Pure Water in Clinical Diagnostics and Patient Management

6 Jul 2020

Medical technology concept.

The Key Role of Pure Water in Clinical Diagnostics and Patient Management

Pure water plays a key role in clinical diagnostics, with applications varying from the identification of small molecules as biomarkers of non-communicable diseases, such as heart disease, to their use in identifying different pathogens, such as specific influenza viral subtypes in epidemiological studies.^1-3 Here we imagine a scenario where a patient has suffered a heart attack, and we consider the role of water in the overall diagnosis and management of their condition.

The Role of Water in Measuring Disease Biomarkers

We have established elsewhere that HPLC and LC/MS are routinely used in clinical diagnostics, for example, in the detection and monitoring of biomarkers for both non-communicable and infectious diseases, and in therapeutic drug monitoring.1 Many thousands of papers have been written on the development and use of HPLC- related assays and immunoassays such as ELISA in this area. We have chosen to focus on one key area, heart disease.⁴

Homing in on Heart Disease

Cardiovascular diseases, or CVDs, are a group of disorders of the heart and blood vessels and include coronary heart disease, cerebrovascular disease, rheumatic heart disease and other conditions. CVDs are the number one cause of death globally, taking an estimated 17.9 million lives each year, representing 31% of all global deaths.⁵ Of these deaths, 85% are due to heart attack and stroke, and over 75% take place in low- and middle-income countries.⁵

Measuring Cardiac Biomarkers

Most cardiovascular diseases can be prevented by addressing behavioural risk factors such as tobacco use, unhealthy diet and obesity, physical inactivity and harmful use of alcohol using population-wide strategies. People with cardiovascular disease or who are at high cardiovascular risk (due to the presence of one or more risk factors such as hypertension, diabetes, hyperlipidaemia or other already established disease) need early detection and management using counselling and medication.

What Happens When a Patient has a Suspected Heart Attack?

A patient will sometimes go into cardiac arrest, in other cases there may be a less obvious event that may or may not be the result of damage to the heart. In both cases, blood samples will be taken, and relevant biomarkers will be measured. Cardiac biomarkers are released into the bloodstream when heart muscle is damaged or stressed, and whilst not all tests for heart disease markers are HPLC-related, they are very often immunoassay-related (e.g. troponin I) and will therefore still rely implicitly on the provision of ultrapure water for their accuracy and reproducibility, whether done manually or as part of an automated workflow.⁷

The Role of Pure Water in Cardiac Patient Management

Whilst on the one hand, our heart patient will be having their blood analysed for the evidence of elevated cardiac biomarkers, and be undergoing a range of other tests including a physical exam, an electrocardiogram, electro-cardiographic (EKG) monitoring, and possibly cardiac catheterisation, it is so often taken for granted that they will also be relying on the provision of pure or ultrapure water throughout their interventions and management.

Consider the heart patient who needs emergency surgery, or even just a simple intravenous maintenance drip. Any procedure requiring water in its operation presents a potential hazard. Water supports the growth of Gram-negative bacteria, and calcium and magnesium can stain instruments and inactivate disinfectants. Water is important in all stages of medical device reprocessing, being required for each step in the decontamination process, from soaking, to cleaning, to rinsing, including the final disinfecting rinse.⁸

Decontaminating Surgical Instruments

In recent years, there has been growing awareness about the importance of water in the decontamination of surgical devices and the harmful effects of even minute quantities of contaminants on patients. During open heart surgery, or even heart catheterisation, medical devices can potentially introduce contaminants directly into parts of the body that are normally protected by skin and mucous membranes. Metals, organic compounds, microorganisms and pyrogens can all lead to adverse reactions, and patients are particularly susceptible when surgical instruments bypass the body’s immune system defences in this way.

Is Your Steam Pure Enough?

Water is also the source for steam used to sterilise most surgical devices and patient-care items. In Europe, HTM 2030 provides guidance on the choice, specification, purchase and validation as well as maintenance of automated washers and provides recommendations for purified water standards and system designs as well as steam quality. The standard states, “The sterilisation steam must be free from impurities and should neither impair the sterilisation process nor damage the steriliser or the items to be sterilised.” ^8,9

Medical Water Purification Systems

First, a caveat about water softening systems. These have little control over water purity and downstream protection from chloride corrosion of the hospital washer and surgical instruments. AAMI TIR34:2007 states, “Softened water is water that receives limited treatment (softening) to remove inorganic material from the water. It will not reduce microbial levels, nor will it remove organic material, which acts as nutrients for bacterial growth, from the water.” ⁸

According to TIR34:2007, reverse osmosis has become widely used in medical device water purification systems. The advantage of reverse osmosis water is that it “filters out contaminants to a high degree of efficiency. Reverse osmosis removes particulate matter, organic molecules and pyrogens that deionized water cannot. It is less corrosive to steel and copper.” It is also cheaper to run and maintain than deionized water systems. HTM2030 suggests that reverse osmosis would be the obvious choice as a core treatment technology, given its excellent impurity removal spectrum across ionic, organic and microbiological species.

Quality Assurance of Heart Medication

Finally, it goes without saying that the medications prescribed for our heart attack patient have gone through a rigorous QA procedure, from analysis of the active pharmaceutical ingredients (APIs) to the dissolution testing of the final formulation, a procedure that will have included the use of ultrapure water. These processes are explained in more depth in our white paper on the use of HPLC in pharmaceutical manufacture and quality control.

Drugs that may be prescribed after a heart attack include but are not limited to:

ACE inhibitors, which widen arteries to lower blood pressure and make it easier for the heart to pump blood.
beta-blockers, which block the effects of adrenaline (epinephrine), helping the heart work better, causing your heart to beat slower and with less force and hence lowering blood pressure.
calcium channel blockers to treat chest pain (“angina”) and high blood pressure, which relax blood vessels and increase blood and oxygen to the heart and hence easing its workload.
cholesterol-lowering drugs. Cholesterol helps the body build new cells, insulate nerves, and make hormones. Inflammation may force cholesterol to build up in the walls of your arteries. That build-up increases the chance of heart attack or stroke.⁹

Pure Water: the Essence of Patient Management

We have seen that pure water is key to the effective management of our heart attack patient, from the ELISAs or other tests used for measuring the level of their cardiac biomarkers when they first arrive in the emergency room, via the preparation of the sterile medical devices if they are unfortunate enough to require surgery, to the preparation and QA of the medications prescribed for their recovery. For more detail on the risks associated with water used in pharma HPLC and patient monitoring, check out our white papers.

Download our White Paper HPLC in Pharma / Reducing Risk in LC/MS

References:

1. Christoph Seger and Linda Salzmann (2020) After another decade: LC–MS/MS became routine in clinical diagnostics Clinical Biochemistry, in press. https://doi.org/10.1016/j.clinbiochem.2020.03.004
2. Dhingra, R., & Vasan, R. S. (2017). Biomarkers in cardiovascular disease: Statistical assessment and section on key novel heart failure biomarkers. Trends in cardiovascular medicine, 27(2), 123–133. https://doi.org/10.1016/j.tcm.2016.07.005
3. https://www.cdc.gov/flu/prevent/vaccine-selection.htm Accessed 20 May 2020.
4. Banerjee S. (2020). Empowering Clinical Diagnostics with Mass Spectrometry. ACS omega, 5(5), 2041–2048. https://doi.org/10.1021/acsomega.9b03764
5. https://www.who.int/health-topics/cardiovascular-diseases/#tab=tab_1 Accessed 20 May 2020
6. Farthing, D., Xi, L., Gehr, L., Sica, D., Larus, T., & Karnes, H. T. (2006) High-performance liquid chromatography (HPLC) determination of inosine, a potential biomarker for initial cardiac ischaemia, using isolated mouse hearts, Biomarkers, 11(5): 449-459.
7. https://labtestsonline.org.uk/tests/cardiac-biomarkers Accessed 20 May 2020.
8. https://www.infectioncontroltoday.com/sterile-processing/water-instrument-processing Accessed 20 May 2020.
9. Rashid, M. A., Edwards, D., Walter, F. M., & Mant, J. (2014). Medication taking in coronary artery disease: a systematic review and qualitative synthesis. Annals of family medicine, 12(3), 224–232. https://doi.org/10.1370/afm.1620