The Invisible Killer

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Call Stephen Horrillo at 954-943-3479 or Email:
gotosteve@gmail.com

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Microbubbles: The Invisible Killer by Stephen Horrillo

It is well established in surgical procedures above the heart, such as in the head and neck, where the pressure is less than one atmosphere, that an invasive procedure may let air in. This is one reason why surgeons must be particularly careful when operating on the brain, and why the head of the bed is tilted down when inserting or removing a central line from the jugular or subclavian veins. Air embolism may also occur during other types of surgery such as Cesarean section and orthopedic procedures. Cases have even been reported as a result of sexual intercourse during late pregnancy.

What is not as well known is the ability of microbubbles to bypass the body's natural protective systems. Once microemboli reach the brain they can fuse together forming a larger bubble resulting in aphasia, coma, stroke, and even death. Increasingly popular interventional procedures which allow air to enter via the femoral and renal arteries were once considered safe. The problem we face even today is medical students are taught that it is anatomically and physiologically impossible for an air bubble to reach the brain if said procedure is being done below the heart. As a result, hemodialysis, and renal artery stenting (RAS) patients needlessly suffer symptoms of air embolism. Compounding the problem, much of this goes unreported due to "ageism" on the part of the medical community. Being that most dialysis and renal stenosis patients are of advanced years and of deteriorating health, decreased mental capacity, dementia, and stroke are assumed to be unrelated to the procedure. This is indeed unfortunate.

There is solid evidence as far back as 1944 which demonstrates that air bubbles in the form of Microbubbles have the ability to enter the cerebral circulatory system and embolize the brain. The challenge researchers have been facing is they had no way to accurately measure the presence and size of microbubbles and thereby determine a cut-off point as to what size bubble can make it past the bodies natural protective systems. Thanks to modern ultrasound Doppler systems that is all changing.

In 1986 D.F. Gorman and D.M. Browning, while doing research for the Royal Australian Navy, discovered that, "gas introduced as microbubbles into the femoral artery of upright rabbits caused cerebral arterial gas embolism with gas entering cerebral arterioles in cylindrical configurations... Gas microbubbles infused into the femoral artery of head-up rabbits distributed against aortic flow to embolize the brain circulation. Conversely, regardless of infusion volume, no gas entered the cerebral vessels of rabbits maintained in a head down posture... We knew this was not was not due to mechanical problems with the infusion lines because, "cerebral arterial gas emboli were produced in these animals when reverted to the head-up posture... These observations are consistent with other reports of arterial gas emulous distribution... They support the role of a head-down posture in the treatment of arterial gas embolism. (9,41,81)

In 2005 Michal Barak, MD; and Yeshayahu Katz, MD, DSc reported, "there is a dynamic, constant process of small bubbles fusing to create large bubbles, and large bubbles splitting into many small ones; thus, a few “harmless” microbubbles could coalesce into one injurious large bubble. The microbubble travels in the blood stream until it is lodged in the microcirculation. Circulating in the blood stream, microbubbles lodge in the capillary bed of various organs. Although arterial air emboli could reach any organ, occlusion of cerebral and cardiac circulation is particularly deleterious because these systems are highly vulnerable to hypoxia and go through irreversible cellular damage. The result of such an event may be massive brain ischemia and stroke or myocardial ischemia and infarction. Both could be fatal... Arterial air may have direct access to the cerebral circulation. Venous air may also readily cause cerebral air embolism in the presence of a patent foramen ovale.2,3"


 

 

 

 

 

 

 

A Safe Amount of Air in an IV Line
By
Lynn Hadaway, M.Ed., RNC, CRNI

"Now there is a growing body of knowledge that small amounts of air in the form of microbubbles are not benign. Please see the post from July 2008 about a new report of damage from these microbubbles. To read this post, click here."

Save the Small Air Bubbles for the Champagne!

For many years, we have known the dangers of introducing large amounts of air into the circulatory system. Air can enter during catheter insertion, tubing changes or disconnection and catheter removal. Usually the air travels to the lungs where it produces respiratory symptoms, but it can also move to the brain where it produces neurological problems. These outcomes can be catastrophic for the patient and nurses have learned to employ all means to prevent this serious complication.

See full article http://hadawayassociates.blogspot.com/2008/07/save-small-air-bubbles-for-champagne.html

 

Gas in the cavernous sinus.

Department of Radiology, University of Colorado Health Sciences Center, Denver 80204.

PURPOSE: To evaluate the significance of cavernous sinus gas identified on head CT scans. METHODS: Head CT scans were viewed prospectively for a period of 3 years. The charts of patients who demonstrated cavernous sinus gas were reviewed. RESULTS: Seventeen patients without head trauma and 10 patients with head trauma demonstrated gas in the cavernous sinus. None of the patients had symptoms or developed symptoms originating in the cavernous sinus. All of the patients without trauma had an intravenous line in place. Sphenoid fractures or basilar skull fractures were not a constant finding in trauma patients with cavernous sinus gas. CONCLUSIONS: In patients without symptoms referable to the cavernous sinus, gas in the cavernous sinus does not appear to be a significant finding. The gas is most likely the result of venous air emboli from intravenous lines or penetrating trauma.

PMID: 8197958 [PubMed - indexed for MEDLINE]

 

 

 

Cerebral Vasoreactivity and Arterial Gas Embolism
D. F. GORMAN and D. M. BROWNING
School of Underwater Medicine, Royal Australian Navy

Infusion of gas microbubbles into the femoral artery of upright rabbits caused significant but transient hypertension . respiratory depression, cardiac bradyarrythmia, inhibition of cerebrovascular autoregulation to blood pressure changes, and cerebral arterial gas embolism with entrapment of long emboli in arterioles of 50-200 um in diameter . Compression of casualties with cerebral arterial gas embolism in a recompression chamber within 5 min of onset of symptoms usually results in rapid, complete recovery (4—11) .

Gas Infusion Technique

Gas was introduced into the femoral artery as microbubbles of less than 200um diameter by using a fine hypodermic needle 0.025 ml i.d. at an infusion rate of 0.2 ml/s (12, 45) . Three milliliter of normal saline were infused at 0.1 mils to clear all gas from the arterial line.

METHOD

Basic preparation
New Zealand white rabbits (weighing 2-5 kg) were anesthetized with air and halothane... A tracheotomy was performed below the larynx to allow intubation.... Three ECG electrodes were implanted in the animal's chest to provide a continuous record on a multichannel recorder... The right femoral artery was isolated by dissection and intubated with a 3-cm plastic cannula. This was connected via a three-way tap to a pressure transducer and the multichannel recorder that displayed systolic, diastolic, and mean blood pressure and to an infusion line.

I. Local cerebral circulatory arrest studies

a. Five rabbits were fixed to a frame in a head-up posture at 45° to the horizontal. A single 5-ml saline infusion was given in a method identical to that described for the gas microbubble infusion. This was followed by 5-ml air infusions as microbubbles, given at 2-min intervals until gas entered the cerebral circulation under view and caused local circulatory arrest. Blood pressure, heart rate, respiratory rate, and vessel diameter were recorded throughout the procedure.
b. Five rabbits were prepared as above, except that they were kept in a horizontal posture and a catheter was inserted into the left jugular vein draining the cranial contents. This catheter was connected to a heparinized loop that included a graduated air trap, and was reintroduced into the jugular vein at its distal end. Gas microbubble infusions occurred as above with gas being allowed to escape into the graduated air trap. The amount of gas collected was recorded as a percentage of the total volume of gas microbubbles infused into the femoral artery.
c. Five rabbits were fixed to a frame in a head-down posture at 45° to the horizontal. Five-milliliter air infusions as microbubbles were given at 2-min intervals until either local cerebral circulatory arrest was effected by gas embolism or until 15ml of gas had been infused . If no cerebral arterial gas emboli occurred with animals in the head-down posture they were reverted to a head-up posture at 45 0 to the horizontal . If after a period of 5 min no gas emboli had spontaneously entered the cerebral circulation, a further 5 ml of air was infused as microbubbles into the femoral artery. The animals were monitored throughout the procedure as for the first group of animals.

RESULTS

Local cerebral circulatory arrest studies

General observations

Gas introduced as microbubbles into the femoral artery of upright rabbits caused cerebral arterial gas embolism with gas entering cerebral arterioles in cylindrical configurations. No discrete microbubbles were observed. Conversely, regardless of infusion volume, no gas entered the cerebral vessels of rabbits maintained in a headdown posture. This was not due to mechanical problems with the infusion lines because cerebral arterial gas emboli were produced in these animals when reverted to the head-up posture.

Embolus distribution

Gas microbubbles infused into the femoral artery of head-up rabbits distributed against aortic flow to embolize the brain circulation. Conversely, cerebral arterial gas emboli were never observed in head-down rabbits . These observations are consistent with other reports of arterial gas embolus distribution (21, 49, 60, 74-76) and with the frequency of neurological involvement in divers and submariners who develop arterial gas emboli (4, 7-9, 56, 76-80). They also support the role of a head-down posture in the treatment of arterial gas embolism (9, 41 .81)

 

Microbubbles* Pathophysiology and Clinical Implications

Michal Barak, MD; and Yeshayahu Katz, MD, DSc
*From the Department of Anesthesiology (Dr. Barak), Rambam
Medical Center, Haifa; and Bruce Rappaport Faculty of Medicine
(Dr. Katz), Technion-Israel Institute of Technology, Haifa,
Israel.
Manuscript received January 17, 2005; revision accepted April
18, 2005. Correspondence to: Yeshayahu Katz, MD, DSc, Department
of Anesthesiology, HaEmek Medical Center, Afula 18101,
Israel; e-mail: ykatz18@hotmail.com

ABSTRACT: Gas embolism is a known complication of various invasive procedures, and its management is well established. The consequence of gas microemboli, microbubbles, is under recognized and usually overlooked in daily practice... Microbubbles originate mainly in extracorporeal lines and devices, such as cardiopulmonary bypass and dialysis machines... Circulating in the blood stream, microbubbles lodge in the capillary bed of various organs... 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. (CHEST 2005; 128:2918–2932)

...Our natural tendency is to overlook minute particles, some of which are invisible, believing them to be harmless. However, solid data show that microbubbles are of clinical importance.

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 bubble of a diameter smaller than the capillary can travel through the circulatory system without leaving an imprint and be accepted as safe.4 Furthermore, in the biological setting, there is a dynamic, constant process of small bubbles fusing to create large bubbles, and large bubbles splitting into many small ones; thus, a few “harmless” microbubbles could coalesce into one injurious large bubble.

The microbubble travels in the blood stream until it is lodged in the microcirculation. During its course, the bubble is compressed against the endothelial capillary wall, causing functional stripping of endothelial cells and an increase of large-pore radii.28

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.56–58 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 preload, followed by cardiovascular collapse.1,59 Air emboli in arterial vessels cause symptoms of end-artery obstruction and tissue ischemia and necrosis. Although arterial air emboli could reach any organ, occlusion of cerebral and cardiac circulation is particularly deleterious because these systems are highly vulnerable to hypoxia and go through irreversible cellular damage. The result of such an event may be massive brain ischemia and stroke or myocardial ischemia and infarction. Both could be fatal. The detection of such catastrophic events and resuscitative measurements are well known.1,60,61 Less is known about the results of small air emboli in the venous or arterial circulation. A small quantity of microbubbles may be clinically silent, while recurrent exposure to microbubbles causes a slow smoldering chronic effect that is difficult to detect but has important consequences. The patient’s comorbidity may also influence the outcome of circulating air emboli. When there is a right-to-left shunt, venous air emboli may traverse to the arterial circulation and cause organ ischemia. Such a course of events is termed paradoxical air embolism,62 and there are a few mechanisms by which it may occur. One is passage of gas through a cardiac right-to-left shunt into the systemic circulation. The prevalence of a cardiac right-to-left shunt ranges between 15 to 40% in various studies,63,64 usually as a result of patent foramen ovale but may be caused by other cardiac anatomic anomalies... A right-to-left shunt might also be extra-cardiac, mostly from dilatation of pulmonary vessels, causing an intrapulmonary shunt in ARDS. In many cases the existence of such a shunt is unknown to the patient or physician, and the risk of paradoxical emboli is not taken into account.

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.

The incidence of cognitive dysfunction at 1 week following cardiac surgery is approximately twice that of noncardiac surgery.89... Roach and colleagues81 calculated the additional cost of in-hospital neurologic morbidity after cardiac surgery as approximately $400 million annually. They estimated that true costs, including long-term out-of-hospital medical and rehabilitative services, probably result in additional expenditures ranging from 5 to 10 times narrow in-hospital costs, or $2 to $4 billion annually.81

Hemodialysis

As far back as 1975, there was evidence of pulmonary microembolization during hemodialysis.105

Microbubbles originate from the dialysis tubes or filter flow in the venous vasculature and are trapped in the pulmonary circulation. Thus, the hemodialysis patient may suffer both acute and chronic lung injury due to a microbubble shower.

The damage caused by microbubbles may be more detrimental in case of cardiac or extracardiac right to left shunt, which may be found in up to 40% of the population.64 In those cases, air emboli may enter the cerebral circulation and cause varying degrees of neurologic damage.119 Indeed, the above noted clinical studies106–109 that described microemboli during dialysis had either no patient with a shunt108,109 or did not report that detail in the study.106,107 Nevertheless, it is reasonable to believe that a patient with a right-to-left shunt is at higher risk for neurologic morbidity as a result of venous air embolism during hemodialysis. Cerebral atrophy and deterioration of neurocognitive functions in chronic hemodialysis patients is a recognized problem that correlates with the duration of dialysis treatment.120–122

Diving and Decompression Sickness

DCS is an accurate example of humans exposed to microbubbles in the circulation, and thus can demonstrate the clinical presentation of that event.... The neurologic manifestations are attributed to bubble embolization in the CNS. Again, clinical studies140,141 suggest that subclinical cerebral damage occurs in divers, raising the possibility that microbubble damage is underdiagnosed due to difficulties in detection and not because they are not present.

Management

The treatment of large air emboli is well established. 1,60,61 Little is written about the management of microbubble injury. While the detection of large air emboli is easy, usually manifested by acute cardiovascular collapse or sudden overt deterioration of the neurocognitive or motor functions, catastrophic in nature, the presentation of a microbubble event is more subtle and difficult to detect.

Hyperbaric Oxygen should be employed as soon as  possible after the insult, although delayed treatment is also helpful.168

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. Contemporary technology offers us tools to cope with various difficulties. The best way to utilize highly developed technology is in cooperation between scientists and engineers in search of a resolution for a recognized problem. The problem of microbubbles awaits a breakthrough technological solution that will provide their detection and elimination, facilitating better care for the patient.


 
Home page
 
ChestHome page
M. Barak and Y. Katz
Microbubbles: Pathophysiology and Clinical Implications
Chest, October 1, 2005; 128(4): 2918 - 2932.
[Abstract] [Full Text] [PDF]

 
Home page
 
NEJMHome page
C. M. Muth and E. S. Shank
Gas Embolism
N. Engl. J. Med., February 17, 2000; 342(7): 476 - 482.
[Full Text] [PDF]

 
Home page
 
J. Appl. Physiol.Home page
J. E. Souders, J. B. Doshier, N. L. Polissar, and M. P. Hlastala
Spatial distribution of venous gas emboli in the lungs
J Appl Physiol, November 1, 1999; 87(5): 1937 - 1947.
[Abstract] [Full Text] [PDF]

 
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PerfusionHome page
B. Butler and M. Kurusz
Review article : Gaseous microemboli: a review
Perfusion, April 1, 1990; 5(2): 81 - 99.
[PDF]

 

 

Cerebral Air Embolism Resulting from Invasive Medical Procedures
Treatment With Hyperbaric Oxygen
(Full Text PDF)

From the United States Air Force School of Aerospace
Medicine, Brooks AFB, and the Department of General
Surgery, Wilford Hall USAF Medical Center,
Lackland AFB, San Antonio, Texas

BRIAN P. MURPHY, CAPT, USAF, MC
FRANCIS J. HARFORD, COL, USAF, MC
FREDERICK S. CRAMER, COL, USAF, MC

The introduction of air into the venous or arterial circulation can cause cerebral air embolism, leading to severe neurological deficit or death. Air injected into the arterial circulation may have direct access to the cerebral circulation. A patent foramen ovale provides a right-to-left shunt for venous air to embolize to the cerebral arteries. The ability of the pulmonary vasculature to filter air may be exceeded by bolus injections of large amounts of air. Sixteen patients underwent hyperbaric oxygen therapy for cerebral air embolism. Neurological symptoms included focal motor deficit, changes in sensorium, and visual and sensory deficits.

FROM 1970 TO 1984, 16 cases of cerebral air embolism resulting from invasive medical procedures were treated with hyperbaric oxygen at the United States Air Force School of Aerospace Medicine... All patients underwent hyperbaric oxygen therapy in a large multiplace chamber accompanied by a physician... Eight of 16 patients (50%) became asymptomatic while undergoing or shortly after completing hyperbaric therapy. Five patients had partial resolution of symptoms (31%). Three patients had no response; two of these died while in the hyperbaric chamber and the third was left with a severe neurological deficit. Overall mortality was 13%.

Arterial air may have direct access to the cerebral circulation. Venous air may also readily cause cerebral air embolism in the presence of a patent foramen ovale.2,3 A recent autopsy study found a 27.3% incidence of patent foreamen ovale in the general population, and an incidence of 34% in the first 3 decades of life.4 If a bolus of air lodges in the pulmonary arteries and causes obstruction to pulmonary outflow, a hemodynamically significant right-to-left shunt (see illus. 1) through a patent foramen ovale is likely to occur, with subsequent cerebral air embolism.

circulation. The pulmonary arterioles and capillaries are generally considered an effective filter for thrombi, platelet aggregates, and fat emboli, but trapping of air may not be so effective.5 Marquez reported a fatal cerebral air embolism resulting from a neurosurgical procedure in which postmortem examination detected no intracardiac septal defects.6 Butler demonstrated in a canine model that the lung is normally a very effective filter for air bubbles of greater than 22 micrometers in diameter when infused slowly.7 (see Microbubbles by M. Barak & Y. Katz in CHEST) However, a bolus injection of 30 cc of air into a central vein exceeded the filtering capacity of the lung and produced embolization through the left heart and into the arterial circulation.

Prevention of cerebral air embolism by meticulous technique in the performance of invasive procedures and preservation of the integrity of in-dwelling vascular access catheters is essential. However, the steady growth in the application of percutaneous and endoscopic procedures, total parenteral nutrition, cancer chemotherapy, hemodynamic monitoring, and other invasive procedures will continue to provide opportunities for the accidental injection of air. Hyperbaric oxygen therapy is based on sound physiologic principles of compression of air bubbles and delivery of high doses of oxygen to ischemic neurologic tissues. With an increasing number of hyperbaric chambers in both civilian and military medical facilities, physicians should be aware of the benefits of hyperbaric oxygen in cerebral air embolism and pursue prompt treatment in symptomatic cases.

5. Heinemann HO, Fishman AP. Nonrespiratory functions of the
mammalian lung
. Physiol Rec 1969; 49:1-47.

7. Butler BD, Hills BA. The lung as a filter for microbubbles. J Appl
Physiol 1979; 47:537-543.

8. Spencer MP, Oyama Y. Pulmonary capacity for dissipation of
venous gas emboli. Aerospace Med 1971; 42:822-827.

 


 

Gas embolism complicating obstetric or gynecologic procedures. Case reports and review of the literature

Yaron MushkatCorresponding Author Informationa, Dov Luxmana, Zohar Nachumb, Menachem P. Davida, Yehuda Melamedb

Abstract

Gas embolism is a rare life-threatening complication of obstetric or gynecologic procedures, arising as a result of gas bubbles being introduced into the circulation via severed blood vessels. Extensive brain damage and acute cardiovascular collapse will lead to a fatal outcome. A favourable outcome depends on early diagnosis and prompt treatment. Hyperbaric oxygenation, which reduces bubble size and increases the supply of oxygen to hypoxic tissues, is the definitive treatment for gas embolism. We report four cases of gas embolism complicating obstetric or gynecologic procedures which were treated at the Israel Naval Medical Institute followed by an updated review of the literature.

 

HYPERBARIC OXYGEN THERAPY FOR MASSIVE ARTERIAL AIR EMBOLISM DURING CARDIAC OPERATIONS

Avishai Ziser, MDa
Yochai Adir, MDb
Haim Lavon, MDb
Avi Shupak, MDb

Background: Massive arterial air embolism is a rare but devastating complication of cardiac operations. Several treatment modalities have been proposed, but hyperbaric oxygen is the specific therapy. Methods: The Israel Naval Medical Institute is the only referral hyperbaric center in this country for acute care patients. We reviewed our experience in the hyperbaric oxygen treatment of massive arterial air embolism during cardiac operations. Results: Seventeen patients were treated between 1985 and 1998. Eight patients (47.1%) experienced a complete neurologic recovery; 6 patients (35.3%) remained unconscious at discharge, and 3 patients (17.6%) died.

When massive arterial air embolism is diagnosed during the operation, radiologic studies of the brain provide very little information and may cause an unnecessary delay of treatment.16 In the different situation, at which a neurologic deficit is diagnosed the first time in the intensive care unit, but the cause is uncertain, radiologic study will probably be the next step. Macroemboli were found in the brain several hours17 and even days after an embolic event.18 Delayed treatment with HBO for systemic air embolism was reported,19 including cases of cardiac operations, 20,21 and recovery might be achieved. Therefore HBO therapy should be given even after a long delay. The exact limit of this delay is unknown.

In summary, HBO is the specific treatment for massive arterial air embolism during cardiac operations. It should be administered as soon as possible after the end of the operation.