Medtronic Ltd

Building 9
Croxley Green Business Park
Hatters Lane
Watford
Herts WD18 8WW
Tel: 01923 212213
Facsimile: 01923 241004

Urgent Field Safety Notice Update

SynchroMed II Implantable Drug Infusion Pump
Update to the March 2014 Communication on Overinfusion
October 2016
Medtronic reference: FA596 Phase II
Dear Healthcare Professional, Risk Manager,
This communication is an update to Medtronics March 2014 notification regarding the
potential for SynchroMed II pump overinfusion. This notification provides updated
information related to contributing causes, occurrence rate and patient management
recommendations. Consistent with the March 2014 communication, Medtronic is not
retrieving SynchroMed II pumps from the field or recommending prophylactic
replacement of the pumps. Please share the enclosed recommendations and this
update with personnel responsible for the management of patients implanted with a
SynchroMed II pump.
Explanation of the Issue:
Overinfusion is defined as the delivery of more drug volume than the programmed
rate, exceeding the pumps flow rate accuracy specification. Pump reservoir contents
aspirated during a refill procedure that are less than expected may indicate that the
pump has overinfused. Overinfusion may or may not be associated with clinically
relevant symptoms. When the pump delivers more drug volume than the programmed
rate, patients may experience overdose symptoms, and the pump reservoir will deplete
more quickly than expected. Patients may experience underdose or withdrawal
symptoms if the drug is depleted prior to the scheduled refill date from an overinfusing
pump.
The low reservoir alarm of an overinfusing pump will not sound if the pump reservoir is
prematurely depleted. The low reservoir alarm is calculated from the pumps
programmed delivery rate and is not a direct measurement of the actual drug volume in
the pump reservoir. Therefore, it is important to follow the enclosed
recommendations.
Investigation Results:
Medtronics investigation has not identified any single factor that results in
overinfusion; rather the interaction of several variables increases the likelihood that a
given pump will overinfuse. Some risk factors are associated with normal variability with
pump components and manufacturing processes, while other factors are associated
with clinical use conditions. Examples of clinical use conditions that have been shown to
increase the likelihood of overinfusion are the use of non-indicated drug formulations,

Medtronic Limited is a wholly owned subsidiary of Medtronic Inc. whose registered office is Building 9, Croxley Green
Business Park, Hatters Lane, Watford, Herts WD18 8WW. Registered in England No. 1070807

overfilling of the pump reservoir, operation of the pump with no fluid in the reservoir,
catheter occlusion, and pump stops or motor stalls lasting more than 48 hours.
Occurrence Rate Based on Registry Data:
Five occurrences of overinfusion have been identified in Medtronics prospective, longterm multi-center registry study (Product Surveillance Registry) as of January 2016,
resulting in a rate estimate of less than 0.14%1 (approximately 1-in-700). All 5
occurrences of overinfusion noted in the Registry were associated with pumps used to
infuse drug formulations that are not indicated for use with the SynchroMed II pump.
Reports of Adverse Events:
Since commercial release of the SynchroMed II pump, over 238.000 pumps have been
implanted. During Medtronics investigation of overinfusion, complaint data and
returned product analysis were assessed, resulting in 103 pumps with related adverse
events through 5 July 2016. Medtronic has been unable to establish a definitive causal
relationship between the adverse events and overinfusion due to potential contributing
factors. However, it is reasonable to conclude that overinfusion was a contributing
factor in these cases. Other factors that may have contributed to an adverse event are:
infused drug dosage, the patients medical history, and the concomitant use of other
drugs, such as oral opioids and other central nervous system (CNS) depressants.
Reported patient outcomes associated with these adverse events ranged from
temporary discomfort to life threatening overdose and/or withdrawal as well as two
reports of death. While the full drug history of these pumps is unknown, 99 of the 103
pumps were associated with non-indicated drug formulations in use at the time of the
pumps last refill. The estimated implant duration for the 103 pumps is 3.7 years (with a
range of 0.4 6.4 years).
Recommendations: See the enclosed Recommendations and Guidelines.
The Competent Authority of your country has been notified of this communication.
We are committed to continuing to improve our product performance and services to
enable you to manage your patients in a safe and effective manner. If you have
questions, please contact your Medtronic Representative directly or via Tel. No: 01923
212213
Sincerely,

Keith Taverner: Regulatory Affairs Manager UK & Ireland

Enclosure: Recommendations and Guidelines

Through 31 January 2016, there have been five reports of overinfusion in 7.505 SynchroMed II pumps
included in Medtronics prospective, long-term multi-center registry study (PSR, formerly ISPR), providing
an upper 95% confidence bound on the occurrence rate of 0.0014 (0.14%). Based on investigation results,
this rate is not significantly changed from the 0.16% upper 95% confidence bound reported in the March
2014 communication.

Update to the March 2014 Communication on Overinfusion (FA596 Phase II)

Recommendations and Guidelines
Recommendations (Developed in collaboration with clinical experts):
Medtronic does not recommend prophylactic removal of SynchroMed II pumps.
To minimize the risk of overinfusion, use the approved/indicated drug formulations for the SynchroMed II
pump. The use of non-indicated drug formulations (such as admixtures, compounded drugs and unapproved
drug concentrations) increases the likelihood of overinfusion.
Educate patients, caregivers and family members to recognize the signs and symptoms associated with
intrathecal drug therapy overdose, underdose or withdrawal.
At every refill visit, question and examine the patient for signs and symptoms of overdose, underdose or
withdrawal.
Follow the refill instructions in the approved labeling so that any volume discrepancy can be detected based
on the amount of medication withdrawn (expected) prior to refilling with new solution. (See Important
Guidelines below).
At every refill visit record the actual and expected reservoir volume.
Review prior refill data to identify any changes in volume discrepancy over time. If there are increases in
volume discrepancy over time (volume withdrawn from the pump is less than expected) or if there is a
volume discrepancy of more than 2 ml:
Evaluate for other potential causes of volume discrepancy, for example: inaccurate volume
measurements, incomplete pump aspiration, incorrect volume entry into clinician programmer at
refills, unrecognized partial pocket fill, or aspiration of pump medication by patient or caregiver.
Evaluate for factors that may increase the likelihood of overinfusion. These factors include: nonindicated drug formulations, overfilling of the pump reservoir, operation of the pump with no fluid in
the reservoir, catheter occlusion, and pump stops or motor stalls lasting more than 48 hours.
If overinfusion is suspected, consider scheduling an interim pump reservoir volume check prior to the
next scheduled refill. Evaluate and question the patient for symptoms consistent with overinfusion. If
after the interim check, overinfusion continues to be of concern, clinically monitor the patient and
consider pump replacement.
Reducing the dose and/or concentration is not a recommended mitigation for overinfusion due to the
identified failure modalities.
To stop delivery of drug from a pump suspected of overinfusion, program a therapy stop, which sets
the pump to minimum rate, and aspirate any remaining drug from the reservoir to avoid continued drug
delivery.
Important Guidelines:
Always follow pump refill instructions per the device labeling. The following steps should be conducted during
each pump refill procedure to allow detection of an overinfusing pump:
Aspirate all fluid from the reservoir until air bubbles no longer appear in the syringe, and record as the amount
withdrawn.
Compare the amount withdrawn from the pump reservoir with the expected volume displayed by the pump
programmer. The amount withdrawn should approximately equal the expected volume.
Determine fill volume (fill with no more than the labeled reservoir volume, 20 or 40 ml).
Accurately measure the volume to be instilled.
If you are unsure whether drug was injected correctly into the pump, completely aspirate the pump to verify
that the entire injected volume of drug has been removed.
Ensure that the refill date is chosen sufficiently in advance of the low reservoir alarm date so the drug
reservoir of an overinfusing pump is not prematurely depleted.
Contact your Medtronic Representative directly or via Tel. No: 01923 212213 if overinfusion is suspected. Please
return any explanted products to Medtronic for mechanical and functional analysis. To minimize changes in the
pump condition after explant, pumps that are suspected of overinfusion should be returned with fluid in the
reservoir, set to a minimum infusion rate, and returned using the designated returned product mailer. Your local
Medtronic representative can assist you in return of product.
October 2016

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