Chest
Volume 128, Issue 4, October 2005, Pages 2918-2932
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Reviews
Microbubbles

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Gas embolism is a known complication of various invasive procedures, and its management is well established. The consequence of gas microemboli, microbubbles, is underrecognized and usually overlooked in daily practice. We present the current data regarding the pathophysiology of microemboli and their clinical consequences. Microbubbles originate mainly in extracorporeal lines and devices, such as cardiopulmonary bypass and dialysis machines, but may be endogenous in cases of decompression sickness or mechanical heart valves. Circulating in the blood stream, microbubbles lodge in the capillary bed of various organs, mainly the lungs. The microbubble obstructs blood flow in the capillary, thus causing tissue ischemia, followed by inflammatory response and complement activation. Aggregation of platelets and clot formation occurs as well, leading to further obstruction of microcirculation and tissue damage. In this review, we present evidence of the biological and clinical detrimental effects of microbubbles as demonstrated by studies in animal models and humans, and discuss management of the microbubble problem with regard to detection, prevention, and treatment.

Section snippets

Definition

Gas embolism is an iatrogenic event in which gas enters the circulation and can result in serious morbidity and death.1 Animal studies23 have shown that rapid infusion of a large volume of air may be fatal. Our knowledge of the consequences of small-quantity air emboli is lacking. The cutoff point between the occurrence of a major catastrophic episode and subtle but unequivocally important symptoms is yet undefined. An arbitrary definition of microbubble size may be erroneous since only a

Dynamics of Microbubble Elimination

The fundamentals for the dissolvance of a gas bubble in a solution have been formulated by Epstein and Plesset.15 The formula takes into account several parameters, including the gas-liquid diffusion constant, universal gas constant, saturation concentration of the given gas, temperature, surface tension, ambient pressure, and the radius of the bubble (Appendix). When using the equation for elimination of air microbubbles in the bloodstream, some of these parameters can be regarded as constants

Mechanisms of Microbubble Tissue Damage

The immediate and more rapid event following microbubble injection is the obstruction of blood flow in the capillary distal and proximal to the occluding particle. This causes antegrade and retrograde tissue ischemia along with changes of pressures in the circulation and interstitium around the affected blood vessel. Instantaneously, the inflammatory response and complement activation takes place since the body reacts toward the bubble as a foreign substance (Table 1). We discuss each of these

Clinical Consequences of Circulating Microbubbles

The clinical outcome of air embolism depends on the size of the bubble, location (organ/tissue), general status, and comorbidity of the patient, plus many known and unknown factors.55 Large air embolism is usually disastrous, both in the venous and arterial circulation.565758 The natural course of a large venous embolism is migration into the pulmonary circulation and obstruction of the right ventricular outflow, acute increased resistance to the right ventricle and diminished left ventricular

Procedures and Events Generating Microbubbles

Almost every invasive procedure may cause the introduction of microbubbles into the blood stream.77 Of course, the more invasive and interventional the procedure, the greater is the risk of microbubble generation. There have been an increasing number of reports7879 about air microemboli in some procedures, such as cerebral angiography and left-heart catheterization. Admittedly, most microembolic events are silent,80 but some are symptomatic and the phenomenon cannot be ignored. We concentrated

Detection

Attempting to prevent the threat of air embolism during a cardiopulmonary bypass machine event, numerous devices were designed. In 1980, an air embolism detection device (Air-Bubble Detector System; Sarns; Ann Arbor, MI) was presented as a tool capable of detecting the presence of macroscopic air emboli (10−6 m3 [1 mL] or larger) using an infrared light source and a photocell receptor.148 When the detector was turned on, a control unit caused the cardiopulmonary bypass pump to shut off. A few

Management

The treatment of large air emboli is well established.16061 Little is written about the management of microbubble injury. Some of the known therapeutic modalities employed for massive air embolism may be applied in the case of microbubbles. In both scenarios, prevention is the best approach as “an ounce of prevention is worth a pound of cure.” When the event of air embolism, macro as well as micro, has occurred, early detection is required to facilitate immediate action to interrupt the cause.

Summary

We have presented published data concerning the microbubble phenomenon and its detrimental consequences. Indeed, the microbubble event and its significance have been proved in open-heart surgery and DCS. However, it awaits clinical confirmation in other conditions such as hemodialysis and rapid fluid infusion. To date, there is a limited knowledge about the management of the microbubble events. Nevertheless, acknowledgment of the problem is the first step in the path toward finding a solution.

The Epstein-Plesset equation

drdt=-DLP*+2σ/rpatm+4σ/3r{1r+1πDT} where D is the diffusivity of gas in fluid; L is the partition coefficient of gas, Patm is the atmospheric pressure, P* is the excess pressure, σ is the surface tension, r is the radius of the bubble, and t is time.

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