Not again!
BMJ 2001; 322 doi: https://doi.org/10.1136/bmj.322.7285.548 (Published 03 March 2001) Cite this as: BMJ 2001;322:548
All rapid responses
To the EDITOR: The consequences of errors involving anticancer drugs
can be devastating. Seale correctly states that protocols requiring
intrathecal methotrexate and intravenous vincristine to be administered on
the same day are contributing factors to the erroneous intrathecal
injection of vincristine.1 Such errors in administration arise from
inadequate time, training and supervision of medical staff.1 However,
errors can also occur due to poorly written or structured protocols. A
patient at a comprehensive cancer centre in the US died of a drug overdose
during treatment for metastatic breast cancer.2 An ambiguous order for
cyclophosphamide 4g/m2 over 4 days was misinterpreted by several health
professionals. What should have been ordered was a daily dose of 1g/m2 for
4 consecutive days. Instead, the patient received 4g/m2 per day for 4
days. The patient died. This error was due to the ambiguous way the
protocol was written. Such ambiguity is associated with the nomenclature
for bleomycin. Protocols in the literature quote bleomycin doses in
milligrams (mg), international units (IU) or United States Pharmacopoeia
units (USP units). This inconsistency in nomenclature appears to be
universal and can lead to incorrect interpretation of medical literature.
Better protocols and standardized nomenclature are important aspects in
preventing medical errors.
Historically, bleomycin dosage has been described in terms of
milligram-potency (mg-potency), where 1mg-potency corresponded to 1 unit.
In the original preparations, 1mg-potency was also equivalent to 1mg by
weight (mg-weight), but modifications and improvements in purification
meant that ampoules labelled as containing 15mg (ie.15 units) contained
less than 15mg-weight of bleomycin.3 This alteration, coupled with the
fact that differences also exist in the term units used in the US and
those used in Europe, Britain and Australia, can lead to confusion.
In 1995, the labelling of the bleomycin products in Australia changed
from USP units to IU in line with changes in the British Pharmacopoeia
(BP) and European Pharmacopoeia (Ph Eur). The 10mg vial, formerly labelled
as containing 15 USP units, is now labelled as containing 15,000 IU. This
has resulted in considerable confusion when older protocols are used or
when referring to literature from the US. Currently, the BP and Ph Eur
specify a potency of 1,500 IU per mg, while the USP specifies a potency of
1.5-2 USP units per mg.3-5 That is, 1.5-2 USP units is equivalent to
1,500 IU, and is equivalent to 1mg (by weight, not by potency). Protocols
that state bleomycin in mg or mg/m2, refer to mg-potency, not mg-weight.
Therefore, 1.5-2 USP units is equivalent to 1,500 IU, which is
approximately 1.5mg (by potency).
Considerable problems arise when consulting protocols where the
bleomycin nomenclature is stated as mg or mg/m2. We have anecdotal
evidence of patients prescribed bleomycin 30mg as part of the BEP
(bleomycin, etoposide, cisplatin) protocol, erroneously receiving 45,000
IU. In the original BEP protocol, the total dose of bleomycin is specified
as 30 units.6 This refers to 30mg-potency (not 30mg-weight), which is
equivalent to 30 USP units or 30,000 IU.
This highlights the essential need for bleomycin dosages to be
stated in terms of units (USP units in the US, or IU in Europe, Britain,
Australia), and NOT as mg or mg/m2. The risk of misinterpretation,
incorrect conversion and potential overdose of bleomycin is dangerous.
Variations in nomenclature will lead to incorrect interpretation of
medical literature and potential overdoses of bleomycin. Standardization
of bleomycin nomenclature is an important issue for all health care
professionals and is one method of minimizing errors with cytotoxic
chemotherapy.
Angela Stefanou BPharm
Senior Pharmacist, Drug Information Service
Peter MacCallum
Cancer Institute, East Melbourne, 3002, Australia
Jim Siderov BPharm Grad Dip Hosp Pharm BCOP CHP
Senior Pharmacist, Research and Cancer Services
Austin & Repatriation Medical Centre, Heidelberg, 3084, Australia.
On behalf of the Society of Hospital Pharmacists of Australia Committee of
Specialty Practice in Oncology.
Address for correspondence:
Angela Stefanou,
Senior Pharmacist, Drug Information Service,
Peter MacCallum Cancer Institute,
St Andrew’s Place,
East Melbourne, 3002, Australia
e-mail. StefanouAngela@petermac.unimelb.edu.au
REFERENCES
1. Seale JRC. Erroneous intrathecal injection results from a problem
with protocols. BMJ 2001;322:548
2. Knox RA. Response is slow to deadly mix-ups. Too little done to avert
cancer drug errors. Boston Globe 1995; Jun 26; 29,33
3. Parfitt K, editor. Martindale The Complete Drug Reference. 32nd ed.
London: Pharmaceutical Press, 1999: 507-9
4. United States Pharmacopoeial Convention, Inc. The United States
Pharmacopoeia. 24th revision. And The national formulary, 19th ed., 1999.
Rockville: USPC Inc.; 1999 and supplements
5. British Pharmacopoeia Commission. British Pharmacopoeia. London: Her
Majesty’s Stationery Office; 1993, and addenda
6. Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ.
Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and
either vinblastine or etoposide. N Engl J Med 1987;316: 1435-40
Competing interests: No competing interests
A first step in the process toward unique connectors for tubing with
separate uses, can perhaps already be made.
I refer to the bimetal luer slip conector used on sphygmomanometers
to connect cuff to gauge. Surely this can be abandoned immediately.
After all this connector is virtually useless for it's intended purpose.
Metal to metal luer slip won't make a repeated gas tight connection.
Polymers are the way to go. But not luer.
Please feel free to contact me for details of an "O" ring connector
now used in some areas of some public hospitals with great success on
sphygmomanometers. And you can't connect it to a luer be assured.
Curiously, the manufacturers inform me that attempts to promote this
connector's use on sphygmomanometers, were met by claims of "plastic is
cheap". Cheap but good.
Phillip J Colquitt
Independent Technical Advisor
New Farm, Queensland, Australia
Competing interests: No competing interests
EDITOR-The responses to recent high profile medical errors [1] have
focused on what may be termed the 'systems' aspects, with calls for anti-
confusion devices on syringes and needles [2], better protocols [3]
and guidelines [4], and improved packaging [5]. Some aspects may well
require improvement, but change can sometimes introduce alternative risks,
as some of your correspondents acknowledge. However, none refers to the
importance of individual responsibility, particularly in regard to
injection errors. Malhotra and colleagues illustrate their concerns about
the packaging of lignocaine, but even with my eyesight (badly myopic and
increasingly presbyopic also) I can see, without glasses and at arms
length, that one of the ampoules in their illustration is very different
to the other three. How much different do some people need a drug ampoule
label to be before they read it properly?
Because of the multiplicity of injectable drugs used in modern
practice anaesthetists have to be particularly careful about ampoule
identification. At an early stage in my anaesthetic career I was given
some excellent advice that has, so far, stood me in very good stead:
1. Read the label before you open the ampoule.
2. Read it again as you draw up the solution.
3. Read it a third time before you dispose of the ampoule.
4. Label (preferably with an indelible marker) the syringe or other
administration device BEFORE you put it down.
5. Check that secondary label before each and every administration.
Such attention to detail, and the determination not to be distracted
from it in any situation no matter how urgent, is the best safeguard we
have. As Jackson notes [6], Najiyah Hussain (the little girl given nitrous
oxide instead of oxygen) "was the victim of a mistake that you would not
expect could happen" because of the plethora of anti-confusion devices
that should prevent it happening. Thus eternal personal vigilance is the
price of safety.
J A W Wildsmith
professor of anaesthesia
Ninewells Hospital & Medical School, Dundee DD1 9SY
j.a.w.wildsmith@dundee.ac.uk
1. Berwick DM. Not again! BMJ 2001;322:247-8. (3 February.)
2. Bickford Smith PJ. BMJ 2001;322:548. (3 March.)
3. Seale JRC. BMJ 2001;322:548. (3 March.)
4. Rassam SMB. BMJ;322:548-9. (3 March.)
5. Malhotra A, Matson M, Chan O. BMJ 2001;322:549. (3 March.)
6. Jackson T. BMJ 2001;322:562. (3 March.)
Competing interests: No competing interests
Editor
the correspondance relating to the similar labelling and packaging of
drugs which could lead to incorrect administration is not new. Several
years ago, I raised this with the company that supplies my own hospital.
In this case, it was again the lignocaine and saline packaging that was
similar. The response I was given is that "it is the doctor's
responsibility to check the drug". There is certainly no arguing with
this, and yet why are the companies allowed to make it so easy for a n
error to occur?
The resuscitation guidelines have just changed so that the three most
commonly used drugs now all have similar names: adrenaline, Atropine,
amiodarone. Aurum pharmaceuticals have just produced an excellent set of
emergency drugs. Each comes ready to give in a syringe which has been
indelibly labelled by the company. In addition, each syringe is presented
in a sealed individual box which is also labelled by the company. Such a
system must make clinical incidents where the administration of the wrong
drug occurs less common. Why cannot all drug companies be forced by
legislation to produce clearly labelled, ready made drugs, or even produce
them in colour coded syringes? Surely if medical error costs the NHS as
much as the Government states, they should not be afraid to take the
initiative.
Competing interests: No competing interests
The underlying cause - failing to manage risks
The underlying cause for the fatal intrathecal injection of
vincristine at Nottingham this year was a failure to adequately manage the
risk. At first sight this may seem like stating the obvious. However a
careful read of Professor Brian Tofts' excellent and very readable
investigation report will back me up.
Letters from JRC Seale and Saad M B Rassam focus on particular
aspects of the overall risk management strategy in respect of the hazard
posed by vincristine. Professor Tofts' report refers to some of these
precautions as ones that are theoretically already in place. The incident
was not avoided by these existing precautions not because they were absent
but because they were neither robust enough nor comprehensive enough.
There are a great many complex procedures being carried out daily in
health services which rely on an equally complex set of precautions to
keep them safe. At the very core of these precautions and with those
immediately responsible for controlling the risks must rest a good
understanding of the basic principles of risk management. The
investigation report into the latest fatal maladministered spinal
injection incident makes this point very clearly and recommends that we
ensure that appropriate education is provided.
Competing interests: No competing interests