It's Time to Focus on Infusion Pollution

We Know About Air & Water Pollution, But Now It's Time to Focus on Infusion Pollution!

March 21, 2022

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It has become accepted wisdom that particle pollution of the air and water affects our health daily. To reduce or prevent the risk of particles in air and water, regulators have taken the all-important first step towards quantifying the risk to people’s health by measuring exposure: Almost every city in the world today records and publishes daily levels of particles in the air1 and the ‘California State Water Resources Control Board’ is the world’s first regulatory authority to announce standard methods for quantifying microplastic concentrations in drinking water2.


Around 15 years ago, clinicians and researchers started to voice their concerns about the number of particles that are below the regulated sizes in infusion therapy. These are likely to affect the most vulnerable patients of all – those on the intensive care unit (ICU).


Chapter <788> of the United States Pharmacopeia (USP), Particulate Matter in Injections, defines particulate matter as “mobile undissolved particles, other than gas bubbles, unintentionally present in the solutions”3.


This blog focuses on current knowledge regarding particles associated with water and air pollution and compares this knowledge to what we know about particles in infusion therapy – or simply called “infusion pollution”.  




Comparison of particle uptake from air, water, and intravenous infusions



To evaluate the quality of air, health departments measure fine particulate matter (PM2.5): teeny tiny particles or droplets with a diameter of 2.5 microns (= µm, a thousandth of a millimeter) or less (to compare: The average hair is 50µm thick). How many PM2.5 you inhale depends on where you live: In  London, it may be around 44 million particles per day, in Beijing, up to 220 million per day.4




In the oceans, the most predominant microplastic particles range in size from 150 to 500 µm5; on average, each of us consume anywhere between 518 to 3,078 microplastic items per year just by eating fish.6



In much the same vein as in water and air, medical researchers started counting the number of particles that are infused into ICU patients7,8,9. The results allow for two conclusions. One, the more volume is infused into a patient, the more particles are infused. Two, the number of particles depends strongly on the size of particles: The smaller the particles, the more are infused into the ICU patient. Some recent studies have shown.




  • NICU (neonatal ICU) patients receive 85,000 particles > 1µm in a 24 h infusion period7
  • PICU (pediatric ICU) patients receive 416,974 particles > 1µm in a 24 h infusion period8
  • PICU patients receive 25,000,000,000 particles with a size < 1µm in a 24 h infusion period9.



The sheer number of particles infused into ICU patients may come as a surprise and can only serve to reinforce the validity of the concerns about their potential impact on the health of our ICU patients. 



Comparison of death numbers, health effects and pathologies associated with particles from air, water, and intravenous infusions



According to the World Health Organization (WHO), exposure to ambient (outdoor) air pollution causes 4.2 million deaths per year10. In the United States alone, PM2.5 is the largest environmental risk factor, resulting in >100,000 premature deaths per year – more than traffic accidents and homicides combined.11 The exposure to PM2.5 is a major risk factor for both mortality and morbidity, with associations demonstrated for everything from asthma over lung cancer to heart attack and stroke, atherosclerosis, thrombosis, hypertension, and arrhythmia; more recently, type 2 diabetes, dementia, and loss of cognitive function were added to this already depressively long list10-15.




In the oceans, plastic debris causes the deaths of more than million seabirds and more than 100,000 marine mammals per year16. In humans, data indicate that microplastics can induce cellular damage, immune responses, neurotoxic and even metabolic changes17,18,19. Further, microplastic has been now for the first time documented in the placentas of unborn babies, which is of major concern20.




And what do we know about intravenously infused particles? Over the last 15 years, studies have demonstrated that infused particles can block blood vessels, have systemic hypercoagulability effects, impair microcirculation, and have immune-modulatory and inflammatory effects21-31. Clinical studies on IV in-line filters have suggested that infused particles are associated with multi-organ failure, systemic inflammatory response syndrome, as well as renal, hematologic, and respiratory dysfunction32-38. To what extent infused particles cause or contribute to deaths of ICU patients is so far unknown. However, one study did reveal a statistical trend towards lower mortality in those pediatric ICU patients in whom particles were removed with an IV in-line filter before the infusion entered the blood stream28.



Inflammatory and immune-modulatory processes seem to be the common and underlying reactions in all three particle associated pathologies.



Comparison of the chemical composition of particles in air, water, and intravenous infusions



In urban environments, carbon also plays a major part, followed by non-carbon constituents such as minerals, ammonium, nitrates, or sulfates 39,40.




Most microplastics floating in the ocean are polyethylene, the rest are made up of various other forms of plastic, including polypropylene, polystyrene, and polyester19.




Particles infused into ICU patients range from various plastics to titanium oxide and silicon oil41. The main source of these particles is the infusion equipment; other causes might be drug incompatibilities42,43, ampoules (glass particles)44 and foreign particles in drug products, such as cellulose fibres41.






Particles in air are rather different in their chemical composition in comparison to particles in water and infusions.



Comparison of our natural defenses for the prevention of particles entering the bloodstream



According to a report from the World Wide Fund (WWF) combining the results of more than 50 studies worldwide, people could on average be ingesting about 5 g of particles every week. That is the equivalent of one credit card that we take in through the air we breathe, the food we eat, and the water we drink45.




Fortunately, not all particles reach the blood stream, since healthy lungs, gut and skin normally function as effective biological barriers. Regarding air particles, our natural defenses help us to cough or sneeze some coarse particles out of our bodies.




By contrast, particles in infusions can enter the blood stream directly without any natural defense – unless an IV in-line filter prevents them from doing so.







Particles that we breath and particles that we drink or ingest may be prevented to enter the bloodstream via the lung and gut, but particles that we infuse enter the bloodstream without any barrier.  



Comparison of guidelines and policies fighting particle pollution in air, water, and intravenous infusions



In 2012, the U.S. Environmental Protection Agency (EPA) strengthened the nation’s air quality standards for fine particle pollution by revising the primary annual PM2.5 standard to 12 µg per cubic meter (µg/m3)46. The European Union (EU) Clean Air Directive is currently among the strictest acts of legislation worldwide concerning PM10 air pollution. Its most visible result has been the rapid adoption of “Low Emission Zones” (LEZs), which define areas that vehicles may only enter if they are classified as low PM10 emitting vehicles47. The World Health Organization has set a target for cities to achieve an average of 10 micrograms of PM2.5 per cubic metre48




So, what have regulators been doing against this particle tidal wave? As you might expect, lots of international and national meetings have resulted in goals and policies to decrease the amount of microplastics in water. Amongst these was the G20 Osaka Summit in 2019 with its “Osaka Blue Ocean Vision”, aiming to reduce additional pollution by marine plastic litter to zero by 2050; all G20 leaders called on other members of the international community to share this vision49. What else? For example, California is set to establish the first ever health-based guidelines for acceptable levels of microplastics in drinking water50.




So, what about policies that aim to minimize the risk of particle harm to patients via infusions? Well, standards and regulations do exist today to control particle contaminations of injectable products. For example, both the United States Pharmacopoeia (USP) and the European Pharmacopeia (EP) have chapters on particulate contamination, and both set limits for the number of particles (≥10µm and  ≥25 µm) allowed to be contained in injectable drugs51,52. Apart from pharmacopeias, manufacturers also face rules: They must ensure the absence of any contaminants such as glass fragments in accordance with Good Manufacturing Practices (GMPs) to obtain quality products52.



Regulators are aware of the potential risk of particles to humans and tremendous efforts are made to minimize this risk.




Comparison of potential measures to prevent particle uptake from air, water, and intravenous infusions



Various organizations have handed out practical advice. For instance, the ‘American Lung Association’ instigated the ‘Healthy Air Campaign’, encouraging everyone to check daily air pollution forecasts in their area, avoid outdoor exercise during high pollution levels and to generally walk, bike or carpool instead of driving53. Protective face masks are another option: The most effective ones filter up to 95% of airborne particles (down to 0.3µm)54. In China and other Asian countries with severe air pollution, wearing a mask was common before the Corona pandemic started and has now increased even more54. Beside wearing a face mask, you may consider relocation. As an US citizen you may  decide to move to South Burlington in Vermont, which boasts the cleanest air in the United States55.




Protecting yourself from microplastic in the ocean might be difficult, but technologies to improve household drinking water do exist, which include point-of-use and point-of-entry filters56.




Drug manufacturers control the risk of particles by recommending the use of IV in-line filters for specific drugs in their instructions for use. The recently updated chart of IV drugs to be used with a syringe or with an in-line filter, published in ‘Hospital Pharmacy’, offers an extensive list of different drug categories, including monoclonal antibody formulations, antimicrobial drugs, cancer drugs and more57. Besides drug manufacturers, medical societies such as ASPEN and INS (American Society for Enteral Nutrition, Infusion Nurses Society) also attempt to minimize the risk of particles by recommending the use of in-line filters58,59.



Research is the crucial factor to enable authorities to make rational decisions on how we can protect us from particle risks. Beside that we all need to be aware of the risks and must act accordingly. 





“Particles affect human health as a function of their properties such as chemical composition, size and shape, but also depending upon complex interactions in a living organism that occur at various levels between uptake of the particle and responses of the target organ”.60


While the public is mostly aware of air and water pollution, researchers have expressed increased concerns about the health impact of infusion pollution on ICU patients. This is an issue that surely deserves more attention, with the goal of protecting our patients.


In a nutshell: particles do matter for the air we breathe, do matter for the water we drink and do matter for the infusions we give.



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Dr. Volker Luibl, MBA

Dr. Luibl is Pall Medical’s accomplished Demand Generation Marketing Manager with extensive expertise in medical device and clinical science.
Dr. Luibl is Pall Medical’s accomplished Demand Generation Marketing Manager with extensive expertise in medical device and clinical science.
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