National Drug Strategy Consultation

Harm reduction by filtration

National Drug Strategy Consultation

MDP 27

GPO Box 9848

Canberra ACT 2601

Submission to National Drug Strategy

Harm reduction by syringe filters: A cost-effective means of improving the health of injecting drug users

Professor Stuart McLean and Dr Raimondo Bruno

5 February 2010

Summary

Injecting drug users (IDUs) are liable to suffer harm not only from the illicit drugs themselves, but also from inadvertent injection of unwanted material present in these illicit drugs. This additional material includes insoluble particles and infectious microorganisms, and these are responsible for much of the medical complications associated with injecting illicit drugs: skin and soft tissue infections, endocarditis (infection of heart valves), pulmonary (lung) complications, and impaired blood flow to the limbs, leading to necrosis (tissue death) and amputation.

The needle and syringe program (NSP) was introduced in Australia in the 1980s to counter the HIV epidemic, and it has been highly cost-effective in reducing viral infections by HIV and hepatitis C1. Filters are able to remove microorganisms and other particles but they are not uniformly available through NSP sites, and may not be used if available because of problems with the filters blocking and a belief amongst IDUs that some of the drug is lost on the filter. Despite these concerns and limited availability, one-third of frequent IDU in mainland jurisdictions have recently used syringe filters 2, and this rate is significantly greater in Tasmania (45%) where access to filters is subsidised 3. However, one-fifth of IDUs do not use any filters and a further two-fifths use cigarette filters, which are ineffective as they only remove the largest particles 4 5.

The problem of particles is particularly severe when IDUs prepare injections from tablets that are designed for oral administration. The tablets are crushed and mixed with water and the mixture is injected. However, tablets contain a large proportion of inactive ingredients to facilitate the manufacture, storage and therapeutic effect of the drug. Many of these ingredients are not water soluble and their injection can cause complications. The long-acting formulations of morphine sulfate, such as MS Contin®, are commonly used this way. These tablets contain a wax matrix which is used to confer the prolonged effect of morphine. A major problem is that the wax produces a large amount of insoluble particulate material when the tablet is crushed for injection. The prevalence of injection of morphine and other pharmaceutical opiates has increased in recent years, and has been noted as an issue of concern by the Royal Australian College of Physicians [see: http://www.racp.edu.au/index.cfm?objectid=EA87198D-CA47-AB21-072D9B2F26FD4AA3]

We have studied the particle content of injections prepared from long-acting morphine tablets (MS Contin®) 5. Each unfiltered injection contained tens of millions of particles which ranged in size from smaller than 5 mm to greater than 400 mm. Intravenous injection of these particles is harmful, as they will lodge as emboli in the blood vessels, leading to tissue death. We found that virtually all of the particles can be removed by appropriate filtration, and that effectively the full dose of the drug can be retained by good preparation practices.

It is our recommendation that effective filters and instructions on their use should be uniformly provided at NSP outlets. Appropriate syringe filters are able to remove particles and, using the 0.2 mm pore size, can also remove microorganisms (bacteria and fungi, although not viruses). Thus with a single additional step, much of the harm caused by injections prepared from pharmaceutical tablets can be eliminated. The use of effective filters would also be expected to reduce the harm caused by injection of illicit drugs other than morphine from tablets, at least so far as this is due to the presence of insoluble particles and non-viral microorganisms.

A full cost-benefit evaluation of this intervention has not yet been done. However, since the filters would be supplied through existing NSP outlets the costs of implementation would be not much more than the wholesale price of the filters ($1-2 each). The most common causes of hospital admissions of IDUs, soft-tissue infections and lung complications, can be prevented by effective skin-swabbing and filtration of injections, saving the cost of hospitalization which is $A3,907 per average of all hospital admissions 6. Some idea of the national cost comes from the estimated cost to the public health system of treating injection-related injuries and diseases (excluding HIV and other viral infections) for Victoria, NSW and Queensland, which was $19 million in 2005/6 7. Usually IDUs only seek treatment for the most serious reactions, and these are greatly outnumbered by potentially serious and non-serious reactions7. Therefore these known health costs represent only a small fraction of the total health impact of injecting drug use.
Background

Harm due to non-drug contaminants of injections

Injecting drug users (IDUs) are liable to suffer harm due to the adverse effects of the drugs, such as respiratory failure after overdose with opiates or psychotic episodes after heavy use of amphetamines 8. However, in addition to these drug-related harms, a great number of medical complications can be attributed to, or are aggravated by, contaminants and other extraneous material in the injections 9-12. Some of these contaminants are deliberately added to illicit drug preparations as diluents (eg quinine, lactose, caffeine, sucrose) and some occur during production (eg chemical byproducts, dirt) 13. In the case of pharmaceutical tablets, various inactive substances are added during production to facilitate the manufacture, stability and therapeutic effectiveness of the tablet 14. The additives, or excipients, include a number of substances which are not soluble in water: talc, cornstarch, cellulose, magnesium stearate, waxes. Whatever their source, the injection of insoluble particles can cause health complications.

Effects of injection of particles

There are two broad types of problem which arise from the injection of particles. Particles tend to be irritant to tissue (think of dust in the eye), and can cause inflammation at the site of injection. Damage to the vein can lead to inflammation (phlebitis), formation of a clot (thrombus) or both (thrombophlebitis). This can block the flow of blood leading to a lack of oxygen in the downstream tissue (ischaemia). This condition can occur near the site of injection or in a deep vein (deep venous thrombosis or DVT) and is considered to be common amongst IDUs although often untreated12. Sometimes the injection is made into the skin or muscle, either because it misses the vein, or because the vein has been too damaged from previous injections 10 13. The inflammation in these tissues leads to a lump (granuloma) involving accumulation of white blood cells and deposition of scar tissue. This can progress, for example it it becomes infected, leading to an abscess, and chronic skin ulcer 15.

The second type of problem occurs when a particle is injected into the bloodstream where it moves downstream until it encounters a vessel too small to pass, where it lodges forming a blockage, or embolism. This results in a lack of blood flow to the downstream tissue (ischaemia) which can lead to death of this tissue (necrosis) 9 16. When injected into a vein in the arm or leg, particles will be carried through ever-larger vessels to the heart, and then to the pulmonary circulation where they will encounter progressively smaller vessels from arteries to arterioles to capillaries 17. Particles larger than capillaries (about 7-9 mm, where one mm or micrometer is one thousandth of a millimetre) will block there, while larger particles will block the arterioles (9-40 mm diameter) or small arteries (300-400 mm diameter). Particles larger than this are unlikely to be taken up through the syringe needle and will not be injected.

Sometimes the injection is made into an artery in the arm or leg, either accidentally or deliberately when the veins have become too damaged to access. In this case the embolism and consequent ischaemic damage occurs in the limb and can lead to amputation of digits or the limb itself, depending on the site of the blockage 13 18.

Microorganisms, such as bacteria and fungi, are also particles and can be removed by filtration provided the pore size is small enough 19. A filter size of 0.2 mm is regarded as sterilizing since it will remove these microorganisms, although it will not remove viruses. Fortunately, the viruses of most concern for IDUs (HIV and hepatitis C) are blood borne and can be avoided by not sharing injection equipment 10.

Medical complications of injecting drug use

In some cases the drug itself can produce critical illness, for example stroke and myocardial infarction after cocaine injection 8. Many substances have been used to dilute illicit drugs, including quinine, lactose, caffeine, sucrose 13. Although it is water-soluble, quinine is capable of damaging the walls of blood vessels and its injection can cause clotting (thrombosis) in veins 15.

However, there are a large number of medical complications of injecting drug use which are attributable, wholly or in part, to particles and microorganisms present in the injection and which could be removed by filtration. The most common complications requiring treatment which are experienced by IDUs are skin and soft tissue infections, and diseases of the heart and lungs (Table 1). These sites have the greatest contact with the injection constituents, either as sites of injection (skin, muscle), or as the first organ of contact in the circulation (heart), or as having the first microcirculation of contact (in the lungs).

Table 1. Selected1 Medical Complications of Injecting Drug Use

Tissue Complication2

Injection into vein

Skin and muscle

Cellulitis Necrosis

Abscesses Necrotizing ulcers

Nodules Necrotizing fasciitis

Blood vessels and lymphatics

Thrombophlebetis Chronic venous insufficiency

Thrombosis Lymphoedema

Pseudoaneurysm

Heart

Endocarditis

Lungs

Fibrosis Conglomerate masses

Granuloma Pulmonary hypertension

Nodules Panacinar emphysema

Skeleton

Septic arthritis Osteomyelitis

Injection into artery

Limbs

Ischaemia Gangrene

Necrosis Amputation

Infections

Local and systemic infections with Staphylococci, Streptococci, Psudomonas, Clostridium.

1A very large number of complications have been reported, involving almost any body organ 20

2All of these complications have been associated with injection of particles

References: 9-11 13 16 21 22

The initial damage may lead to local tissue necrosis which enables pathogenic microorganisms to colonise the tissue, and the resulting infection leads to more serious disease. For example, in the skin, irritation causes a type of inflammation (cellulitis), then a lump of scar tissue (granuloma). The damage can progress to local infection (skin abscess) and, if this should spread to the bloodstream, a serious systemic infection.

The microoganisms usually involved are bacteria which are commonly found on the skin (Staphylococcus aureus and Streptococcus species), and infections are associated with a failure to disinfect the injection site 13 15 23, indicating that the IDU has probably become infected by omitting to sterilize their skin 10 15. In the heart, it is the tricuspid valve which has been most commonly infected in IDU-related endocarditis 11 24. The tricuspid is the valve through which the injection constituents pass on the way to the lungs. Here, the major pathogens are Staphylococci, Pseudomonas and the fungus, Candida, all of which are commonly present in the environment 10.

The lungs are the primary target organ in which small vessels are blocked following the intravenous injection of particles. This has been well described for talc, which produces characteristic lesions in the lungs 9 16. With repeated injections the talc accumulates in the lungs. The talc can migrate out of the blood vessels into the lung tissue where an inflammatory reaction leads to the development of scar tissue (fibrosis) which takes the form of small lumps or nodules. These nodules can coalesce into larger conglomerate masses. The overall picture is one of progressive damage involving the lung and other chest structures leading to a reduction in lung efficiency (emphysema) and impaired breathing (dyspnoea) and sometimes elevated blood pressure (pulmonary hypertension). The latter carries a high risk of heart failure.

Evidence that particles cause complications

The most direct evidence that particles cause complications comes from studies of IDUs who used crushed tablets. Talc and other insoluble tablet fillers have been implicated in lung and other thoracic complications 9 16 25-27. The talc deposits could be seen in histological specimens from the lung. Injection of crushed buprenorphine tablets causes many skin conditions: cellulitis, abscess, nodules, necrosis, thrombophlebitis and oedema 13. Crospovidine, an insoluble polymer used in pharmaceutical tablets, has been found as particles in the pulmonary arteries and extravascular foreign body granulomas in the lungs of injecting drug users 28. Deep neck abscesses have been found in injecting Ritalin® users 29. This was related to an inflammatory foreign body reaction to the inactive components in the tablet, followed by superinfection with oral or skin flora. Injection of buprenorphine tablets has been assocated with puffy hand due to obstruction of the lymph ducts 30. Injection of buprenorphine tablets has also been associated with infective endocarditis and Staph. aureus septicaemia with a high mortality rate of 42% 22.

Other illicit drug preparations contain insoluble particles, although the composition of these is not well understood. However, the characteristic track marks seen in regular IDUs are due to the deposition of particles under the skin 10. It is also generally considered among experts that contaminating particles are a major contributing factor to physical complications of drug abuse, especially when microbes are considered 9-11 13 15 16.

Finally, it is biologically plausible that insoluble particles are major contributors to health complications. Unlike insoluble particles, drugs and other substances which are in solution are not usually able to cause blockages in blood vessels or deposit in tissues. Also, despite the exceptions of quinine, and cocaine (which can excessively constrict blood vessels), drugs and inert diluents in solution do not usually cause damage to blood vessels, unlike particles which can physically damage the vessel walls leading to thrombosis or even laceration and ballooning of the wall (pseudoaneurysm) 9.

The infection which commonly follows tissue damage is due to non-viral micoorganisms, bacteri and fungi, which are also particles. These infections may be a primary cause of complications 9 13. Infections which commence locally (eg in the skin or a heart valve) can progress to involve the entire body 10 15.