TORADOL (ketorolac) linked to Recurrence Prevention
Comments
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I asked a question in the reconstruction thread if there is a surgery trauma correlation with reoccurrence. I had a consult with a PS and presented this toradol info. she won't use it before or during surgery because it increases bleeding risk. She did agree to use it post surgery if all goes well. Do you think there is still benefits of using Toradol post recon surgery?
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Hi Peace, this is why we have to do our own research. Docs learn something and they get stuck. Unless something comes along to unstick them i.e. change their mind. This study was a large study concluding that bleeding risk was not increased. Published March 2014
http://www.ncbi.nlm.nih.gov/pubmed/24572864
See comment in PubMed Commons belowPlast Reconstr Surg. 2014 Mar;133(3):741-55. doi: 10.1097/01.prs.0000438459.60474.b5.Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials.
Gobble RM1, Hoang HL, Kachniarz B, Orgill DP.
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CONCLUSIONS:
This is the first meta-analysis of randomized controlled trials examining whether there is increased postoperative bleeding with ketorolac. Postoperative bleeding was not significantly increased with ketorolac compared with controls, and adverse effects were not statistically different between the groups. Pain control was found to be superior with ketorolac compared with controls. Ketorolac should be considered for postoperative pain control, especially to limit the use of opioid pain medications.
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This is a peds study on Ibuprofen. Thought I wrote in this thread about it. Of course Ibuprofen is not Toradol. But if the docs won't accept Torodol then see what the think of Ibuprofenfor postop use.
http://www.ncbi.nlm.nih.gov/pubmed/20890608
http://www.ncbi.nlm.nih.gov/pubmed/18209131
This study said it was inconclusive
http://www.ncbi.nlm.nih.gov/pubmed/23881651- This is a review of the above Lewis Cardwell Study
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http://www.ncbi.nlm.nih.gov/pubmed/22434401
Retrospective analysis of perioperative ketorolac and postoperative bleeding in reduction mammoplasty.
Abstract
PURPOSE:
We conducted a retrospective review following concerns involving a suspected increase in the requirement for surgical re-exploration for hematoma evacuation when ketorolac was administered perioperatively in patients undergoing reduction mammoplasty.
METHODS:
Following ethics approval, a retrospective chart review was conducted of all patients who underwent reduction mammoplasty at our two institutions from the time ketorolac became available in 2004 until surgeons requested its use discontinued in 2007. The data we collected included patient demographics, ketorolac administration, requirement for surgical re-exploration, documented hematoma formation not requiring surgical re-exploration, and excessive bleeding in the perioperative period. Three hundred and seventy-nine patient records were reviewed; 127 of the patients received a single intravenous dose of ketorolac (15 or 30 mg), and 252 of the patients did not receive ketorolac.
RESULTS:
Patients who received ketorolac were at an increased risk of requiring surgical re-exploration for hematoma evacuation (relative risk [RR] = 3.6; 95% confidence interval [CI], 1.4 to 9.6) and hematoma formation not requiring re-exploration (RR = 2.2; 95% CI, 1.3 to 3.6).
CONCLUSIONS:
A single perioperative intravenous dose of ketorolac was associated with a greater than three-fold increase in the likelihood of requirement for surgical hematoma evacuation. Our data suggest that it may be prudent to consider carefully whether the potential risks associated with the use of ketorolac outweigh the potential benefits of using ketorolac in patients undergoing reduction mammoplasty.
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This is a link to the full Red. Mammo study
http://link.springer.com/article/10.1007/s12630-01...The problem with studies is once they get into print. They're quoted. The reduction Mammo study makes it sound ominous "threefold increase". If you look at the whole study and the numbers. I think the impression is different. It's part of why I think it's important to read the whole study. They can be annoying as hell, but if my life or quality of life is at issue. I want the unadulterated facts.
Abstracts are supposed to be written stating the facts found in the study. Words can be tweaked though.
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Peace, please read Forget's study and the companion article. Then the article on Reduction Mammoplasty's and companion article. If I remember correctly in the reduction Mammoplasty study the risk was 1:16. The Reduction Mammoplasty looks like a well done study. While it does conclude they're is a 1:16 risk. If this was the difference between me receiving a drug that may prevent recurrence. I would fight that as a reasonable risk. Particularly, since no one died. A few had transfusions. If that's a concern then donate for yourself pre-op it's called Autologous donation.
I'll revise maybe
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Peace, also, in the Red. Mammo article they're was discussion on Tram flaps, but I was brain dead at that point. Found the tram reference. It's below
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Not sure if this has been cited here yet. It was cited in the Reduction Mammoplasty study. Tracked it down.
http://www.ncbi.nlm.nih.gov/pubmed/11214049
Plast Reconstr Surg. 2001 Feb;107(2):352-5.
Incidence of hematoma associated with ketorolac after TRAM flap breast reconstruction.
Sharma S1, Chang DW, Koutz C, Evans GR, Robb GL, Langstein HN, Kroll SS.
Author information
- 1Department of Plastic Surgery, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Abstract
Ketorolac is frequently used as an adjunct for postoperative pain relief, especially by anesthesiologists during the immediate postoperative period. It can be used alone as an analgesic but is more often used to potentiate the actions of narcotics such as morphine or meperidine in an attempt to reduce the total dose and side effects of those drugs. The manufacturer of ketorolac cautions against its use in patients who have a high risk of postoperative bleeding, for fear of increasing the risk of hematoma, but the risk in transverse rectus abdominis musculocutaneous (TRAM) flap patients has never been reported. In a study of 215 patients who had undergone TRAM flap breast reconstruction, it was determined that patients who received intravenous ketorolac (n = 65) as an adjunct to their treatment with morphine administered by use of a patient-controlled analgesia device required less morphine (mean cumulative dose, 1.39 mg/kg) than did patients who did not receive ketorolac (n = 150; mean cumulative dose, 1.75 mg/kg; p = 0.02). There was no increase in the incidence of hematoma in patients who were treated with ketorolac. The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma.
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sas, thanks so much for all this research...I will read through everything. I really appreciate it! I received toradol after my bi-lateral oph.
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I think the doctors have so little time they devote to reading new studies...so if a catch phrase comes along, they stick with it - like "it causes bleeding". My surgeon initially told me the same thing, but I had pulled my records from my first surgery, where I DID have the drug with no bleeding response. The surgeon made me have a pre-op consult with the anasthesiologist who just shrugged his shoulders and said, "Fine". And when I had my knee surgery (tennis injury) last year, I did the same thing only argued for a regional and was awake behind a sheet for the whole thing. I did not feel much of anything and healed pretty quick. My surgeon was a teensy freaked out having me awake.
And now, I am armed with the great research from this thread to further my cause with the docs. My onc always told me that care is patient driven...from the bottom up. The docs won't initiate change unless patients become their own advocates and demand it. It's just a win-win all the way around to stay informed.
And thanks for the coffee Sas- its much appreciated ; )
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I am getting a bilateral mastectomy sept 21..so from the studies they are saying torodol should be used over an opiod such as morphine? I'm just trying to figure this out so I can discuss it with my surgeon I know I already recieved morphine which is too late now but I would like to do all I can for surgery
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I am going to chime in again regarding my experience with Toradol. When I was recovering from lung surgery twenty years ago, IV Toradol was the only pain med that worked and didn't make me vomit. Since then, I've had many other surgeries that required pain relief. I fill a prescription for Toradol ahead of surgery because most pharmacies don't stock it. Often, doctors aren't happy about giving me a script for it. However, with a little pro-activism, I prevail!
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I also wonder if this is different for people who recieved adjuvant chemo such as myself because hopefully I had a pcR and no cancer is left
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Hi folks glad you are here. The more of us reading, the more details from the research we can pick up and share. Myself I find each time I read a study, I pick up more.
Retsky has the most complete description of how regional and circulating tumor cells can lead to recurrence. Also, his description of distant dormant cells that are stimulated to grow when the cascading inflammatory response "wakens" them, is an easier read than other sources. How inflammation influences these two scenarios regional /circulating cells and distant dormant cells has been in research for years and years. Even back to observations made several thousand years ago. Yep that long ago. For me, Retsky put it best. It's like he's sitting in an arm chair with me at his knee taking one thought at a time and explaining so deftly.
VR. your experience follows the research of the last 20 + years. Nice. Please, I would like you to repost the recent study you posted in this forum. It dovetails into this discussion in that the results from 100,000 women, they conclude they don't know the why's about recurrence. That study also addresses inflammation, but doesn't follow through to the conclusions Retsky does. If we take that study and compare it to what Retsky is saying, it will make for some interesting discussion. Rater than split the discussion, if you bring it here the overall will be enhanced.
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Steph, could you expand on what you are saying , I didn't quite get it? pcR---post chemo recurrence? Fallleaves has brought to this discussion the influence of opiods and recurrence. I haven't started the reading on that. I will defer to her. This subject is huge and basically we are rookies in the scope of things. But again that supports why the more of us involved in one area focused on not just toradol, but this whole picture of recurrence prevention, will help all of us.
geewhiz, you go girl
Change the world one doc at a time. The more we all push, the more they will talk and even search on their own. It helps when we hand them copies of studies. Have you read Retsky and Forget the complete studies? You will so enjoy them.Peace, your welcome. Stay with us
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pcR is pathological complete response what everyone hopes and wishes for when doing neoadjuvant chemo..I don't have much to add to everyones disabusing although I am very interested in these studies and what they mean
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In many posts here and elsewhere, I have referred to bias. Bias is the bane of research. When a study is completed and it is submitted to a journal for consideration of publication, the journal assigns (asks) professionals i.e peers in the field to review the study. The choice of the reviewer is made by level of expertise regarding that subject. The belief being that if they're is an error the knowledgeable reviewer will recognize it. The reviewer task is to look at all sections of the study for accuracy. Generally, several or more reviewers are assigned to evaluate a study. This reflects back to what I said earlier re: the internet and the explosion of information. The controls of publishing studies only after serious peer review have been weakened. Plus, people that wish to skip scientific review have learned how to do this, and publish on the internet. Making their subjects appear to fit the rules of scientific review.
I'm happier now. I presented this better than I did before. The original thought for this post, was to find a working definition of bias that we could use. In this case, I love the internet LOL. I located a tutorial about bias that is mostly user friendly. Takes about 20 minutes to get through. Not that I expect any of us to become perfect about detecting bias, but I do believe we will be more questioning of what we are reading. It will, also, help when comparing several studies at one time.
One of the things I do, is read the objective(opening paragraph) and the conclusion of a study, or the abstract first. This allows me to focus on the key points within the study that the authors used to come to their conclusion. I find that it helps me detect bias within the study orbetween study results that don't jive with the conclusion. Hope this helps
http://familymed.uthscsa.edu/facultydevelopment/elearning/biasinresearch.htm
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Steph "disabusing" please define, not familiar in this context? pcR--thanks perhaps have seen that term before, perhaps not. We live in an acronym world. I used to joke that anyone coming into nursing /medicine had to learn the correct medical term, the acronym, and the slang. Effectively three languages. My classic example of this was Coronary Artery By-Pass Graft, CABG, slang cabbage. Another Left Coronary Artery, LCA, slang Widow Maker. I'm so thankful, I don't have to learn it all now. Reminds me as a young one suggesting to the foreign resident who was still learning our language. " Can you look at his left cheek, I think he's developing a pressure sore." He comes back and says "His cheek is fine". Since I knew it wasn't, I asked "Where did you look". Yup, he pointed at the cheek on the face. We went through the American slang, he checked the guys butt. He then took out this little black book and wrote in it.
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Sas....So how do you contact these guys?! I would like to know their viewpoint on the use of NSAIDS post tumor removal & recurrence. It sounds to me that the benefit of NSAIDS in reducing recurrence is up to the point of the actual surgery but not after the fact. (I may be wrong on this....won't be the first time!)0
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123 So how do you contact these guys?! You call them. But don't do that unless you have essentially digested i.e. studied their works, and are able to keep up your ended of the conversation. Think of it as if someone called you about your expertise. You quickly recognize the caller didn't do their homework. Phone call is over. But it can be so much fun when the conversation keeps going
A real high."I would like to know their viewpoint on the use of NSAIDS post tumor removal & recurrence. It sounds to me that the benefit of NSAIDS in It sounds to me that the benefit of NSAIDS in . " Actually, you need to do some more homework b/c you have produced some studies/article espousing long term use of NSAIDs. You need to go back and digest them. Then compare it to the use of Toradol perioperatively. From that you ask /develop your questions. About 3-5. Beyond that your expert that you call will loose interest.
123 It sounds to me that the benefit of NSAIDS in reducing recurrence is up to the point of the actual surgery but not after the fact." Since we have had PM's on the topic, I will attempt to explain what I know from your stated PM's.
You looked at allot of research studies and articles about NSAIDS used after surgery. The articles/studies were in regard to aspirin a NSAID. They're is evidence supporting Aspirin for the prevention of recurrence. The research needs further research to be related to it to become practice.
Retsky's and Forget's research, also, needs further research. But what is compelling to me in both of their works IS they have identified that a single shot(IV push) of Toradol is associated with a lack of recurrence at the predictable windows of recurrence.
Forget first identified it in her initial study of 325(7). Retsky seized on the value of her study and went on to see if he could find if it was noted anywhere else in the world. He did find other studies. He produced his study of what he found. He put the dots together. He clearly states in his first study that for him that it was a leap forward. Next post I will bring his words forward.
Forget then went onto study another 725(please forgive if that number is off a bit). Her findings were the same.
These two are on a mission. When researchers believe they have found a solution to a hypothesis( a question with potential ). They can spend their whole careers trying to prove that hypothesis.
I find their work compelling enough to tag along.
To those new to the discussion, I can't stress enough the importance of reading their studies. Not articles about their studies. Articles can have bias b/c they are not subject to peer review, or are subject to little peer review. Read the studies, please.
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Retsky's words in the beginning of his study
" The history and philosophy of science describes progress not simply in steady incremental steps but with rare and welcome sudden leaps forward. Karl Popper described the hypothetico-deductive process of observation and experimentation as "normal science" [1] whereas Thomas Kuhn described the occasional leap forward as "revolutionary science" and coined the expression "paradigm shift" to describe this phenomenon [2]. Normal science demands a method but revolutionary science demands an open mind. The recent history of the search for the cure for breast cancer can be described in this way."
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It was so much fun reading Retsky's words. He compared the nice neat methodical approach to science and the science of the ' moment of insight' that changes what is accepted. That moment of insight can take us off into a different journey in the search of knowledge. It was so beautifully put. It took my breath away. I knew I was in for a great ride. This is the thing of Nobel Prizes. The hypothesis/theory may in the end prove wrong. That's okay. The beauty is that if we simply followed what is, when what is, is no longer taking us anywhere, then we need to find something else that does.
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Retsky again
"Toward a New Understanding of the Natural History of the Disease
Among the most striking inconsistencies between the "Fisherian" model and clinical observations, is the pattern of hazard rates for local and distant recurrences after surgery for clinically localized disease. Instead of these demonstrating a shape that would be consistent with a stochastic pattern of transition from sub-clinical micro-metastases at different stages of progression and different rates of cellular proliferation, we witness a double peak, the first a steep and narrow based peak at about one or two years after surgery and a second lower and wider based curve reaching its plateau at about five or six years. [See Figs 11 and 22]. These observations, repeated in almost every data set examined by smoothed hazard rate plots, cannot be explained by a linear dynamic implicit in the current conceptual model of breast cancer [13-17].
If the facts don't fit the model then the model is wrong, not the observations. Or in the words of Nassim Nicholas Taleb, "The black swan is an outlier, as it lays outside the realm of regular expectations….it carries an extreme impact and in spite of its outlier status, human nature makes us concoct explanations for its occurrence after the fact, making it explainable and predictable" [18]."
Using non-linear (chaos theory) models, an adequate explanation can be found for the "black swans" that include the biphasic relapse pattern but at the same time can account for the undoubted successes of the contemporary paradigm. Although the number of metastases that are seeded by the primary tumor would be, at least as a working hypothesis, linearly related to the tumor size and biological aggressiveness, we suggest that the clinical appearance of metastases is often triggered or accelerated only after the primary tumor has been perturbed or removed. One has to assume that the majority of metastases at the time of diagnosis are dormant rather than actively growing. Within the "dormant" metastases, we can conceive of single quiescent isolated tumor cells and, moreover, others where there is some type of balance between cell growth and cell death. The latter may be partly determined by factors that inhibit angiogenesis without which a clump of cancer cells cannot grow to more than 106 or 107 cells in number and other factors that inhibit epithelial proliferation or encourage apoptosis. Immune related factors may also be involved. If stimulating factors are increased or inhibiting factors are reduced, the dormant condition can no longer be maintained [19-21].
It is well documented in animal models and humans that removal of the primary tumor can reduce the inhibition of angiogenesis and it is recognized that following surgery, there is a surge in cytokine production that promotes angiogenesis and growth factors aiding wound healing [15,22,23]. Thus it is not surprising that tumor angiogenesis and proliferation may be provoked by the surgery involved in the attempt to control primary cancer. Thus a likely trigger for 'kick-starting' the growth of dormant metastases could be the act of surgery itself. In support of this thesis is the observation that a wound response gene expression signature can predict breast cancer survival [24].
After surgery for breast cancer, the first peak in the incidence of secondary disease occurs at about 1-2 years irrespective of whether the tumor was at stage I or stage III [25]. It is only the height of the peak that changes with stage, the later the stage at presentation the higher is the peak, but the timing of the signal remains the same. These phenomena suggest a nonlinear dynamic model for breast cancer, which, like all chaotic systems, is determined by initial conditions around the time of diagnosis [26].
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Doesn't that just give you shivers:)
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Chit on a roll lost it
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Peace, here's ammunition to use with your doc. It does much more justice to your question about bleeding. Also, Retsky used the Reduction Mammoplasty study I discussed, but he did it better. Plus. he has several more resources. All identified in the bibliography and hyperlinked.
From Retsky's study
"Concerns About Bleeding Complications
One of the issues related to the perioperative use of ketorolac has been concern about bleeding complications. What is the evidence, if any, regarding the occurrence of increased blood loss and its clinical significance after a single or limited number of doses of ketorolac when administered during the perioperative period?
This topic has been recently addressed in an editorial by White, Raeder and Kehlet, accompanying a meta-analysis of De Oliveira et al. [92,93]. In the meta-analysis, the authors noted that the combined effect did show a statistically significant increase in bleeding with ketorolac compared with placebo. This effect was however shown only in two studies focusing on surgeries with "raw" surface areas (adenotonsillectomy and major orthopedic surgery) and without any additional red blood cell transfusion needed, questioning the clinical significance in other surgeries.
In breast surgery, a recent retrospective study in major plastic breast reconstructive surgery (mammoplasty) reported a greater likelihood of requirement for surgical hematoma evacuation [94]. But, as in surgeries with "raw" surface areas, such major plastic surgeries are associated with greater difficulties in hemostasis than lumpectomy (often performed on a day-case basis) or mastectomy. Two studies in breast cancer surgery prospectively compared ketorolac with placebo. The first did not show any difference in drain output, but is difficult to interpret because ketorolac was administered near the end of surgery (in place of preincisional) [95]. The second showed a statistically significant difference but no clinical implications including no need of transfusion in any group [96].
As a consequence, if the use of ketorolac has been associated with a greater amount of blood loss in a limited number of studies and not in others, the clinical significance remains unknown in breast cancer surgery. If any, it seems to be low since ketorolac has never been associated with greater transfusion need of red blood cells. Studies even tend to report a better functional outcome in the postoperative period with ketorolac, suggesting that the clinical significance of this blood loss could be largely counterbalanced by the advantage of the drug [92,93]. As a consequence, the American Society of Anesthesiologists recommended in their latest guidelines that unless contraindicated, all the patients should receive balanced analgesia, including NSAIDs [97].
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An external file that holds a picture, illustration, etc.
Object name is CMC-20-4163_F7.jpg
I get the 10 and 30 month increase in recurrence but I am having a hard time with the 36-48 month peak with or without Toradol.....0 -
123, couldn't locate the jpg. ??? 36-48 month peak with or without Toradol. Excellent question.
No clue. Put that on your list for when you call Retsky. I'm not kidding about calling him. If you have absorbed every aspect of what a researcher has written -----or based on your best ability tried to decipher what they have written and can't find an answer---call. It serves two purposes 1. you get an answer, if they know. 2. it may be a hole in the research or accepted knowledge of a subject. What's fun about that is it may give them another avenue to look at. Never underestimate a question. Plus, based on my experience of a call to a person that has published, is they are flattered that someone thinks enough of their research that they would take time to call. Only once, was that not the case. That was a researcher at the CDC. LOL just remembered about her. The question was about measles in 1988 when I was writing an employee health manual. She started the conversation with "you have 5 minutes" No hello. LOL
All of life moved forward because of questions.
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If you do a turn about and want me to call him then, we have too talk. I got no problem doing it. But then how I approach things here changes. I have to get more intense. My goal till now has been to bring information together that allows people to make an informed choice /request based on knowledge that is not mainstream, but researched well and may become main stream soon.
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