Last week, the Australian Therapeutic Goods Administration added intravenous (IV) fluids to the growing list of medicines in short supply. The shortage is due to higher-than-expected demand and manufacturing issues.

Two particular IV fluids are affected: saline and compound sodium lactate (also called Hartmann’s solution). Both fluids are made with salts.

There are IV fluids that use other components, such as sugar, rather than salt. But instead of switching patients to those fluids, the government has chosen to approve salt-based solutions by other overseas brands.

So why do IV fluids contain different chemicals? And why can’t they just be interchanged when one runs low?

We can’t just inject water into a vein

Drugs are always injected into veins in a water-based solution. But we can’t do this with pure water, we need to add other chemicals. That’s because of a scientific principle called osmosis.

Osmosis occurs when water moves rapidly in and out of the cells in the blood stream, in response to changes to the concentration of chemicals dissolved in the blood plasma. Think salts, sugars, nutrients, drugs and proteins.

Too high a concentration of chemicals and protein in your blood stream leads it to being in a “hypertonic” state, which causes your blood cells to shrink. Not enough chemicals and proteins in your blood stream causes your blood cells to expand. Just the right amount is called “isotonic”.

Mixing the drug with the right amount of chemicals, via an injection or infusion, ensures the concentration inside the syringe or IV bag remains close to isotonic.

What are the different types of IV fluids?

There are a range of IV fluids available to administer drugs. The two most popular are:

• 0.9% saline, which is an isotonic solution of table salt. This is one of the IV fluids in short supply
• a 5% solution of the sugar glucose/dextrose. This fluid is not in short supply.

There are also IV fluids that combine both saline and glucose, and IV fluids that have other salts:

• Ringer’s solution is an IV fluid which has sodium, potassium and calcium salts
• Plasma-Lyte has different sodium salts, as well as magnesium
• Hartmann’s solution (compound sodium lactate) contains a range of different salts. It is generally used to treat a condition called metabolic acidosis, where patients have increased acid in their blood stream. This is in short supply.

What if you use the wrong solution?

Some drugs are only stable in specific IV fluids, for instance, only in salt-based IV fluids or only in glucose.

Putting a drug into the wrong IV fluid can potentially cause the drug to “crash out” of the solution, meaning patients won’t get the full dose.

Or it could cause the drug to decompose: not only will it not work, but it could also cause serious side effects.

An example of where a drug can be transformed into something toxic is the cancer chemotherapy drug cisplatin. When administered in saline it is safe, but administration in pure glucose can cause life-threatening damage to a patients’ kidneys.

What can hospitals use instead?

The IV fluids in short supply are saline and Hartmann’s solution. They are provided by three approved Australian suppliers: Baxter Healthcare, B.Braun and Fresenius Kabi.

The government’s solution to this is to approve multiple overseas-registered alternative saline brands, which they are allowed to do under current legislation without it going through the normal Australian quality checks and approval process. They will have received approval in their country of manufacture.

The government is taking this approach because it may not be effective or safe to formulate medicines that are meant to be in saline into different IV fluids. And we don’t have sufficient capacity to manufacture saline IV fluids here in Australia.

The Australian Society of Hospital Pharmacists provides guidance to other health staff about what drugs have to go with which IV fluids in their Australian Injectable Drugs Handbook. If there is a shortage of saline or Hartmann’s solution, and shipments of other overseas brands have not arrived, this guidance can be used to select another appropriate IV fluid.

Why don’t we make it locally?

The current shortage of IV fluids is just another example of the problems Australia faces when it is almost completely reliant on its critical medicines from overseas manufacturers.

Fortunately, we have workarounds to address the current shortage. But Australia is likely to face ongoing shortages, not only for IV fluids but for any medicines that we rely on overseas manufacturers to produce. Shortages like this put Australian lives at risk.

In the past both myself, and others, have called for the federal government to develop or back the development of medicines manufacturing in Australia. This could involve manufacturing off-patent medicines with an emphasis on those medicines most used in Australia.

Not only would this create stable, high technology jobs in Australia, it would also contribute to our economy and make us less susceptible to future global drug supply problems.

Nial Wheate, Professor and Director Academic Excellence, Macquarie University and Shoohb Alassadi, Casual academic, pharmaceutical sciences, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

If you Google the terms “constipation” and “heart attack” it’s not long before the name Elvis Presley crops up. Elvis had a longstanding history of chronic constipation and it’s believed he was straining very hard to poo, which then led to a fatal heart attack.

We don’t know what really happened to the so-called King of Rock “n” Roll back in 1977. There were likely several contributing factors to his death, and this theory is one of many.

But after this famous case researchers took a strong interest in the link between constipation and the risk of a heart attack.

This includes a recent study led by Australian researchers involving data from thousands of people.

Are constipation and heart attacks linked?

Large population studies show constipation is linked to an increased risk of heart attacks.

For example, an Australian study involved more than 540,000 people over 60 in hospital for a range of conditions. It found constipated patients had a higher risk of high blood pressure, heart attacks and strokes compared to non-constipated patients of the same age.

A Danish study of more than 900,000 people from hospitals and hospital outpatient clinics also found that people who were constipated had an increased risk of heart attacks and strokes.

It was unclear, however, if this relationship between constipation and an increased risk of heart attacks and strokes would hold true for healthy people outside hospital.

These Australian and Danish studies also did not factor in the effects of drugs used to treat high blood pressure (hypertension), which can make you constipated.

How about this new study?

The recent international study led by Monash University researchers found a connection between constipation and an increased risk of heart attacks, strokes and heart failure in a general population.

The researchers analysed data from the UK Biobank, a database of health-related information from about half a million people in the United Kingdom.

The researchers identified more than 23,000 cases of constipation and accounted for the effect of drugs to treat high blood pressure, which can lead to constipation.

People with constipation (identified through medical records or via a questionnaire) were twice as likely to have a heart attack, stroke or heart failure as those without constipation.

The researchers found a strong link between high blood pressure and constipation. Individuals with hypertension who were also constipated had a 34% increased risk of a major heart event compared to those with just hypertension.

The study only looked at the data from people of European ancestry. However, there is good reason to believe the link between constipation and heart attacks applies to other populations.

A Japanese study looked at more than 45,000 men and women in the general population. It found people passing a bowel motion once every two to three days had a higher risk of dying from heart disease compared with ones who passed at least one bowel motion a day.

How might constipation cause a heart attack?

Chronic constipation can lead to straining when passing a stool. This can result in laboured breathing and can lead to a rise in blood pressure.

In one Japanese study including ten elderly people, blood pressure was high just before passing a bowel motion and continued to rise during the bowel motion. This increase in blood pressure lasted for an hour afterwards, a pattern not seen in younger Japanese people.

One theory is that older people have stiffer blood vessels due to atherosclerosis (thickening or hardening of the arteries caused by a build-up of plaque) and other age-related changes. So their high blood pressure can persist for some time after straining. But the blood pressure of younger people returns quickly to normal as they have more elastic blood vessels.

As blood pressure rises, the risk of heart disease increases. The risk of developing heart disease doubles when systolic blood pressure (the top number in your blood pressure reading) rises permanently by 20 mmHg (millimetres of mercury, a standard measure of blood pressure).

The systolic blood pressure rise with straining in passing a stool has been reported to be as high as 70 mmHg. This rise is only temporary but with persistent straining in chronic constipation this could lead to an increased risk of heart attacks.

Some people with chronic constipation may have an impaired function of their vagus nerve, which controls various bodily functions, including digestion, heart rate and breathing.

This impaired function can result in abnormalities of heart rate and over-activation of the flight-fight response. This can, in turn, lead to elevated blood pressure.

Another intriguing avenue of research examines the imbalance in gut bacteria in people with constipation.

This imbalance, known as dysbiosis, can result in microbes and other substances leaking through the gut barrier into the bloodstream and triggering an immune response. This, in turn, can lead to low-grade inflammation in the blood circulation and arteries becoming stiffer, increasing the risk of a heart attack.

This latest study also explored genetic links between constipation and heart disease. The researchers found shared genetic factors that underlie both constipation and heart disease.

What can we do about this?

Constipation affects around 19% of the global population aged 60 and older. So there is a substantial portion of the population at an increased risk of heart disease due to their bowel health.

Managing chronic constipation through dietary changes (particularly increased dietary fibre), increased physical activity, ensuring adequate hydration and using medications, if necessary, are all important ways to help improve bowel function and reduce the risk of heart disease.

Vincent Ho, Associate Professor and clinical academic gastroenterologist, Western Sydney University

This article is republished from The Conversation under a Creative Commons license. Read the original article.