characteristics of GME with a video camera.

Statistical analysis
Repeated measures analysis of variance was used to test the effects of venous drainage, flow rate, and air delivery on the emboli count in the arterial line. Residual analyses determined that log(x + 1) transformation of the emboli counts was necessary to normalize the data. Geometric means with their 95% confidence limits are reported as appropriate after log-transformation. Bonferroni corrections were made for multiple comparisons on post-hoc comparisons only when the corresponding repeated measures main effects or their interactions were not statistically significant. All analyses were performed using SAS version 8 (SAS Institute, Cary, NC) at an {alpha} of 0.05.


    Results
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
In all circuits, under all study conditions, before the introduction of air into the venous line there was no spontaneous GME activity recorded. After the introduction of 60 ml of air into the venous line, GMEs were detected in the arterial line beyond the arterial filter during all conditions. Negative pressure measured at the top of the venous reservoir was always within ±5% of the pressure set on the vacuum regulator. The hematocrit was 24 for all blood primed circuits.

The emboli counts for the blood filled circuits are presented in Table 1. The rate of air delivery did not influence arterial line GME counts, but the main effects for suction and flow rate were significant. Increased flow rates resulted in significantly more emboli during GSVD (p= 0.022) and VAVD -65 mm Hg (p= 0.010), but not during VAVD -40 mm Hg (p= 0.144). Similarly, increased suction (VAVD -65 mm Hg) was associated with increased arterial GME counts compared with GSVD (p= 0.011). The effect of GSVD versus VAVD -40 mm Hg was not statistically significant at 4 L/min flow rate (p= 0.095), but it did become significant at 6 L/min (p= 0.044).


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Table 1. Blood: Geometric Means and Their 95% Confidence Limits

 
Performance of circuit components
The use of five detectors enabled the air handling performance of each circuit component to be studied simultaneously. Figure 3 illustrates the progression of GME through the blood primed circuits. The majority of GME were removed by the venous reservoir and arterial filter.



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Fig 3. The progression of gaseous microemboli through a cardiopulmonary bypass circuit primed with blood. (GSVD= gravity siphon venous drainage;VAVD -40= vacuum-assisted venous drainage at -40 mm Hg pressure;VAVD -65= vacuum-assisted venous drainage at -65 mm Hg pressure.)

 
Water primed circuits
In the circuits primed with deionized water the method of venous drainage, pump flow rate and rate of air delivery did not statistically influence the ability of the circuit to remove GME. In contrast to the blood primed circuits, GME removal principally occurred at the venous reservoir and the oxygenator as illustrated in Figure 4. The emboli counts for the venous line and arterial line are presented in Table 2.



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Fig 4. The progression of gaseous microemboli through a cardiopulmonary bypass circuit primed with distilled water. (GSVD= gravity siphon venous drainage; VAVD -40= vacuum-assisted venous drainage at -40 mm Hg pressure; VAVD -65= vacuum-assisted venous drainage at -65 mm Hg pressure.)

 

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Table 2. Distilled Water: Geometric Means and Their 95% Confidence Limits

 

    Comment
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
In this model of CPB, the introduction of 60 mL air into the venous line always resulted in detection of GME distal to the arterial filter in every circuit tested (both blood and deionized water primed). In blood primed circuits, increased flow rates (6 L/min) and higher levels of VAVD (-65 mm Hg) were independently associated with increased numbers of GME in the arterial line. VAVD at -40 mm Hg did not increase GME activity when compared with GSVD at 4 L/min.

The observation that the GME handling characteristics of the oxygenator was reduced in the blood circuits may be explained by the fact that bubbles develop a platelet, lipoprotein capsule when exposed to blood [11, 12]. The formation of the capsule increases the residence time of the bubble [13] and may reduce the ability of CPB components to remove GME.

In a similar in vitro study, Willcox and associates [10] also detected GME after the arterial filter after the entrainment of air into the venous line when using VAVD (-60 mm Hg) and GSVD. They reported a direct relationship between the volume of air entrained and the number of GME detected postarterial filter. When introducing air at a fixed rate they were unable to demonstrate a significant difference in arterial line GME counts between GSVD and VAVD. In contrast when they introduced 50 mL air at an unrestricted rate there was a 10-fold increase in arterial line GME counts when using VAVD compared with GSVD. We introduced the same volume of air in a controlled manner at different rates, and this did not significantly influence arterial line GME counts under any condition. This suggests either the unrestricted introduction of a volume of air changes the physical property of the resulting GME or the pressure dynamics of the circuit or the difference may be accounted for by variations in study design. Willcox and associates [10] ventilated the oxygenator but the circuits were studied at room temperature as compared with the present study where the circuits were maintained at 37°C. Colder solutions contain a greater number of molecules and therefore become saturated sooner than warmer solutions [14]. In addition, they studied salvaged, reused clinical CPB circuits consisting of a Medtronic (Minneapolis, MN) venous reservoir and oxygenator in combination with a Baxter (Irvine, CA) arterial filter.

In a recent study LaPietra and associates [15] used a nonblood prime to study the effects of VAVD and kinetically assisted venous drainage on entrained venous air. In agreement with the present study and the findings of Willcox and associates they demonstrated GME after the arterial filter after the introduction of air into the CPB venous line. Undetermined volumes of air were introduced into the venous line and the group reported that VAVD at increasing levels of suction (-15 mm Hg, -45 mm Hg, and -75 mm Hg) was associated with increasing GME counts in the arterial line.

The association between intraoperative emboli and brain injury during cardiac surgery has been established [2, 16, 17] but our inability to identify the type of embolus has made it difficult to study the precise role of GME in postoperative brain injury. The optimal method for counting, sizing, and identifying different types of embolic material remains controversial [18, 19]. Different techniques and equipment produce markedly different embolic counts [20]. The most common technique used is ultrasound. Increasingly, the frequency, amplitude, intensity, and spectral array of the reflected signal are being analyzed to make assumptions about embolic numbers, size, and material; however, most systems have never been validated. Deal and associates [21] investigated the reliability of pulsed and continuous wave Doppler to count emboli in both in vitro and in vivo models. They noted that detectors from the same and different systems placed in series on a tube did not count the same number of emboli. Detectors are easily "tricked" by artifactual noise arising from tapping the tubing or from bubbles trapped in connectors or bifurcations. Similarly the angle of orientation, coating of acoustic gel, and application and reapplication of the transducer will influence the GME count. Changing ultrasound settings such as gain and power between recordings will result in changes in sensitivity and specificity making it difficult to compare GME counts. In the present study, we used five identically configured EDAC systems simultaneously with purposefully made detector holders to reduce these problems. The detectors were not disturbed until each experiment was complete and all settings were maintained throughout the study.

A consistent finding between VAVD and GSVD studies is the presence of GME in the arterial line after the introduction of air into venous line independent of the method of venous drainage. Clinically air is frequently introduced into the venous line due to nonocclusive atrial purse-strings or caval snares, during blood sampling, injecting drugs [7], and at the initiation of CPB. Traditionally it has been assumed that entrained venous air will be removed by the CPB circuit components. All studies to date have demonstrated this assumption to be incorrect.

The results of this study suggest that VAVD at -40 mm Hg does not statistically reduce the ability of the CPB circuit components to remove GME at lower pump flow rates. High levels of vacuum and increased pump flow rates should be avoided. Under all conditions and with all methods of venous drainage, entrained venous air results in the detection of GME after the arterial filter. Air in the venous line should be avoided and if present it should be dealt with promptly.


    Acknowledgments
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
This study was funded by the National Institutes of Health, the National Medical Technology Testbed, and Baxter Healthcare Corp. We gratefully acknowledge the technical advice and support provided by the staff of Embolus Inc and Orincon Corp, particularly John Sevick. We thank members of the CardioNeuroprotection team and Department of Perfusion at Wake Forest University School of Medicine for their continued support. We are very grateful to Robert James for his statistical expertise and to Wilson Somerville and members of the editorial team for their help in the preparation of this manuscript.


    References
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Roach G.W., Kanchuger M., Mangano C.M., et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996;335:1857-1863.[Abstract/Free Full Text]
  2. Hammon J.W., Jr, Stump D.A., Kon N.D., et al. Risk factors and solutions for the development of neurobehavioral changes after coronary artery bypass grafting. Ann Thorac Surg 1997;63:1613-1618.[Abstract/Free Full Text]
  3. Mangano C.M., Diamondstone L.S., Ramsay J.G., Aggarwal A., Herskowitz A., Mangano D.T. Renal dysfunction after myocardial revascularization: risk factors, adverse outcomes, and hospital resource utilization. The Multicenter Study of Perioperative Ischemia Research Group. Ann Intern Med 1998;128:194-203.[Abstract/Free Full Text]
  4. Riddington D.W., Venkatesh B., Boivin C.M., et al. Intestinal permeability, gastric intramucosal pH, and systemic endotoxemia in patients undergoing cardiopulmonary bypass. JAMA 1996;275:1007-1012.[Abstract/Free Full Text]
  5. Taylor K.M. Brain damage during cardiopulmonary bypass. Ann Thorac Surg 1998;65(Suppl):20-26.
  6. Stump D.A., Rogers A.T., Hammon J.W., Newman S.P. Cerebral emboli and cognitive outcome after cardiac surgery. J Cardiothorac Vasc Anesth 1996;10:113-118.[Medline]
  7. Taylor R.L., Borger M.A., Weisel R.D., Fedorko L., Feindel C.M. Cerebral microemboli during cardiopulmonary bypass: increased emboli during perfusionist interventions. Ann Thorac Surg 1999;68:89-93.[Abstract/Free Full Text]
  8. Kurusz M. Gaseous microemboli: sources, causes, and clinical considerations. Med Instrum 1985;19:73-75.[Medline]
  9. Mitchell S.J., Willcox T., Gorman D.F. Bubble generation and venous air filtration by hard-shell venous reservoirs: a comparative study. Perfusion 1997;12:325-333.[Abstract/Free Full Text]
  10. Willcox T.W., Mitchell S.J., Gorman D.F. Venous air in the bypass circuit: a source of arterial line emboli exacerbated by vacuum-assisted drainage. Ann Thorac Surg 1999;68:1285-1289.[Abstract/Free Full Text]
  11. Philp R.B., Inwood M.J., Warren B.A. Interactions between gas bubbles and components of the blood: implications in decompression sickness. Aerosp Med 1972;43:946-953.[Medline]
  12. Thorsen T., Klausen H., Lie R.T., Holmsen H. Bubble-induced aggregation of platelets: effects of gas species, proteins, and decompression. Undersea Hyperb Med 1993;20:101-119.[Medline]
  13. Butler B.D. Biophysical aspects of gas bubbles in blood. Med Instrum 1985;19:59-62.[Medline]
  14. Butler B.D., Kurusz M. Embolic events. In: Gravlee G.P., Davis R.F., Kurusz M., Utley J., eds. Cardiopulmonary bypass: principles and practice. Philadelphia: Lippincott Williams & Wilkins, 2000:320-341.
  15. LaPietra A., Grossi E.A., Pua B.B., et al. Assisted venous drainage presents the risk of undetected air microembolism. J Thorac Cardiovasc Surg 2000;120:856-862.[Abstract/Free Full Text]
  16. Pugsley W., Klinger L., Paschalis C., Treasure T., Harrison M., Newman S. The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke 1994;25:1393-1399.[Abstract]
  17. Clark R.E., Brillman J., Davis D.A., Lovell M.R., Price T.R., Magovern G.J. Microemboli during coronary artery bypass grafting. Genesis and effect on outcome. J Thorac Cardiovasc Surg 1995;109:249-257.[Abstract/Free Full Text]
  18. Richardson P.D. Qualitative and quantitative methods for investigating gas emboli in blood. Med Instrum 1985;19:55-58.[Medline]
  19. Stump D.A., Jones T.J., Rorie K.D. Neurophysiologic monitoring and outcomes in cardiovascular surgery. J Cardiothorac Vasc Anesth 1999;13:600-613.[Medline]
  20. Stump D.A., Newman S.P. Emboli detection during cardiopulmonary bypass. In: Tegeler C.H., Babinian V.L., Gomez C.R., eds. Neurosonology. St. Louis: Mosby, 1995:252-255.
  21. Deal D.D., Stump D.A., Brooker M.D. Ultrasonic monitoring for emboli in the operating room: errors of detection. J Neuroimaging 1997;7:254.



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