celebrex and coumadin

Wallcur Practi bags – not quite finished

Thursday, January 15th, 2015

Posted by Dr Dan Carter
FDA MedWatch came out with this safety alert yesterday. Thanks to Dr Tim Murbach for sending this to me.

Simulated IV Solutions from Wallcur: CDER Statement- FDA’s Investigation into Patients being Injected

[Posted 1/14/2015]

AUDIENCE: Risk Manager, Health Professionals, Pharmacy

ISSUE: FDA and the Centers for Disease Control and Prevention (CDC) are continuing to investigate multiple instances of Wallcur’s simulated intravenous (IV) saline products being administered to patients. These products are not sterile and should not be injected in humans or animals. So far, more than 40 patients have received infusions of the simulated saline products, and there have been many adverse events associated with these incidents including fever, chills, tremors and headache. Some patients were hospitalized, and there is one death associated with the use of these products; it is not known if this death is directly related to the use of the product.

BACKGROUND: Wallcur’s simulated IV saline solution, Practi-0.9% sodium chloride solution, was shipped to medical clinics, surgical centers, and urgent care facilities in numerous states. While Sodium Chloride 0.9% Injection (IV normal saline) has been in tight supply, FDA has been working with manufacturers to increase supply. In addition, FDA is not objecting to the temporary distribution of additional IV normal saline from alternate sources Fresenius Kabi USA, Baxter Healthcare Corp., and B. Braun Medical Inc. Currently, there is supply available from several manufacturers as posted on FDA’s website.

RECOMMENDATION:
Healthcare Providers

Clinicians and office staff are encouraged to take steps to ensure IV solution simulation products are removed from office inventory to eliminate the possible injection of Wallcur simulated products into patients.

Visually inspect all current IV saline solution bags. Ensure none of the bags are labeled “Wallcur,” “Practi-products,” “For clinical simulation,” or “Not for use in human or animal patients.”
If you have products labeled with any of these words, or you suspect you may have received other products intended for training purposes, separate simulation products from existing inventory and contact your distributor for directions on how to return these products.
If you have received Wallcur Practi-products by mistake, please contact the distributor, or Wallcur, LLC of San Diego for return instructions.
Consider reviewing your office procedures and make sure there are procedures in place to visually inspect all future shipments of normal saline products to ensure they are for clinical use.

If you suspect that any Wallcur training IV products may have been administered to a patient, whether or not the incident has resulted in an adverse event:

Evaluate all potentially exposed patients with new, or ongoing symptoms;
Use appropriate treatment;
Report suspected cases to the state health department; and
Report any adverse events following use of these products to FDA’s MedWatch program online or at 1-800-332-1088.

Patients

Patients who believe they received an injection of Wallcur simulated IV solution should contact their health care provider.
Patients who received simulated IV saline almost immediately upon injection experienced fever, chills, muscle aches, headaches, and some required hospitalization. In most reported cases, these signs and symptoms were immediately recognized and patients received appropriate medical attention.
You may also file a report of the incident through FDA’s MedWatch program, and assist the FDA with this ongoing investigation.
If you know you will be receiving normal saline, ask your doctor or nurse to visually inspect the bag, and ensure they are using normal saline for human use. Ensure the bag is not labeled or printed with any of the following: “Wallcur,” “Practi-products,” “For clinical simulation” or “Not for use in human or animal patients.” If the saline bag contains any of these words, ask your health care provider NOT to administer the solution.

Wholesalers, Distributors, Suppliers

Inspect your inventory and ensure you are not distributing simulated products as clinical use products.
It is incumbent upon wholesalers, distributors, and suppliers to clearly and accurately label and distribute their products to prevent medical product mix-ups from occurring.
If you suspect you may have distributed this product to clients by mistake, immediately attempt to recall the products and warn clients of the potential risks. You should also contact Wallcur, your distributor and file a report to FDA’s MedWatch program.

[1/14/2015 – CDER Statement – FDA]
[1/10/2015- MedWatch Safety Alert]

Wallcur Practi bag update – final?

Wednesday, January 7th, 2015

Posted by Dr Dan Carter

I relayed this information a couple of days ago via our IV chat line, and am including it in our blog to have a more permanent “information location” until this matter is concluded. See our two previous blog posts to get the full story.

There are no warnings on the bags stating “Not for human or animal injection. For simulation practice only.” This bolded quote is taken from Wallcur’s order page for the “Practi-50 mL I.V. Solution Bag (for simulation). The bags themselves do not have this warning.

In another email to me on January 5, our very helpful Florida physician further elucidated what is known:
[Quote]
The FDA, CDC and State Health Departments (I think in all 50 states) are involved in notifying Health Care Facilities and Hospitals. I think they have been in the process of doing so since at least 12/30/2014. However, another problem is that they do not seem to have a complete list of providers or facilities that may have received this fluid.

The Florida Department of Health from what I understand has 10-20 facilities on their list that have received this product, however they did not have my facility on their list, so at this point it may be an open question in regards to how many facilities have this product but are not on their State Health Department’s lists to contact. Hence, even more important to disseminate this information, especially as it appears many of these erroneous supplies may have been shipped in between the Holidays and during a time of limited need.

We ordered Normal Saline (not distilled water) and received this product from a distributor called Moore Medical which is a subsidiary of McKesson Medical Supplies.
[Unquote]

It would appear that some suppliers, in this case Moore Medical, sent out the Wallcur Practi bags INSTEAD of Normal Saline for Injection. Do not, under any circumstances, use Wallcur Practi-0.9% Sodium Chloride for human or animal infusions. If you have received these bags as a substitution or mis-order from your supplier, contact your supplier with the above information. Contacting your state health department would also be helpful.

Update to Wallcur Practi IV Solution Bags – Urgent

Saturday, January 3rd, 2015

Posted by Dr Dan Carter

The FDA needs to take immediate and emergency action in the case of Wallcur Practi IV Solution Bags that are supposed to be used only for IV start practice. I (Dr Carter) received an email from a physician in Florida who has personal experience with the Practi Bags in question. I have anonymized his email…

[Quote]
Dr Carter,

I am an Internal Medicine Physician in [City], Florida and I read your blog in reference to the Wallcur IV solutions being administered to patients.

The problem with this particular “practice” solution is that it has found its way in to the normal supply chains for hospitals and clinics and reading the label three times over as you suggest, is not going to change the fact that all it says is Normal Saline, however when administered to a patient it causes severe illness, shock and inflammation and in some cases death. As a provider who ordered this fluid I can ensure you that this is a matter of erroneous and false labeling for an extremely dangerous product floating around in the IV supply chain. Nowhere on this bag does it say “Do not use in humans or animals,” “For practice use only,” or any such thing, in short, it needs to be removed quickly from the shelves of clinics and hospitals and then there needs to be some serious new regulations in regards to the labeling of “practice” IV solutions.

[Name] MD
[City], FL

Thank you very much doctor, for your personal experience and for replying to the blog post. I went to Wallcur’s website in order to see if they had a photo of the Practi Bag in question – they did and a link to the photo is located below:

Practi 0.9% Sodium Chloride

The only possible clue I can see in the photo that this is not a normal IV bag for human/animal use is the word “Practi” preceding the expiration date. Nowhere on the front of the back does it state “Do not use in humans or animals,” “For practice use only.” This is a very dangerous issue and must be addressed quickly.

When you go to Wallcur’s order page for Practi-50 mL I.V. Solution Bag (for simulation) it does state “Not for human or animal injection. For simulation practice only.” The major problem is – the nurse or physician getting this bag from stock only sees “Practi 0.9% Sodium Chloride.” Many health care professionals could take the “Practi” as being the brand name. The warning to not infuse in humans/animals MUST be on the bag.

The physician’s email did not state that either Wallcur or the FDA had contacted health care facilities that may have ordered the bags, so I will assume at this point that they have not. If I later find that they have, I will immediately correct this information.

Importance of correct label reading hits the news

Wednesday, December 31st, 2014

Posted by Dr Dan Carter

Physicians who administer or supervise the administration of intravenous drugs and solutions know how critical it is to read the labels of these products before giving them to patients. IV set-up protocols normally require redundant reading of labels at least three times prior to administration, in order to insure that the correct drug/solution is given. A recent posting from the FDA illustrates this important point once again:

[Quote] IV Solutions from Wallcur of San Diego: CDER Statement – FDA Warns Health Care Professionals Not to Inject Patients
AUDIENCE: Risk Manager, Health Professionals, Pharmacy

ISSUE: The U.S. Food and Drug Administration is alerting health care professionals not to use Wallcur, LLC, simulated intravenous (IV) products in human or animal patients. These products are for training purposes only. There have been reports of serious adverse events associated with the use of certain of these products – i.e., Practi IV Solution Bags.

BACKGROUND: FDA has become aware that some Wallcur training IV products have been distributed to health care facilities and administered to patients. FDA will continue to investigate and monitor this issue. The agency is also working with the Centers for Disease Control and Prevention to inform health care professionals and state health departments.

RECOMMENDATION: Before administering IV solutions to patients, health care providers should carefully check the labels to ensure that the products are not training products, such as Practi IV Solution Bags marketed by Wallcur. Wallcur’s training products, which may bear the words “for clinical simulation,” are not to be administered to patients.

If you suspect that any Wallcur training IV products may have been administered to a patient, whether or not the incident has resulted in an adverse event, please report the incident to FDA’s MedWatch Adverse Event Reporting program by:

Complete and submit the report online at www.fda.gov/medwatch/report.htm
Download and complete the form, then submit it via fax at 1-800-FDA-0178.

[12/30/2014 – CDER Statement- FDA]
[End quote]

Protect your patients – read IV drug and solution labels with a hypercritical eye.

The TACT Trial – Presentation by PI* Dr Gervasio Lamas & the movie Unleaded

Sunday, September 1st, 2013

Posted by Dr Dan Carter

I was fortunate to be present at a talk given by Dr Gervasio Lamas, the principle investigator *(PI) for the TACT (Trial to Assess Chelation Therapy) trial; he gave a good overview of the trial design and results at the ACAM spring meeting, held May 31-June 2, 2013. Dr. Lamas is the Chairman of Medicine at Mount Sinai Medical Center and Chief of the Columbia University Division of Cardiology at Mount Sinai Medical Center. This LINK http://www.miami-cardiology.com/dr-gervasio-lamas.php  gives you access to his complete bio. I got the sense that he was very courageous to serve as study chair for the TACT trail, as he has received his fair share of grief from mainstream medicine due to what has been termed the “inconvenient evidence” that chelation therapy is both safe and effective. Ref: [http://www.forbes.com/sites/harlankrumholz/2013/03/27/chelation-therapy-what-to-do-with-inconvenient-evidence/]

Dr Lamas is not the only person being denigrated for his willingness to be associated with the trial, the editors of  JAMA, the Journal of the American Medical Association have received a lot of criticism for publishing the trial results in the journal.  A lot of the criticism bordering on fanaticism is being leveled at the trial, where only specific dogma that is aligned with certain factions’ beliefs are acceptable; this is a real problem in today’s medical community. Before the trial, the critics argued that EDTA chelation was unproven as no trials had been done, and now that the first RPCCT (Randomized placebo controlled clinical trial) has been completed, it is still not sufficient. Some physicians within mainstream medicine go frankly apoplectic if they are presented with ideas/trial results that are outside their narrow paradigms, to wit: David Gorski, a surgical oncologist, in an assault on TACT, JAMA, and Arlen Krumholz (of Forbes Magazine), writes “that JAMA is every bit as guilty as The Lancet was in 1998 when it published Andrew Wakefield’s anti-vaccine nonsense…. If published at all, TACT should have been published in some crappy, bottom-feeding journal, because that’s all that it deserves.” So it would seem that vitriolic reactive fervor trumps scientific reason whenever it’s not in alignment with one’s world view.

Dr Lamas went over the Study Design in some detail. Ref. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243954/#!po=31.2500 One important element he mentioned, and that is brought out in the movie Unleaded as well (see review below), is that the patients enrolled in the trial were maintained on ALL conventional treatments that were prescribed before the trial started. So no (conventional) treatments were taken away; the only change was the addition of the TACT protocol of either active treatment or placebo. One argument that critics have mentioned, is that the trial was not ethical – if they actually read the full text article, they will find that this trial was one of the most ethical performed in recent history. The trial was halted for a period of time, while concerns about the informed consent were addressed and corrected – this was the area where complaints about unethical  conduct were broached, and once this was corrected, the trial was continued.  The results speak for themselves (see previous blog post, July 13, 2013). Trials administered by pharmaceutical companies are much more likely to see problems with ethical conduct, especially when those trials take place in developing countries. Ref. [http://somo.nl/publications-en/Publication_2534]

Sidebar

Bias in medicine is common, and old ideas die hard. It seems as though critics delight in negativity toward any subject they do not agree with. Even when bias or outright fabrications are found in clinical research, it is difficult to correct the misconceptions that have already been accepted as truth. This article points out many of the issues faced by medicine: http://www.theatlantic.com/magazine/archive/2010/11/lies-damned-lies-and-medical-science/308269/ . Another article speaks to some of the questionable teaching methods that shape the thinking of most future physicians: [Haizlip J, et al. Perspective: the negativity bias, medical education, and the cuture of academic medicine: why culture change is hard. Acad Med. 2012 Sep;87(9):1205-9. PMID 22836850]

 

 

Unleaded – The movie [Movie website & trailer: http://www.elemental-films.com/]

Note: My review is 3 months after watching the movie, so the memories may be selective and incomplete; my apologies, as the movie is well worth watching. Unleaded is presented as interviews with two of the clinical investigators for the trial, Roy Heilbron, MD and Angelique Hart, MD, as well as interviews with several trial participants. From the Elemental Films website: “On Nov. 4, 2012, Dr. Gervasio Lamas, the director of the TACT study presented the stunning results of the 10 year study that involved over 130 clinics and 1,700 patients at the annual American Heart Association’s (AHA) 2012 Scientific Sessions. Later that day, Elliott Antman, MD, Director of the AHA, announced that there was not enough information to recommend Chelation Therapy until more studies were done, although TACT was designed to be the definitive 10 year study. Normally published the same day as the presentations, the NIH TACT statistical results were not published by the Journal of the American Medicine Association for an unprecedented 5 months, until March 27, 2013, at which time they were either not reported or obscured within any articles by mainstream media.” Dr Heilbron brought out several rather amazing observations about the AHA meeting…

  • The significance of the TACT trial results were much more striking than the degree of significance of most drug trials, and yet this was dismissed by critics
  • The dismissive statement by Dr Antman was carried by all of the major news media, but the results of the trial were not
  • The JAMA publication of statistical results was delayed, because the editors were justifiably worried about political (the politics of medicine) fallout

The trial participant interviews were very interesting as well, and since the trial results did show significance, they cannot be dismissed as anecdote.

 

The TACT Trial

Friday, July 12th, 2013

Posted by Dr Dan Carter

The Trial to Assess Chelation Therapy (TACT) was published in the Journal of the American Medical Association (JAMA) on March 27, 2013. The objective was to determine if an EDTA-based chelation treatment reduces cardiovascular events. The trail was a double-blind, placebo-controlled, 2 × 2 factorial randomized design, enrolling 1708 patients aged 50 years or older who had experienced a myocardial infarction (MI) at least 6 weeks prior and had serum creatinine levels of 2.0 mg/dL or less. Participants were recruited in the US and Canada. Enrollment commenced in September 2003 and follow-up continued until October 2011 (median, 55 months). Two hundred eighty nine patients (17% of total; 115 in the EDTA group and 174 in the placebo group) withdrew consent during the trial.

A synopsis of the JAMA abstract: http://jama.jamanetwork.com/article.aspx?articleid=1672238

Patients were randomized to receive 40 infusions of 500 mL chelation solution (3 g disodium EDTA, 7 g ascorbate, B vitamins, electrolytes, procaine, and heparin) (n=839) vs. placebo (n=869) and an oral vitamin-mineral regimen vs. an oral placebo. Weekly infusions were administered for 30 weeks, followed by 10 infusions 2-8 weeks apart. Sixteen percent discontinued infusions (n=38 [16%] in the chelation group and n=41 [15%] in the placebo group) due to adverse events.

The pre-defined primary end point was a composite of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. This report describes the treatment comparison of EDTA chelation vs. placebo. The significance threshold required for final analysis was P = .036.

Qualifying previous MIs occurred a median of 4.6 years prior to enrollment. Median age was 65 years, 18% female, 9% nonwhite, and 31% diabetic. The primary end point occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.99]; P = .035). There was no effect on total mortality (chelation: 87 deaths [10%]; placebo, 93 deaths [11%]; HR, 0.93 [95% CI, 0.70-1.25]; P = .64). The effect of EDTA chelation on the components of the primary end point other than death was of similar magnitude as its overall effect (MI: chelation, 6%; placebo, 8%; HR, 0.77 [95% CI, 0.54-1.11]; stroke: chelation, 1.2%; placebo, 1.5%; HR, 0.77 [95% CI, 0.34-1.76]; coronary revascularization: chelation, 15%; placebo, 18%; HR, 0.81 [95% CI, 0.64-1.02]; hospitalization for angina: chelation, 1.6%; placebo, 2.1%; HR, 0.72 [95% CI, 0.35-1.47]). Sensitivity analyses examining the effect of patient dropout and treatment adherence did not alter the results.

Among stable patients with a history of MI, use of an intravenous chelation regimen with disodium EDTA, compared with placebo, modestly reduced the risk of adverse cardiovascular outcomes, many of which were revascularization procedures. These results provide evidence to guide further research but are not sufficient to support the routine use of chelation therapy for treatment of patients who have had an MI.

End synopsis

 

The Mayo Clinic website gave better detail of the infusion solutions:

“For the TACT study, the protocol specified 40 infusions of at least three hours each — 30 weekly infusions followed by 10 maintenance infusions two to eight weeks apart. For the active chelation arm, a 10-component chelation solution was selected to match most closely the standard solution used by chelation practitioners. The solution contained up to 3 g of disodium EDTA, 7 g of ascorbic acid, 2 g of magnesium chloride, 100 mg of procaine hydrochloride, 2,500 U of unfractionated heparin, 2 mEq of potassium chloride, 840 mg of sodium bicarbonate, 250 mg of pantothenic acid, 100 mg of thiamine, 100 mg of pyridoxine, 100 mg of procaine, and sterile water to make up 500 mL of solution. The placebo solution consisted of 500 mL of normal saline and 1.2 percent dextrose.”

The following is a summary from http://my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/@scon/documents/downloadable/ucm_446204.pdf and gives an easier visualization of the benefits of EDTA chelation therapy.

  • Composite endpoints: 18% reduction EDTA vs. placebo (p=0.035)
  • Subgroups
  • Diabetes: 39% reduction in composite endpoints vs. placebo (p=0.002)
  • Non-diabetics: 0.04 % reduction vs. placebo (p=0.725)
  • Anterior MI: 37% reduction vs. placebo (p=0.03)

The trial results were discussed extensively at the 2012 American Heart Association (AHA) annual meeting in Los Angeles, where the TACT results were presented. The usual answer in randomized placebo-controlled clinical trials — that the active treatment (chelation) is better than placebo — was not believed by most in attendance to be the cause. Three possible reasons were offered, including:

1. Difference in low-density lipoprotein cholesterol levels at baseline. Subjects randomly assigned to active chelation therapy had a lower baseline LDL than the placebo group (87 mg/dL vs. 90 mg/dL). This level of difference would be expected to result in 3 percent less major cardiovascular events after five years, very close to the 3.5 percent actually seen in the study.

  • Comment Dr Carter – Cholesterol Treatment Trialists (CTT) meta-analysis in 2005, which reported the results for more than 90,000 subjects treated with statins in primary and secondary prevention trials. It found that for every 1 mmol/L (39 mg/dL) reduction in LDL-C, there was a 21% relative reduction in risk for major vascular events. This paper implies that the relationship between LDL-C and CV events is not linear, and in fact a 3 mg LDL-C decrease would lead to 1.6% less risk. This paper later suggests that there is a Log-linear relationship between LDL-C levels and relative risk for CHD.

Ref: Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R, Cholesterol Treatment Trialists’ (CTT) Collaborators. Lancet. 2005 Oct 8; 366(9493):1267-78. http://www.ncbi.nlm.nih.gov/pubmed/?term=16214597. PMID: 16214597

2. Placebo glucose infusion in the diabetic group. Since most of the benefit of chelation was seen in diabetic patients, some postulated that the placebo glucose infusion may have led to increased adverse outcomes in this subset.

  • Comment Dr Carter – It would be very difficult to design a trial using different placebos for different subgroups; analysis would be too confounded. The placebo infusion used in the TACT trial contained 1.2% dextrose (glucose) in 500 mL solution, this amounts to 6000 mg or 6 grams dextrose once a week, administered over 3 hours, during the most active portion of the trial. To put this in context, a 12 ounce Coca Cola contains 39 grams of sugar (19.5 grams each of dextrose and fructose), 8 ounces Minute Maid orange juice contains 21 grams sugar (mainly fructose), one slice white bread contains 50 grams carbohydrate (blood sugar spike will not be as rapid as glucose, but amount of carbohydrate is significant). It would seem that 6 grams glucose consumed over 3 hours would not spike blood glucose significantly.
  • This from http://care.diabetesjournals.org/content/30/suppl_1/S48.full, Nutrition Recommendations and Interventions for Diabetes: A position statement of the American Diabetes Association, illustrates the point that 6 grams carbohydrate once a week is not significant; they are searching for implausible reasons!

    Low-carbohydrate diets, restricting total carbohydrate to <130 g/day, are not recommended in the management of diabetes.

3. Incomplete data due to dropout. Seventeen percent of patients withdrew consent (3 percent-5 percent is common in large trials), which prohibited investigators from ascertaining any endpoint data, thereby potentially missing some major cardiovascular events.

  • Comment Dr Carter – The TACT trial demanded major time commitments from enrollees. Travel time, administration of the infusion (3 hours plus time to start and disconnect IV, perform vital sign exams), and blood test collections. The majority of drug trials involve administration of an oral drug; something that can be done at the patient’s home or work, so it is not too surprising that 17% withdrew from the trial.

The AHA appears to be applying weak arguments to contest the significance of the outcomes.

Next post: A talk by the TACT Trial principle investigator and a review of the movie “Unleaded.”

Position statement regarding use of single and multiple dose parenteral drug vials

Friday, February 8th, 2013

Posted by Dr Dan Carter

Position statement from International IV Nutrient Therapy for Professionals

http://ivnutritionaltherapy.com/

Our position as IV educators is that we recommend full compliance with CDC and USP 797 guidelines; Local or profession based practices that deviate from these standards (i.e. “that is not how I was trained” or “no one I know follows those” …) are not acceptable defense when an adverse event occurs and never supersede USP and CDC guidelines.

Below are the guidelines as prepared by the agencies mentioned. After each section comment regarding the guideline germane to IV Nutrient Therapy practices is made.

Single Dose Vials

Source: http://www.cdc.gov/injectionsafety/PDF/CDC-SDV-Position05022012.pdf
CDC’s Position: Protect Patients Against Preventable Harm from Improper Use of Single-dose/Single-use Vials
These medications typically lack antimicrobial preservatives and can become contaminated and serve as a source of infection when they are used inappropriately.
The Centers for Disease Control and Prevention’s guidelines call for medications labeled as “single dose” or “single use” to be used for only one patient. This practice protects patients from life-threatening infections that occur when medications get contaminated from unsafe use. Concerns have been raised about whether these guidelines and related policies contribute to drug shortages and increased medical costs to healthcare providers. CDC recognizes the problem of drug shortages; however, such shortages are a result of manufacturing, shipping, and other issues unrelated to the above guidelines (http://www.fda.gov/DrugShortageReport ).

CDC ’s priority is protecting patients from harm. CDC routinely investigates and is apprised of infectious disease outbreaks involving single-dose/single-use vials being used for multiple patients. These outbreaks cause extensive harm to patients, and they are associated with significant healthcare and legal expenses. Therefore, CDC continues to strongly support its current policies regarding single-dose/single-use vials. It is imperative that drug shortages and drug waste concerns are dealt with appropriately and do not lead to unsafe medical practices that impose increased disease risk on patients.

In times of critical need, contents from unopened single–dose ⁄ single–use vials can be repackaged for multiple patients. However, this should only be performed by qualified healthcare personnel in accordance with standards in United States Pharmacopeia General Chapter ‹797› Pharmaceutical Compounding — Sterile Preparations. Following the USP standards is imperative, as medication contamination and patient harm can occur when repackaging (e.g. splitting doses) is not done properly.*

*Clarification for IV nutrient therapy practice
Medical practices using preservative free drugs/nutrients are advised to ask their compounding pharmacy to repackage commonly used products in unit dose vials in order to reduce waste, in accordance with the above standards.

Multiple Dose Vials

Source: http://www.cdc.gov/injectionsafety/providers/provider_faqs_multivials.html
A multi-dose vial is a vial of liquid medication intended for parenteral administration (injection or infusion) that contains more than one dose of medication. Multi-dose vials are labeled as such by the manufacturer and typically contain an antimicrobial preservative to help prevent the growth of bacteria. The preservative has no effect on viruses and does not protect against contamination when healthcare personnel fail to follow safe injection practices.

Multi-dose vials should be dedicated to a single patient whenever possible.**
If multi-dose vials must be used for more than one patient, they should not be kept or accessed in the immediate patient treatment area. This is to prevent inadvertent contamination of the vial through direct or indirect contact with potentially contaminated surfaces or equipment that could then lead to infections in subsequent patients. If a multi-dose vial enters the immediate patient treatment area, it should be dedicated to that patient only and discarded after use. Examples of the immediate patient treatment area include patient rooms or bays, and operating rooms.
 
Medication vials should always be discarded whenever sterility is compromised or questionable.
In addition, the United States Pharmacopeia (USP) General Chapter 797 recommends the following for multi-dose vials of sterile pharmaceuticals:
• If a multi-dose has been opened or accessed (e.g., needle-punctured) the vial should be dated and discarded within 28 days unless the manufacturer specifies a different (shorter or longer) date for that opened vial.
• If a multi-dose vial has not been opened or accessed (e.g., needle-punctured), it should be discarded according to the manufacturer’s expiration date.
 
**Clarification for IV nutrient therapy practice
A multi-dose vial kept exclusively in the clean IV preparation area may be used for multiple (different) patient infusions. Vial adaptor spikes with needless access are recommended as a further measure of preventing contamination. If a vial is used in a patient treatment area the above standards must be followed.

Stability and Sterility of Parenteral Solutions – A Short Case

Monday, March 5th, 2012

Posted by Dr Dan Carter

A prospective patient called my office and inquired about intramuscular vitamin B12 injections. She stated that she had undergone an ileectomy and required B12 injections since that time. She had heard from a friend that methylcobalamin may be more beneficial for her than the “regular kind” she was using. After a rather pointed question and answer period I found that her “regular kind” was cyanocobalamin, 30 mL vial, 1000 micrograms per mL and she was injecting 2 mL once a month. She stated that the vial was stored at room temperature and was used until gone, which typically took over a year. She admitted that effectiveness seemed less when the vial was getting empty, but said that no infection occurred at injection sites.

There were two important issues the patient brought up: how long can a multi-dose vial maintain sterility after multiple entries, and what happens to drug potency after prolonged exposure to variable room temperature and air? Sterility is the main safety issue and prevention of iatrogenic infection is a primary objective of any physician.

The current practice guideline for multiple dose vials is that they may be used for one month after first entry. Storage recommendations depend on what type of drug is involved. Cyanocobalamin is usually stored at room temperature, whereas other B-vitamins, methyl and hydroxo cobalamins, and minerals are normally stored in the refrigerator after first entry.

What is the best procedure to prevent infection when using parenteral drugs? Every check on the following list needs to be followed with every use of the drug. Note: this list covers correct drug use only. It does not address administration.

  1. Confirm the drug name
  2. Check the expiration date
  3. Check for clarity if the drug is a solution. Suspensions may be cloudy. Examine for precipitates
  4. Clean the top of the vial well with IPA or other approved antiseptic
  5. Enter the vial with a new sterile needle attached to an unused sterile syringe, introduce a volume of air that matches the drug volume and withdraw the drug
  6. Store appropriately

Another method to decrease contamination of frequently used vials is to use a needleless vial adapter. Vial adapters are inserted into a vial once, and stay in place until the vial is empty or it outdates. Air does not need to be pushed into the vial because the adapter has a filter that allows air entry as the drug is withdrawn. Here are two different brands:

This one is a Codan C350N vial adapter with Swan Lock needless entry.

 

 

 

 

 

And here is a B Braun Ultrasite adapter

 

 

 

 

 

I ordered her some methylcoblamin and instructed her in its proper and safe application.

Ascorbate Oxidation Protocols: What should be added to the mix?

Friday, October 28th, 2011

About the time IVNTP started offering our 2-day Advanced Topics seminars (2009), research was coming out of the University of Kansas Medical Center, via Dr. Jeanne Drisko, director of the program of Integrative Medicine, indicating that ascorbic acid protocols in use at the time may not be the best for supporting cancer patients. When cancer patients are given high dose IV vitamin C (HDIVC), the objective is to cause oxidative effects at the tissue/tumor level by using the vitamin C to generate hydrogen peroxide.[i] IVNTP concurred with this research and incorporated the concept that future HDIVC protocols should contain only ascorbic acid and balancing amounts of specific minerals, e.g. calcium, magnesium and potassium. At this time we did not differentiate any advantages to specific mineral salts, such as calcium gluconate vs. calcium chloride.

In the recent Volume 16 online supplement of Alternative Medicine Review in an article titled ” The Concern about B-Vitamins Affecting the Oxidant Effect of Intravenous Ascorbate for Malignancy,” Lamson, et al. presented a summary of in vitro research that indicates B-vitamins interfere with the generation of hydrogen peroxide.[ii] From the paper summary:

“… the anti-tumor effect of high concentration ascorbate performs its function in the interstitial fluid beyond the blood circulation. Ascorbate is converted to superoxide, which proceeds to the hydrogen peroxide believed to be the active agent. Most of the B-vitamins can quench superoxide under some conditions and would presumably lower the concentration of hydrogen peroxide available for anti-malignant action. Therefore a caution seems appropriate against the inclusion of B-vitamins with intravenous ascorbate aimed at tumor cell cytotoxicity. However, this general recommendation based on chemistry cited above needs the support of in vivo studies for certainty.”

Within the last few years the Bastyr University Integrative Oncology Research Center has been performing clinical research on HDIVC, among other projects. Dr Paul Anderson, IVNTP instructor, headed up an analysis regarding the effect of HDIVC infusions on electrolyte balance. The upshot being that we now recommend using only the chloride salts of calcium, magnesium and potassium to balance the large sodium load resulting from the ascorbic acid. Stock ascorbic acid has a pH of about 2, which is much too acid for an IV infusion; the manufacturer buffers the ascorbic acid with sodium hydroxide and sodium bicarbonate, resulting in sodium ascorbate at a pH tolerable for intravenous applications but at the cost of a high sodium concentration. Chloride mineral salts balance the sodium load resulting in less blood electrolyte imbalance. Our two day Clinical Applications and Advanced Topics of IV Nutrient Therapies seminar covers the safe and effective use of HDIVC and dosing of the chloride mineral salts in detail.


[i] Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues. Proceedings of the National Academy of Sciences2005.102;38:13604-13609

[ii] Lamson DW, Ochi M, Hetherington J. The Concern about B-Vitamins Affecting the Oxidant Effect of Intravenous Ascorbate for Malignancy. Alternative Medicine Review. Volume 16 supplement (ePub), 2011.

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Arteries Anyone?

Wednesday, August 10th, 2011

We call it intravenous (IV) therapy for a reason, because we only access veins for infusions. This is done for several reasons: veins are more superficial and easier to access; there are more frequent and serious complications when arteries are cannulated; infusion into arteries requires a pump and competent nursing care; IV infusions are the standard of care for drug and nutrient administration.

Arterial cannulation is a commonly performed procedure in the management of patients who are critically ill. Approximately 8 million arterial catheters are placed yearly in the United States.(1)An indwelling arterial catheter allows for continuous blood pressure (BP) monitoring, frequent blood sampling, and arterial blood gas measurement.

When a physician performs IV infusions on a regular basis for many years they may encounter situations that they have not previously experienced. I had been treating an 84 year old male for cancer with high dose vitamin C for five months; infusions have been done once or twice weekly during this time and venous access had never been a problem. The patient came in for another infusion, which turned out to be an interesting experience for me. After preliminaries such as vital signs were completed, I attempted to insert a catheter (24 gauge by 3/4 inch) into the Dorsal Metacarpal Vein of his right hand; this was unsuccessful. I then attempted the Accessory Cephalic Vein in his right forearm; no go. I asked the patient about his hydration status and he claimed that he had been drinking extra water prior to his appointment as instructed. I then moved to the left antecubital fossa and palpated a vein I have accessed before; there was no palpable pulsation. I inserted the catheter but did not see returns in the flash chamber; the catheter was redirected with similar results. I then advanced the catheter to the hub and noted blood returns, at which point I removed the tourniquet, occluded the catheter tip with digital pressure, removed the stylet, and attached the IV tubing. As soon as digital pressure was removed from the catheter tip, bright red blood entered the IV tubing in a pulsatile  manner.

I thought but did not verbalize “woops.” I obtained several gauze sponges from the chairside table, applied them to the puncture site, and removed the catheter without incident. I told the patient that the site was unsuitable. I then held direct pressure over the site for 10 minutes, during which time I reassured the patient, telling him that I had accessed an artery and that all was well. After 10 minutes I checked the site and did not see any swelling or hematoma. Pressure was re-applied for another 5 minutes after which a pressure bandage was placed. Vital signs were taken and the patient was instructed to call me if he noticed any pain or swelling at the site. He was discharged from the clinic feeling well. I called him at home and told him to examine the site; it was free of swelling or discoloration. I reminded him to call me if anything unusual happened at the site. A phone call the next morning revealed no problems.

Post incident analysis indicated that it was most likely the Ulnar artery that was punctured just distal from its bifurcation with its parent artery, the Brachial. When I was working as a medical technologist I would occasionally be asked to collect arterial blood. The radial artery was the site of choice, and I performed this procedure several times over the years without incident. Just be aware that more superficial arteries are accessible with even a short catheter, and be prepared to treat the arterial puncture appropriately.

Here is an interesting case of inadvertent carotid artery cannulation and the ensuing complications. This patient was dehydrated so venous access was difficult.(2) Paste the reference link into your browser

References

1. Scheer B, Perel A, Pfeiffer UJ. Clinical review: complications and risk factors of peripheral arterial catheters used for haemodynamic monitoring in anaesthesia and intensive care medicine. Crit Care. Jun 2002;6(3):199-204.

2. Nair S, et al. A case of accidental carotid artery cannulation in a patient for Hemofilter: complication and management. BJMP 2009:2(3)57-58. http://www.bjmp.org/content/case-accidental-carotid-artery-cannulation-patient-hemofilter-complication-and-management Accessed 8.8.11.