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Manipulation of Blood in Sport
- 1. Blood manipulation in Sport …and some clinical applications
- 2. Dubin Inquiry World Athlete of the CenturySportsman of the Century Olympian of the Century Cheating American Hero
- 3. 1984 Olympics Los Angeles
- 5. Vo2max • Plateau of oxygen uptake during maximal exercise, despite a further increase in workload, defining the limit of the cardiorespiratory system
- 6. VO2AT • Highest sustained intensity of exercise for which measurement of VO2 can account for the entire energy requirement
- 7. VO2 • Supply • Atmospheric oxygen • Diffusion capacity • Cardiac output • Oxygen carrying capacity • Demand • Mitochondrial utilization
- 8. VO2 VO2 = CO x (CaO2 – CvO2) 1.34 x Hb x (SaO2 – SvO2) Exogenous • Transfusion Endogenous • EPO • HIF • Live high, train low
- 9. evidence • Transfusion • Multiple studies, pre-1982 • Generally poor, ethically questionable • At least 2 units to see effect on VO2 • EPO • Increased VO2 6-10% • Hct - ~42 ~51 • 1985 – 2000
- 10. alternatives • Live high, train low • Fair alternative • VO2 max increased 5% • Hypoxia tents • No appreciable improvement in O2 carrying capacity • Elite female cyclists, male multisport • HIF activators/stabilizers • Xenon • Argon • Cobalt
- 11. Clinical correlation required • Perioperative anemia is bad • Increased mortality • More time in ICU • Longer hospital stay • More complications • Transfusion is not the answer • Infectious • Immunogenic • Hemolytic • Volume related
- 12. Clinical correlation required • Perioperative blood management • EPO • Iron • TXA, cell saver, ANH • ‘anemic’ ‘slightly less anemic’ • Supranormal Hb • ? autologous blood transfusion • Increases VO2AT • Effect may not last
- 13. VO2 • Supply • Atmospheric oxygen • Diffusion capacity • Cardiac output • Oxygen carrying capacity • Demand • Mitochondrial utilization
- 14. Prehabilitation • Enhance functional capacity before a subsequent stressor • Enhanced recovery programs • Evidence • Role of CPET • Improvements can be made in short time-frame • Clinical data evolving
- 15. Latest on doping • Rio 2016 • Russian athletics team ban • Athlete Biological Passport • Longitudinal monitoring • Targeted testing for specific agents
- 16. ?
Notes de l'éditeur
- Ben Johnson, who originally won the gold medal in the 100m at the 1988 summer olympics, but several days later was disqualified and stripped of his medal when he tested positive for the anabolic steroid stanozolol, a testosterone derivative. Johnson was vilified in the international press and was disgraced in Canada, this incident catalyzing something called the Dubin inquiry, a large scale investigation into the use of performance enhancing drugs in Canadian sport. Johnson attempted several comebacks, but they failed and he ultimately ended up as a personal trainer for the child of Muammar Gaddafi, the Libyan dictator, his name synonymous with cheating. Which was interesting considering that 6 of the 8 sprinters in that 100m final were later found to have used PEDs at some point in their career. That included this man, who finished second in the race but was awarded the gold medal on Johnson’s disqualification. This is Carl Lewis, who over the course of his career won 10 Olympic medals, including 9 gold, being hailed as World Athlete of the Century, Sportsman of the Century by the IOC and Olympican of the Century by Sports Illustrated. In 2003 it was discovered that he had tested positive for ephedrine, pseudoephedrine and a bronchodilator at the 1988 Olympic trials, results that had been swept under the rug. He is generally considered an American athletic hero. Now this isn’t blood doping, but it illustrates the fine line these people were walking.
- US cycling team 1984 Olympics. 9 medals total, including 4 gold Hadn’t won a cycling medal since 1912 8 of 20 members of the team, including 5 medalists admitted to having blood tranfusions during the games Rolling Stone article the next year caused some controversy, but all the riders still have their medals because technically transfusions weren’t against the rules then Transfusions not banned by UCI until 1985, mainly because they couldn’t test for it Heterologous, whole blood transfusion, cardiologist/cycling fan, ? Blood group compatible, courier rushed samples on motorcycle, Ramada Inn, AIDS
- Of course the most well known case of blood doping is Lance Armstrong. Most of us know the story, after a remarkable struggle with and recovery from metastatic testicular cancer, Lance won the Tour de France, the world’s most prestigious cycling race, 7 consecutive times, 1999-2005, in the process becoming an international celebrity and using his cancer history and subsequent philanthropy to shield himself from the doping allegations that dogged him throughout his career. He was ultimately undone by his former teammate, Tyler Hamilton, among others, who’s affidavit to the US anti doping agency is available to read online, detailing their doping practice. During the 1999 tour they self-injected themselves with subQ EPO every 3-4 days, getting it from a friend who they hired to follow the tour in a motorcycle and at the end of a stage, zip past the press and cameras and deliver the epo cooler to the team bus. They used autologous transfusions starting in 2000, traveling to Spain in the months leading up to the Tour for extractions. The blood would be stored and then reinfused, usually in a hotel room, during the race just before big mountain stages when they were looking for a boost.
- Plain english, the maximum amount of oxygen that can be taken up and used by the cell.
- Otherwise called lactate threshold, this is the exercise level at which lactate starts building up in the blood. This is what these endurance athletes are trying to increase, because production of energy by anaerobic means is inefficient and unsustainable relative to aerobic production.
- Diffusion capacity both at the level of the lungs Demand: ability of the mitochondria to reduce that oxygen to make ATP
- HIF activators
- Transfusion studies ethically questionable, mostly autologous blood. Improvements in vo2 max highly variable, from 1-2% to one study with an improvement of 30%. Anecdotal evidence is pretty remarkable. That includes the story of Francesco Moser, a champion Italian cyclist who with the help of transfusion broke the hour record held for over a decade by Eddy Merckx, one of the greatest cyclists ever. This is an interesting and simple event, basically the rider races around a velodrome for exactly an hour and the total distance is measured. Moser, while a strong professional, was at the end of his career, and added nearly 2km to Merckx’s record. This is also the first appearance of the Italian doctors Conconi and Ferrari, who would go on to play prominent roles in the doping scandals of the 90s and 2000s and who helped Moser break this record. Interestingly these doctors were also employees of the Italian Olympic Committee, speaking to the penetration of doping knowledge into the cycling hierarchy. EPO evidence more convincing. It came in vogue after 1985 when transfusion were officially banned and studies done on EPO showed consistent increases in vo2max from 6-10% with concurrent increases in hct. It was banned officially in 1991 but its abuse persisted as the main blood doping agent due to convenience over transfusion and lack of a test to detect it. With the introduction of a test for EPO at the 2000 olympics in sydney, the practice of transfusions made a comeback and a combination of the two was common through the 2000s, though instead of subQ dosing of EPO every few days, cyclist would microdose EPO IV every night. Overall though, lack of formal evidence on endurance performance, though anecdotal evidence from those who have come forward sounds convincing, with better times and faster recovery while on EPO. Maybe the best evidence of that is the average speed of the tour de france over the course of the whole race. Through the EPO years from the late 80s through the early 2000s we can see a steady increase.
- Live high train low. Came into vogue after the 1968 summer olympics in Mexico City, which at ~2300m was the first major world sporting event at elevation. Conceptually, background exposure to the relative hypoxia of that elevation induces erythropoeitin production, increasing red cell mass and oxygen carrying capacity. Training ‘low’, at elevations closer to sea level prevents early fatigue and allows maximization of training time. ‘Locking in’ the improvement from the increased oxygen carrying capacity. Interestingly similar improvements in oxygen carrying capacity were not found when simulating the live high train low regimen with the use of hypobaric tents. One study had athletes spend 23 nights at a simulated altitude of 3000m matched with a control at sea level and training at 600m, with no increase in hb mass in the intervention group. The next target to stimulate erythropoeisis is the transcription factor HIF (hypoxia inducible factor), which helps stimulate erythropoetin production in hypoxic conditions. Turns out it is activated under normal circumstances by xenon and argon and stabilized by cobalt. Evidence is scarce, but anecdotally Russian skiers and biathletes admitted breathing a 50:50 mixture of oxygen and xenon at the 2014 sochi olympics. All 3 are now on the WADA prohibited list.
- Like running or cycling or any sort of exercise, a surgical procedure is a physiologic insult. And as your 10k time wouldn’t be very good after you go to Canadian Blood Services and donate blood, you generally don’t do well if you’re anemic perioperatively. Well the answer should be simple, right? Increase that oxygen carrying capacity by giving blood. Well actually no, as we know well.
- PBM reduces transfusion rates, which is a good thing, reducing complications as a result of transfusion. Interestingly, this mirrors what elite sport did. When transfusion got complicated by health concerns and logistics, EPO became more popular and demonstrated very good improvements in performance. But most of what we see and do in this area takes anemic patients and makes them slightly less anemic, which makes me wonder, as we have sort of touched on in PBMP rounds, about targeting supranormal hemoglobin levels, as we do for JW patients. What would happen if we treated everybody like a JW patient? From a physiologic perspective it makes sense, increasing oxygen delivery and oxygen uptake should improve ‘performance’ if you will perioperatively as it does in elite sport, but is the risk/benefit balance appropriate? I also wonder about the role of autologous blood transfusion perioperatively, as there is good physiologic evidence that it increases lactate thresholds in anemic patients. Study of hip replacement patients about 10 years ago did not demonstrate a lasting effect, but there is not a ton of data on this. It’s a complicated process, but it does avoid some of the pitfalls of homologous transfusion.
- So what else can we learn from elite sport? Well back to physiologic principles, we’ve talked about blood manipulation and increasing oxygen carrying capacity. But the main difference between elite athletes and our typical surgical population is that before they even consider blood doping to max oxygen carrying capacity, they’re already elite athletes, meaning they’ve optimized all of these other parameters by being in good shape. Through aerobic training they improve their cardiopulmonary reserve and the efficiency with which they can move oxygen. Their lean muscle mass maximizes their efficiency in utilizing it. Perioperatively we try to do some of these things, we try to OPTIMIZE heart and lung function preoperatively, provide oxygen perioperatively, but sometimes it feels more like bailing out a sinking ship. So can we turn our patient population into elite cross-country skiers and ultra-marathoners? Well no, but we probably can do a better job of preparing them for surgery.
- This brings us to the concept of prehabilitation, which is the process through which functional capacity is enhanced prior to a subsequent stressor. Just like you would train for the Sun Run, we get our patients in shape before their surgery. Its intuitive, but we sort of just say eat better and lose weight. This evolved from the arena of enhanced recovery programs, which have met with some success looking at integrating our current evidence into best practices instead of focusing on obtaining new knowledge. What evidence is out there for this? Well there is good evidence that it can be done in a relatively short period of time, guided by cardiopulmonary exercise testing. But the clinical date is evolving. Study in Ontario and Quebec happening right now where they’re randomizing prostatectomy patients. They’ve got half these old guys chugging away on a 4 day a week exercise program vs the other half who just get a pamphlet and are told to eat better. It is still recruiting and so will be interesting to see the results.
- I thought I would finish with a little update on doping. Russian athletics team banned late last year after evidence emerged of widespread, state-sanctioned doping as well as bribes to various IOC officials to cover up positive tests.