Friday, February 3, 2017
Bubble and infusion set update – September, 2013
Miscellaneous comments. These apply only to Minimed Paradigm pumps and Dexcom System 7 Plus CGMs – we don’t know anything about other systems.
1. Minimed infusion sets. The last time I wrote, we had switched from 6 mm Quick-Sets to 13 mm Silhouette infusion sets, because of problems with both bubbles and infusion sets “going bad” after 2 to 2½ days (“going bad” means there were rapid, unexplained increases in blood glucose, not associated with food or anything else, and with the blood glucose rapidly brought down by a new infusion set). The Silhouettes resulted in fewer infusion sets going bad, and fewer bubbles, but at the cost of more bleeding and bruising at the insertion site.
Eventually, we decided to try the 9 mm Quick-Sets. A quick geometry calculation shows that a 13 mm Silhouette at a 45° angle goes in about 9 mm, the same as the 9 mm Quick-Sets. These Quick-Sets appear to be the best solution we’ve found.
a. Bubbles are minimized. We find about 1 significant bubble in the tubing (more than 1” long in the tubing) about once a week, although we still check for bubbles three times a day. We still have no idea why the bubbles form; I’ve written about that in detail previously. I’ve since read about some sort of vents in the infusion sets. Maybe the bubbles have something to do with pressure fluctuations at the infusion site causing small back-and-forth motion at the O-rings in the reservoir, which could cause air to leak into the reservoir, but that’s only speculation.
b. Infusion sets almost never go bad. In the 6 months or so we’ve used the 9 mm Quick-Sets, only one time have we had to change an infusion set before three days were up.
c. Bleeding and bruising are much, much less of a problem than with the Silhouettes.
Different people have different thicknesses of fat in their tummies, different activity levels, etc., so what works for us may well not work for everyone – your mileage may vary.
2. Dexcom Seven Plus CGM. There’s been much talk of the “artificial pancreas,” where the pump responds to CGM readings to determine how much insulin to deliver. Unfortunately, CGMs – although they are lifesavers!! – just aren’t accurate enough to be given the task of giving orders to the pump. As our most extreme example of a non-so-good sensor, of 22 calibrations of CGM readings against a BG meter, the CGM was off by more than 40 mg/dL 7 times. One example: CGM: 151, BG meter: 74. In this case, if we had followed the CGM reading, a bolus would have been given, which could have led to a BIG problem with hypoglycemia. We changed out that CGM sensor, and the next one worked much better. But occasionally we find the CGM reading to be in error by as much a 100 mg/dL. When this happens, sometimes we even do two calibrations with two different BG meters and test strips from two different batches. The readings from the BG meters are very seldom erroneous (note: “very seldom” doesn’t mean “never”; perhaps once every six months we get readings from two different BG meters that differ significantly.)
Monday, September 23, 2013
Bubble and infusion set update – September, 2013
Note:
For the list of blogs, click HERE or go to
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Miscellaneous comments. These apply only to Minimed Paradigm pumps and Dexcom System 7 Plus CGMs – we don’t know anything about other systems.
1. Minimed infusion sets. The last time I wrote, we had switched from 6 mm Quick-Sets to 13 mm Silhouette infusion sets, because of problems with both bubbles and infusion sets “going bad” after 2 to 2½ days (“going bad” means there were rapid, unexplained increases in blood glucose, not associated with food or anything else, and with the blood glucose rapidly brought down by a new infusion set). The Silhouettes resulted in fewer infusion sets going bad, and fewer bubbles, but at the cost of more bleeding and bruising at the insertion site. Eventually, we decided to try the 9 mm Quick-Sets. A quick geometry calculation shows that a 13 mm Silhouette at a 45° angle goes in about 9 mm, the same as the 9 mm Quick-Sets. These Quick-Sets appear to be the best solution we’ve found.
a. Bubbles are minimized. We find about 1 significant bubble in the tubing (more than 1” long in the tubing) about once a week, although we still check for bubbles three times a day. We still have no idea why the bubbles form; I’ve written about that in detail previously. I’ve since read about some sort of vents in the infusion sets. Maybe the bubbles have something to do with pressure fluctuations at the infusion site causing small back-and-forth motion at the O-rings in the reservoir, which could cause air to leak into the reservoir, but that’s only speculation.
b. Infusion sets almost never go bad. In the 6 months or so we’ve used the 9 mm Quick-Sets, only one time have we had to change an infusion set before three days were up.
c. Bleeding and bruising are much, much less of a problem than with the Silhouettes.
Different people have different thicknesses of fat in their tummies, different activity levels, etc., so what works for us may well not work for everyone – your mileage may vary.
2. Dexcom Seven Plus CGM. There’s been much talk of the “artificial pancreas,” where the pump responds to CGM readings to determine how much insulin to deliver. Unfortunately, CGMs – although they are lifesavers!! – just aren’t accurate enough to be given the task of giving orders to the pump. As our most extreme example of a not-so-good sensor, of 22 calibrations of CGM readings against a BG meter, the CGM was off by more than 40 mg/dL 7 times. One example: CGM: 151, BG meter: 74. In this case, if we had followed the CGM reading, a bolus would have been given, which could have led to a BIG problem with hypoglycemia. We changed out that CGM sensor, and the next one worked much better. But occasionally we find the CGM reading to be in error by as much a 100 mg/dL. When this happens, sometimes we even do two calibrations with two different BG meters and test strips from two different batches. The readings from the BG meters are very seldom erroneous (note: “very seldom” doesn’t mean “never”; perhaps once every six months we get readings from two different BG meters that differ significantly.)
Wednesday, February 8, 2012
Bubble update - February, 2012
Bubble update - February, 2012
We've been using the 6 mm Quick-Set infusion sets with the Quick-Serter for several years; this is for a Medtronic Paradigm pump. Over a period of a few months recently, there were increasing problems with the infusion sets. The main problem was a rapid increase in blood glucose, not associated with meals or anything else. This generally happened about 2 to 2½ days after the infusion set was inserted. When the infusion set was changed, the blood glucose rapidly returned to the normal range and all was well - at least for another 2 to 2½ days. Also, air bubbles in the tubing continued to be a problem.
We decided to switch from the 6 mm Quick-Sets to 13 mm Silhouette infusion sets, using the Sil-Serter for insertion. What a difference! Essentially no more bubbles, although we still check the tubing for bubbles three times a day. Infusion sets almost always last a full three days. The only problem is increased bleeding around the infusion set, mainly when it's removed. We have no idea why changing the type of infusion set changes the bubble situation, because the bubbles originate in the reservoir. The increased bleeding is probably reasonable. A quick geometry calculation shows that a 13 mm Silhouette cannula inserted at 45° goes in a "perpendicular" distance of 9 mm, compared to 6 mm for the Quick-Sets we used, so there's both a longer penetration and a deeper penetration by the needle and cannula. We've thought about trying the 9 mm Quick-Sets (which wouldn't be as long but would go in as deep as the 13 mm Silhouettes), but haven't bothered so far.
So for people who are having problems with bubbles in their tubing, a possible solution to try is to use Silhouette infusion sets.
We've been using the 6 mm Quick-Set infusion sets with the Quick-Serter for several years; this is for a Medtronic Paradigm pump. Over a period of a few months recently, there were increasing problems with the infusion sets. The main problem was a rapid increase in blood glucose, not associated with meals or anything else. This generally happened about 2 to 2½ days after the infusion set was inserted. When the infusion set was changed, the blood glucose rapidly returned to the normal range and all was well - at least for another 2 to 2½ days. Also, air bubbles in the tubing continued to be a problem.
We decided to switch from the 6 mm Quick-Sets to 13 mm Silhouette infusion sets, using the Sil-Serter for insertion. What a difference! Essentially no more bubbles, although we still check the tubing for bubbles three times a day. Infusion sets almost always last a full three days. The only problem is increased bleeding around the infusion set, mainly when it's removed. We have no idea why changing the type of infusion set changes the bubble situation, because the bubbles originate in the reservoir. The increased bleeding is probably reasonable. A quick geometry calculation shows that a 13 mm Silhouette cannula inserted at 45° goes in a "perpendicular" distance of 9 mm, compared to 6 mm for the Quick-Sets we used, so there's both a longer penetration and a deeper penetration by the needle and cannula. We've thought about trying the 9 mm Quick-Sets (which wouldn't be as long but would go in as deep as the 13 mm Silhouettes), but haven't bothered so far.
So for people who are having problems with bubbles in their tubing, a possible solution to try is to use Silhouette infusion sets.
Saturday, August 28, 2010
Entries in this blog:
May 28, 2010 - More perspectives on insulin pump bubble problems
March 14, 2009 - Do insulin pump bubbles cause medical emergencies?
March 13, 2009 - Insulin pump bubbles continued
January 13, 2009 - Insulin pump bubbles
Friday, May 28, 2010
More perspectives on insulin pump bubble problems.
1. From what I've read on forums about bubbles in insulin pump tubing, and from what I've heard from other pump-users with bubble troubles, physicians almost always say, "This is new to me. I haven't seen this problem before." A friend who's a relatively young physician said that physicians are almost obligated to say this. If they acknowledge they are aware there's a problem, then it can held to be their responsibility if something goes wrong and one of their patients is admitted to the hospital because of sky-high BG due to bubbles.
Also, it would be a LOT of work for a physician to go up against Medtronic, and few physicians would want to use their time fighting against large corporations. They want to follow their protocols; and they are less likely to be sued if they follow the conventional wisdom. And if nothing in the FDA approval literature says to watch out for bubbles, then bubbles don't exist.
2. From Medtronic's perspective, they're certainly going to deny there's a problem and blame bubbles on "patient error." Since we live in southern California, we offered to go to the Medtronic facility in the San Fernando Valley and discuss the situation with them. They said that would be fine with them, as long as we signed a nondisclosure agreement saying we would never ever divulge ANYTHING they told us, with the penalty for disclosure being major liability in a lawsuit. Needless to say, we haven't taken them up on their offer.
In a way, a bubble in the tubing is a perfect poison. There's no trace of it left after it goes into the body; and if someone ends up in the emergency room with high BG readings it's impossible to prove a bubble was the problem. The only way to prove bubbles cause problems is for a patient to deliberately allow a long (6" or longer) bubble to go through the tubing and into their body, take a video as the bubble moves, and then go to the emergency room with a BG higher than 500. In the emergency room, the patient, of course, would be likely to be referred to the psych ward for doing that to themselves.
"What about the FDA?" you ask. There is a system for reporting problems with medical devices and drugs. Here's the link:
https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
Lots of luck getting a meaningful response. The FDA is unlikely to get involved unless there's been real harm to a patient and, again, it's almost impossible to prove the harm was due to a bubble.
For now, all I know that people with bubble problems can do is to check their tubing 2-3 times a day, and prime out the bubbles before they reach the body. See my other postings for lots of detail.
Saturday, March 14, 2009
Do insulin pump bubbles cause medical emergencies?
We recently got an e-mail from another person who's had problems with insulin pump bubbles.
If bubbles in the pump cause a few strange high blood glucose readings (say in the 200s or low 300s), that's probably not a big deal - almost every insulin-dependent diabetic has these from time to time when they mis-guess the number of carbs in a meal. But a number of 420 and a trip to the emergency room is a big deal, both health-wise and bottom-line-wise for patients and insurance companies, and - we can hope - for federal regulators who are supposed to watch out for problems with medical devices.
Here is what the person said (personal identifying information has been removed):
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Hello,
I just found your information about air bubbles in the Medtronic Insulin pump.
It was as you had read my mind!!
I was put on the pump in December ....
My problems were first found Jan.... I noticed a long air bubble in my tubing as I was about to bolus for a meal.
No telling how many more had gone through without my knowledge!
I even had to go to the E.R. one night with a 420 reading!
While there...I found a 2" air gap in my tubing line!
Since that time...it's been a pain, checking...purging....wasting insulin.
I called and talked to the help line also... actually talked to Christine...and yes she's a jewel!! Very nice helpful person.
Switched infusions, reservoirs with Medtronics...changed insulins...finally got a new pump. Still have bubbles...none as large as before...but yes, I do still have to check constantly to see if there is a air gap in the line. I actually have had 5" bubbles!!
Talk about a big problem if I hadn't checked!!
I'm sending your blog and your posting in the forum to the Diabetes Clinic that I go to...Just to let them know it's NOT just me!
One thing that was offered to me was to fill the reservoir ahead of time...let it sit (hoping the fizzie bubbles will all come to the top) before changing my sets. I'm like you...I think that bubbles come in from the o-ring. When I tap the bottle to remove bubbles...there seem to be more coming from the o-ring, and that doesn't make sense.
I hope to hear back from you, hopefully with information on this problem!!
Friday, March 13, 2009
Insulin pump bubbles continued
Since we sent the letter to Medtronic about the bubble problems, we got a letter back from Shirajul Karim, the "Sr. Dr. of Quality" dated January 16, 2009. Here's the important sentence in his letter:
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"While our experience with our products is not consistent with the observations and testing described in your letter, we will carefully and fully investigate your claims."
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And here's the letter we sent back to him. He hasn't replied, nor is there any evidence they made any attempt to "carefully and fully investigate" our findings. Nada.
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Shirajul Karim, Senior Director of Quality
Medtronic Minimed
18000 Devonshire Street
Northridge, CA 91325
Dear Mr. Karim:
Thank you for your letter of January 16 acknowledging our letter of December 24. Let us first note that, despite the bubble problems we (and others) have reported, we are pleased with our experience with the pump. The fine control over insulin delivery rates it offers is a vast improvement over that available with injections.
It is surprising that ongoing problems with bubbles and air pockets have not previously been brought to the attention of Medtronic Minimed Quality Control. The issue certainly has been addressed to your HelpLine personnel by other people in addition to us. Here’s a link that illustrates the point:
http://tudiabetes.com/group/minimedparadigmusers/forum/topics/583967:Topic:147765
And here’s another link where “Dave” gives a sure-fire method to avoid bubbles – we have followed all of his suggestions, with no difference in bubble formation:
http://tudiabetes.com/forum/topics/583967:Topic:256260
As our December 24 letter shows, the bubbles develop only after and only if the insertion set is in FFFF’s body, take several days to grow, and their growth appears to involve leakage of air at the o-ring-reservoir interface (at least, that’s where the large bubbles are found before they break loose and enter the tubing).
It obviously would be simple for Medtronic Minimed to survey 100 or so patients who use the pump to see if they have bubbles in their reservoirs (e.g., by asking callers to the HelpLine to look at their pump reservoirs). However, the failure of Medtronic Minimed to have a substantive response to our letter in more than a month, the content of your letter, and the protocols used by the HelpLine personnel indicate that Medtronic Minimed has already made up its mind that the only problem is “patient error.” Presumably the solution will be for an outside agency (e.g., the FDA) or health plan (e.g., Kaiser Permanente) to investigate bubble formation in reservoirs and the possible risks to their patients. As we noted previously, the largest bubble we’ve “primed out” was equivalent to more than 2 Units of insulin that would not have been delivered, enough to increase my BG reading by about 150 mg/dL.
In the meantime, we would be interested to know if Medtronic Minimed comes up with any ideas for how the bubbles develop. As you may know, our first pump has been tested and found to be working flawlessly – as we said in our letter we expected to be the case. Please let us know if we can give you any additional information.
Tuesday, January 13, 2009
Insulin Pump Bubbles
Note: Our names, address, etc. have been replaced by capital letters to preserve privacy. Feel free to send us an e-mail at wands65mail-blogspot@yahoo.com, and we’ll be glad to reply.
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XXX YYYY Street
San Diego, CA 92ZZZ
Phone: AAA-BBB-CCCC
E-mail:
wands65mail-QQQ@yahoo.com
December 24, 2008
Medtronic:
Quality Control, Customer Support Center
Christopher J. O'Connell, Senior Vice President and President, Diabetes
The purpose of this letter is to ensure that you are aware of what we believe to be a significant safety issue with the Paradigm pump system involving formation of air bubbles in the pump reservoir and propagation of such bubbles through the tubing into patients' bodies. Such bubbles have the potential of resulting in serious or even catastrophic health effects on patients. This letter is - unfortunately - quite long, because we have tried to document it as completely as possible with the resources available to us, and because of the potential seriousness of the problem.
Contents of this letter:
1. Disclaimer/qualification
2. Executive summary
3. Our background
4. Our observations
5. Our interactions with the Medtronic HelpLine
6. Experiences of others
7. Our experiments
8. Chemistry 1 exercises
9. Our conclusions
10. Draft URGENT WARNING statement
1. Disclaimer/qualification
The information and conclusions in this letter represent our good-faith attempt to understand and describe the problems with our Paradigm 522 pump. We do not have access to the laboratory equipment that would be required to determine the precise origin of the problem. Every statement of fact in this letter should be understood to include an initial clause, "In our experience/judgment,...."
2. Executive summary
Air bubbles can develop at the interface between the o-ring and the reservoir body of the Paradigm pump (we'll term this the O-R interface). These bubbles can develop no matter how carefully the patient removes air bubbles during the infusion set insertion procedure; they appear to develop because of leakage of air into the reservoir around the o-ring as the pump operates. These bubbles can grow to become of significant size (>2 mm diameter), break loose, migrate to the top of the pump, into the tubing, and into the body of the patient, causing a significant (>1 Unit) loss of insulin flow into the patient's body. In turn, this loss can cause high blood sugar readings (>300 mg/dL); such spurious readings could also cause patients and their physicians to increase insulin doses with the possibility of resulting severe hypoglycemia and its severe consequences.
On or - preferably - before January 12, 2009, we ask Medtronic:
a. To convince us that our analysis of the situation is faulty. We regard ourselves as reasonable people, and would be delighted to be shown that something we (and other Paradigm pump users - see Section 6 below) are doing is wrong.
or
b. To resolve the problem and take the steps required to ensure that air bubbles resulting from action of the pump do not pose a significant danger to patients using the pump.
or
c. To contact every user of a Paradigm pump and every physician who prescribes Paradigm pumps to inform them of the possibility of development of such bubbles, the danger these bubbles present, ways of checking for bubbles in the reservoir and, and ways of checking for and removing air pockets in the infusion tubing. A draft of such an URGENT WARNING statement is given as Section 10 of this letter.
or
d. To take other appropriate action to address this problem.
3. Our Background
DDDD's bachelor's degree is in chemistry from the California Institute of Technology; his Ph.D. is also in chemistry from Stanford University; and he did postdoctoral work in biochemical neurology at the Columbia College of Physicians and Surgeons. He was a chemistry professor for 25 years at the University of California, EEEE, and is now an emeritus professor of chemistry. He has worked with and taught students about scientific instruments throughout his professional career.
FFFF was diagnosed with Type 1 diabetes in 2007 at the age of 63(!!). She has been using a Paradigm 522 pump since June, 2008. FFFF eats a very controlled diet, with ~90-105 g carbs per day. She uses ~20 Units of Novolog insulin per day.
4. Our observations
Approximately the first of November, 2008, FFFF began to have increased problems with high (sometimes >300 mg/dL) and erratic blood glucose (BG) readings. We eventually learned that the situation could be corrected by a new infusion set insertion, and thought perhaps the cannula had been inserted into a muscle (??) from which the insulin was not as well absorbed.
However, one time we noticed that there were large (>2 mm diameter) bubbles in the old pump reservoir when the infusion set was changed. We reasoned that if such a bubble worked its way into the tubing and into FFFF's body that a significant shortfall of insulin delivery could result.
We are scrupulous in eliminating bubbles during the infusion set insertion. We inspect both the reservoir and the tubing using a magnifying lens and (currently) a flashlight. We see absolutely no bubbles when the insertion set process is complete - the bubbles develop afterward, and the bubbles of significant size develop at the O-R interface.
Typically, a bubble will first be noticed by us when it's ~0.5-1 mm in diameter. Over the next day or so, additional bubbles develop, some bubbles stay the same size, and others become larger while they remain at the O-R interface, eventually becoming as large as 2-3 mm in diameter. When such a bubble works its way into the tubing, we currently "prime the bubble out" (see Section 10).
When we first began notice bubbles in the reservoir at the O-R interface, we saw only a few - or even no - bubbles at each infusion set change. However, as time has passed, the frequency of bubble formation has increased, so that we now see 5-15 bubbles at the O-R interface every time the infusion set is changed.
5. Our Interactions with Medtronic
(Dates are approximate, and some conversations are summarized or their substance mixed together - Medtronic has recordings of the conversations and can transcribe them, but we doubt that is important.)
First, a compliment: we talked mostly with Christine on the HelpLine. She was wonderful to work with: interested, empathetic, and obviously trying to do the best she could for us with the information available to her. Can you clone her to handle all HelpLine calls?
We called the Medtronic HelpLine, and the following was recommended:
a. Keep the insulin vial that is currently being used at room temperature rather than in the refrigerator. Note: as best we can tell, this instruction is NOT in the User's Guide for the pump.
b. Try de-gassing the insulin vial by repeatedly withdrawing air and creating a partial vacuum before filling the reservoir. We tried this procedure, found that it did not prevent subsequent formation of bubbles at the O-R interface, and it actually made it difficult to fill the reservoir because of the vacuum. In fact, this procedure tends to cause air bubbles to come into the reservoir around the o-ring. Aha! Air can leak around the o-rings. Note: as best we can tell, this instruction is NOT in the User's Guide for the pump.
c. Move the reservoir plunger up and down several times before filling the reservoir with insulin to better distribute o-ring lubricant. Note: as best we can tell, this instruction is NOT in the User's Guide for the pump.
d. Try different lot numbers for the reservoirs, and different batches of insulin. So far we're used at least 3 different lots numbers for reservoirs and 2 different insulin batches.
Following any or all of these recommendations had no effect. Air bubbles continued to develop at the O-R interface, to grow, and sometimes to break loose and enter the tubing. The longest air pocket we've seen in the tubing so far was about 6" (!!!) long, corresponding to a shortfall of more than 2 Units of insulin that would not have been delivered.
We were told that Medtronic believes that development of air bubbles in the reservoir is due to faulty patient technique, not to design or manufacturing flaws. We went over our insertion technique with the HelpLine, and they were unable to identify any deficiencies.
After several other conversations, a Medtronic contract nurse was assigned to come observe our technique on Tuesday, December 16. Also, Christine told us that replacing the pump was a possibility if the problems became more severe.
On Saturday, December 13, we did a regular infusion set replacement. We had seen one large bubble (~2 mm diameter) at the O-R interface that had remained unchanged for several days. However, one can see only a fraction of the circumference of the reservoir through the window in the pump. When we removed the reservoir from the pump, we observed 8 bubbles at the O-R interface, ranging in diameter between approximately 1 mm and 2.5 mm. Any of these could have broken loose and entered the tubing without us being aware of that happening unless we inspected the tubing.
We called the Medtronic HelpLine, talked to Shari (Christine was not working on that day), and explained our concerns. Shari said that, since a nurse was scheduled to come on the following Tuesday, there was no possibility of replacing the pump before that time, and that her decision to that effect reflected Medtronic policy. She further said that Medtronic believes all cases they have seen of bubbles developing in the reservoir are due to operator/patient error. Period.
The nurse on contract to Medtronic came on Tuesday, December 16 and observed our technique for insertion of an infusion set. Another compliment: the nurse (Sarah Johnson) was helpful, empathetic, and clearly cared about the patients she deals with. Ms. Johnson observed our technique for infusion set insertion, and found no defects in our procedure.
6. Experiences of others
We thought that we had a unique problem, or that something was wrong with our technique until we did a simple internet search and found that others have had similar problems. See, for example,
http://www.diabetesforums.com/forum/pumping-insulin/15923-air-bubbles-reservoir-tubing.html
Here's a posting:
"The pump is a minimed 722. The past two sets, when I was under 40 units remaining, I discovered air bubbles both in the reservoir and in the tube. When I filled the reservoir I was careful both times to make sure no bubbles were present so I don't know how they got introduced into the system. These bubbles caused my sugar to go >300 with corrections not working since I was not really getting the correct dosage (I started a new set immediately when I noticed this)."
(Searching in www.diabetesforum.com for, say, "pump bubbles" gives many discussions about problems with bubbles in the reservoir and tubing.)
http://www.diabetesdaily.com/forum/insulin-pumps/20871-air-bubble
Here's a posting:
"I got up this morning, checked my BG and it read 160. It should have been lower, but oh well. I programmed my pump for a 40carb breakfast and ate. After 1.5 hours I wanted to head to the gym so I checked my BG again—300! %$#$%! I started a correction bolus and while it was delivering I noticed a slight color change in a section of my infusion set tube. I looked closed and saw that it was moving! Turns out, it was an air bubble about 2 inches long. Have any of you had this problem? I have been having trouble with my morning boluses and now I’m beginning to wonder if I’m getting air bubbles in my line while I sleep."
http://tudiabetes.com/forum/topic/show?id=583967%3ATopic%3A109266
Here's a posting:
"I recently started using the Minimed Paradigm pump. I love using the pump it has made everything so much more convenient but I am having problems with bubbles. I have made sure the insulin is room temperature and when I fill the cartridge I make sure there are no bubbles. However, a couple of times I have had soaring blood sugars and after trying to work out what else it could be have changed my cartridge and found it full of bubbles. Has anyone else had this problem and what can I do?thanks"
There's even a youtube video on getting rid of bubbles!
http://www.youtube.com/watch?v=OwbelFCNGz4
The general rule of the internet is that for every such posting there are many, many more people with a similar problem.
In our opinion, it is difficult to believe that Medtronic is not aware of such forum discussions and problems people have with bubbles in the reservoir. One presumes that Medtronic monitors postings to such forums. Medtronic's policy to attribute air bubbles exclusively to operator/patient error ("Blame the patient") is, at best, irresponsible.
7. Our experiments
a. We filled normal disposable syringes with insulin, both with room-temperature insulin and with insulin taken directly from the refrigerator, inserted the needles into a rubber stopper to prevent leakage, and observed the syringes for several days. Did any bubbles develop? Of course not - neither in the room-temperature insulin nor in the straight-from-the-frig insulin. Medtronic's recommendation to begin with the insulin at room temperature to prevent formation of large bubbles appears to be irrelevant. Note that normal syringe plungers have a rubber-like end on the piston, not an o-ring seal. More on that later.
b. We filled a reservoir with insulin straight from the frig, did a "prime" with the reservoir plunger (that is, we didn't put the reservoir in the pump), clamped off the tubing, and cut off the end of the tubing to remove the insertion needle. We then allowed this reservoir to sit around for several days, and put it in a shirt pocket for several hours several times to allow it to warm to close to body temperature. Here is what we found.
There were several small, insignificant (see Chemistry 1 exercise in Section 8 below) bubbles (0.2 to 0.6 mm in diameter) at apparently-random places inside the reservoir. NO bubbles developed at the O-R interface. There might have been even fewer and smaller bubbles if we had used room-temperature insulin. It doesn't matter; the bubbles we did observe were insignificant.
This observation also answered one of our technical questions about whether bubbles might be more likely to develop spontaneously at the O-R interface than at random places on the plastic reservoir body because of gas nucleation dynamics. They didn't.
This observation also confirms that our technique for filling the reservoir without bubbles works. The bubbles aren't introduced by operator/patient error - Medtronic can't "Blame the patient." The bubbles at the O-R interface occur after the bubble-free reservoir is in the pump, the pump is operating, and the insulin is going into the patient.
After additional discussion with Christine, we were sent a new pump. This gave us the opportunity for additional experiments.
c. The problem is NOT with the pump! After FFFF began using the new pump, we filled the reservoir for the old pump, and did everything except the insertion of the Quick-set cannula into her body. We allowed the pump to run according to its usual settings, again, with the insulin flowing into the air instead of into her body. NO significant bubbles formed no matter what we did - e.g., fixed primes with the end of the tubing open to the air or clamped off. We believe that no problems will be found with the pump when it is tested.
d. We used the same infusion set lot numbers and the same insulin vial that was used for experiment c. above with the new pump, with the cannula inserted into her body. Bubbles formed in the reservoir for the new pump, just as with the old pump, with the bubbles of significant size forming at the O-R interface.
e. We thought that perhaps the pump and reservoir could get warm enough under the bedcovers at night to cause bubbles to form. The temperature of the surface of the pump can be as high as 95°F (it's under the bedcovers and close to the body). Parenthetically, we have no idea if a temperature of 95°F causes insulin to degrade too rapidly; we haven't observed any problems in the typical three days a reservoir is used. We slept with the pump that was being replaced (again, pumping insulin into the air instead of into her body), and there was no significant formation of bubbles.
To summarize these three experiments:
i. The bubbles apparently do not form because of a malfunction of the pump. Bubbles of significant size do not form unless the pump is operating to pump insulin into her body. Apparently, bubbles form because of an interaction involving some combination of the pump, the reservoir, the Quick-set cannula system, and the patient's body.
ii. Our technique for filling the reservoir and removing bubbles appears to be flawless, since bubbles do not form in a reservoir that isn't pumping insulin into her body but otherwise is operating normally.
iii. It's hard to imagine that anything we do with the Quick-set insertion could affect bubble formation.
iv. We have no idea what mechanism is responsible for the bubble formation.
8. Chemistry 1 exercises
a. 1 Unit of insulin corresponds to 0.01 mL of insulin. Exercise: Show that the number of Units of insulin in a bubble of diameter X mm is about 0.05 X3.
So if the diameter of a bubble is less than 1 mm, the number of units in a bubble is less than 0.05 - insignificant.
On the other hand, since the number of Units goes as the cube of the bubble diameter, a bubble 2 mm in diameter corresponds to 0.4 Units - if such a bubble goes into a patient, that represents a significant insulin defect. And a bubble 3 mm in diameter corresponds to about 1.35 Units of insulin. An insulin dose that's missing that much insulin because air rather than insulin gets into the patient could cause large changes in BG readings.
b. The diameter of the tubing corresponds to 1 Unit of insulin per about 2½-3" of tubing. Exercise: Show that a 1/4" air pocket in the tubing is insignificant, but an air pocket 1/2" or more is a concern.
9. Our conclusions
A joke of sorts: Somebody suggested that perhaps the people who designed o-rings for NASA in the 1980s are now designing o-rings for Medtronic.
We have discussed this problem with two friends. One is an instrumentation expert who repairs and rebuilds scientific instruments. His reaction: "It's most likely a problem with a mismatch between the o-ring and the reservoir. The o-ring seal simply isn't tight enough."
The other is a NASA scientist, who noted that o-rings are normally used for permanent seals between two stationary surfaces, not to form a seal between moving parts. Using o-rings to form a seal between moving surfaces is a dicey proposition. Again, note that the interface between the piston and the reservoir body on a normal disposable syringe is a rubberized end on the piston, not o-rings; and there's no air leakage into a syringe as a syringe piston moves forward.
We continue to be mystified about the development of bubbles at the O-R interface, especially about the following two points:
a. Why isn't bubble formation reported by many more patients? Perhaps the reason bubbles are not, according to Medtronic, regularly reported as a problem is because many patients use far more insulin than FFFF (she uses ~20 Units per day). A loss of a Unit or so every once in a while because of an air pocket in the tubing wouldn't be as significant to someone who uses much more insulin. We don't know the answer to this question.
b. What's the reason for bubbles to develop at the O-R interface and grow in size? Since the piston presumably moves only forward and is essentially under "forward" pressure, it seems unreasonable for bubbles to develop in the reservoir that's under positive pressure. Development of bubbles would, of course, be expected if the piston sometimes moved backward rather than always forward.
We simply do not know the reason for the origin and growth over time of the bubbles at the O-R interface. Perhaps the design of the system is faulty. Perhaps temperature cycling or pressure cycling of the o-rings and piston is causing the piston to move back and forth enough to cause air leakage. Perhaps pressure variations in the body (systolic/diastolic??) are transmitted to the o-ring seal system? We can only make wild guesses.
An obvious solution is to abandon the o-ring-based plunger and move to a plunger with a rubberized end, as in a regular disposable syringe. Presumably Medtronic considered such a possibility when the pump was designed, but a tighter-fitting plunger might make it more difficult to sense occlusions.
10. Draft URGENT WARNING statement
If Medtronic cannot find an error in our procedure for inserting an infusion set or cannot fix the problem of air bubbles, we believe that a statement along the lines of the draft below should be sent to every patient who uses a Paradigm pump and to every physician that prescribes them. We believe that bubbles that develop in the pump reservoir pose a significant danger to patients.
Notice: The URGENT WARNING statement below is Copyright 2008 by DDDD and FFFF HHHH.
Any private individual may reproduce or transmit this statement to any person of his/her choice.
However, any reproduction of any portion of this statement or any of the recommendations in this statement in any form (plagiarized, adapted, modified, etc.) by any corporation or company, or any representative of any corporation or company, will be regarded as a severe infringement of copyright laws and will subject the violator to criminal penalties and civil damages, unless they receive express permission from DDDD and FFFF HHHH.
The purpose of this notification is to prevent a company (e.g., Medtronic) from issuing a weasel-word warning in which they essentially continue to "Blame the patient" for formation of air bubbles in the pump reservoir. We will, of course, be more than happy to give permission to Medtronic or other companies to issue warning statements that show where responsibility lies as well as give vital information to patients and their doctors.
Caveat: The statement which follows is a draft statement. We are not physicians; nor are we experts on insulin pump design and problems. This statement is based on our experience on how to minimize the danger caused by bubbles which develop in insulin pump reservoirs. Patients should consult their physicians about their treatment regimen and how to operate the insulin pump.
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URGENT WARNING
It has been found that air bubbles of significant size can develop in insulin pump reservoirs, mainly at the interface between the o-ring and the body of the reservoir. Such bubbles can develop no matter how scrupulously the patient removes bubbles during the process for insertion of the infusion set.
These bubbles can result in air pockets moving into the infusion-set tubing and into the patient's body - air rather than insulin goes into the patient's body. This replacement of insulin by air can cause high and even dangerous blood glucose readings (>300 mg/dL).
At this time, no one knows the reason for the origin of these bubbles. While the problem is being studied, the following procedure is recommended to avoid air pockets moving into the patient's body.
1. At least four times a day (e.g., before each meal and at bedtime), inspect
(a) the pump reservoir for bubbles through its window on one side of the pump and
(b) the tubing for air pockets in the tubing.
If a bubble in the reservoir disappears, it is likely to show up later as an air pocket in the tubing.
Inspection is assisted if a magnifying glass is used, and if a flashlight is also used (holding the flashlight under the tubing helps to identify air pockets in the tubing). Roughly speaking, when insulin is in a section of the tubing, the entire cross-section of the tubing looks similar to frosted glass. When there is an air pocket, one can see what looks like an empty space in the middle of the cross-section of the tubing. Look carefully; air pockets in the tubing are difficult to see.
2. If a significant air pocket (length >1/4" or >6 mm) is seen, disconnect the "Quick-set" (or equivalent) from your body. See your health-care provider if you do not know how to do this.
3. "Prime the bubble out." That is, deliver a "Fixed prime" sufficient to cause the air pocket to move completely through and out of the tubing. One Unit of insulin corresponds to 2½" of tubing. For example, if the air pocket is 6" from the end of the tubing, you could deliver a "Fixed prime" of 5 Units and be reasonably sure the air pocket would be removed from the tubing. Consult with your health-care provider before the first time you do this.
VERY, VERY IMPORTANT: After you have delivered the "Fixed prime" as described above, deliver another "Fixed prime" that corresponds to the "Fixed prime" you normally deliver when you insert the infusion set (typically 0.3 Unit). The reason for this additional "Fixed prime" is to make sure you have returned the pump to its original settings. If you do not, the next time you do a "Fixed prime," you could deliver, say, 5 Units, which could be disastrous.
4. If you see such air bubbles at the interface between the o-ring and the reservoir body or air pockets in the tubing, call 1-800-XXX-XXXX [phone number to be added] to report the problem.
Also important: An air bubble in the reservoir less than about 1/16" (or 1 mm) in diameter is not significant, nor is an air pocket in the tubing shorter than about 1/4" (or 6 mm). Small bubbles in the reservoir and small bubbles in the tubing are completely normal and pose no danger. Do not be concerned about these, and don't bother calling to report these.
If you have followed this inspection procedure through several infusion set changes and have seen no significant bubbles in the reservoir, you can probably do these inspections less frequently than four times per day. But if you have any otherwise-inexplicable high blood glucose readings, you should suspect that air bubbles in the reservoir are the cause.
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Thank you for your attention to this letter.
Sincerely,
DDDD J. HHHH, Ph.D. FFFF L. HHHH
May 28, 2010 - More perspectives on insulin pump bubble problems
March 14, 2009 - Do insulin pump bubbles cause medical emergencies?
March 13, 2009 - Insulin pump bubbles continued
January 13, 2009 - Insulin pump bubbles
Friday, May 28, 2010
More perspectives on insulin pump bubble problems.
1. From what I've read on forums about bubbles in insulin pump tubing, and from what I've heard from other pump-users with bubble troubles, physicians almost always say, "This is new to me. I haven't seen this problem before." A friend who's a relatively young physician said that physicians are almost obligated to say this. If they acknowledge they are aware there's a problem, then it can held to be their responsibility if something goes wrong and one of their patients is admitted to the hospital because of sky-high BG due to bubbles.
Also, it would be a LOT of work for a physician to go up against Medtronic, and few physicians would want to use their time fighting against large corporations. They want to follow their protocols; and they are less likely to be sued if they follow the conventional wisdom. And if nothing in the FDA approval literature says to watch out for bubbles, then bubbles don't exist.
2. From Medtronic's perspective, they're certainly going to deny there's a problem and blame bubbles on "patient error." Since we live in southern California, we offered to go to the Medtronic facility in the San Fernando Valley and discuss the situation with them. They said that would be fine with them, as long as we signed a nondisclosure agreement saying we would never ever divulge ANYTHING they told us, with the penalty for disclosure being major liability in a lawsuit. Needless to say, we haven't taken them up on their offer.
In a way, a bubble in the tubing is a perfect poison. There's no trace of it left after it goes into the body; and if someone ends up in the emergency room with high BG readings it's impossible to prove a bubble was the problem. The only way to prove bubbles cause problems is for a patient to deliberately allow a long (6" or longer) bubble to go through the tubing and into their body, take a video as the bubble moves, and then go to the emergency room with a BG higher than 500. In the emergency room, the patient, of course, would be likely to be referred to the psych ward for doing that to themselves.
"What about the FDA?" you ask. There is a system for reporting problems with medical devices and drugs. Here's the link:
https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
Lots of luck getting a meaningful response. The FDA is unlikely to get involved unless there's been real harm to a patient and, again, it's almost impossible to prove the harm was due to a bubble.
For now, all I know that people with bubble problems can do is to check their tubing 2-3 times a day, and prime out the bubbles before they reach the body. See my other postings for lots of detail.
Saturday, March 14, 2009
Do insulin pump bubbles cause medical emergencies?
We recently got an e-mail from another person who's had problems with insulin pump bubbles.
If bubbles in the pump cause a few strange high blood glucose readings (say in the 200s or low 300s), that's probably not a big deal - almost every insulin-dependent diabetic has these from time to time when they mis-guess the number of carbs in a meal. But a number of 420 and a trip to the emergency room is a big deal, both health-wise and bottom-line-wise for patients and insurance companies, and - we can hope - for federal regulators who are supposed to watch out for problems with medical devices.
Here is what the person said (personal identifying information has been removed):
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Hello,
I just found your information about air bubbles in the Medtronic Insulin pump.
It was as you had read my mind!!
I was put on the pump in December ....
My problems were first found Jan.... I noticed a long air bubble in my tubing as I was about to bolus for a meal.
No telling how many more had gone through without my knowledge!
I even had to go to the E.R. one night with a 420 reading!
While there...I found a 2" air gap in my tubing line!
Since that time...it's been a pain, checking...purging....wasting insulin.
I called and talked to the help line also... actually talked to Christine...and yes she's a jewel!! Very nice helpful person.
Switched infusions, reservoirs with Medtronics...changed insulins...finally got a new pump. Still have bubbles...none as large as before...but yes, I do still have to check constantly to see if there is a air gap in the line. I actually have had 5" bubbles!!
Talk about a big problem if I hadn't checked!!
I'm sending your blog and your posting in the forum to the Diabetes Clinic that I go to...Just to let them know it's NOT just me!
One thing that was offered to me was to fill the reservoir ahead of time...let it sit (hoping the fizzie bubbles will all come to the top) before changing my sets. I'm like you...I think that bubbles come in from the o-ring. When I tap the bottle to remove bubbles...there seem to be more coming from the o-ring, and that doesn't make sense.
I hope to hear back from you, hopefully with information on this problem!!
Friday, March 13, 2009
Insulin pump bubbles continued
Since we sent the letter to Medtronic about the bubble problems, we got a letter back from Shirajul Karim, the "Sr. Dr. of Quality" dated January 16, 2009. Here's the important sentence in his letter:
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"While our experience with our products is not consistent with the observations and testing described in your letter, we will carefully and fully investigate your claims."
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And here's the letter we sent back to him. He hasn't replied, nor is there any evidence they made any attempt to "carefully and fully investigate" our findings. Nada.
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Shirajul Karim, Senior Director of Quality
Medtronic Minimed
18000 Devonshire Street
Northridge, CA 91325
Dear Mr. Karim:
Thank you for your letter of January 16 acknowledging our letter of December 24. Let us first note that, despite the bubble problems we (and others) have reported, we are pleased with our experience with the pump. The fine control over insulin delivery rates it offers is a vast improvement over that available with injections.
It is surprising that ongoing problems with bubbles and air pockets have not previously been brought to the attention of Medtronic Minimed Quality Control. The issue certainly has been addressed to your HelpLine personnel by other people in addition to us. Here’s a link that illustrates the point:
http://tudiabetes.com/group/minimedparadigmusers/forum/topics/583967:Topic:147765
And here’s another link where “Dave” gives a sure-fire method to avoid bubbles – we have followed all of his suggestions, with no difference in bubble formation:
http://tudiabetes.com/forum/topics/583967:Topic:256260
As our December 24 letter shows, the bubbles develop only after and only if the insertion set is in FFFF’s body, take several days to grow, and their growth appears to involve leakage of air at the o-ring-reservoir interface (at least, that’s where the large bubbles are found before they break loose and enter the tubing).
It obviously would be simple for Medtronic Minimed to survey 100 or so patients who use the pump to see if they have bubbles in their reservoirs (e.g., by asking callers to the HelpLine to look at their pump reservoirs). However, the failure of Medtronic Minimed to have a substantive response to our letter in more than a month, the content of your letter, and the protocols used by the HelpLine personnel indicate that Medtronic Minimed has already made up its mind that the only problem is “patient error.” Presumably the solution will be for an outside agency (e.g., the FDA) or health plan (e.g., Kaiser Permanente) to investigate bubble formation in reservoirs and the possible risks to their patients. As we noted previously, the largest bubble we’ve “primed out” was equivalent to more than 2 Units of insulin that would not have been delivered, enough to increase my BG reading by about 150 mg/dL.
In the meantime, we would be interested to know if Medtronic Minimed comes up with any ideas for how the bubbles develop. As you may know, our first pump has been tested and found to be working flawlessly – as we said in our letter we expected to be the case. Please let us know if we can give you any additional information.
Tuesday, January 13, 2009
Insulin Pump Bubbles
Note: Our names, address, etc. have been replaced by capital letters to preserve privacy. Feel free to send us an e-mail at wands65mail-blogspot@yahoo.com, and we’ll be glad to reply.
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XXX YYYY Street
San Diego, CA 92ZZZ
Phone: AAA-BBB-CCCC
E-mail:
wands65mail-QQQ@yahoo.com
December 24, 2008
Medtronic:
Quality Control, Customer Support Center
Christopher J. O'Connell, Senior Vice President and President, Diabetes
The purpose of this letter is to ensure that you are aware of what we believe to be a significant safety issue with the Paradigm pump system involving formation of air bubbles in the pump reservoir and propagation of such bubbles through the tubing into patients' bodies. Such bubbles have the potential of resulting in serious or even catastrophic health effects on patients. This letter is - unfortunately - quite long, because we have tried to document it as completely as possible with the resources available to us, and because of the potential seriousness of the problem.
Contents of this letter:
1. Disclaimer/qualification
2. Executive summary
3. Our background
4. Our observations
5. Our interactions with the Medtronic HelpLine
6. Experiences of others
7. Our experiments
8. Chemistry 1 exercises
9. Our conclusions
10. Draft URGENT WARNING statement
1. Disclaimer/qualification
The information and conclusions in this letter represent our good-faith attempt to understand and describe the problems with our Paradigm 522 pump. We do not have access to the laboratory equipment that would be required to determine the precise origin of the problem. Every statement of fact in this letter should be understood to include an initial clause, "In our experience/judgment,...."
2. Executive summary
Air bubbles can develop at the interface between the o-ring and the reservoir body of the Paradigm pump (we'll term this the O-R interface). These bubbles can develop no matter how carefully the patient removes air bubbles during the infusion set insertion procedure; they appear to develop because of leakage of air into the reservoir around the o-ring as the pump operates. These bubbles can grow to become of significant size (>2 mm diameter), break loose, migrate to the top of the pump, into the tubing, and into the body of the patient, causing a significant (>1 Unit) loss of insulin flow into the patient's body. In turn, this loss can cause high blood sugar readings (>300 mg/dL); such spurious readings could also cause patients and their physicians to increase insulin doses with the possibility of resulting severe hypoglycemia and its severe consequences.
On or - preferably - before January 12, 2009, we ask Medtronic:
a. To convince us that our analysis of the situation is faulty. We regard ourselves as reasonable people, and would be delighted to be shown that something we (and other Paradigm pump users - see Section 6 below) are doing is wrong.
or
b. To resolve the problem and take the steps required to ensure that air bubbles resulting from action of the pump do not pose a significant danger to patients using the pump.
or
c. To contact every user of a Paradigm pump and every physician who prescribes Paradigm pumps to inform them of the possibility of development of such bubbles, the danger these bubbles present, ways of checking for bubbles in the reservoir and, and ways of checking for and removing air pockets in the infusion tubing. A draft of such an URGENT WARNING statement is given as Section 10 of this letter.
or
d. To take other appropriate action to address this problem.
3. Our Background
DDDD's bachelor's degree is in chemistry from the California Institute of Technology; his Ph.D. is also in chemistry from Stanford University; and he did postdoctoral work in biochemical neurology at the Columbia College of Physicians and Surgeons. He was a chemistry professor for 25 years at the University of California, EEEE, and is now an emeritus professor of chemistry. He has worked with and taught students about scientific instruments throughout his professional career.
FFFF was diagnosed with Type 1 diabetes in 2007 at the age of 63(!!). She has been using a Paradigm 522 pump since June, 2008. FFFF eats a very controlled diet, with ~90-105 g carbs per day. She uses ~20 Units of Novolog insulin per day.
4. Our observations
Approximately the first of November, 2008, FFFF began to have increased problems with high (sometimes >300 mg/dL) and erratic blood glucose (BG) readings. We eventually learned that the situation could be corrected by a new infusion set insertion, and thought perhaps the cannula had been inserted into a muscle (??) from which the insulin was not as well absorbed.
However, one time we noticed that there were large (>2 mm diameter) bubbles in the old pump reservoir when the infusion set was changed. We reasoned that if such a bubble worked its way into the tubing and into FFFF's body that a significant shortfall of insulin delivery could result.
We are scrupulous in eliminating bubbles during the infusion set insertion. We inspect both the reservoir and the tubing using a magnifying lens and (currently) a flashlight. We see absolutely no bubbles when the insertion set process is complete - the bubbles develop afterward, and the bubbles of significant size develop at the O-R interface.
Typically, a bubble will first be noticed by us when it's ~0.5-1 mm in diameter. Over the next day or so, additional bubbles develop, some bubbles stay the same size, and others become larger while they remain at the O-R interface, eventually becoming as large as 2-3 mm in diameter. When such a bubble works its way into the tubing, we currently "prime the bubble out" (see Section 10).
When we first began notice bubbles in the reservoir at the O-R interface, we saw only a few - or even no - bubbles at each infusion set change. However, as time has passed, the frequency of bubble formation has increased, so that we now see 5-15 bubbles at the O-R interface every time the infusion set is changed.
5. Our Interactions with Medtronic
(Dates are approximate, and some conversations are summarized or their substance mixed together - Medtronic has recordings of the conversations and can transcribe them, but we doubt that is important.)
First, a compliment: we talked mostly with Christine on the HelpLine. She was wonderful to work with: interested, empathetic, and obviously trying to do the best she could for us with the information available to her. Can you clone her to handle all HelpLine calls?
We called the Medtronic HelpLine, and the following was recommended:
a. Keep the insulin vial that is currently being used at room temperature rather than in the refrigerator. Note: as best we can tell, this instruction is NOT in the User's Guide for the pump.
b. Try de-gassing the insulin vial by repeatedly withdrawing air and creating a partial vacuum before filling the reservoir. We tried this procedure, found that it did not prevent subsequent formation of bubbles at the O-R interface, and it actually made it difficult to fill the reservoir because of the vacuum. In fact, this procedure tends to cause air bubbles to come into the reservoir around the o-ring. Aha! Air can leak around the o-rings. Note: as best we can tell, this instruction is NOT in the User's Guide for the pump.
c. Move the reservoir plunger up and down several times before filling the reservoir with insulin to better distribute o-ring lubricant. Note: as best we can tell, this instruction is NOT in the User's Guide for the pump.
d. Try different lot numbers for the reservoirs, and different batches of insulin. So far we're used at least 3 different lots numbers for reservoirs and 2 different insulin batches.
Following any or all of these recommendations had no effect. Air bubbles continued to develop at the O-R interface, to grow, and sometimes to break loose and enter the tubing. The longest air pocket we've seen in the tubing so far was about 6" (!!!) long, corresponding to a shortfall of more than 2 Units of insulin that would not have been delivered.
We were told that Medtronic believes that development of air bubbles in the reservoir is due to faulty patient technique, not to design or manufacturing flaws. We went over our insertion technique with the HelpLine, and they were unable to identify any deficiencies.
After several other conversations, a Medtronic contract nurse was assigned to come observe our technique on Tuesday, December 16. Also, Christine told us that replacing the pump was a possibility if the problems became more severe.
On Saturday, December 13, we did a regular infusion set replacement. We had seen one large bubble (~2 mm diameter) at the O-R interface that had remained unchanged for several days. However, one can see only a fraction of the circumference of the reservoir through the window in the pump. When we removed the reservoir from the pump, we observed 8 bubbles at the O-R interface, ranging in diameter between approximately 1 mm and 2.5 mm. Any of these could have broken loose and entered the tubing without us being aware of that happening unless we inspected the tubing.
We called the Medtronic HelpLine, talked to Shari (Christine was not working on that day), and explained our concerns. Shari said that, since a nurse was scheduled to come on the following Tuesday, there was no possibility of replacing the pump before that time, and that her decision to that effect reflected Medtronic policy. She further said that Medtronic believes all cases they have seen of bubbles developing in the reservoir are due to operator/patient error. Period.
The nurse on contract to Medtronic came on Tuesday, December 16 and observed our technique for insertion of an infusion set. Another compliment: the nurse (Sarah Johnson) was helpful, empathetic, and clearly cared about the patients she deals with. Ms. Johnson observed our technique for infusion set insertion, and found no defects in our procedure.
6. Experiences of others
We thought that we had a unique problem, or that something was wrong with our technique until we did a simple internet search and found that others have had similar problems. See, for example,
http://www.diabetesforums.com/forum/pumping-insulin/15923-air-bubbles-reservoir-tubing.html
Here's a posting:
"The pump is a minimed 722. The past two sets, when I was under 40 units remaining, I discovered air bubbles both in the reservoir and in the tube. When I filled the reservoir I was careful both times to make sure no bubbles were present so I don't know how they got introduced into the system. These bubbles caused my sugar to go >300 with corrections not working since I was not really getting the correct dosage (I started a new set immediately when I noticed this)."
(Searching in www.diabetesforum.com for, say, "pump bubbles" gives many discussions about problems with bubbles in the reservoir and tubing.)
http://www.diabetesdaily.com/forum/insulin-pumps/20871-air-bubble
Here's a posting:
"I got up this morning, checked my BG and it read 160. It should have been lower, but oh well. I programmed my pump for a 40carb breakfast and ate. After 1.5 hours I wanted to head to the gym so I checked my BG again—300! %$#$%! I started a correction bolus and while it was delivering I noticed a slight color change in a section of my infusion set tube. I looked closed and saw that it was moving! Turns out, it was an air bubble about 2 inches long. Have any of you had this problem? I have been having trouble with my morning boluses and now I’m beginning to wonder if I’m getting air bubbles in my line while I sleep."
http://tudiabetes.com/forum/topic/show?id=583967%3ATopic%3A109266
Here's a posting:
"I recently started using the Minimed Paradigm pump. I love using the pump it has made everything so much more convenient but I am having problems with bubbles. I have made sure the insulin is room temperature and when I fill the cartridge I make sure there are no bubbles. However, a couple of times I have had soaring blood sugars and after trying to work out what else it could be have changed my cartridge and found it full of bubbles. Has anyone else had this problem and what can I do?thanks"
There's even a youtube video on getting rid of bubbles!
http://www.youtube.com/watch?v=OwbelFCNGz4
The general rule of the internet is that for every such posting there are many, many more people with a similar problem.
In our opinion, it is difficult to believe that Medtronic is not aware of such forum discussions and problems people have with bubbles in the reservoir. One presumes that Medtronic monitors postings to such forums. Medtronic's policy to attribute air bubbles exclusively to operator/patient error ("Blame the patient") is, at best, irresponsible.
7. Our experiments
a. We filled normal disposable syringes with insulin, both with room-temperature insulin and with insulin taken directly from the refrigerator, inserted the needles into a rubber stopper to prevent leakage, and observed the syringes for several days. Did any bubbles develop? Of course not - neither in the room-temperature insulin nor in the straight-from-the-frig insulin. Medtronic's recommendation to begin with the insulin at room temperature to prevent formation of large bubbles appears to be irrelevant. Note that normal syringe plungers have a rubber-like end on the piston, not an o-ring seal. More on that later.
b. We filled a reservoir with insulin straight from the frig, did a "prime" with the reservoir plunger (that is, we didn't put the reservoir in the pump), clamped off the tubing, and cut off the end of the tubing to remove the insertion needle. We then allowed this reservoir to sit around for several days, and put it in a shirt pocket for several hours several times to allow it to warm to close to body temperature. Here is what we found.
There were several small, insignificant (see Chemistry 1 exercise in Section 8 below) bubbles (0.2 to 0.6 mm in diameter) at apparently-random places inside the reservoir. NO bubbles developed at the O-R interface. There might have been even fewer and smaller bubbles if we had used room-temperature insulin. It doesn't matter; the bubbles we did observe were insignificant.
This observation also answered one of our technical questions about whether bubbles might be more likely to develop spontaneously at the O-R interface than at random places on the plastic reservoir body because of gas nucleation dynamics. They didn't.
This observation also confirms that our technique for filling the reservoir without bubbles works. The bubbles aren't introduced by operator/patient error - Medtronic can't "Blame the patient." The bubbles at the O-R interface occur after the bubble-free reservoir is in the pump, the pump is operating, and the insulin is going into the patient.
After additional discussion with Christine, we were sent a new pump. This gave us the opportunity for additional experiments.
c. The problem is NOT with the pump! After FFFF began using the new pump, we filled the reservoir for the old pump, and did everything except the insertion of the Quick-set cannula into her body. We allowed the pump to run according to its usual settings, again, with the insulin flowing into the air instead of into her body. NO significant bubbles formed no matter what we did - e.g., fixed primes with the end of the tubing open to the air or clamped off. We believe that no problems will be found with the pump when it is tested.
d. We used the same infusion set lot numbers and the same insulin vial that was used for experiment c. above with the new pump, with the cannula inserted into her body. Bubbles formed in the reservoir for the new pump, just as with the old pump, with the bubbles of significant size forming at the O-R interface.
e. We thought that perhaps the pump and reservoir could get warm enough under the bedcovers at night to cause bubbles to form. The temperature of the surface of the pump can be as high as 95°F (it's under the bedcovers and close to the body). Parenthetically, we have no idea if a temperature of 95°F causes insulin to degrade too rapidly; we haven't observed any problems in the typical three days a reservoir is used. We slept with the pump that was being replaced (again, pumping insulin into the air instead of into her body), and there was no significant formation of bubbles.
To summarize these three experiments:
i. The bubbles apparently do not form because of a malfunction of the pump. Bubbles of significant size do not form unless the pump is operating to pump insulin into her body. Apparently, bubbles form because of an interaction involving some combination of the pump, the reservoir, the Quick-set cannula system, and the patient's body.
ii. Our technique for filling the reservoir and removing bubbles appears to be flawless, since bubbles do not form in a reservoir that isn't pumping insulin into her body but otherwise is operating normally.
iii. It's hard to imagine that anything we do with the Quick-set insertion could affect bubble formation.
iv. We have no idea what mechanism is responsible for the bubble formation.
8. Chemistry 1 exercises
a. 1 Unit of insulin corresponds to 0.01 mL of insulin. Exercise: Show that the number of Units of insulin in a bubble of diameter X mm is about 0.05 X3.
So if the diameter of a bubble is less than 1 mm, the number of units in a bubble is less than 0.05 - insignificant.
On the other hand, since the number of Units goes as the cube of the bubble diameter, a bubble 2 mm in diameter corresponds to 0.4 Units - if such a bubble goes into a patient, that represents a significant insulin defect. And a bubble 3 mm in diameter corresponds to about 1.35 Units of insulin. An insulin dose that's missing that much insulin because air rather than insulin gets into the patient could cause large changes in BG readings.
b. The diameter of the tubing corresponds to 1 Unit of insulin per about 2½-3" of tubing. Exercise: Show that a 1/4" air pocket in the tubing is insignificant, but an air pocket 1/2" or more is a concern.
9. Our conclusions
A joke of sorts: Somebody suggested that perhaps the people who designed o-rings for NASA in the 1980s are now designing o-rings for Medtronic.
We have discussed this problem with two friends. One is an instrumentation expert who repairs and rebuilds scientific instruments. His reaction: "It's most likely a problem with a mismatch between the o-ring and the reservoir. The o-ring seal simply isn't tight enough."
The other is a NASA scientist, who noted that o-rings are normally used for permanent seals between two stationary surfaces, not to form a seal between moving parts. Using o-rings to form a seal between moving surfaces is a dicey proposition. Again, note that the interface between the piston and the reservoir body on a normal disposable syringe is a rubberized end on the piston, not o-rings; and there's no air leakage into a syringe as a syringe piston moves forward.
We continue to be mystified about the development of bubbles at the O-R interface, especially about the following two points:
a. Why isn't bubble formation reported by many more patients? Perhaps the reason bubbles are not, according to Medtronic, regularly reported as a problem is because many patients use far more insulin than FFFF (she uses ~20 Units per day). A loss of a Unit or so every once in a while because of an air pocket in the tubing wouldn't be as significant to someone who uses much more insulin. We don't know the answer to this question.
b. What's the reason for bubbles to develop at the O-R interface and grow in size? Since the piston presumably moves only forward and is essentially under "forward" pressure, it seems unreasonable for bubbles to develop in the reservoir that's under positive pressure. Development of bubbles would, of course, be expected if the piston sometimes moved backward rather than always forward.
We simply do not know the reason for the origin and growth over time of the bubbles at the O-R interface. Perhaps the design of the system is faulty. Perhaps temperature cycling or pressure cycling of the o-rings and piston is causing the piston to move back and forth enough to cause air leakage. Perhaps pressure variations in the body (systolic/diastolic??) are transmitted to the o-ring seal system? We can only make wild guesses.
An obvious solution is to abandon the o-ring-based plunger and move to a plunger with a rubberized end, as in a regular disposable syringe. Presumably Medtronic considered such a possibility when the pump was designed, but a tighter-fitting plunger might make it more difficult to sense occlusions.
10. Draft URGENT WARNING statement
If Medtronic cannot find an error in our procedure for inserting an infusion set or cannot fix the problem of air bubbles, we believe that a statement along the lines of the draft below should be sent to every patient who uses a Paradigm pump and to every physician that prescribes them. We believe that bubbles that develop in the pump reservoir pose a significant danger to patients.
Notice: The URGENT WARNING statement below is Copyright 2008 by DDDD and FFFF HHHH.
Any private individual may reproduce or transmit this statement to any person of his/her choice.
However, any reproduction of any portion of this statement or any of the recommendations in this statement in any form (plagiarized, adapted, modified, etc.) by any corporation or company, or any representative of any corporation or company, will be regarded as a severe infringement of copyright laws and will subject the violator to criminal penalties and civil damages, unless they receive express permission from DDDD and FFFF HHHH.
The purpose of this notification is to prevent a company (e.g., Medtronic) from issuing a weasel-word warning in which they essentially continue to "Blame the patient" for formation of air bubbles in the pump reservoir. We will, of course, be more than happy to give permission to Medtronic or other companies to issue warning statements that show where responsibility lies as well as give vital information to patients and their doctors.
Caveat: The statement which follows is a draft statement. We are not physicians; nor are we experts on insulin pump design and problems. This statement is based on our experience on how to minimize the danger caused by bubbles which develop in insulin pump reservoirs. Patients should consult their physicians about their treatment regimen and how to operate the insulin pump.
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URGENT WARNING
It has been found that air bubbles of significant size can develop in insulin pump reservoirs, mainly at the interface between the o-ring and the body of the reservoir. Such bubbles can develop no matter how scrupulously the patient removes bubbles during the process for insertion of the infusion set.
These bubbles can result in air pockets moving into the infusion-set tubing and into the patient's body - air rather than insulin goes into the patient's body. This replacement of insulin by air can cause high and even dangerous blood glucose readings (>300 mg/dL).
At this time, no one knows the reason for the origin of these bubbles. While the problem is being studied, the following procedure is recommended to avoid air pockets moving into the patient's body.
1. At least four times a day (e.g., before each meal and at bedtime), inspect
(a) the pump reservoir for bubbles through its window on one side of the pump and
(b) the tubing for air pockets in the tubing.
If a bubble in the reservoir disappears, it is likely to show up later as an air pocket in the tubing.
Inspection is assisted if a magnifying glass is used, and if a flashlight is also used (holding the flashlight under the tubing helps to identify air pockets in the tubing). Roughly speaking, when insulin is in a section of the tubing, the entire cross-section of the tubing looks similar to frosted glass. When there is an air pocket, one can see what looks like an empty space in the middle of the cross-section of the tubing. Look carefully; air pockets in the tubing are difficult to see.
2. If a significant air pocket (length >1/4" or >6 mm) is seen, disconnect the "Quick-set" (or equivalent) from your body. See your health-care provider if you do not know how to do this.
3. "Prime the bubble out." That is, deliver a "Fixed prime" sufficient to cause the air pocket to move completely through and out of the tubing. One Unit of insulin corresponds to 2½" of tubing. For example, if the air pocket is 6" from the end of the tubing, you could deliver a "Fixed prime" of 5 Units and be reasonably sure the air pocket would be removed from the tubing. Consult with your health-care provider before the first time you do this.
VERY, VERY IMPORTANT: After you have delivered the "Fixed prime" as described above, deliver another "Fixed prime" that corresponds to the "Fixed prime" you normally deliver when you insert the infusion set (typically 0.3 Unit). The reason for this additional "Fixed prime" is to make sure you have returned the pump to its original settings. If you do not, the next time you do a "Fixed prime," you could deliver, say, 5 Units, which could be disastrous.
4. If you see such air bubbles at the interface between the o-ring and the reservoir body or air pockets in the tubing, call 1-800-XXX-XXXX [phone number to be added] to report the problem.
Also important: An air bubble in the reservoir less than about 1/16" (or 1 mm) in diameter is not significant, nor is an air pocket in the tubing shorter than about 1/4" (or 6 mm). Small bubbles in the reservoir and small bubbles in the tubing are completely normal and pose no danger. Do not be concerned about these, and don't bother calling to report these.
If you have followed this inspection procedure through several infusion set changes and have seen no significant bubbles in the reservoir, you can probably do these inspections less frequently than four times per day. But if you have any otherwise-inexplicable high blood glucose readings, you should suspect that air bubbles in the reservoir are the cause.
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Thank you for your attention to this letter.
Sincerely,
DDDD J. HHHH, Ph.D. FFFF L. HHHH
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