ORIGINAL ARTICLE
Intrathecal Vincristine
3 Fatal Cases and a Review of the Literature
Bernadette Hennipman, MBBS,* Esther de Vries, MD, PhD,w Jos P. M. Bökkerink, MD, PhD,zy
Lynn M. Ball, MD, FRCP, FRCPath, FRCPCH,J and Anjo J. P. Veerman, MD, PhD*y
Summary: We report 3 cases of accidental intrathecal vincristine
administration. All 3 patients died between 8 and 18 days after the
incident because of decerebration. In the literature, we found
41 cases of accidental intrathecal injection of vincristine. These
reports represent only a fraction of the existing problem. New in
our report is the fact that the first 2 cases were attributed to viral
infection, only after the detection of high levels of vincristine in
the cerebrospinal fluid was the real cause of death ascertained.
The third case occurred during the implementation of rules by the
Dutch Childhood Oncology Group on how to handle intrathecal
triple therapy; and despite sequential safety measures, the accident
still occurred. In the Netherlands no more accidents of this nature
have occurred in children after the introduction of a quadruple
syringe system 8 years ago. In our opinion the best fail-safe
solution would be the development of a unique connection that is
incompatible with a standard Luer syringe.
Key Words: intrathecal, vincristine, death, decerebration, toxicity
(J Pediatr Hematol Oncol 2009;31:816–819)
T he treatment of leukemia, and especially acute lympho-
blastic leukemia (ALL), involves oral and intravenous
(IV) medication as well as cytostatics given intrathecally
by lumbar puncture (LP). Vincristine is a vinca alkaloid
antineoplastic agent intended for IV use only. It is an
important component of leukemia protocols. Vincristine
should never be administered subcutaneously, intramuscu-
larly or intrathecally, as this results in tissue necrosis. In the
literature, 41 case reports describe inadvertent intrathecal
administration of vincristine.1–39 In a World Health
Organization alert 55 cases are mentioned, some of these
only in newspapers.38 Only 8 patients in our survey
survived, most of them paralyzed.
We report 3 fatal incidents that occurred between 1998
and 2000. All 3 children were diagnosed as having
ALL. They were treated according to the Dutch Children
Oncology Group (DCOG)-ALL-9 protocol, which encom-
Received for publication September 10, 2008; accepted July 18, 2009.
From the *Department of Paediatric Oncology/Haematology, Vrije
Universiteit Medical Centre, Amsterdam; wDepartment of Paedia-
trics, Jeroen Bosch Hospital, ‘s Hertogenbosch; zDepartment
of Paediatric Haematology and Oncology, University Medical
Hospital St Radboud, Nimegen; yDutch Childhood Oncology
Group (DCOG) the Hague; and JDepartment of Paediatric
Haematology and Oncology, Leiden University Medical Centre,
Leiden, The Netherlands.
Reprints: Anjo J. P. Veerman, MD, PhD, Department of Paediatric
Haematology and Oncology, Vrije Universiteit University Medical
Centre, Postbus 7057, 1007 MB Amsterdam, The Netherlands
(e-mail: ajp.veerman@vumc.nl).
Copyright r 2009 by Lippincott Williams & Wilkins
816 | www.jpho-online.com J Pediatr Hematol Oncol
passes 13 intrathecal-injections with triple therapy (metho-
trexate, cytarabine, prednisolone; all to be flushed with
saline). These injections are scheduled on the same day as
an IV-injection of vincristine. Although they occurred a
long time ago, we still report these cases because they show
that the ascending myelopathy that occurs after intrathecal
vincristine injection is sometimes contributed to other
causes and procedural measures are not always sufficient.
CASE REPORTS
Case 1
A 2-year-old boy received his intrathecal medication under
general anesthesia. The labels on the syringes were removed, so that
they would not stick to the gloves of the pediatrician. Twelve hours
later the patient started to vomit and had bladder retention. In the
next few days he developed apnoea, bradycardia, and ascending
myelopathy. He was transferred to the paediatric intensive
care unit (PICU), intubated and artificially ventilated. His pupils
became dilated and there were neurologic signs indicating
brainstem-encephalopathy. On day 7 he became comatose, while
simultaneously developing pareses of the arms and legs. He died
on day 8. Autopsy was not performed. At this time, possible
interchange of medication was deemed unlikely. However, a few
months later, a stored cerebrospinal fluid (CSF) sample, taken
1 day after the incident, was sent for analysis of vincristine level.
The vincristine level in the CSF was 19 mg/L.
Case 2
A 6-year-old girl received intrathecal medication during
outpatients’ treatment. Three days later she presented at the
emergency room with pain in her neck and legs, along with urinary
and fecal incontinence. Later that night she developed a fever
(38.61C), and empiric antibiotic therapy was commenced. In the
following days she developed ascending paralysis with areflexia.
Meningitis was ruled out by LP. She developed respiratory
insufficiency and was transferred to the PICU. In the following
days she showed signs of transverse myelitis. On day 17 she was
diagnosed as being brain dead. At the limited brain autopsy
myelitis was seen which could have been caused by cytostatics.
Until then, inadvertent intrathecal administration of vincristine
had not been suspected. Stored CSF samples, taken 3 and 5 days
after the incident, were sent for analysis of vincristine levels. These
showed vincristine levels of 18.2 mg/L and 9.3 mg/L, respectively.
Case 3
A 3.5-year-old girl received her medication under general
anesthesia. The procedure had to be postponed because all the
operating theaters (OT) became acutely occupied. When eventually
there was space, she was brought to the OT. Vincristine accom-
panied the intrathecal drugs. A junior doctor then administered all
the syringes intrathecally. The error was recognized at once, and
CSF was drained immediately with a new LP. Within 1 hour of the
incident 2 drains were placed in the ventricular system for
continuous flushing of the CSF space with Ringer lactate-saline.
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J Pediatr Hematol Oncol  Volume 31, Number 11, November 2009 Case Reports on Intrathecal Vincristine Deaths

The patient was transferred to the PICU and ventilated. Treatment
with folinic acid, pyridoxine, and glutamic acid was commenced.
She developed paralysis of the legs with areflexia, but retained
bladder control. On day 2, the myelitis became progressive, and she
developed urinary and fecal incontinence, she became respiratory
insufficient and comatose. She did not improve, and a decision was
made that further treatment would be futile. She died 8 days after
intrathecal vincristine in spite of all measures taken.
DISCUSSION
Vincristine levels in CSF after an IV dose are <0.1
mg/L.40 The levels found in the first 2 cases were much
higher, proving that indeed vincristine had been injected
intrathecally. In all 3 cases the circumstances were not
optimal. In case 1 the removal of labels led to exchange
of syringes. In case 2, the labels on the syringes were
presumably not checked before administration.
After these first 2 incidents the DCOG recommended a
number of safety guidelines:
1. All personnel performing intrathecal therapy should
be adequately instructed about the consequences of
vincristine intrathecal;
2. Intrathecal therapy should not be administered on the
same day as IV therapy;
3. Intrathecal therapy should always be prepared in a
manifold (quadruple) valve system,41 also when only
1 drug is administered;
4. Vincristine should not be present in the room where the
LP is performed;
5. Vincristine should be diluted in at least 10 mL.
These cases also illustrate that unexpected neurologic
symptoms after intrathecal medication may be diagnosed
by CSF evaluation of vincristine (or other drug) levels. For
that reason it may be wise to store some CSF after a LP in
those patients. Erroneous administration of vincristine or
other drugs, or wrong dosages may be detected in this way.
Case 3 occurred during the implementation of
the procedures and despite sequential safety measures, the
accident still occurred. The IV and intrathecal syringes were
inadvertently all the same size (2.5 mL) and the manifold
valve system was due to be introduced. All syringes,
including the vincristine, were brought to the OT. In light
of the accumulation of problems, the junior doctor injected
the vincristine intrathecally despite having received the
instruction. He recognized shortly afterward the accidental
nature of his actions. This case illustrates that fatal
incidents may happen as a result of an accumulation of
minor deviances from protocol. In this case, analysis of the
CSF vincristine level was not performed, as the inadvertent
exchange was detected immediately after the event.
Medical errors can have many different causes. Lack
of experience, fatigue, haste, and negligence are only a few
of them.42 All these causes can result in unnecessary
mistakes and in worst case scenario these mistakes are fatal.
Not all these causes can be prevented at any given moment,
but everything possible must be done to limit the
possibilities to make these unnecessary mistakes. Most
often not one, but an accumulation of small errors, like in
our cases, lead to disaster.
The problem of inadvertent intrathecal administration
of medication is not unique to the leukemia protocols.
Mistakes also occur in other areas where intrathecal adminis-
tration is used, as in neurology, radiology, and anesthesia
(lumbar and epidural medications). It is important to

TABLE 1. Recommendations Made in the Literature Concerning Different Steps in the Protocol to Prevent Accidental Intrathecal
Injection of the Wrong Medicines
Personnel  Intrathecal chemotherapy should be ordered by an oncology physician and must be cosigned by a similarly qualified
doctor
 The administering physician is responsible; 2 qualified medical professionals (physicians and/or nurse) will identify
the patient, check the drug orders, read the drug labels out loud, and only the responsible physician will place any
chemotherapy on the lumbar puncture tray
 Intrathecal chemotherapy should only be administered by an experienced physician certified in the procedure and
the risks of chemotherapy; uncertified physicians must be directly supervised
 Medical personnel administering intrathecal chemotherapy should be required to review the case reports on intrathecal
vincristine administration
 Medical personnel should be fully informed as to the side effects and complications of chemotherapy
Preparation  Never prepare and administer more than 1 type of cytostatic at the time
 Vincristine should be diluted to at least 10 mL
 Multiple intrathecal drugs should be prepared in a single syringe (this can cause unwanted interactions)
 All intrathecal therapy should be prepared in a special quadruple syringe system
 Intrathecal syringes should have a different sized fitting from intravenous ones
 Intrathecal syringes should be prepared, packaged, transported and stored separate from all other drugs, so intravenous
and intrathecal drugs are physically separated
 All dosage calculations should be documented in the permanent charts
Labels  All cytostatics should be labeled with patients name and date, generic drug name, dose, the route of administration
highlighted and labels attached to the prefilled syringe and the outer security wrap
 All syringes containing vinca alkaloids should have an additional warning label on the syringe or infusion bag and the
outer container ‘‘For intravenous use only—fatal if injected intrathecally’’
 Intrathecal syringes should have slip tip (not Luer lock) and an auxiliary label stating ‘‘intrathecal’’
Administration  Intrathecal doses should be preferably administered after the drugs to be given by other routes have been supplied to the
ward and administered
 Intrathecal drugs should be administered in a designated area, for example an operating theatre
New system  Systems need to be developed to prevent inadvertent intrathecal and intraventricular administrations
 The use of unique lumbar puncture needles that can only be connected to special intrathecal-syringes either by color-
coding, size-coding, or shape-coding
 Altering the caliber of the connection ports on all equipment intended for spinal or epidural use to a new standard size

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Hennipman et al
realize that the published cases probably represent only a
fraction of the events, as medical incidents are generally
not published and reported.43 The first 2 cases described
here, illustrated that sometimes the mistake is not even
noticed, and other causes are held responsible for the death
of the patient.
Two of our 3 patients, had a very good prognosis of
their leukemia before the incident, making it extremely
difficult for the parents and relatives to accept that they
died because of an error in drug administration. This led to
anger and frustration as they felt, justifiably, that they did
not have to lose their child in this way. Finally, there is also
a great impact on the healthcare providers who made the
mistake. Many experience a great deal of emotional stress,
guilt, and regret after being involved in such an incident. In
some cases, staff members involved were made to face
medico-legal procedures.
We feel that it is imperative to once and for all
stop these unfortunate and avoidable deaths. As doctors,
we have to act in the best interest of our patients. Therefore
we must try to make it impossible to administer vincristine
intrathecally. The measures taken by the DCOG have
certainly helped, and no further accidents of this nature
have occurred in children with ALL in the Netherlands
since 2000.
Besides the measures of the DCOG, there have been
made many recommendations in the literature to avoid
vincristine-related incidents (Table 1), but none of these
have proved fail-safe as far as they only address procedures.
Human error is inherent in all procedures and thus no rule
or protocol can compensate for the fact that the operator
remains the weakest link in the process. Manifold systems41
may partially prevent these incidents, but at present any
syringe can still be connected to the spinal needle. There-
fore, to make it impossible to administer vincristine
intrathecally, we advocate that the connection of spinal
needles be made incompatible with the IV system. This
would be the only fail-safe solution. This is also the
recommendation of the World Health Organization.38
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