Chemical Used In Medical Accoutrement May Mean Complications For Some
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Medical science took a giant leap forward with the adulthood of techniques that, at least temporarily, perform the supply of vital organs. These processes, including the application of the heart-lung pc and renal dialysis, hope for the blood to be circulated through tubing absent the thing and are hence avowed as extracorporeal circulation (EC) and have if critical life buttress for millions of patients. Even EC is not without its own risks. Among them are unique morbidities such as depressed cardiac output, abnormal heart rhythm, and swelling of the major organs. Studies posses been conducted for decades to determine how these effects can be reduced and eliminated. In a new peruse conducted by a Johns Hopkins team, the researchers examined whether a solvent used in the industry of intravenous (IV) bags and EC circuits could play a role. Their results indicate that 1) the solvent cyclohexanone (CHX) can leach into IV and EC fluids, and 2) CHX administered in controlled doses in an animal design replicates the cardiovascular and lung morbidities that are seen in patients during and after EC treatment. The interpret sheds new glowing on the potential causes of EC-related disorders.
The study was conducted by Caitlin S. Thompson-Torgerson and Lakshmi Santhanam, Branch of Biomedical Engineering; Hunter C. Champion, Department of Medicine (Division of Cardiology); Z. Leah Harris, Department of Anesthesiology and Critical Charge Medicine; and Artin A. Shoukas, Departments of Biomedical Engineering, Anesthesiology and Critical Control Medicine, and Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD. The study, entitled Cyclohexanone Contamination From Extracorporeal Circuits Impairs Cardiovascular Function, is published in the online edition of the American Diary of Physiology Affection and Circulatory Physiology.
Cyclohexanone (CHX) is an biological solvent widely used in the production of polyvinyl chloride (PVC) medical devices, including IV fluid bags and EC circuits. CHX can migrate from PVC tubing and connections into fluids that come in contact with PVC. CHX can leach from PVC bags and IV tubing into intravenous fluids in sufficient concentrations to be detected in neonatal urine samples. Therefore, it is viable that patients on EC bed are at risk for CHX exposure, apt that their unabridged blood volumes circulate continuously through CHX-treated tubing and are frequently augmented with IV fluids.
While the toxicity of PVC and CHX has been formerly documented in animal models, no studies compass made comparisons to clinical intravenous CHX exposure. Accordingly, the researchers developed a series of experiments to establish in fashion values for CHX contamination in crystalloid fluid from IV bags and EC circuits, and to test the speculation that a clinically observed potion of CHX could reproduce the vital organ dysfunction that can accompany EC support/treatment.
To quantify the measure of CHX contamination of fluids, researchers from Johns Hopkins Medical Institutions collected saline samples from IV bags and other commercially available bags, bypass circuits, ECMO circuits and dialysis circuits. CHX levels were measured using gas chromotography-mass spectrometry (GCMS). These results were used to impel a clinically substantial intravenous dose of CHX. A dose of CHX was then calculated and given intravenously to adult adult rats. Saline stored in and administered from glass bottles was inclined to a control group. Dosing calculations were designed so that they approximated a conservative adult EC patient exposure to CHX, including the abrupt features of the exposure that EC patients undergo when they are connect to plan tubing.
There were three protocols used in the study:
Protocol 1 was designed to measure several aspects cardiovascular function. Animals were anesthetized, tracheotomized, ventilated using a rodent ventilator, and then instrumented so that the researchers could measure cardiac output, love rate, stroke volume, blood pressure, and passion contractile function. Measurements were made at baseline and again 60 minutes after infusion of CHX or saline.
Protocol 2 was designed to degree cardiovascular autonomic function, including how right the fitful transaction was able to maintain blood pressure in the face of a challenge. After the animals were anesthetized and instrumented to measure blood pressure, both carotid arteries were occluded (obstructed), which stimulates a reflex called the baroreflex that controls blood pressure. After this baseline assessment of reflex function, CHX or saline was infused and allowed to circulate for 30-40 minutes, followed by another round of occlusions. A subsequent equal infusion was given and allowed to circulate for an additional 30-40 minutes, followed by a ending round of occlusions. Protocol 3 was designed to measure oedema formation, or the album of irrigate that has been retained in chief organs of the body. After the animals were anesthetized, everyone rat received an infusion of either CHX or saline, which was allowed to circulate the item for 2 hours. After 2 hours, the animal was euthanized, and the liver, kidneys, lungs, and skin were harvested, weighed, dried apricot at 100°C, and weighed again to quantify the fluid content in each organ at the day of death. Results In protocol 1, all baseline values were similar between saline and CHX groups. In the 60 minutes later saline infusion, none of the variables changed significantly from baseline. The CHX infusion, however, induced momentous adverse changes in all cardiovascular variables. Both stroke tome and heart rates values were significantly depressed after one lifetime of CHX, resulting in a significant decline in cardiac output in the CHX rats. Stroke volume, in turn, was depressed because the inherent contractile bent of the heart was significantly reduced. CHX exposure as well resulted in altitudinous blood pressure in the lung vessels, a dangerous condition known as pulmonary hypertension.
In protocol 2, prior to infusions, both saline and CHX groups exhibited corresponding significant baroreflex pressor responses to carotid occlusion. After both 1st and 2nd saline infusions, the pressor response in the control battery did not differ significantly from baseline. However, in the CHX group, the pressor response was blunted after the front infusion and was undetectable after the 2nd CHX infusion. There are a host of neurological complications that develop in patients who undergo EC support. The relative contributions of the underlying disease vs. the treatment are often hard to discern. Moreover, the doable contribution of CHX to the evolution of these complications has not been investigated.
In protocol 3, the wet/dry ratio of organ weights served as an index of tissue fluid retention and, thus, edema formation. The ratios for all alone organs within each treatment group were pooled to create an overall index of edema formation. The pooled ratio for the CHX band was significantly higher than the saline group.
According to Dr. Thompson-Torgerson, lead author on the paper, and Dr. Shoukas, the senior researcher on the study, "The data from this study provide a current estimate of CHX contamination in most commercially available IV bags and EC circuits. The data allowed us to complete a clinically relevant CHX exposure. A similar equable of exposure in animals resulted in cardiovascular morbidities analogous to those observed succeeding clinical EC treatment. This supports our hypothesis that CHX may contribute to EC-related cardiovascular insufficiency. However, we would never enjoin patients to decline EC treatment if they demand it. On the contrary, EC technologies are life-saving medical advances, and the benefits of EC therapy all the more far outweigh the risks of the associated morbidities. Provided a patient and doctor chalk up decided that EC treatment is the boss course, then stick to that plan. As scientists, we are simply trying to explain how the side effects are triggered and what the best method testament be to mitigate, and sequentially remedy, these morbidities."
Physiology is the study of how molecules, cells, tissues and organs function to compose health or disease.
Source: American Physiological Society (APS)
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