Filters in Anaesthesia and Intensive Care

Abstract

The use of various types of filters in anaesthesia and intensive care seems ubiquitous, yet authentication of the practice is scarce and controversies abound. This review examines evidence for the practice of using filters with blood and blood product transfusion (standard blood filter, microfilter, leucocyte depletion filter), infusion of fluids, breathing systems, epidural catheters, and at less common sites such as with Entonox inhalation in non-intubated patients, forced air convection warmers, and air-conditioning systems. For most filters, the literature failed to support routine usage, despite this seemingly being popular and innocuous. The controversies, as well as guidelines if available, for each type of filter, are discussed. The review aims to rationalize the place of various filters in the anaesthesia and intensive care environment.

Full text

Anaesthesia and Intensive Care, Vol. 31, No. 4, August 2003
Anaesth Intensive Care 2003; 31: 418-433
Reviews
Filters in Anaesthesia and Intensive Care
A. TYAGI*, R. KUMAR†, A. BHATTACHARYA‡, A. K. SETHI§
Department of Anaesthesiology and Intensive Care, University College of Medical Sciences and GTB Hospital, New Delhi,
India
SUMMARY
The use of various types of filters in anaesthesia and intensive care seems ubiquitous, yet authentication of the practice
is scarce and controversies abound. This review examines evidence for the practice of using filters with blood and
blood product transfusion (standard blood filter, microfilter, leucocyte depletion filter), infusion of fluids, breathing
systems, epidural catheters, and at less common sites such as with Entonox inhalation in non-intubated patients,
forced air convection warmers, and air-conditioning systems. For most filters, the literature failed to support routine
usage, despite this seemingly being popular and innocuous. The controversies, as well as guidelines if available, for
each type of filter, are discussed. The review aims to rationalize the place of various filters in the anaesthesia and
intensive care environment.
Key Words: FILTERS: breathing system filters, blood filters, leucocyte depleting filter, microfilter, in-line filters.
EPIDURAL: filter. INTENSIVE CARE: filters
Despite blood and blood product transfusions
being handled frequently by anaesthetists, anaes-
thesia texts seldom review the practice and contro-
versies of filter use during transfusion therapy. Two
relevant and increasingly well-known issues for
modern medicine are the spread of infection by
medical intervention, and effective cost utilization in
hospitals. Anaesthesia and intensive care are not
exempt from implementation of practices designed to
achieve these goals. One of several methods pro-
posed to limit the spread of infection is routine use
of filters. Use of various types of filters in our
speciality seems ubiquitous, yet authentication of the
practice is scarce and controversies abound. In addi-
tion, our search did not reveal any comprehensive
account of the various filters used in anaesthesia and
intensive care. Thus, this review examines evidence
related to the practice of using filters with blood and
blood product transfusion, infusion of fluids, breath-
ing systems, epidural catheters, and relatively less
common sites of filter usage such as with Entonox
(nitrous oxide/oxygen) inhalation in unintubated
patients, forced air convection warmers, and air-
conditioning systems. Controversies, as well as guide-
lines if available, for each of these filters, are dis-
cussed. We hope to rationalize the place of various
filters in anaesthesia and intensive care in the
current environment. For data collection we con-
ducted a Medline search, studied previous reviews of
different types of filters1-3, their cross-references, and
other articles gathered on the subject while reading
relevant journals.
BLOOD FILTERS
Anaesthetists constitute one of the largest percent-
ages of specialists dealing with blood and blood
products. Consequently discussion about complica-
tions of blood transfusion is common and extensive.
However, the use of blood filters has not been subject
to the comprehensive review it merits in anaesthesia
texts. The need to filter clots and other debris formed
in stored blood was recognized at an early stage as a
means of preventing embolization4,5. Early removal
techniques used combinations of wire screens and
cotton gauze to filter larger clots6. Great advances
*M.B., B.S., M.D., D.N.B., Lecturer, Department of Anaesthesiology and
Intensive Care, University College of Medical Sciences and GTB Hospital.
†M.B., B.S., M.D., Senior Resident, Department of Anaesthesiology and
Intensive Care, University College of Medical Sciences and GTB Hospital.
‡M.B., B.S., D.A., M.D., D.Acup., Senior Consultant, Department of
Anaesthesiology and Intensive Care, Sir Ganga Ram Hospital.
§M.B., B.S., D.A., M.D., Professor and Head, Department of
Anaesthesiology and Intensive Care, University College of Medical
Sciences and GTB Hospital.
Address for reprints: Dr A. Tyagi, 103 Siddhartha Enclave, New Delhi-14,
India.
Accepted for publication on March 28, 2003.

have been made in the field of blood filtration, with
three generations of filters now available (Table 1).
The use of a first generation blood filter (Figure 1)
appears indispensable and is well accepted. Our goal
was to determine whether the less common practice
of using a second generation blood filter for microfil-
tration or a third generation blood filter for leucocyte
reduction of blood and blood products has a place in
modern transfusion therapy.
SECOND GENERATION BLOOD FILTERS
(MICROFILTERS)
The 1960s witnessed development of open-heart
surgical techniques and improved methods of resusci-
tation of trauma victims, wherein massive blood
transfusions are frequently used. Consequently,
recommendations to use microfilters7of pore size
20-40 µm to remove microaggregates (MAs) from the
transfusion8appeared. Initial enthusiasm for micro-
filters led to further investigation of the clinical
importance of removing MAs9-11. This unfurled con-
trary views, but before considering microfilter use
in current practice, the pathophysiology of MA
formation and sequelae are discussed.
Microaggregates (MAs)
Within a few hours of blood collection, platelets
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TABLE 1
Comparison of various blood filters (BF)
First generation BF Second generation BF Third generation BF
Standard blood filter Screen Microfilter Depth Microfilter Leucocyte reduction filter
Pore size, µm 170-260 20-40 20-40 0.3-3
Construction material — Woven polyester Packed adsorptive Surface treated synthetic
material microfibres
Indication Remove gross debris Remove Remove Remove leucocytes
and blood clots microaggregates microaggregates
Mechanism of action Mechanical barrier Mechanical barrier Adsorptive separation & Mechanical barrier,
limited mechanical biologic interactions, cell
barrier adhesion to media
Advantages — Fixed pore size — Up to 99.9% (3 log 10)
(1x103) reduction in
leucocytes
Disadvantages — Fall in efficiency with Fall in efficiency with Different and non-
use use. interchangeable filters
In comparison to screen for packed red blood
filters. cells and platelet
Greater red blood cell loss transfusions.
(larger dead space).
Prolonged contact time
with blood.
Unloading and channeling
of filtered particles
FIGURE 1: A standard blood filter.

aggregate in stored blood to form loosely bound
structures that by 24 to 48 hours also trap degenerat-
ing white blood cells and fibrin precipitates12. These
MAs, of 10-40 µm size, are formed in a time-
dependent process such that numbers are increasing
significantly after five or more days of storage13.
Though formation of MAs is independent of the
nature of anticoagulant used, their rate of formation
depends on the type of anticoagulant used, being
most rapid in heparinized blood. Although citrate-
phosphate-dextrose-adenine (CPDA) anticoagulated
blood develops MAs faster than blood containing
ACD in the first week, formation occurs irrespective
of storage solution by two weeks, with eventually 50-
250 million MAs present per unit. Blood stored in
saline-adenine-glucose-mannitol (SAGM) solution is
also not exempt from MA formation14,15 although
the number formed is significantly less16 than in
CPDA blood.
Given the average size of MA debris, their trans-
fusion is not prevented by a standard 170 µm filter.
Screen or depth filters must be used to prevent infu-
sion of MAs (Table 1). Owing to the disadvantages of
depth type microfilters, screen microfilters are more
commonly used.
Is Microaggregate Transfusion Harmful?
Microaggregates and Nonhaemolytic Febrile
Transfusion Reaction (NHFTR)
Febrile transfusion reaction is defined as a temper-
ature rise of >1°C above baseline during transfusion
of blood or leucocyte-containing blood components,
that is without other explanation. These reactions are
due to interaction between HLA Class I antigens
present on transfused lymphocytes, granulocytes or
platelets and mostly leucocytes17 in donor units, and
antibody in previously alloimmunized recipients. The
incidence of NHFTRs varies from 0.5%17 to 6.6%18
but may be as high as 45% in chronically infused
patients, such as those suffering from thalassaemia18.
It is the commonest reaction, accounting for 70% of
all transfusion-related problems19. Transfusion of ex-
pensive leucocyte-reduced red cell concentrates is
one method of avoiding NHFTRs.
A simpler and less expensive method of preventing
NHTRs is use of a microfilter to remove leucocyte-
containing MAs. Different studies16,20,21 confirm that
microfilters reduce the rate of NHFTR by fivefold
and if combined with centrifugation (which probably
incorporates granulocytes into MAs) by 98%.
Microaggregates and Pulmonary Injury
A relationship between microembolic blockage
of pre-capillary arterioles and acute respiratory
distress syndrome (ARDS) is often proposed22-24.
Stored platelet concentrate MAs have been shown to
result in ultrastructural lesions similar to those
observed in situations leading to pulmonary dys-
function25. Several authors8,15,26,27 suggest altered pul-
monary function in the pulmonary circulation after
only two to three units of transfused blood.
Despite animal and human studies, the issue of
MA related lung injury is contentious and the benefit
of microfilters in decreasing lung dysfunction is not
firmly established. The routine use of microfilters to
decrease lung dysfunction is not supported6,7,28.
Other adverse effects of MA transfusion
Thrombocytopenia following blood transfusions
can occur after less than a five unit transfusion29. The
fall in platelet count is greatest at 72 hours after
transfusion29 and can be only partially be explained by
the dilutional effect29-31. Lim et al32 found that the fall
in platelet count decreased tenfold if microfilters
were used. This effect was studied using radiolabelled
platelets by Bareford29 who showed that splenic
sequestration of platelets was less after a microfilter
was included during transfusion.
Fibronectin is an opsonic circulating glycoprotein
involved in coating invading organisms and debris
and presenting them to reticulo-endothelial system
(RES) for elimination from the circulation. It has
been hypothesized that MAs probably adhere to
fibronectin, leading to its premature removal from
circulation by the RES23,29 and subsequent depletion.
Blood transfusion through a standard filter results
in a significant fall in fibronectin levels compared
with transfusion through a microfilter33. In an in vitro
study of stored blood collected via microfilters, a
decrease in the number of basophils and thus in the
histamine levels was noted34.
There is little information about the potential
complications associated with MAS during trans-
fusion, and there is no case report or scientific trial
that identifies potential adverse effects as clinically
relevant.
Complications with Microfilters
Haemolysis
Depth filters may result in significant haemolysis,
especially when transfusing older blood35,36. In an early
case report of a fatality allegedly from massive
haemolysis, the probable cause was a neonatal micro-
filter used inappropriately in an infant37-39. We could
find no case report of haemolysis associated with
microfilter usage in the past five years.
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Exsanguination
The time used to prime filters and the resistance to
blood flow through them are seen as impediments
to efficiency when transfusing a bleeding, critically
hypovolaemic patient26. However, the priming of a
filter seldom takes more than one minute36. Also,
resistance to flow through microfilters is not signifi-
cantly different from that of standard filters until
three to four units of whole blood have passed
through a depth filter or seven or eight units of whole
blood through a screen filter36. Czaika et al40 reported
that flow rates of packed red cells through a 170 µm
standard blood filter were slower that through three
different types of microfilters. An interesting finding
by Linko41 was that pre-warming blood to 37°C
increased the blood flow through microfilters by 49 to
86%. As expected, screen filters gave higher flow
rates than depth filters. Of clinical relevance was the
fact that the size of the venous cannula and the trans-
fusion set were a greater influence on flow resistance
than the type of blood filter.
The weight of evidence suggests the problem of
exsanguination in a critically hypovolaemic patient is
overemphasized. Other factors affecting blood flow
rate are more important determinants of rate of
transfusion than the filters themselves.
Platelet retention
Loss of platelets occurs if fresh blood is transfused
through microfilters42. Snyder et al43 also showed that
transfusing whole blood transfusion through a depth
microfilter caused significant loss of donor platelets,
although infusion of donor platelet concentrates
through screen or depth type microfilters did not
cause significant numerical, biochemical or in vitro
functional changes.
Complement activation
Paradoxically, MA formation by microfilters fol-
lowing complement system activation has been
reported42. Yellon and colleagues44 demonstrated a
17% increase in C3 when nylon filter material was
incubated with heparinized blood for 60 minutes.
Complement activation was less when citrated blood
was passed through microfilters45 with only a 3% rise
in C3 levels. This is probably because citrate chelates
Mg2+ and Ca2+ ions, which are essential for coagu-
lation and complement activation. This postulate
was confirmed by Synder45 in both experimental
and clinical settings. A difference in extent of
complement activation might also depend on the
material used in the microfilter46. However animal47
and human45 studies show that even though MAs
secondary to complement activation by microfilters
are present, they are too small to be detected histo-
logically in the lung or to produce a clinical risk, and
thus the phenomenon is not of great significance.
Absorption of Proteins
Walsh et al48 observed that cellulose-nitrate-con-
taining filters remove IgG and to a lesser extent IgA
and IgM, but there was no significant adsorption of
albumin or transferrin by any of the filters studied. If
the filters were pre-washed with polyethylene glycol,
IgG adsorption was not seen.
Release of foreign particles
Because of the inability to flush individual filters
during manufacture, there is a theoretical possibility
of foreign particles being released into the blood
when using depth filters3.
Recommendations for Usage of Microfilters
We conclude that there are no guidelines support-
ing the routine use of microfilters during blood trans-
fusion and use is not justified. Microfilters meet the
specifications of American Association of Blood
Banks (AABB) for reducing leucocytes to the desired
number per unit of blood to prevent NHFTRs7.
Despite successfully producing leucocyte-depleted
blood and preventing febrile reactions, they fail to
comply with AABB standards for prevention of trans-
mission of CMV or HLA alloimmunization and
should not be used for these purposes. The third
edition of the booklet Questions and Answers About
Transfusion Practices, by the 1996-97 Committee on
Transfusion Medicine of ASA (American Society
of Anesthesiologists)49 does not recommend the
routine usage of microfilters, even when large
volumes of blood are administered. The only indica-
tion cited is cardiopulmonary bypass (arterial inflow
cannulae), during which MAs can enter the systemic
circulation.
THIRD GENERATION BLOOD FILTERS
(LEUCOCYTE REDUCTION FILTERS)
Leucocyte reduction refers to decreasing the
number of residual donor leucocytes in cellular blood
components such as packed red blood cells and
platelets. The current guidelines of the AABB and
the United States Food and Drug Administration
(FDA) for leucocyte reduction are as follows: Leuco-
reduced whole blood, leucoreduced packed red blood
cells and leucoreduced apheresis platelets should
contain no more than 5x106leucocytes per unit.
Leucoreduced platelet concentrates should contain
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no more than 0.83x106leucocytes per unit. By com-
parison, European standards demand a count of less
than 1x106leucocytes per unit50. However there is no
scientific evidence favouring either of the values.
Nevertheless, when used properly, current filters are
capable of producing components with residual
leucocyte counts well below 106.
Of the various techniques available for leucocyte
reduction, filtration is the most frequently used
because it is simple, rapid and cost-effective. While
early leucocyte filters were capable of achieving only
90-99% (1-2 log 10) leucocyte reduction, current
high performance leucocyte removal filters reduce
residual white blood cell content by at least 3 logs
(Table 1).
Uses of Leucoreduction Filters
Leucoreduction of blood and blood products aims
to reduce certain complications associated with
transfusion of a residual leucocyte population.
Non-haemolytic Febrile Transfusion Reactions
(NHFTRs)
The use of leucoreduced packed red blood cells
performed before or after storage is extremely effec-
tive in preventing these reactions20,51,52. However in the
case of platelet units that have been leucoreduced
after storage, pyrogenic cytokines may continue
to accumulate and be released53, resulting in
NHFTRs54,55. Pre-storage leucoreduction of plate-
lets may prove beneficial in preventing this cytokine
accumulation51,52.
Primary HLA Alloimmunization
HLA molecules on co-transfused leucocytes may
cause HLA alloimmunization, leading to platelet
refractory states and difficulty with solid organ
and bone marrow transplant acceptance and
maintenance. It is generally accepted that residual
leucocyte counts of less than 5x106leucocytes per
unit will prevent HLA alloimmunization56-58 and thus
leucoreduction of allogenic blood decreases the
incidence of HLA alloimmunization among patients
with haematologic malignancy52,59. A national trial
designed to reduce alloimmunization to platelets
(TRAP) also concluded that the incidence of HLA
alloantibody sensitization was significantly lower
among patients receiving leucoreduced platelets60.
The beneficial effect on platelet refractoriness is
said to be less pronounced when using leucoreduced
products52,61.
Hiruma et al62 found that even fresh frozen plasma
contains a leucocyte population in the range of 0.99-
8.38x106per unit and leucoreduction filters appear
effective in suppressing its alloimmunogenecity.
Effect on Transfusion-Related Immunomodulation
(TRIM)
A reduction in transfusion-related immunomodu-
lation (TRIM) might be anticipated to reduce the
incidence of postoperative infections and rate of
recurrence of tumours after primary surgical re-
sections. It is controversial whether leucoreduced
products reduce the incidence of of TRIM63, with
some studies after colorectal cancer, gastrointestinal
and cardiac surgery showing a reduction and others
not63-66. There is clinical evidence both supporting
and discrediting an association between leucocyte
reduction and postoperative infections66-69.
Cytomegalovirus (CMV) Transmission in At-Risk
Recipients
A subset of patients is considered to be at high risk
of clinical morbidity from transfusion transmitted
cytomegalovirus (CMV) infection. This includes
those with congenital immunodeficiency states,
human immunodeficiency virus infection, CMV
negative individuals, very low birth weight infants,
bone marrow transplant patients, patients awaiting
transplant surgery and those requiring long-term
blood product support. In such patients the risk of
transfusion transmitted CMV can be reduced by using
CMV negative blood products or leucoreduced blood
from CMV-positive or CMV-negative blood61,70-73.
Leucoreduction and SIRS (Systemic Inflammatory
Response Syndrome)
In a recent study by Brown and associates74, the use
of leucoreduced blood in SIRS was evaluated. Using
a laboratory-designed extracorporeal circuit, leuco-
reduction of SIRS blood was seen to limit the binding
of polymorphonuclear cells to blood vessel walls
and thereby reduce pathological manifestations
associated with SIRS.
Leucocyte reduction and its role in post-
transfusion bacterial sepsis, especially related to
Yersinia enterocolitica, is also a subject of on-going
research75-81.
Complications of leucocyte reduction filters
Hypotension has been reported when leucocyte
reduction filters are used for bedside filtration,
especially among patients receiving ACE in-
hibitors82-84. Following several such reports an FDA
Alert was issued in 1999. This suggested the aetiology
was dysmetabolism of bradykinin, a potent vaso-
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dilator. Recommendations in the event of hypoten-
sion occurring were to watch for a precipitous fall in
blood pressure; to immediately stop the transfusion
and when indicated, to use blood products that were
leucocyte-reduced at the time of collection or during
laboratory storage.
Leucoreduction filters may cause a loss of certain
coagulation factors and alter complement levels,
dependant on the type and charge of filter used85.
However, changes observed are unlikely to be clini-
cally significant unless subsequent processing of
plasma (such as pathogen inactivation) results in
further coagulation factor loss.
Anaphylaxis attributed to a negatively charged
leucodepletion filter has been reported86 after initiat-
ing platelet transfusion through the filter in a patient
with myelodysplastic syndrome.
Recommendations for use of Leucocyte Reduction
Filters
The ASA document49, AABB recommendations61,
and British recommendations52 regarding the use of
leucoreduction support use only for specific indica-
tions. Some situations in which leucoreduction has
been used remain controversial or the benefit
unproven, for example platelet refractoriness and
immunomodulation.
The role of these third generation filters needs to
be discussed and a consensus reached. In certain
countries of Western Europe and Canada all blood
components are now leucoreduced, whereas in the
United States, Australia and Asia leucoreduction is
indicated only under specific circumstances.
IN-LINE FILTERS
Administration of intravenous fluids or drugs
allows microbiological as well as particulate contami-
nation of blood stream. The former includes both the
presence of bacteria and biological by-products.
While particulate contaminants may be a cause of
post infusion phlebitis, the eventual sequelae of
infused contaminants are dependent on their size.
Particles larger than 8 µm are filtered by the lung
and may result in pulmonary granulomas, particles
smaller than 8 µm are cleared by phagocytosis and
ultimately presented to liver and spleen.
Contamination of Intravenous Infusates and
Equipment
Trautmann and colleagues87 studied bacterial
colonization and endotoxin contamination of intra-
venous infusion fluids and catheter systems in an
intensive care unit. The rate of bacterial colonization
of bottles/burettes was 7.8% at 48 hours after com-
mencing infusions and rose to a significantly higher
incidence of 15.7% at 96 hours. At both these time
intervals studied, the colonization rates of catheter
fluid were higher than that in bottles/burettes (34%
and 24.1% respectively). Cell-bound endotoxin was
found in 8.8% of samples, even though only 2.5% of
the samples contained free endotoxin.
Uses of In-line Filters
Septicaemia
Whether prevention of bacterial and endotoxin
influx into patients from the contaminated fluid and
fluid systems results in decreased incidence of septi-
caemia remains to be proven. Our search identified
a single study looking into this aspect, which was
the experience in an Australian paediatric teaching
hospital88. In this prospective study a total of 19,221
intravenous days were monitored spread over one-
year periods before and after withdrawal of in-line
intravenous filters from central venous access in 88
children. There were no differences in incidence of
septicaemia between children with filters fitted and
those without.
Phlebitis and Intravenous Line Survival
Incidence of phlebitis and intravenous line survival
of peripheral intravenous catheters in patients receiv-
ing drugs through in-line filters was found to be the
same as in those without an in-line filter but receiving
infusates containing heparin 500 units and hydro-
cortisone 10 mg/l89. The authors concluded that use of
filters, while decreasing incidence of phlebitis and
increasing survival time of peripheral intravenous
cannulae also served to circumvent heparin/hydro-
cortisone-related problems. Falchuk and colleagues90
studied the effect of a filter on the incidence of
phlebitis associated with intravenous infusion in 541
patients in a double-blinded prospective study. The
incidence was reduced by approximately two thirds in
patients infused through a 0.22 µ IVEX-HP filter. On
the contrary, the same year Hessov91 noted that the
efficacy of in-line membrane filters to prevent in-
fusion phlebitis is not convincing, Richards et al92
reported no significant improvement associated with
the use of filters to prolong the life of intravenous
cannulae in patients with cystic fibrosis receiving
intravenous antibiotics.
Other Uses
By prolonging the intravenous life of central can-
nulae the decrease in expenditure incurred in an ICU
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has been calculated to be a substantial amount of up
to £stg35,000 per year93.
Use of in-line filters to aspirate drugs from
ampoules has been noted to decrease glass particle
contamination94. The average number of glass par-
ticles aspirated per ampoule was noted to be 1.2±0.3
if an in-line filter was used and 100.6±16.3 without.
Complications with In-line Filters
Absorption of drugs delivered through in-line
filters has been studied by several authors. Studies
negating as well as confirming the problem could be
found. Hirakawa and colleagues95 found that in-line
filters decrease concentration of amphotericin B in
filtered fluid, the proportion being dependent on the
type of filter material used. Other authors have also
reported a decrease in the availability of drugs such as
digoxin and diazepam when infused through in-line
filters96.
Contrasting with the above results, Stevens and
Wilkins97 found 96% or greater recovery of four
cytotoxic drugs, namely mitozantrone, doxorubicin,
daunorubicin and methotrexate through an 0.2 µm
endotoxin retentive end-line filter. Similarly, other
authors have reported lack of significant binding
of vancomycin98, phenobarbitone98, isosorbide-5-
mononitrate99 and fentanyl96 to in-line filters.
Other complications associated with the use of
in-line filters include air locking and clogging100.
Recommendations For Usage of In-line Filters
Notwithstanding the rather limited and contro-
versial data and opinions voiced regarding use of in-
line filters101 (Figure 2), their use is recommended
with parenteral nutrition infusions102,103. This is in
keeping with a recent FDA (USA) Safety Alert
recommendation for in-line filtration of all total
parenteral nutrition admixtures.
The use of these filters for fluid and drug infusions
lacks a large database and our search failed to reveal
any guidelines or recommendations for their use. It is
to be reiterated that large scientific trials have yet to
confirm the utility of this practice.
BREATHING SYSTEM FILTERS (BSFs)
The controversy regarding usage of bacterial and
viral filters in breathing systems is fuelled by the
increasing awareness of infection risk during anaes-
thesia. Infections can be transmitted through breath-
ing systems either by gaseous dispersion or in blood
and secretions. Blood is present quite commonly in
the airway of intubated patients104,105, but the incidence
of blood in the mouth of non-intubated patients is
much lower—1% versus 76%106. Thus anaesthetic
apparatus may be a source of cross infection of blood-
borne infection. Traditionally, the same breathing
circuit was commonly used for several consecutive
patients.
The risk, if any, of a contaminated breathing
system leading to crossinfection of patients is con-
sidered before discussion of the role of BSFs in
decreasing morbidity. Evidence has been gathered
from previous reviews on the topic1,2, cross referenc-
ing and a Medline®search of all English language
text and abstracts for the years 1995-2001.
Contamination of breathing systems
Breathing systems can be contaminated by micro-
organisms originating from the patient as well as the
environment. Lutttropp and Berntmann107 found that
seven of eight contaminated unused sets of breathing
system tubing grew bacteria such as Staphylococcus
epidermis, Propionibacterium acnes and Micrococcus.
Both Shiotani et al108 and du Moulin and Sauber-
mann109 demonstrated that the contamination of
clean unused breathing system tubing was by
microbes of environmental origin. These microbes
were of low pathogenicity and have not been
implicated in the aetiology of postoperative infection.
No text was found implicating contamination of
breathing systems by microbes of high pathogenicity.
Several authors have studied breathing system con-
tamination experimentally by simulation, using nebu-
lized bacterial aerosol. After spraying bacterial
aerosol into the anaesthetic and ventilator breathing
system, tubing is variably contaminated (12%110 to
71%108) with nebulized bacteria. Up to one metre of
corrugated tubing can be traversed by 50% of air-
borne salivary organisms111. Langevin et al112 reported
that, if the gas flow through a circuit was interrupted
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FIGURE 2: An “in-line” filter.

for up to an hour following the nebulization period,
almost 100% of the organisms could be collected
from the inspiratory gas.
There are also several relevant clinical studies re-
garding direct contamination. Pandit et al113 examined
anaesthetic equipment that had been exposed to
patients with several different infections, including
tonsillitis, pharyngitis, lung abscess, bronchiectasis
and pulmonary tuberculosis, and confirmed contami-
nation had occurred. Importantly, they concluded
that most organisms isolated from the equipment
were commensals or low pathogenic organisms such
as Staphylococcus albus, Streptococcus viridians and
diptheroids. Pathogenic organisms like Pseudomonas
aeruginosa and Staphylococcus pyogenes were princi-
pally isolated from the facemask and angle piece.
Retrograde contamination of the inspiratory tubing
against gas flow has also been demonstrated114.
This colonization of a breathing system may be
rapid. Craven et al115 found 33% of the sets of tubing
studied were colonized within two hours and 80%
in 24 hours. The colonization of humidification
apparatus, which may also be a source of bacteria,
was equally rapid. Malecka-Griggs and Reinhardt116
were the first to perform a qualitative and quantita-
tive microbial assessment of breathing system using
direct dilution sampling. Within 24 hours 95% of ven-
tilator breathing systems, 57% of water traps, 55% of
cascade humidifiers and 85% of inspiratory tubing
became contaminated, the microbes being pre-
dominantly gram-negative non-fermenters. Other
authors117-120 also support contamination of breathing
systems by bacteria from patients.
There are several studies that fail to confirm con-
tamination of anaesthesia equipment after patient
use. Ibrahim and Perceval121 suggested that patients
do not contaminate breathing system tubing. Nielson
and associates117 showed that gas from a previously
used anaesthetic system is contaminated only to the
same extent as hospital air, and with bacteria of low
pathogenicity. Stemmermann and Stern122 failed to
demonstrate contamination of an anaesthetic circuit
by Mycobacterium tuberculosis after use in individuals
with known active pulmonary tuberculosis. Ziegler
and Jacoby123 found that colonization did not occur
despite use for up to four hours.
In conclusion, there is contradictory and inconsis-
tent evidence regarding the potential for microbial
contamination of breathing systems by patients. If
contamination occurs it is usually by non-pathogenic
organisms. Such organisms are probably only ex-
pelled from the airway during forceful expira-
tion, such as by a cough or sneeze124. During quiet
breathing under anaesthesia, very few organisms are
liberated, even from an infected patient125.
Cross infection with Breathing Systems
There are several studies implicating contamina-
tion of anaesthetic equipment as a cause of respira-
tory infections and morbidity. Phillips and Spencer126
reported an outbreak of pseudomonas infection in
patients under mechanical ventilation that resulted in
the death of two patients. They pointed to heavy con-
tamination of ventilator parts with pseudomonas,
particularly the humidifier and the inspiratory tubing.
Another report127 also emphasised the problem of
ventilator contamination with pseudomonas in
intensive therapy units and ventilatory equipment
associated outbreaks of pulmonary infection are
extensively documented128-134.
In contrast, some studies do not support cross-
infection of patients secondary to anaesthetic equip-
ment contamination. Pandit et al113 examined gas
passing through an artificially contaminated circuit
attached to a Boyle’s machine and found no
organisms could be isolated, as did Ibrahim and
Perceval121 after seeding anaesthetic circuit tubing with
Streptococcus viridans and Staphylococcal bacterio-
phage. du Moulin and Saubermann109 deliberately
contaminated the expiratory port of a breathing cir-
cuit and ventilated the circuit for three hours at fresh
gas flow of 6 l/min. They reported the disappearance
of inoculums over several hours. These and other
studies support the view that evidence implicating the
role of anaesthetic machines and breathing circuits in
patient infection is weak127,135,136.
It should be noted that almost all studies implicat-
ing anaesthetic equipment as a vector for spread of
infection between patients are narratives or retro-
spective reviews. There are no randomized controlled
trials in this area and an obvious failure to mention
other possible sources of infection or infection
control measures taken to interrupt outbreaks of
infection.
Role of Filters in Breathing Systems
Using filters in the breathing system (Figure 3) and
then re-using the breathing circuit is common prac-
tice137-139. The utility of breathing system filters lies in
a potential decrease in the incidence of respiratory
morbidity. There is evidence that the incidence of
bacterial pneumonia is less when a BSF is used
in ICU patients130,140,141. As expected, a marked de-
crease in recovery of bacteria from the anaesthesia
breathing system when using filters has been well
demonstrated107,108,119,130.
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FILTERS IN ANAESTHESIA AND INTENSIVE CARE
Anaesthesia and Intensive Care, Vol. 31, No. 4, August 2003

Compared to this setting of prolonged ventilation
in ICU, there are fewer studies evaluating the role
of BSFs during anaesthesia. Pottecher et al142 found
a high contamination rate of the Y-piece, with or
without a filter. However, the bacterial titre was
extremely low. Nevertheless, many studies demon-
strate the efficacy of BSFs107,143-145. Most have a small
sample size, but Vezina et al145 studied breathing
system contamination with a filter in place in 2,001
patients. In vivo filtration efficacy was 98.08%, indi-
cating that the cross-contamination rate in the
breathing system is less than 1 in 250 when a BSF is
used.
Some authorities do not support the use of filters in
breathing circuits because of failure to reduce the
incidence of ventilator-associated pneumonia146 or
respiratory infection. A surveillance of postoperative
respiratory tract infections carried out over nine
years147 concluded that patient factors are most
important in the development of postoperative lower
respiratory infections and that the value of a bacterial
filter as a preventive measure is negligible.
Complications of Breathing System Filters
BSFs may adversely affect end-tidal carbon dioxide
measurement148. Hypocapnia on the machine side of
the system, probably caused by the extra deadspace
and increased resistance of the filter, has been docu-
mented148. The resistance to gas flow increases signifi-
cantly during anaesthesia because of condensation on
the filter149. Loss of capnograph tracing and of venti-
latory volume monitoring, due to mixing of gas at low
tidal volume, has been reported149. BSFs have been
incriminated as a cause of barotrauma, pneumo-
thorax150,151 and obstruction152. Bronchospasm has
followed the use of a filter inappropriately sterilized
with formaldehyde, the inhalation of which resulted
in diffuse bronchospasm153.
Types of Breathing System Filters
These filters can be broadly divided into two
groups:
a) Pleated, hydrophobic membrane filters: These
have a large surface area and very small pores,
such that the membrane area has to be large to
minimize airflow resistance. To maintain a small
filter size the large membrane is folded (pleated).
The design prevents ingress of water droplets,
ensuring that liquids do not pass through and that
airflow resistance remains low even under wet
conditions.
b) Composite filters: They consist of a hygroscopic
layer and a large pore felt filter layer. The felt is
sometimes subjected to an electric field, an electret
felt, to increase its polarity (electrostatic filters).
This process improves dry gas filtration efficiency
while maintaining a low airflow resistance. In
comparison to hydrophobic pleated filters, electro-
static filters are unable to prevent the passage of
water154. This property is a consequence of the
smaller internal volume, a larger volume of water
added, and a horizontal rather than vertical filter
layer in composite filters154.
Several authors have compared the performance of
these two types of BSFs, and most concluded that
electrostatic filters are less efficient than pleated
hydrophobic filters155-161.
Methods of Testing Performance
All BSFs are assessed for bacterial filtration
efficiency and less often for viral filtration efficiency
using various methods155-161. Viral filtration efficiency
is more difficult to assess, as the viral suspension
required to challenge the filters requires initial
preparation in a bacterial medium. The suspension is
then cleared and collected over a suitable surface,
such as an agar plate overlayed with bacteria, that
supports viral growth.
The wide array of test methods for studying
efficiency of filters is an independent reason why
results comparing different filters are variable.
Recently, a standard for respiratory protective
devices has been published by the National Institute
426 A. TYAG I , R. KUMAR ET AL
Anaesthesia and Intensive Care, Vol. 31, No. 4, August 2003
FIGURE 3: A breathing system filter.

for Occupational Safety and Health162 using sodium
chloride crystals as challenge particles. Based on
these standards, a draft European standard for BSFs
has now been proposed163. This will hopefully meet
the long felt need for a standard and uniform test of
BSFs and enable objective comparisons to be made.
Recommendations for use of Breathing System
Filters
Recommendations of the (American Society of
Anesthesiologists164, Centres for Disease Control165
and the Canadian Laboratory Centre for Disease
Control166 do not endorse the use of BSFs. The
American Society document notes “there is insuffi-
cient clinical outcome data to support the routine
use of bacterial filters for breathing circuits or anes-
thesia ventilators at this time”164. However it does
recommend using a filter on the anesthesia breath-
ing circuit between the patient’s airway and the
Y-connector, prior to contacting a patient with, or at
high risk of, pulmonary tuberculosis. The Canadian
Laboratory Centre for Disease Control “requires, at
a minimum, high-level disinfection” of breathing
circuits between use but makes no mention of the use
of BSFs166.
The only organization to advocate BSFs is the
Association of Anaesthetists of Great Britain and
Ireland167. Their working group considering blood-
borne virus infection had investigated the report from
a private hospital in Australia, where the anaesthetic
breathing system was implicated in transmission of
Hepatitis C virus between patients168. In response
to this investigation they made the following recom-
mendations:
a) Either an appropriate filter should be placed
between the patients and the breathing system,
with a new filter used for each patient, or a new
breathing system used for each new patient.
b) Where expired gas sampling is used the sample
should be taken from the breathing system side of
the filter.
c) In paediatric practice where use of filter would
increase deadspace and/or resistance unaccept-
ably, filters should not be used but the breathing
system should be changed between patients.
An innocuous argument offered in the favour of
BSF use is the reduction in cost incurred, without
patient harm, despite no proven decrease in the rate
of cross-infection. If the cost of a filter is significantly
less than that of a breathing circuit or its sterilization,
a cost-benefit may be achieved.
Regarding the more pertinent and controversial
issue regarding prevention of cross-infection, much
remains to be answered. With respect to the incident
of Hepatitis C transmission reported by Chant et al168,
that led to the recommendation of the Association of
Anaesthetists of Great Britain and Ireland167 in favour
of using filters, it must be appreciated that there
could have been several alternative explanations.
The most obvious of these were excluded and the
breathing system incriminated only by a process of
exclusion.
We consider there are several reasons that make an
attempt to justify routine usage of filters in breathing
systems presumptive and non-scientific. First there is
a definite lack of prospective randomized controlled
trials. Second, the outcome measure of most rele-
vance is postoperative respiratory morbidity and mor-
tality, rather than the widely investigated microbial
contamination of breathing systems. Respiratory
morbidity is a difficult outcome to evaluate, given
its low incidence in the general surgical population
and multitude of causes. Third, BSFs need to be
effective against airborne, as well as liquid-borne,
contamination and the spectrum of efficacy should
include bacteria, viruses, fungi and mycobacterium.
Mostly filters are tested only for bacterial efficacy,
with adequate viral filtration efficacy reported in very
few studies. Fourth, these shortcomings are com-
pounded by the lack of a standard method of testing
filters. Last, whenever studies are performed or cases
incriminating the breathing system as the vector for
cross-infection are reported, alternative routes of
cross-infection are rarely mentioned.
In conclusion, the use of microbial filters in long-
term ventilated patients in ICU appears an appro-
priate option, given evidence showing a reduction of
condensation and bacterial colonization in circuits,
and of respiratory tract infections. The same cannot
be concluded in the shorter setting of anaesthesia,
where there are far fewer studies and evidence for a
benefit is lacking. Thus, even though BSFs have
become an accepted method of infection control, the
scientific evidence does not support routine use. In
addition, BSFs are only one of several methods of
cross-infection control, given multiple possible
sources of contamination, and the presence of a
filter does not make sterilization of the connectors
and the ventilator circuits unnecessary.
EPIDURAL FILTERS
The last decade has witnessed an increasing role
for analgesia via long-term epidural catheterization.
Microbial colonization of epidural space is a serious
complication because of the possible delayed appear-
ance of symptoms of infection and the poor prog-
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nosis. Prospective studies reveal the prevalence of
positive bacterial culture to be as high as 22% follow-
ing routine testing of epidural catheters169,170. Du Pen
et al171 reported an epidural infection rate of 5.4%
in immunocompromised patients receiving prolonged
epidural analgesia.
There can be three routes of contamination of an
epidural catheter: 1) from the skin via the needle
track (entry point), 2) haematogenous spread, and
3) through the catheter. The catheter hub has been
recognised as the main route of microbial coloni-
zation170,171. Thus it appears logical to use a microbial
filter on an epidural catheter (Figure 4) to prevent
infection in the epidural space.
A literature search provided little information
about epidural catheter filter use. Discussing the
results of a double-blind prospective study Abouleish
et al172 suggested that bacterial filters were not
required if sound sterile techniques were applied.
The reasons cited were the effectiveness of pre-
cautions for each refill injection, the antimicrobial
activity of local anaesthetics, the small number of
injections and the limited duration of catheter inser-
tion173,174. In contrast, use of a filter was recommended
by James et al173 after their study in 101 labouring
patients, which was not however a randomized trial.
Several other authors have reported on the tradi-
tional use of epidural catheter filters during pain
relief in cancer patients175-177.
These filters may prevent foreign particulate
matter, such as glass particles, from gaining access to
the epidural space.
Recommendations for Epidural Catheter Filters
Given the lack of data, it cannot be assumed these
filters are useful, especially during short-term
catheterization. They may also not be foolproof with
respect to filtration of foreign particulate matter.
Friable or shreddable foreign material can be caught
in the epidural needle and projected into the epidural
space as the catheter is advanced178. A filter needle
may be a cheaper, adequate and less cumbersome
means of aspirating drugs from glass ampoules and
protecting the epidural space from inoculation with
foreign material179.
We were unable to locate any specific guidelines
regarding epidural filters in short or long-term usage.
Given the relative lack of pertinent prospective trials,
even with long-term epidural catheterization, prac-
tice appears to be influenced more by logical reason-
ing than sound scientific evidence. Use of a filter is
common175-177, and apparently without detriment to the
patient. The cost is not high, given the conclusions of
several authors175-177,180 that filters need not be changed
for at least a month. Thus, pending prospective ran-
domized controlled trials, long-term epidural
catheterization may merit use of a bacterial filter.
FILTERS IN CONVECTION WARMERS
Forced air convection warming devices used for the
management of hypothermia have a microbial filter
(0.2 µm pore size) that manufacturers recommend
should be changed every six months or after 600
hours of use. A single study181 found that these
warmers, when used in the operating theatre, were
potential sources of microbial infection due to
colonization of their hoses. Since a filter cannot pre-
vent colonization distal to it, the authors recommend
fixing the microbial filter to the nozzle of the hose
connecting the warmer to heating blanket.
FILTERS IN ENTONOX EQUIPMENT
Filter use has also been recommended on Entonox
equipment182,183. However it should be emphasized
that these reports were surveys and not controlled
trials. There is no evidence indicating cross-infection
of unintubated patients associated with Entonox
apparatus, or to support the efficacy of BSFs to
prevent such a risk, should it exist.
FILTERS IN AIR CLEANING
The use of filters in air-conditioning systems is
ubiquitous and there are no controversies. Most com-
428 A. TYAG I , R. KUMAR ET AL
Anaesthesia and Intensive Care, Vol. 31, No. 4, August 2003
FIGURE 4: A microbial filter for an epidural catheter.

mercially available filters remove almost all bacteria
and a few special filters also remove inorganic par-
ticles sized 0.1 µm. In operating rooms and intensive
care units, ideally two filter beds are indicated. The
first should be upstream of the air-conditioning
equipment and have a filtration efficiency of 25%.
The second filter bed should be downstream of the
supply fan, any recirculating spray water systems,
and the water-reservoir type humidifier, and have
filtration efficiency of 90% to 95%.
SUMMARY
This review focuses on a number of commonly used
filters in anaesthesia and intensive care. The prac-
ticalities of use and opinions regarding their value in
clinical practice are as varied as their sites of usage.
First generation blood filters, filters used during total
parenteral nutrition and filters for air-conditioning
are the only types free from controversy and recom-
mended for routine usage. The other filters, including
microfilters, leucocyte depletion filters, breathing
system filters, epidural catheter filters, in-line filters
for fluid and drug administration and filters for
Entonox delivery in unintubated patients, cannot be
recommended for routine use.
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