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Apr 12, 2016 05:53PM
Aug 17, 2017 04:17PM
Dear Doctor, I request that you consider the use of Toradol pre-incision for my upcoming surgery. Below are the relevant studies.
The amount and timing recommended by Dr.Patrice Forget is 20 mg pre-incision in patients under 60 kg, and 30 mg in patients over 60 kg.
There has been ongoing research that is looking at the specific use of Torodal/ketorolac in the perioperative(preincision) phase of breast surgery. The initial study was from Belgium. This study is known as the Forget study published in 2010. A particular isolated group of patients that had an unusually low rate of breast cancer recurrence. All had the same breast surgeon and one of two anesthesiologist. The anesthesiologists had a common approach to drugs used for surgery. Toradol was identified as the common drug given intraoperative.
This link is to an article about the Dr. Forget study, 2010. Patient cohort 327.
Dr. Forget' s study. This is benchmark original research.
Dr. Forget' s study 2014. Follow up retrospective study of the 2010 retrospective study. Patient cohort 720.
Dr. Retsky' s study is a broader based analysis of Dr. Forget' s
Curr Med Chem. 2013 Nov; 20(33): 4163–4176.
Published online 2013 Nov. doi: 10.2174/09298673113209990250
Reduction of Breast Cancer Relapses with Perioperative Non-Steroidal Anti-Inflammatory Drugs: New Findings and a Review
Michael Retsky,1,2,* Romano Demicheli,3 William J.M Hrushesky,4 Patrice Forget,5 Marc De Kock,5 Isaac Gukas,6 Rick A Rogers,1 Michael Baum,7 Vikas Sukhatme,8 and Jayant S Vaidya7
Quotes and graphs from Dr. Retsky's study.
"Using Computer Simulation to Analyze Bimodal Relapse Pattern
Based on computer simulation, to explain the 10 month peak we postulated that induction of angiogenesis at the time of surgery provoked sudden exits from dormant avascular phases to active growth and then to detection. That mode is quite sharp and most often seen among premenopausal patients with axillary lymph node involvement (N+). We suggested the remainder of relapses within the first 40 or so months to be surgery-induced growth of previously dormant single malignant cells. We proposed that the broad late peak relapses result from steady stochastic progressions from single dormant malignant cells to avascular micro-metastases and then on to growing deposits with no apparent synchronization to the time of surgery.
Most Important Finding – Early Relapses are the Result of Something that Happens at Surgery
The most important finding of this early work is that something happens at or about the time of surgery to accelerate or induce metastatic activity that results in early relapses. These early relapses comprise over half of all relapses. Surgery-induced angiogenesis of dormant avascular micrometastases and surgery-induced activity of single malignant cells are implicated. Late relapses are apparently not accelerated by surgery but the shallow peak at 5 years occurs as a result of shedding from primary ceasing after primary removal. We have been vigilantly looking for new data with which we can learn more about surgery-induced tumor activity and that perhaps will also lead to improved outcomes. As we describe here, there has been an important development."
Forget et al.  data from Universite catholique de Louvain in Brussels, Belgium. Relapse hazard is shown for mastectomy patients given ketorolac or not. Data are smoothed as indicated for fig. fig.11.
Forget et al. data were updated September 2011 and shown in hazard form but not smoothed as in fig. fig.7.7. Patient data are presented in the table. Patients included in this figure were less than 80 years of age, tumor less than 9 cm diameter and disease free survival greater than 2 months. It can be seen that relapses in months 9 -18 accounted for the major difference between ketorolac and non-ketorolac patients.
Very often the excuse to not use Toradol is because of concern about postop bleeding. Here are links and abstracts related to studies re: Toradol and postop bleeding.
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.
Postoperative pain control is essential for optimal patient outcomes. Ketorolac is an attractive alternative for achieving pain control postoperatively, but concerns over postoperative bleeding have limited its use.
Computer searches of the MEDLINE, EMBASE, and Cochrane Library databases were performed. Twenty-seven double-blind, randomized, controlled studies were reviewed by two independent investigators for the incidence of adverse events, including postoperative bleeding. Comprehensive meta-analysis software was used to evaluate the differences between ketorolac and control groups.
Twenty-seven studies with 2314 patients were analyzed. Postoperative bleeding occurred in 33 of 1304 patients (2.5 percent) in the ketorolac group compared with 21 of 1010 (2.1 percent) in the control group (OR, 1.1; 95 percent CI, 0.61 to 2.06; p = 0.72). Adverse events were similar in the groups, 31.7 percent in the control group and 27.9 percent in the ketorolac group (OR, 0.64; 95 percent CI, 0.41 to 1.01; p = 0.06). There was a lower incidence of adverse effects with low-dose ketorolac (OR, 0.49; 95 percent CI, 0.27 to 0.91; p = 0.02). Pain control with ketorolac was superior to controls and equivalent to opioids.
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.
CLINICAL QUESTION/LEVEL OF EVIDENCE:
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.
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.
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.
///////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////This study states a three fold increase in hematoma formation after a reduction mammoplasty. if you evaluate the numbers sited in the study, they are small in actual occurrence, but when the phrase "three fold increase" is used in the conclusion of the actual study and then repeated in the abstract, the implication is the numbers are ominous. Another way the authors of the study describe the risk is a 1:16 ratio. When the risk of recurrence is balanced against the hematoma risk, the reduction in recurrence should be weighted in favor of disease free survival(opinion)
Retrospective analysis of perioperative ketorolac and postoperative bleeding in reduction mammoplasty.
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.
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.
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).
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.
thank you for consideration of this information.
Life's journey is not to arrive at the grave safely in a well preserved body, but rather to skid in sideways, totally worn out shouting "holy crap....what a ride".