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===Ice, Inflammation and Healing===
If NSAIDs are bad for healing, should we treat with ice? So far I have found no definitive studies, but ice has a difference mechanism of action from NSAIDs. By cooling the tissues, ice temporarily reduces inflammation, thereby flushing the wound. It does not directly impact any of the body's enzymes or other processes. If applied for a longer period of time, ice will produce a periodic increase in blood supply that creates a further flushing effect. I have found that ice can produce dramatic improvements in healing speed. See [[Cryotherapy - Ice for Healing]] for more details.
=NSAIDs and Acute kidney failure=Kidney failure while running is extremely rare, and seems to require multiple factors to come together. Looking<ref name="rhabdo1"/> at the [http://en.wikipedia.org/wiki/Comrades_Marathon Comrades Marathon], 90 Km/56 Mile ultramarathon in South Africa, there have only been 19 cases of kidney failure between 1969 and 1986, it even though thousands of people participate each year. The following are considered factors in acute kidney failure related to running.* '''Dehydration'''. Exercise reduces blood flow to the kidneys and dehydration makes this worse.* '''NSAIDs'''. NSAIDs also reduce blood flow to the kidneys <ref name="coxibs"/>. NSAIDs reduce prostaglandin production, and prostaglandins are vital to maintaining blood flow to the kidneys. While NSAIDs are considered safe drugs, NSAIDs are associated with a relatively high incidence of adverse drug reactions involving the kidneys. Generally NSAID side effects are restricted to individuals with predisposition to kidney problems, so extra care should be taken if you have a history of kidney problems. However, athletes push their bodies to extremes, so what applies to the general population may not be valid for runners. One runner was told<ref name="Anecdote"/> by doctors that 2400mg Ibuprofen in an ultramarathon was a contributing factor to his kidney failure. * '''Rhabdomyolysis'''. All strenuous exercise causes some muscle damage, but this is generally resolved without a problem. However large amounts of a protein called myoglobin from damaged muscle can cause a condition called [http://en.wikipedia.org/wiki/Rhabdomyolysis rhabdomyolysis] (AKA 'rhabdo'). While serious rhabdomyolysis is rare, it is worth understanding one key symptom, which is low volume, dark urine, often likened to 'coca-cola'. The other symptoms include severe, incapacitating muscle pain and elevated levels of creatine kinase (CK) in the blood (which requires a specialist test). Some individuals<ref name="rhabdoGenes"/> have a genetic condition that makes rhabdomyolysis possible after relatively moderate exercise. Rhabdomyolysis is also more likely after eccentric exercise, such as [[Downhill Running]].* '''Sickness'''. A viral or bacterial infection is often a factor in exercise related kidney failure.Looking at the analysis<ref name="coxibs"/> of nine cases of continued kidney failure in Comrades Marathon, seven had taken NSAIDs, four may have had a viral or bacterial infection. The combination of dehydration, rhabdomyolysis, infection and NSAIDs are a perfect storm for the kidneys. =NSAIDs and Hyponatremia=The kidneys are responsible for removing excess fluid from the blood as well as excreting or withholding sodium. If kidney function is compromised, then this can result in [[Hyponatremia]], which can be fatal. Some studies<ref name="hypo"/><ref name="hypo2"/><ref name="siadh"/> have shown a correlation between NSAID use in races and [[Hyponatremia]], but others<ref name="nohypo"/> have not. Using NSAIDs when hydration is a concern increases the risk of problems occuring. =NSAIDs and Sickness=Because a bacterial or viral infection puts more stress on the body, including the kidneys, taking NSAIDs and continuing to run increases your risk of complications. If the sickness is too bad to run without NSAIDs, you probably shouldn't run. =NSAIDs for Pain Reduction=To followThe primary purpose of NSAIDs is generally for reducing pain, and they are remarkably effective at achieving this.If you need a painkiller, acetaminophen is probably a better choice than ibuprofen, though be careful as it's easy to overdose on Acetaminophen (see below). Acetaminophen has limited anti-inflammatory properties, so it shouldn't impair healing as much as ibuprofen, but it is still good as a painkiller. Combining acetaminophen or other NSAIDs with caffeine further improves their painkilling effectiveness. After a major race I can sometimes have so much leg pain that I can't sleep and a little acetaminophen can make all the difference. While the acetaminophen may impair healing somewhat I believe the trade-off in improved sleep is worthwhile. After all, the lack of sleep itself will impair healing, so it's a reasonable compromise. =NSAIDs and Racing =Taking NSAIDs in ultramarathon events can improve performance by reducing pain and racingacute inflammation, but doing so represents a significant risk. There is some evidence<ref name="wser1"/> <ref name="wser2"/> that many runners taking NSAIDs have the same level of pain and greater damage markers compared with non-users. This may be because the runners push themselves to a similar level of pain, with the NSAIDs allowing them to do more damage. To follow* It seems likely that NSAIDs will increase the risk of injury rather than reducing it, as the symptoms of damage will be masked. * The most common NSAID for racing seems to be ibuprofen. I've not seen any evidence of the relative effectiveness of different NSAIDs on performance. * Before an ultramarathon race, you should think through under what circumstances you will consider using NSAIDs and what dosage. Make sure your crew knows that you're taking NSAIDs in case anything happens.=* Extra care should be taken when NSAIDs are used in combination with dehydration, sickness or running the causes serious muscle damage.* Taking NSAIDs in marathon or shorter races is probably ineffective as the level of damage seen is not as great as in ultramarathon events. * If you need NSAIDs to start a race, you probably should not compete. =Longer Term NSAID usage==Using NSAIDs for longer periods of time can lead so some to serious health problemsand can be fatal. A I have a running friend who had a bleeding ulcer from using Ibuprofen, which is a known <ref name="IbuprophenSideEffects"/> side effect. The likelihood of a bleeding or perforated ulcer goes up with time, from 1% after 3-6 months, to 2-4% after 12 months. (Taking a 35% of long term Ibuprofen/Famotidine combination has been shownusers get an ulcer<ref name="Famotidine"/> to reduce the incidence gastric ulcers from 35% to 14% in longer term users, which is grim odds. =Acetaminophen Overdose Danger (AKA Paracetamol, Tylenol) =Acetaminophen does not have the same risk of ulcers, but it is linked to liver damage, especially in those who drink alcohol. Acetaminophen is the leading cause of acute liver failure<ref name="AcetaAcuteLiver"/><ref name="Staggered"/>. There are concerns <ref name="AcetaNormalDoseLiver"/> that even the standard dose can cause changes in liver function. Acetaminophen can cause delayed symptoms<ref name="Staggered"/>, with people seeking medical help up to 5 days after the overdose (20% < 12 hours, 35% 12-24 hours, 45% 24 hours+). Overdoses of Acetaminophen can be caused by taking slightly too much over several days, with the toxicity building up<ref name="Staggered"/>. This problem is again exacerbated by those taking alcohol with Acetaminophen<ref name="AcetaNormalDoseLiverStaggered"/>. (One factor that increases the risk is that some common medications, such as cold remedies, include Acetaminophen. If people do not add in the dose of Acetaminophen from these other sources, it is easy to unwittingly exceed the safe dosage.) ==Tangent - Is Acetaminophen really an NSAID?==
There are differing opinions around the classification of Acetaminophen as an NSAID with some resources<ref name="NotAnNsaid"/> stating it is not an NSAID. While Acetaminophen has limited anti-inflammatory properties, it shares the same mechanism of action with most NSAIDs of inhibiting the COX enzyme and the inhibition of prostaglandin synthesis. It is therefore reasonable and useful to classify Acetaminophen as an NSAID.
<references>
<ref name="bone">JBJS | Dose and Time-Dependent Effects of Cyclooxygenase-2 Inhibition on Fracture-Healing http://www.jbjs.org/article.aspx?Volume=89&page=500</ref>
<ref name="VitaminI">Urban Dictionary: Vitamin I http://www.urbandictionary.com/define.php?term=Vitamin%20I</ref>
<ref name="NotAnNsaid">ACETAMINOPHEN (PARACETAMOL) http://www.chemicalland21.com/lifescience/phar/ACETAMINOPHEN.htm</ref>
<ref name="Staggered">Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2011.04067.x/full</ref>
<ref name="Anecdote">KIDNEY FAILURE AND ULTRAMARATHONING http://www.lehigh.edu/\~dmd1/kidney.html</ref>
<ref name="coxibs"> http://journals.lww.com/acsm-csmr/Abstract/2010/03000/Athletes,_NSAID,_Coxibs,_and_the_Gastrointestinal.11.aspx</ref>
<ref name="hypo">NSAID Use Increases the Risk of Developing Hyponatremia duri... : Medicine & Science in Sports & Exercise http://journals.lww.com/acsm-msse/Abstract/2006/04000/NSAID_Use_Increases_the_Risk_of_Developing.2.aspx</ref>
<ref name="hypo2"> http://journals.lww.com/cjsportsmed/Abstract/2007/01000/Exercise_Associated_Hyponatremia,_Renal_Function,.8.aspx</ref>
<ref name="nohypo"> http://journals.lww.com/cjsportsmed/Abstract/2003/01000/The_Incidence,_Risk_Factors,_and_Clinical.8.aspx</ref>
<ref name="wser1">Ibuprofen use during extreme exercise: ... [Med Sci Sports Exerc. 2007] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/17596774</ref>
<ref name="wser2">Ibuprofen use, endotoxemia, inflammation, ... [Brain Behav Immun. 2006] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/16554145</ref>
<ref name="rhabdo1">Exertional rhabdomyolysis and acute renal failure... [Sports Med. 2007] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/17465608</ref>
<ref name="rhabdoGenes">Recurrent rhabdomyolysis in a collegiat... [Med Sci Sports Exerc. 2006] - PubMed - NCBI http://www.ncbi.nlm.nih.gov/pubmed/16540825</ref>
<ref name="siadh"> http://www.sciencedirect.com/science/article/pii/S0002934307001672</ref>
</references>