A 65 y.o. woman with a history of recent brain surgery suffered respiratory and cardiac arrest after inadvertently being given intravenously the neuromuscular blocking agent (NMBA) rocuronium instead of the anti-seizure medication fosphenytoin at an Oregon hospital recently (Bannow 2014). She suffered irreversible brain damage and was subsequently removed from life support and died.
Neuromuscular blocking agents (NMBA’s) are high-alert medications that cause paralysis and respiratory arrest when given to non-intubated, non-ventilated patients. As a result, inadvertent administration of NMBA’s often results in fatal outcomes. We first wrote about NMBA incidents back in 2007 and tragic NMBA incidents have continued to occur. Our February 7, 2012 Patient Safety Tip of the Week “Another Neuromuscular Blocking Agent Incident” described several unfortunate incidents involving NMBA’s and had numerous recommendations, relying heavily on excellent resources from ISMP (ISMP 2005), ISMP Canada (Koczmara 2007), and the Pennsylvania Patient Safety Authority (PPSA 2009).
The hospital in the current incident openly admitted the mistake and apologized to the patient’s family and said it would be transparent in explaining what it finds in its root cause analysis. We hope they will disseminate that RCA publicly because the lessons learned will be valuable to many healthcare organizations. That RCA, like almost all related to serious events with untoward patient outcomes, will undoubtedly show a cascade of events that came together to allow the tragic outcome. System-related factors likely put frontline healthcare workers at the sharp end of this incident and those same system-related factors are likely in play at many other organizations.
We actually know very few details about this case at present. But below are the questions we’d be asking in the RCA. Many of them are obvious and are part of every RCA done on an event (eg. Were staffing levels adequate? Were there distractions? etc.). But others may be overlooked. For example, though the focus is on the NMBA and the mixup with the anti-seizure medication what about the decision to use this particular anti-seizure medication in the first place? That decision started the cascade. So let’s start there.
Were the indications for fosphenytoin appropriate?
Fosphenytoin is a drug with very limited indications. It is most commonly used for treatment of generalized tonic-clonic status epilepticus or for treating seizures during neurosurgery. It sometimes may also be substituted, short-term, for oral phenytoin but it should be used only when oral phenytoin administration is not possible. We really don’t know from the current published reports what the indication for fosphenytoin was. Those reports simply say she went to the ER because of anxiety and concerns about her anticonvulsant medications.
Where and how were the fosphenytoin and rocuronium stored?
Were they in floor stock? Or in the pharmacy? Were they in refrigerators? Were they in automated dispensing machines? Limiting access to NMBA’s is arguably the most important intervention to prevent incidents. Many hospitals restrict them to the OR and pharmacy. In those areas where they might be needed emergently (eg. in the ER or ICU where they may be needed for emergent intubations) the drugs can be “sequestered” or sealed in the intubation kits so that they are available only at the time of intubation.
Both drugs are usually refrigerated but may be stored at room temperatures for certain periods. Fosphenytoin should not be stored at room temperature for more than 48 hours. Rocuronium may be removed from refrigerator and stored at controlled room temperature but must be used within 60 days or within 30 days once vial has been opened. Were they stored in similar locations? It is recommended that NMBA’s be segregated from all other medications in all areas where they are stored (Koczmara 2007).
In our February 7, 2012 Patient Safety Tip of the Week “Another Neuromuscular Blocking Agent Incident” we noted that storage of NMBA’s in automated dispensing machines can be especially problematic. Probably most important is only storing them in areas where they are clearly needed. Where needed, they should be kept in single access drawers. But there needs to be a special warning that the NMBA should not be used in patients who are not intubated/mechanically ventilated. Such a message could be delivered in those automated systems having the capability of messaging when an NMBA is selected for removal from a drawer. Similarly, the type of CPOE error noted in the February 7, 2012 column might be avoided by programming in an alert ensuring the patient is intubated/ventilated when the physician enters an order for an NMBA.
Were sound-alike look-alike issues a factor?
It’s pretty unlikely that sound-alike issues occurred with this drug pair (though we previously discussed sound-alike issues for several other NMBA’s). The generic names here do not sound alike and even the brand names (Zemuron and Cerebyx, respectively, for rocuronium and fosphenytoin) do not sound alike. But look-alike issues certainly are a consideration. In many of the prior incidents vials of NMBA’s have been confused with vials of other medications and vaccines. A recent ISMP Canada article (ISMP Canada 2014) has an excellent discussion of improvements made in the packaging and labeling of NMBA’s in both Canada and the US.
Were there warnings on the NMBA vials that were salient and not obscured?
Most important are warning labels for vials, syringes, bags, or storage boxes containing NMBA’s. Both ISMP and the PPSA recommend using fluorescent red labels that state “Warning: Paralyzing Agent – Causes Respiratory Arrest”. The recent ISMP Canada article (ISMP Canada 2014) noted above describes the various ways that caps, labels, etc. have been redesigned to draw attention to the warnings and notes some differences between Canada and the US.
But regardless of the warnings it is still possible they may not be heeded. The 2007 ISMP Canada review (Koczmara 2007) notes that a form of confirmation bias often is a contributing factor. Specifically, because the vials and labels may look similar to those of the “expected” medication, we tend to see what we expect to see rather than what we actually see. The phenomenon is also sometimes known as “inattentional blindness” (ISMP 2009).
Had any drug shortage led to use of different formulations of rocuronium?
Could a drug shortage have played a role? There has been a recent shortage of at least one rocuronium preparation (ASHP 2014). So one would want to investigate whether rocuronium preparations from other manufacturers or suppliers might conceivably have had different packaging or labeling that confused the local healthcare workers(s). Particularly when manufacturers or suppliers change for high-alert medications it is important that all potentially affected staff are made aware of the changes.
Who prepared the drug?
That is important as it pertains to communication, if any, between the person preparing the drug and the person administering it.
Were any syringes used appropriately labeled?
If the medication were drawn up from the vial into a syringe by someone other than the person administering the drug, was the syringe appropriately labeled? If so, did it also have a salient warning like discussed above? There have been cases also where unused syringes have been (inappropriately) returned to storage and sometimes mixed up with syringes containing other medications. We would actually recommend labeling that syringe even if the same nurse is going to immediately administer the drug to the patient and that label should have the same sort of salient warning described above. That is because interruptions and distractions (eg. a fire alert?) can occur that might lead to an unlabeled syringe with a potentially fatal medication being left lying somewhere.
Was there a change of staff or any other handoff during the key timeframe?
For example, did a second nurse administer the drug after a shift change from a syringe prepared by a previous nurse?
Was a double check done?
See our October 16, 2012 Patient Safety Tip of the Week “What is the Evidence on Double Checks?” and ISMP’s excellent review on independent double checks (ISMP 2013) for discussions on double checks. NMBA’s should be on your list of high-alert medications (see the ISMP List of High-Alert Medications in Acute Care Settings for examples) and should require independent double checks prior to administration. But remember that in this case it is unlikely that the person administering the drug thought it was an NMBA. They apparently thought they were administering fosphenytoin. The latter drug is not likely on a hospital’s formal list of drugs requiring independent double checks. However, fosphenytoin is a seldom-used drug and, hence, is likely unfamiliar to many healthcare workers. But even ISMP recommends against requiring independent double checks on too many drugs (ISMP 2013). That said, with unfamiliar drugs it still makes sense to do some sort of double check, such as consulting a drug reference. But there are always barriers to doing double checks (inconvenience, lack of easy access to drug reference materials, second staff not readily available, fear of appearing uninformed, etc.). But even a “mental” double check could have been important here. The dosing on a mg basis is quite different for the two drugs (that for fosphenytoin being on the order of 10 times higher than that for rocuronium). That could have alerted staff to a problem.
Was barcoding available and used?
Barcoding for bedside medication verification would be very useful in preventing this sort of error. However, many hospitals that have barcoding and bedside medication verification in place have not yet implemented it in the ER.
Were there any significant distractions?
This certainly is a possibility here. Apparently there was a “code red” (fire alert) around the time of the incident and apparently the door to the patient room closed automatically. She was said to have been found in arrest when the door was reentered. Since details of the timing of that “code red” were not specified in the early press coverage, it would be important to know if that fire alert interrupted the administration of the drug or led to a problem monitoring the patient after the administration. Note that in several of our columns (most recently in our October 21, 2014 Patient Safety Tip of the Week “The Fire Department and Your Hospital”) we’ve mentioned “dual scenarios” in which one event (such as a patient elopement or infant abduction) may occur in conjunction with a fire drill or fire alert. Sometimes it’s valuable to add a second nuance to one of your fire drills.
How was the drug administered?
If the staff thought they were administering fosphenytoin how did they administer it? Was it administered by slow IV push? Or was it administered by an unobserved infusion? The dose of IV fosphenytoin (15 to 20 mg phenytoin equivalents/kg) that is used to treat status epilepticus is administered at a maximum rate of 150 mg phenytoin equivalents/min. The typical fosphenytoin infusion administered to a 50 kg patient would take between 5 and 7 minutes, considerably shorter than it would take to administer a comparable dose of IV phenytoin to a patient (a theoretical advantage of fosphenytoin when rapid dosing is needed). Remember, we don’t yet know how much fosphenytoin was thought to be being given or how long the administration process took here. But since fosphenytoin may have similar cardiovascular side effects to phenytoin (eg. hypotension and dysrhythmias) it is prudent to observe the patient while the drug is being infused. One would anticipate that paralysis would likely have been observed by someone administering the recuronium if they were present during the administration.
How was the patient monitored?
As above it is prudent to observe the patient while the drug (presumed to be fosphenytoin) is being infused. So one would anticipate that monitoring (by direct observation, EKG) one would have been alerted that the patient had been paralyzed by an NMBA. However, respiratory depression would not be immediately detected unless the patient had capnography or apnea monitoring ongoing. Eventually, however, one should have been alerted by arrhythmias as the patient became hypoxic. If the patient was being monitored by EKG, were the alarm volumes and limits appropriate? Was pulse oximetry being used? Might the fire alert have interfered with audibility of any alarms?
Was staffing adequate at the time of the event? Were any gaps caused by factors such as change of shift? Did staff fatigue come into play? Were there issues with education and training of staff? Were any of the staff involved new to the organization or to the unit where the event occurred?
Is rocuronium or any other NMBA accessible in floor stock anywhere else it shouldn’t be?
This should be an opportunity to audit stocks of NMBA’s and ensure that they are not accessible in any sites other than where there is an absolute necessity.
The hospital already did several positive things we would also include in our checklist for investigation of any serious event (see our July 24, 2007 Patient Safety Tip of the Week“Serious Incident Response Checklist”):
What did the hospital do once it recognized the mistake that had occurred?
The hospital openly admitted the mistake and apologized to the patient’s family and said it would be transparent in explaining what it finds in its root cause analysis. Oregon did pass legislation this year encouraging disclosure and apology but this hospital had been advocates of that policy long before that. They need to keep the family in the loop as they complete their RCA and take steps to ensure similar events don’t occur again, not just at their hospital but elsewhere too. See the list below of all our columns on disclosure and apology.
Did they recognize the second victims in this unfortunate event?
Yes, they noted that staff directly involved in the event are on administrative leave and receiving counseling through the hospital’s caregiver assistance program. As we discussed in our December 17, 2013 Patient Safety Tip of the Week “The Second Victim” as far back as the early 1990’s we’ve always had an item on our serious incident response checklist to ensure that we provide appropriate attention to staff directly or indirectly involved in such incidents. Staff at the hospital in the current incident have been described as being “devastated” and are true “second victims”. Importantly, just ensuring they get counseling is not enough. We need to make sure all staff understand what they are going through and be wary that their own communication with those staff members, whether verbal or through body language, will play a big role in determining how they will cope with what happened.
In addition to describing several other incidents with accidental administration of NMBA’s to patients, our February 7, 2012 Patient Safety Tip of the Week “Another Neuromuscular Blocking Agent Incident” had several other recommendations worth repeating here:
Obviously, the biggest risk of NMBA’s is in patients who are not being mechanically ventilated. There are a couple circumstances where NMBA’s may be inadvertently ordered and given in non-ventilated patients. We previously mentioned a case (see our June 19, 2007 Patient Safety Tip of the Week “Unintended Consequences of Technological Solutions”) where an unintended consequence of CPOE led to inadvertent administration of a neuromuscular blocking agent to a patient who was not being mechanically ventilated (ISMP 2007). In that case the physician was ordering from a remote site and inadvertently entered orders on the wrong patient. The other circumstance is when a patient in an ICU is extubated and weaned from a respirator and transferred to a regular floor and someone writes “continue all previous orders” not recognizing that such might include orders for NMBA’s in a now unventilated patient.
Look-alike/sound-alike (LASA) issues are root causes in many NMBA incidents. Very often the vials closely resemble vials of other more common medications and solutions. How and where drugs are stored is an important contributing factor in many of the adverse NMBA incidents. Many of the reported incidents involving NMBA’s being confused with another intended drug have involved NMBA’s that were stored in refrigerators, especially in refrigerators where such are not usually stored. The vials have been confused with vials of other substances like normal saline, heparin, and vaccines. The 2005 ISMP alert (ISMP 2005) had several examples. In one instance an anesthesiologist put a vial of an NMBA in a refrigerator on a different unit that does not usually stock NMBA’s and the vial was mistaken for hepatitis B vaccine and was inadvertently given to seven infants. In others, vials of NMBA’s looked similar to vials of either vaccines or the diluents used with those vaccines, resulting in multiple patients being exposed to the NMBA’s.
The sound-alike issues are also problematic. Norcuron (vecuronium) has been mistaken for Narcan, vecuronium for vancomycin, atracurium for Ativan, etc. In other cases, look-alike packaging has been a major contributing factor.
Limiting access to NMBA’s is arguably the most import intervention to prevent incidents. Many hospitals restrict them to the OR and pharmacy. In those areas where they might be needed emergently (eg. in the ER or ICU where they may be needed for emergent intubations) the drugs can be “sequestered” or sealed in the intubation kits so that they are available only at the time of intubation. But while restricting access is important, keep in mind those incidents above where NMBA’s popped up in areas where they were not supposed to be. So there clearly must be other safety measures taken and you need to be ever vigilant to items showing up where they are not supposed to be.
Storage of NMBA’s in automated dispensing machines can be especially problematic. Probably most important is only storing them in areas where they are clearly needed. Where needed, they should be kept in single access drawers. But there needs to be a special warning that the NMBA should not be used in patients who are not intubated/mechanically ventilated. Such a message could be delivered in those automated systems having the capability of messaging when an NMBA is selected for removal from a drawer. Similarly, the type of CPOE error noted earlier might be avoided by programming in an alert ensuring the patient is intubated/ventilated when the physician enters an order for an NMBA.
Most important are warning labels for vials, syringes, bags, or storage boxes containing NMBA’s. Both ISMP and the PPSA recommend using fluorescent red labels that state “Warning: Paralyzing Agent – Causes Respiratory Arrest”.
The ISMP Canada review (Koczmara 2007) notes that a form of confirmation bias often is a contributing factor. Specifically, because the vials and labels may look similar to those of the “expected” medication, we tend to see what we expect to see rather than what we actually see. The phenomenon is also sometimes known as “inattentional blindness” (ISMP 2009).
Part of your medication safety program should include education and communication about NMBA’s. They should never be referred to as “muscle relaxants” and should never be allowed to be ordered on a “prn” basis (PPSA 2009). Similarly, the phrase “renew all previous orders” should never be allowed. Rather, when patients are transferred from one unit to another, the physician should write out each of the orders as if they were brand new orders. The same applies when the physician is using CPOE. While some CPOE systems have functions (or workarounds) that facilitate renewal of a large number of orders, beware that such can give rise to unintended consequences.
Prompt disposal of unused NMBA’s is also essential. Several of the previously mentioned incidents involved use of NMBA preparations that had been poorly labeled and left behind from use with one patient, then were inadvertently administered to other patients. ISMP recommends that unused NMBA’s (whether in vials, bags, or syringes) be placed in a sequestered bin for immediate pickup by pharmacy
Obviously, use of traditional medication safety measures, such as barcoding, are important and NMBA’s, being high-alert drugs, should require independent double checks before being dispensed and before being administered.
Lastly, you may find 2 other resources on NMBA’s helpful. In our July 31, 2007 Patient Safety Tip of the Week “Dangers of Neuromuscular Blocking Agents” we recommended this is a good issue to address in FMEA (Failure Mode and Effects Analysis) in your organization. Susan Paparella (Paparella 2007), from ISMP, did exactly that in the Journal of Emergency Nursing (see our November 2007 What’s New in the Patient Safety World column “FMEA Related to Neuromuscular Blocking Agents”). The ED staff had recognized NMBA’s as high-alert drugs and were contemplating their removal from ED stores, to be replaced in kits prepared for rapid-sequence intubation. FMEA is especially useful in such situations where change is to take place, because it helps identify potential unintended consequences. The article nicely describes how you do a FMEA exercise and provides examples for scoring probability and severity and use of a hazard scoring matrix. Lastly, one of the AHRQ M&M Conference cases (Weinger 2003) on an NMBA incident had 2 terrific downloadable videos addressing some of the communications issues in that case. It is well worth reading and watching the videos.
As above, we hope the Oregon hospital will disseminate their RCA publicly because the lessons learned undoubtedly will be valuable to many healthcare organizations. It is important that you use the narrative of this unfortunate case and the others mentioned in our February 7, 2012 Patient Safety Tip of the Week “Another Neuromuscular Blocking Agent Incident” to help everyone in your organization understand the vulnerabilities you might have to an NMBA incident. Telling stories that your staff can relate to is the best way to promote patient safety vigilance and interventions. Again, also consider formal audits or add NMBA Safety to your list of things you look for in your Patient Safety Walk Rounds and consider doing a FMEA on NMBA use in your organization.
Some of our prior columns on neuromuscular blocking agents (NMBA’s):
June 19, 2007 “Unintended Consequences of Technological Solutions”
July 31, 2007 “Dangers of Neuromuscular Blocking Agents”
November 2007 “FMEA Related to Neuromuscular Blocking Agents”
May 20, 2008 “CPOE Unintended Consequences - Are Wrong Patient Errors More Common?”
January 31, 2012 “Medication Safety in the OR”
February 7, 2012 “Another Neuromuscular Blocking Agent Incident”
October 22, 2013 “How Safe Is Your Radiology Suite?”
Some of our prior columns on Disclosure & Apology:
July 24, 2007 “Serious Incident Response Checklist”
June 16, 2009 “Disclosing Errors That Affect Multiple Patients”
June 22, 2010 “Disclosure and Apology: How to Do It”
September 2010 “Followup to Our Disclosure and Apology Tip of the Week”
November 2010 “IHI: Respectful Management of Serious Clinical Adverse Events”
April 2012 “Error Disclosure by Surgeons”
June 2012 “Oregon Adverse Event Disclosure Guide”
December 17, 2013 “The Second Victim”
Other very valuable resources on disclosure and apology:
Bannow T. St. Charles Bend admits mistake led to patient death. The Bulletin (Bend, Oregon) 2014; Dec. 5, 2014
ISMP (Institute for Safe Medication Practices). Paralyzed by mistakes. Preventing errors with neuromuscular blocking agents. ISMP Medication Safety Alert Acute Care Edition 2005; September 22, 2005 issue
Koczmara C, Jelincic V. Neuromuscular blocking agents: Enhancing safety by reducing the risk of accidental administration. ISMP Canada 2007 in the Spring 2007 publication of the Canadian Association of Critical Care Nurses (CACCN).
PPSA (Pennsylvania Patient Safety Authority). Patient Safety Advisory.
Neuromuscular Blocking Agents: Reducing Associated Wrong-Drug Errors
Pa Patient Saf Advis 2009; 6(4): 109-14.
ISMP Canada. Neuromuscular Blocking Agents: Sustaining Packaging Improvements over Time. ISMP Canada Safety Bulletin 2014; 14(7): 1-5
ISMP (Institute for Safe Medication Practices). Inattentional blindness: What captures your attention? ISMP Medication Safety Alert Acute Care Edition 2009; February 26, 2009
ASHP (American Society of Health-System Pharmacists). Drug Shortages. Rocuronium Injection. 29 October 2014
ISMP. Independent Double Checks: Undervalued and Misused: Selective use of this strategy can play an important role in medication safety. Acute Care ISMP Medication Safety Alert! June 13, 2013
ISMP. ISMP List of High-Alert Medications in Acute Care Settings. ISMP 2014.
Drugs.com for Professionals.Fosphenytoin Sodium Injection, USP.
ISMP (Institute for Safe Medication Practices). Remote CPOE error-a situation that's more than remotely possible. ISMP Medication Safety Alert Acute Care Edition 2007; May 31, 2007
Paparella, Susan RN, MSN Failure Mode and Effects Analysis: A Useful Tool for Risk Identification and Injury Prevention. Journal of Emergency Nursing. 33(4):367-371, August 2007
Weinger MB, Blike GT.
Intubation Mishap. AHRQ Web M&M. September 2003
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