We’ve done several columns on problems with methotrexate
(see our What’s New in the Patient Safety World
columns of July 2010 “Methotrexate
Overdose Due to Prescribing Error” and July 2011 “More
Problems With Methotrexate”). But most of the issues have focused on the
erroneous prescription and administration of daily doses of methotrexate (as
are used for oncological indications) instead of once weekly doses that are
used for rheumatoid arthritis (RA) or other autoimmune diseases.
There are actually
several other dangers associated with low-dose methotrexate, as outlined by a
recent ISMP Canada Safety Bulletin (ISMP
Canada 2015). They provide details of 3 incidents of methotrexate toxicity
in patients with RA or other autoimmune diseases.
In the first
incident a patient with RA and renal dysfunction and hypoalbuminemia doubled
his weekly methotrexate dose (without his prescriber’s knowledge). This
coincided with a course of amoxicillin and initiation of leflunomide
therapy. The patient developed severe pancytopenia and died. The severe
methotrexate toxicity was attributed to the doubled dose, the underlying risk
factors (renal disease and hypoalbuminemia), and the drug interactions with
amoxicillin and leflunomide.
In the second
incident a patient on weekly methotrexate for RA was hospitalized with a
fracture and was begun on diclofenac. Renal failure, pancytopenia, and death
followed.
In the third
incident a patient with an autoimmune disorder was prescribed a once weekly
dose of methotrexate but the pharmacy dispensed a 3-month supply with
instructions to take the medication daily. The patient developed severe harm
necessitating prolonged hospitalization.
The ISMP Canada
safety bulletin notes risk factors for methotrexate toxicity as renal
dysfunction, hypoalbuminemia, and certain concomitant medications (like
NSAID’s and proton pump inhibitors). They stress the importance of careful
monitoring if one of these medications must be used. They also note that folate
supplementation be considered to reduce GI and hepatic side effects.
The ISMP Canada
article has several very practical recommendations for IT systems, prescribers,
and pharmacists.
On the IT side,
it recommends that CPOE and pharmacy IT systems should default to a weekly
dose. If a daily dose is ordered there should be a hard stop requiring
input of the indication and duration of treatment. It recommends
provision of an alert about potential serious adverse effects of daily
dosing, particularly in patients with some of the above risk factors or taking
any of the interacting medications, with suggestions for monitoring. It also
suggests linking lab results to order entry for methotrexate (eg. CBC, LFT’s, albumin, creatinine) so the prescriber and
pharmacist can be reminded to check for risk factors and be reminded of
parameters they may need to monitor.
It also recommends a
robust drug-drug and drug-disease interaction module for methotrexate.
That one is the most problematic. We already know that drug-drug and
drug-disease and drug-food alerts are among the alerts most often ignored by
prescribers. Many EHR’s and CPOE or e-prescribing systems allow for
configuration of alerts to allow only certain more serious alerts to be shown.
But some do not allow selective enabling of these alerts (i.e. allowing
drug-drug or drug-disease alerts for just high alert medications as opposed to
all medications).
On the prescriber
side it recommends baseline values for parameters that may need to
be monitored during therapy (eg. CBC, LFT’s,
creatinine) and notes that a good order entry system could prompt the
provider to order these at the time methotrexate is being ordered. It also
has recommendations for frequency of monitoring these parameters,
screening for hepatitis B and C and HIV prior to initiating therapy, and
considering folate supplementation.
It has 2 excellent
recommendations to avoid the error of patients getting daily methotrexate
rather than intended once weekly methotrexate:
It also reminds the
prescriber to ask the patient about specific prescription and any OTC
medications they may be taking that could increase the likelihood of
methotrexate toxicity.
On the pharmacist
side it recommends a forcing function be developed to ensure that every
prescription of methotrexate is reviewed with the patient (or caregiver).
The patient should be counselled and given written information
about methotrexate and stress the importance of adhering to the prescribed dose
and monitoring. If folate supplementation has not been prescribed the
pharmacist should contact the prescriber. The pharmacist should follow up on
any drug interaction alerts that may appear and discuss with the prescriber
and patient. Specific discussion about OTC medications or other
medications known to interact with methotrexate should occur. And, again, the supply
dispensed should only be for 4 weeks.
Most of the same recommendations appear in a recent article
in the rheumatology literature (Blank
2015). This article has a couple more practical recommendations. It notes
that use of a “dose pack” may help
guide patients to take the proper weekly dose for non-oncologic indications.
When reviewing the dosing schedule with
patients it is important to explain that taking extra doses is dangerous and
discuss that the medication is not to be used “as needed” for symptom
control. Have the patient repeat back the instructions to validate
that he or she understands the dosing schedule and toxicities of the medication
if taken more frequently than prescribed.
In our July 2011 What's New in the Patient Safety World column “More
Problems With Methotrexate” we noted that the patient in a long-term care facility may be especially vulnerable.
In such cases, the original order for methotrexate is usually written by a
specialist. The patient is then followed in the LTC facility typically by a
primary care physician who may be less knowledgeable about the particular use
of methotrexate for that condition. Also, the LTC patient may not be seen by a
physician for periods as long as a month. And many LTC patients have cognitive
impairments that might prevent them from understanding issues about their
medications. So if a medication reconciliation error has occurred and a patient
intended for once weekly dosing is now on daily dosing, the opportunity for
toxicity is greatly increased. So LTC facilities should take steps to ensure
that any of their residents taking methotrexate get the same level of
supervision and protections that non-LTC patients would get.
Methotrexate can be
a very effective drug for RA and other autoimmune diseases and is usually well
tolerated. But, as the above examples demonstrate, even low-dose methotrexate
can be associated with severe toxicity in certain circumstances. It is thus for
good reasons that ISMP (US) includes methotrexate on its list of
high alert medications. ISMP also provides a great consumer
leaflet with safety tips for patients taking methotrexate.
References:
ISMP Canada. Severe Harm and Deaths Associated with
Incidents Involving Low-Dose Methotrexate. ISMP Canada Safety Bulletin 2015;
15(9): 1-5
http://www.ismp-canada.org/download/safetyBulletins/2015/ISMPCSB2015-09_Methotrexate.pdf
Blank C. 10 Ways to Avoid Fatal Methotrexate Errors.
Rheumatology Network 2015; December 2, 2015
http://www.rheumatologynetwork.com/rheumatoid-arthritis/10-ways-avoid-fatal-methotrexate-errors
ISMP (Institute for Safe Medication Practices). ISMP List of
High-Alert Medications in Community/Ambulatory Healthcare.
http://www.ismp.org/communityRx/tools/ambulatoryhighalert.asp
ISMP (Institute for Safe Medication Practices). Consumer
Leaflet with Safety Tips for Methotrexate. 2013
http://www.ismp.org/tools/highalertMedications/methotrexate.pdf
Print “February
2016 Avoiding Methotrexate Errors”
AORN (Association of periOperative
Registered Nurses) has updated its guideline to prevent retained surgical items
(Putnam
2015). The updated guideline stresses the importance of creating a culture
and environment that promotes safety and communication. It highly recommends
formal training programs, such as TeamSTEPPS™, that
improve teamwork, promote respect and recognition of the role everyone in the
OR plays, standardize communication, promote hearback,
and break down hierarchical barriers so that all team members feel free to
speak up at any time. The update also stresses the importance of limiting
distractions to ensure accurate counting. Doing the initial count before the
patient enters the OR is a start at avoiding distractions but it is important
to create “no-interruption” zones when counts are being done, eliminating
non-essential conversations and background noise and ensuring everyone’s attention
is focused on the task at hand, akin to the “sterile cockpit” concept in
aviation.
The guideline
outlines best practices for counting using methods that are consistent and
standardized. It recommends that the RN circulator and the scrub person perform
the counts (with the same individuals performing the initial count and all
subsequent counts). Both individuals should view the items (one separates and
points out each item and counts audibly).
Counts should occur:
Putnam notes the scrub
person should discard all surgical soft goods into a kick bucket immediately
after use and the RN circulator should organize them in a pocketed sponge bag
or similar system, which helps separate the items from one another and increase
visibility for counting. Sponge pocketing systems are widely used now, with
transparent units typically with 5 rows of 2 pockets so there is a total of 10
sponges per unit.
Count sheets and
count boards should be used to avoid miscommunication and make sure all OR participants
understand the status of the count(s). The sequence of the count should follow
the order in which they are listed on the sheets and boards (standardization
usually follows a proximal to distal sequence, e.g. first the surgical field,
then Mayo stand, back table, and soft goods that have been discarded into a
kick bucket).
Putnam also stresses
the importance of perioperative personnel immediately inspecting on their
removal from the surgical site all instruments and any attached labels for
signs of damage or fragmentation. Small retained fragments from these may be
particularly difficult to find because they often do not show up on X-rays.
Verna Gibbs, MD, one
of the founders of the No Thing Left Behind campaign recently had some
practical advice in Outpatient Surgery Magazine on preventing RSI’s (Gibbs
2015). In discussing the factors associated with RSI’s Gibbs, whose work we
have highlighted in most of our previous columns on RSI’s listed below, categorizes
3 separate clinical scenarios:
The first type,
Gibbs says, is most commonly seen in the obstetrical environment. She notes
that perinatal birthing rooms often use gauze sponges that lack radiopaque
markers and often do not have formal sponge management practices. That probably
accounts for why the vagina is the second commonest site for RSI’s (after the
abdomen). But she notes those same factors often occur in cardiac cath labs and sponges may be left behind after pacemaker
implantations. This category accounts for about 10% of RSI cases. The second
type (correct-count retention cases) accounts for about 70% of all retention
cases. And the third type, incorrect-count retention cases, accounts for about
20% of cases.
One problem we’ve
seen over and over occurs when there is a discrepant count and the sponge is
later found. This gives rise to many surgeons complacently dismissing
discrepant counts with statements like “The count was off in our last case and
we found the sponge later”. We’ve seen near misses when that occurs and the staff
speak up and insist an X-ray be performed, which finds the missing sponge in
the patient.
Gibbs also points
out one of what we’ll call an unintended consequence of teamwork: relegation of
individual accountability to the team. She notes that “people often downplay
the importance of their own roles when they know that more than one person has
to slip up for a mistake to happen”. When we do team training and discuss the
fact that an error cascade is usually necessary to breach the “swiss cheese” model of defenses, we stress that in most
incidents with adverse outcomes avoiding any single one of the errors in the
cascade could have prevented the ultimate adverse outcome. (Note that we see
this same phenomenon in double checks, such as those used in medication safety,
that are done incorrectly. We know that the error rate for someone supervising
someone else’s work in any industry may approach 10% but there is probably also
an increase in errors of the original work when someone thinks a second person
will catch any errors they make. That is why double checks need to be done
truly independently. See our October 16, 2012 Patient Safety Tip of the Week “What
is the Evidence on Double Checks?”.)
Gibbs goes on to
describe that the sponge accounting system needs to account for all sponges
opened rather than sponges used. Transparent sponge holders, as noted
above, typically with 5 rows of 2 pockets so there is a total of 10 sponges per
unit. As sponges are used and thrown into a kick bucket they should be put into
the sponge holder, one to a pocket, so they can easily be seen and counted. At
the end of the case all sponges, including any unused ones, should be in the
sponge holder. There should also be an erasable white board that everyone can
see which keeps a count of the sponges. Before closing, surgeons must always do
a methodical wound search (MWS) regardless of whether the count is correct or
discrepant. And before leaving the OR the surgeon and circulating nurse must
look at the sponge holder to make sure no pockets are empty. This is referred
to as the “show me” step and can be included on your surgical safety checklist
or your debriefing checklist. Gibbs advises that an “incorrect-count checklist”
be posted in each OR so that everyone knows what to do when there is a
discrepant count. If the sponge cannot be found, X-rays should be done and a
radiologist (not just the surgeon) must call back the report before the patient
is allowed to leave the OR.
While sponge
accounting systems are at the top of everyone’s list because surgical sponges
are far and away the most commonly retained surgical items, our previous
columns warn you not to lose sight of the fact that all sorts of other RSI’s
have been appearing more and more (blue towels, Kerlix,
cautery tips, Glassman viscera container, KOH cup, instrument labeling tape,
Jackson Pratt drain bulbs, Rainey clips, and others). Even the newest
radiofrequency identification and tracking systems would miss most of those
items.
An article in
Anesthesiology News (Frei
2016) reviewed a poster presentation by Van Doren et al. at the 2015 annual meeting of the
International Society for Pharmacoeconomics and
Outcomes Research that pegged the cost of $6,412 per foreign object left behind
during total joint arthroplasties. The poster authors also calculated that the
rate of RSIs was one per 6,878 primary total hip arthroplasties and one per
11,961 primary total knee arthroplasties, for an overall rate was one per
11,948 procedures. The Frei article includes comments from Robert Cima, MD, who notes true costs are largely hidden and that
this estimate significantly underestimates the cost of RSI’s, noting that
indirect costs, litigation costs, meeting costs, etc. lead to a much higher
financial toll. In our November 5, 2013 Patient Safety Tip of the Week “Joint
Commission Sentinel Event Alert: Unintended Retained Foreign Objects” the
Joint Commission sentinel event alert (TJC
2013) noted that 95% of the incidents result in additional care or extended
hospital stay and additional costs (citing a Pennsylvania Patient Safety
Authority estimate of $166,000 average cost for an RSI or “URFO” as the Joint
Commission now apparently prefers to call them).
Whatever the
financial cost of RSI’s might be, it pales in contrast to the human cost
suffered by the patients affected and the reputation cost to the surgeons,
teams and hospitals where such events occur.
Our prior columns on retained surgical items/retained
foreign objects (RSI’s/RFO’s):
References:
Putnam K. Guideline First Look. Guideline for prevention of
retained surgical items. Periop Briefing 2015;
102(6): P11-P13
http://www.aornjournal.org/article/S0001-2092%2815%2901014-5/pdf
Gibbs V. A Better Way to Eliminate Retained Surgical Items.
Accounting, not counting, will ensure no sponges are left behind. Outpatient
Surgery Magazine 2015
Frei R. Cost
Calculated for Each Retained Surgical Item in Total Knee, Hip Arthroplasty. Anesthesiology News 2016; January 1,
2016
Commenting on: Van Doren B, Odum S, et al. 2015
annual meeting of the International Society for Pharmacoeconomics
and Outcomes Research (abstract PM58)
TJC (The Joint Commission). Sentinel Event Alert. Preventing
unintended retained foreign objects. Issue 51 October 17, 2013
http://www.pwrnewmedia.com/2013/joint_commission/urfo/downloads/SEA_51_URFOs.pdf
Print “February
2016 AORN Updates Guideline to Prevent Retained Surgical Items”
Several recent articles about contrast-induced nephropathy
(CIN) prompted us to search our now nearly 1000 columns to see what we have
written about CIN. Much to our surprise we only found one (see our June 2011
What's New in the Patient Safety World column “Reducing
the Risk of Contrast-Related Damage from Imaging Studies”) and that one
dealt as much with other contrast-related injuries as it did with CIN.
The study that attracted our attention was one that looked
at long-term outcomes in patients who developed CIN (Mitchell
2015). They followed 633 emergency
department patients undergoing contrast-enhanced CT, of whom 11% developed
acute kidney injury consistent with contrast-induced nephropathy. Within one
year 15% experienced at least 1 major adverse event (defined as the combined
outcome of death of any cause, renal failure, myocardial infarction, and stroke
or other arterial vascular events, in any anatomic territory, requiring
invention), including 7% who died. After adjustment for a number of clinical
variables the rate of these adverse events was almost 2 and a half times that
of patients who did not develop CIN.
Our 2011 column
noted many of the risk factors for CIN and mentioned a risk stratification
nomogram for predicting CIN in patients undergoing contrast enhanced abdominal
CT scans in the emergency room (Kim
2011). But another new study was a systematic review of predictive models
that identified patients at risk of contrast induced nephropathy among adults
undergoing a diagnostic or interventional procedure using conventional
radiocontrast media (media used for computed tomography or angiography, and not
gadolinium based contrast) (Silver 2015). Those authors
found a total of 12 prediction models but found that ability to predict CIN was
modest at best and really only relevant
to patients receiving contrast for coronary angiography. The authors conclude
that further research is needed to develop models that can better inform
patient centered decision making, as well as improve the use of prevention
strategies for contrast induced nephropathy.
Pertinent to management, a new study (Qian
2016) addressed prevention of CIN in a particularly high risk group – those
patients with chronic kidney disease (CKD) and congestive heart failure (CHF).
The incidence of CIN in this group of patients is more than 20%. So the Chinese
investigators compared those patients managed with CVP-guided fluid
administration vs. those without CVP monitoring in a randomized controlled
trial. The incidence of CIN was 15.9% in the group managed with CVP-guided
fluid administration vs. 29.5% in the group without CVP monitoring. The former
group overall had a higher volume of fluid replacement and higher urinary
output. The occurrence of acute heart failure did not differ between the two
groups. Since hydration is the cornerstone for prevention of CIN, this study
shows that our fears of precipitating acute heart failure or pulmonary edema
may be keeping us from optimal fluid management in such patients receiving
contrast. It demonstrates that use of CVP monitoring allows for more aggressive
fluid management in this high risk group and helps avoid CIN.
While a CVP might allow for more aggressive fluid
management, we’ll again note that a simple bedside maneuver may obviate the
need for such catheters. Ever since our residency days we’d take great pride in
showing our colleagues how a passive leg raise or equivalent can help with
decisions about fluid/hemodynamic status in patients, avoiding the need for
invasive monitoring.
The Royal College of Physicians also recently made available
a toolkit on acute kidney injury and intravenous fluid therapy that includes
advice on managing AKI and issues related to contrast (Royal
College of Physicians 2015).
References:
Mitchell AM, Kline JA, Jones AE, Tumlin JA. Major Adverse Events One Year after Acute
Kidney Injury After Contrast-Enhanced Computed
Tomography. Ann Emerg Med 2015; 66(3): p267-274.e4;
Published online: May 21 2015
http://www.annemergmed.com/article/S0196-0644%2815%2900377-7/abstract
Kim KS, Kim K, Hwang SK, et al. Risk stratification nomogram
for nephropathy after abdominal contrast-enhanced computed tomography. The
American Journal of Emergency Medicine 2011; 29: 412-417
http://www.ajemjournal.com/article/S0735-6757%2809%2900585-3/abstract
Silver SA, Shah PM, Chertow GM, et
al. Risk prediction models for contrast induced nephropathy: systematic review.
BMJ 2015; 351: h4395
http://www.bmj.com/content/351/bmj.h4395
Qian G, Fu Z, Guo J, et al. Prevention
of Contrast-Induced Nephropathy by Central Venous Pressure–Guided Fluid
Administration in Chronic Kidney Disease and Congestive Heart Failure
Patients. J Am Coll Cardiol
Intv 2016; 9(1): 89-96
http://interventions.onlinejacc.org/article.aspx?articleid=2475328&resultClick=3
Royal College of Physicians. Acute care toolkit 12: Acute
kidney injury and intravenous fluid therapy. September 2015
Print “February
2016 Contrast-Induced Nephropathy Risks”
The ACCP (American College of Chest Physicians) has issued
its new antithrombotic guideline update for treatment of venous thromboembolism
(VTE) (ACCP
2016). This is the 10th edition, updating the 9th
edition that was published in 2012. Since the 9th edition the
clinical trials of several novel oral anticoagulants (NOAC’s) have been
completed and published and the new 10th addition acknowledges the
place of these in the management of VTE.
According to the
press release from the ACCP the key changes to recommendations in the 9th
edition to the 10th edition include:
For VTE and no cancer, as long-term anticoagulant therapy,
the new guideline suggests NOAC’s (dabigatran, rivaroxaban, apixaban,
or edoxaban) over vitamin K antagonist (VKA) therapy
and suggests VKA therapy over LMWH. However, for VTE and cancer it suggests LMWH
over VKA or the NOAC’s.
Importantly, of 54 recommendations included in the total 30
statements, 20 were strong and none was based on high quality evidence. This
highlights the need for further research.
The full guideline
is available in CHEST (Kearon
2016).
References:
ACCP (American College of Chest Physicians). CHEST issues
new antithrombotic guideline update for treatment of VTE disease. Press release
January 7, 2016
https://www.chestnet.org/News/Press-Releases/2016/01/AT10-VTE
Kearon C, Akl EA, Ornelas J, et
al. Antithrombotic Therapy for VTE Disease: CHEST Guideline. Chest 2016;
January 2016
http://journal.publications.chestnet.org/data/Journals/CHEST/0/11026.pdf
Print “February
2016 Updated VTE Guidelines from ACCP”
Print “February
2016 What's New in the Patient Safety World (full
column)”
Print “February
2016 Avoiding Methotrexate Errors”
Print “February
2016 AORN Updates Guideline to Prevent Retained Surgical Items”
Print “February
2016 Contrast-Induced Nephropathy Risks”
Print “February
2016 Updated VTE Guidelines from ACCP”
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