The Obesity Paradox: Obesity and Its Effect on Anesthesia

Joannie Pompee4/29/15

IntroductionAnesthesia has changed into being a routinely administered product that is being used every day from the operating room, to the dentists office. Many research studies, that will be further analyzed in this paper, have been done to figure out the relationship between an individuals body weight and the effect it has on anesthesic dosage. Obesity has become an epidemic in the United States and has been a disease that increases the likelihood of secondary complications. I will be expanding on the subject of whether obesity has a negative or positive effect on anesthesia. Before this analysis can occur, we first have to know the product of anesthesia itself and how it has progressed. William T.G. Morton, the founder of this product in 1846 (8), is the man responsible for the use of this product and it has been used ever since, but there has been no discussion about whether this products efficiency can be compromised by obesity. Brill et. al. conducted a study using both obese patients and patients with normal body weights to test if there were any differences in the distribution of the anesthetic drug, cefazolin (1). Both experimental groups were injected with the same dosage of the cefazolin. What was found is that in the obese patient, there was a lower tissue distribution of the drug, when compared to the relatively healthy patients that had a normal body weight (1). Also in this article, they performed several similar studies, and each of them showed same result. An observation was given about how this could be. Brill et. al. explained that, The lower drug penetration into the subcutaneous adipose tissue of morbidly obese patients found in these studies and in the present study may potentially be explained by lower subcutaneous adipose blood flow. It has been shown before that subcutaneous adipose tissue blood flow in obese and morbidly obese patients is lower than in healthy control subjects. (1) This additional study is significant because it shows that the effectiveness of anesthesia and its dosage are dependent on an individual body composition. Even though this shows some evidence that obesity can affect the usage of anesthesia, we dont know how this is possible, and if there are any complications that can occur.This essay will help better the understanding of how the idea of anesthesia was brought about and how obesity affects its usage. The real significance that will be focused on is whether obesitys effect on anesthesia will contribute to any secondary complications with lowered dosage. These side effects could possibly be negative or positive. One specific aspect that came in a recurrence during my research was the effect on obesity. First, in order to understand the significance of these effects, we must first understand the history behind anesthesia and how it works.History Behind AnesthesiaWilliam T. G. Morton was a dentist/medical student at the time of his discovery. He used ether as a type of pain reliever and this started the ongoing use of anesthesia and furthermore, its importance (7). Mostly, individuals that are about to undergo surgery or are at the dentists office are the ones who benefit the most from the products. Because of Dr. Mortons product, many health professionals grew an appreciation for his work, and devoted their efforts to having a better understanding of how to operate with it and how exactly it functions. A few neo- William T.G. Mortons in particular, contributed more to the practice and added more importance to the use of anesthesia (7).One of the physicians that grew an interest in learning more about anesthesia was Freeman Allen. Even though he was interested in the administration of anesthesia, he wanted to learn a broader range of medicine so he started to learn more about dermatology (7). He even said it himself that he wasnt focused primarily on anesthesia.

I have been practicing my profession in Boston. Although I thought at one time of giving up the administration of anesthetics for Dermatology, since my return from Europe I have resumed the administration of anesthesia and find that [I] am intensely interested in my work. He continued, Since my marriage, on July 20, 1911 to a girl of whom I have always been very fond, I find that my interest in my work and in life in general is at least ten times greater than ever before. (7)

What guided him back to the practice with an even higher passion for it were a number of factors, his trip to London where they were more experienced and knowledgeable about the administration of anesthesia, more specifically chloroform (a different type of anesthesia), his mother since she had been suffering chronic pain ever since his birth, and other factors. Allen gained many accomplishments. He was recognized for being the first anesthesiologist in several different hospitals, including the same hospital where Morton discovered the use of ether as a type of anesthesia, which was Massachusetts General Hospital. He made many contributions to anesthesiology and the administration of it. Allen was one of the first to study different types of anesthesia. William T.G. Morton only made his findings about the use of ether, but Allen focused on the multiple possibilities of other products that could work just as good or work even better. Various products were studied such as adrenaline, novacaine, and etc. (7). There were only a limited amount of types that he could have studied on since there were a finite amount of products that were discovered at that time. This information is significant, because this shows how Freeman Allen gave the right amount of attention to this product and this caused a rippling effect of more highly prestigious physicians to continue Mortons legacy in increasing development of the product and the efficiency of it. Overall, Freeman Allens work helped broaden the field of anesthesiology by peeking the interests of more highly interested individuals. Another physician that helped advance the practice was one of Freeman Allens mentors and a key factor to Allens continued work, Dr. Thomas Bennett. (7)Dr. Bennett was just as interested in the administration of anesthesia and he helped better the proper mechanics of it. His help inspired Freeman Allen to get back to Boston and further research in the development of anesthesia. What made his efforts so important was that, in Kansas City, he was the first to be appointed as an official supervisor of administration of anesthesia. He also grew an interest and studied several common anesthetics, at that time, such as chloroform, ether, and others (7). He even created the instrument to administer anesthesia called the Bennett inhaler. Another factor or group of individuals that pushed Allen to pursue his career of anesthetics, other than his mother and fellow colleagues, were members of his family.His extended family was consumed by many accomplished beings. Both coming from his family and his wifes family, his choice in sticking with anesthesia was almost inevitable. His wife, Mary Ethel Gibsons great grandfather was the first to operate with the use of ether as an anesthetic. Another doctor that became a part of Allens path was Dr. John Collins Warrens grandson, Dr. J Collins Warren (7). With having so many distinguished people that share the same aspirations as he does, it makes more sense as to why his passion for it became even stronger than before. In order to understand how they actually work in relieving pain, we must know what effect anesthesia has on the human body and distinguish between what is true and what is false. The big misconception is that the patient thinks that the favored state they will be in is a sleep-like state, but this is incorrect.The Early Years of AnesthesiaAccording to Dr. Emery Brown (10), a professor of anesthesia at Harvard Medical School, It doesnt really cause a state of sedation or anesthesia (initially). He also states that, Then what we actually see next is the brain starts to slow. [So first you see] a period where the brain is active, and then [when you give] a higher dose, the brain starts to slow. (10). So, what he is saying is that being in a sleep-like state isnt enough. What needs to happen is that the body has to be in a, more or less, in between state. This means that the body physically has to be completely inactive. No movements should be made especially when in the middle of an invasive operation. The only things that should be active and functional are a normal heartbeat, slowed, but fully active brain activity, and basic but essential, vital signs. So the in between state would be the fine line between life and death. Dr. Brown also explained what other extraordinary phenomenon was involved in the process. In contrast, the drug ketamine which is used in conjunction with anesthesia to make certain drugs work better puts the brain into a state of excitation even at higher doses (10). By inducing this drug, ketamine, it acts as the anesthesias balance and is used to help maintain the brains homeostasis. Ketamine is a very active drug, which is very important to use since the anesthesia actually slows down the brain (10). Dr. Emery Browns remarks were only generic descriptions of what actually happens during the process of the administration of anesthesia. This shows that anesthesia is much more complicated and has to deal with a wide range of drugs and a great understanding of the human body and of its neuroscience.By knowing the minor mechanics of how anesthesia works, we can have a better understanding of what different types can typically do and what are their significant differences. With this knowledge, the idea of side effects and the different level of degrees could help identify which of them are more detrimental than others. By knowing which side effects are being triggered, we can manipulate their outcomes and potentially come up with treatments for these side effects, or at least come up with a way to minimize the actions of the side effects that may appear. In this paper, the main side effect that will be examined is obesity and whether anesthesia could cause an individuals risk to increase in some way. In order to know examine if effects on obesity can occur we need to understand the different types of anesthesia and their typical side effects. Also, by differentiating these, we can know if these possible side effects interconnect. By knowing this, we can separate each type to the appropriate fields like dentistry, surgery, gynecology, pediatrics, and others.There are many different types of anesthesia and how they are administered. In a study conducted by Robinson et al. (8), the authors explain in detail the different types of anesthesia that are being used and how they are administered. The first type of method for the administration of anesthesia is by an endotracheal tube. It is used in order to clear an individuals airway if they have a blockage or their airway is compromised in any other way. It was first used/made by Dr. Joseph ODwyer, a pediatrician. Its placement to the trachea was actually by accident (8). This tube is usually used for surgeries that are done in the mouth, throat, face, and or lungs. This invention was used and also upgraded. Even though the tube did go through to the trachea, there were some margins of error, like not having enough room to inspire and expire properly. Many revisions were made to this device and it is still being used today. Such systems that were developed like the insufflation method, the Boyle machine, and the Coleman economizing device are a couple of examples that have been used and upgraded the process of administering anesthesia over a long period of time. Even Mortons facemask was discarded and replaced with a better model (8).The insufflation method was used in order to administer the anesthesia and oxygen properly at the same time. Samuel Meltzer and John Auer are credited with pioneering this technique. This didnt focus on the patients respiration, which placed the patients safety at risk. This is why it was tested mostly on animals (8). It would be inhumane and unethical to test this on actual people since the risk of physically harming them or even causing the death of the participants is too high. Another disadvantage of this method is that it is only limited to two types of gases which makes this method itself very limited and not very effective (8). As stated previously, even if the administration of the gas and oxygen was a success, there cannot be any type of generalization among the animal participants towards human patients, so overall this method is very influential, because it will provide a basis or foundation for later modes of anesthesia administration. A later type of delivery system was the Boyle machine.This machine was named after its creator Edmund G. Boyle and his fellow partner James T. Gwathmey. This worked more so as the first step in a two-step operation. The Boyle machine had the ability to estimate the flow of gas being released by the amount of bubbles that were being formed within the water (8). This device acted as a foundation to the Coleman economizing device. The Coleman economizing device is already much more efficient than the insufflation method. This is because it resolves the problem of respiration. Instead of solely focusing on the flow of anesthesia and oxygen, the Coleman economizing device takes care of the respiration issue while controlling the flow of gas and oxygen at the same time. It does this by the use of its air hose, which is used as an exit pathway for carbon dioxide while still administering optimal oxygen and limited anesthetic gas (8). This eliminates the issue of testing with humans. Now that it is much safer to use, humans can actually benefit from the product. Also another advantage to this, is that, there is no limit to only ether and chloroform. With the right measurements, and calculations, any type of anesthetic gas can and should be able to be administered. The only flaw is that, depending on the gas chosen and its strength, the risk of it being toxic and anesthesia poisoning is increased. This is where the modern mask was introduced. It held the capability of minimizing this risk by having the nose covered as well as the mouth, so this eliminated the need for nose clips (8). Even though all of these different types of developing anesthesia administration methods were tested and scrutinized over a long period of time, there are still many more types of delivery methods. A delivery method isnt necessarily characterized as being a pathway or physical device. The delivery method can be also be a type of anesthetic drug.In order to identify which is a viable source to relieve pain, each drug has to be tested. The way that many physicians, including Dr. Pierre-Cyprien Or, thought of this method is if they tested whether each type of drug could be taken intravenously, instead of inhaling a minute amount of the anesthetic drug (8). Or was the first to succeed with trying this method. There are many unethical issues that follow his method, which would probably explain why his accomplishment wasnt as popular as it should have been. A reoccurring problem that was the main issue was the inability to control side effects. By giving these patients drugs and essentially treating them like laboratory mice, Dr. Or was putting their lives at risk for numerous complications including the risk of death. After the side effects got worse, another physician, Dr. John Lundy, came up with a less dangerous method in testing which drug, or combination of drugs was the most effective, beneficial, and had the least amount of risk. Both experiments were still conducted on humans, which still retain some amount of risk. Ores method only used the pure concentration of one anesthesia at a time. This could explain why there was such an array of side effects present in many of his patients. Dr. John Lundy was the first physician to come up with the idea of balanced anesthesia. This concept has been seen before when I previously explained Dr. Emery Browns theory of the relationship between ketamine and anesthesia. Robinson et al. (8) describes Lundys theory of balanced anesthesia. They state that, by using a combination of drugs for general anesthesia, a smaller dose of each drug could be used. He postulated that this would lead to fewer side effects (8). What Dr. John Lundy may have overlooked is the importance of chemical compatibility. If this balance isnt accomplished, this could lead to even worse side effects than if he were to just use the pure concentration of one anesthetic drug. The emphasis on a stable combination to work together must be clear and taken into account.Using the wrong drug combination could be due to the drugs itself not being compatible with each other causing a negative reaction (8). Another explanation could be that the dosage would be incorrect for one or each drug causing detrimental side effects (8). Or it could be that patient itself that isnt compatible with the combination of anesthetic drugs given. Every person is different and with these drugs, there cannot be any generalization among a population. This means that a young adolescent cannot be given the same exact combination of drugs with the same exact dosage that is given to an elderly woman (8). There has to be a limit for which drugs and how much of those drugs should be given to an individual. By knowing this, we can have a sense of control over certain side effects, and with this control we can have a better understanding of what the triggers are for those side effects. Vomiting or nausea, bloating, headaches, fatigue and loss of memory are a few common side effects that can occur after the administration of anesthesia (10). What isnt so common may be an increase or decrease in body weight. William T.G. Morton was the discoverer of anesthesia, and every source reports evidence stating the surgery that he conducted was a success, but there is no word on the actual patient and whether there was a presence of side effects such as a higher risk for obesity.The Background of Ebenezer FrostWilliam T.G. Mortons surgery that used ether as an anesthesia was a success, but there is little information on whether the patient experienced any side effects to the ether. The patients name was Ebenezer Hopkins Frost (9). The reason why Frost participated as the patient was because he was suffering from a toothache. Morton took advantage of his tooth and made this the opportunity to try out his craft. Both parties were very lucky that there were no complications. Frost was his first participant even though Morton tested his ether anesthesia on several animals and himself. His patient could have not awoken or even worse, died from the amount of ether he inhaled from Mortons handkerchief, but as described in the article written by Ryan LeVausseur and Sukumar Desai, Frost survived with little to no side effects (9). After the experiments success, Frost never really received any recognition for his bravery. On top of that, he went into this experiment completely blind, meaning he was not aware of the experimenters true intentions. Morton never even told him that he would be the first subject he has tested his anesthesia on, and Frost wasnt aware of Dr. Mortons true intention for his demonstration. This would never be allowed to happen today, due to ethical concerns. There are too many risks and only one party is aware of what is actually happening in the experiment.

The elegant faade of Morton's superb performance on that fateful day has been chipped away as more of his earlier exploits surface. As many of his contemporaries had warned, Morton was a villain. Alone, he did not have the scientific knowledge or training to develop and bring to fruition this medical breakthrough. However, the daring he did possess was proven even more important. Thus, we must not dismiss how he employed his talents to draw out information from his resources. He learned from Wells' mistake of using a less potent agent, he heeded Jackson's recommendation to use the more suitable ether, and finally he paid attention to Gould's warning about asphyxiation from rebreathing exhaled gas. He experimented on animals, himself, and Eben Frost before he was emboldened to attempt a public demonstration. (9)

Ebenezer Frosts death was not connected to the ether that he inhaled during his impromptu surgery with Dr. Morton, but this doesnt mean that no side effects will ever appear. No generalizations can be made because Frost is only one individual and cannot represent a whole population. It could be that Dr. Morton administered just the right amount to Frost so that it wasnt harmful to him. There were a couple of studies done with different types of anesthesia that may shed some new information on possible side effects. The first study was conducted by Rahmanian et. al (3) and tested if there was a significant result with using ketamine as a pain reliever. Using a lower dosage of ketamine increased the effectiveness of the anesthesia and its ability to relieve the patients pain with minimal to no side effects. This is important because this shows that using a smaller amount of anesthesia can be just as effective as a normal dosage. Another experiment was done on a pregnant patient and the objective was similar; to test whether there was any significant effect from the use of a spinal block. This was conducted by Ronenson et. al. (6) and the primary endpoint of the study was the frequency of hypotension (6). How they tested the women was by separating them into two groups. One of the groups was given the anesthesia for their cesarean section while the anesthesiologist took to the consideration of the intra-abdominal pressure. The second group was also given anesthesia, but there was no recognition of the womens intra-abdominal pressure. The significance of this study was to show whether there was a big difference between the two groups based on the amount of anesthesia given and the amount of intra-abdominal pressure exhibited in pregnant women. The significance from the results also showed that the decreased amount of anesthesia could be used to control the severity of the anesthesias side effects and its ability to manage pain (6). This shows that there is a positive relationship between the amount of anesthesia usage and the degree of its side effects. Its clear that the use of anesthesia in these pregnant women is relatively normal with little to no side effects. The question of whether obesity has an effect on anesthesia is still ambiguous. We can examine studies that focus on the results coming from an obese source meaning that maybe obesity is the independent variable rather than the dependent variable. There are two studies that were conducted on participants who were overweight or obese. M. Carron and S. Veronese wrote the first article (5), and an excerpt from the Abstract described the common correlation between every study that I have paid attention to in this essay. They wrote this saying, For the treatment of bradycardia atropine sulfate should be adjusted at least to lean body weight in order to avoid paradoxical heart rate response in patients with obesity (5). This statement basically means that for obese patients, the concentration of anesthesia per kg bodyweight should be decreased instead of increased. By decreasing their dosage, the risk of possible anesthetic poisoning is lowered and the effectiveness of the drug is still optimal. This same phenomenon is present in the second article as well. The next article is about the relationship between obesity and lung cancer. (4) The result was that there wasnt any relationship between the two, but as predicted, the same result of using fewer anesthetics is favored. Another particular phenomenon that can looked at is the obesity paradox (4). Rivera et. al (4) describe what this is when interpreting their results. They concur that, Obesity does not contribute to the occurrence of lung cancer, unlike other malignancies. Patients may be more likely to undergo treatment at lower risk. Regarding surgery, obesity makes anesthesia more difficult, increases the operative duration but does not increase postoperative morbidity and mortality. Chemotherapy and radiotherapy seem to be administered according to the same criteria as patients with normal weight. Paradoxically, survival rates of lung cancer are better in obese patients as well after surgery than after non-surgical treatment (4). It is shown in several of the studies that the smaller amount of anesthesia is more effective than a normal dosage. The answer to this paradox still remains unclear, but what is clear, is that there is a significant relationship between obesity affecting the effectiveness of anesthesia and its dosage. The more obese an individual is, the less the amount of anesthesia their body will need in order for the drug to be effective.ConclusionThe study of anesthesia has been evolving ever since William T.G. Mortons discovery of ether as an anesthesia and his public demonstration on September 30, 1846 (8). The field has grown to be a broad range of different types of delivery and different types of anesthesia. The wide range of side effects that used to plague patients is now miniscule. There is evidence of a persons obesity affecting the effectiveness of an anesthesia that is being used. The common misconception was that the higher the body weight, the higher dosage of anesthesia should be used. This means that an individuals body weight is directly proportional with anesthesia dosage. This is incorrect. This evidence is present in more than one study. The truth is that the higher the individuals body weight, the less of an amount of anesthesia is needed/effective. This conception refers to non-obese people as well. This is due to the fact that, in obese individuals, the subcutaneous adipose blood flow is lower (1). Using a lower concentration of anesthesia helps minimize the strength of side effects and the pain.

Literature Cited 1. Brill, Margreke J. E., Houwink, Aletta P. I., Schmidt, Stephan, Van Dongen, Eric P. A., Hazebroek, Eric J., Van Ramshorst, Bert van, Deneer, Vera H., Mouton, Johan W., and Knibbe, Catherine A. J. Reduced subcutaneous tissue distribution of cefazolin in morbidly obese versus non-obese patients determined using clinical microdialysis. Journal of Antimicrobial Chemotherapy 2014; 69: 715-723.2. Boveri, S., JC Brearley, and AH Dugdale. The Effect of Body Condition on Propofol Requirement in Dogs. Veterinary Anaesthesia and Analgesia 2013; 40: 449-54.3. Rahmanian, M., M. Leysi, AA Hemmati, and M. Mirmohammadkhani. The Effect of Low-dose Intravenous Ketamine on Postoperative Pain following Cesarean Section with Spinal Anesthesia: A Randomized Clinical Trial. Oman Med J; 114. Rivera, C., N. Pecuchet, D. Wermert, C. Pricopi, F. Le Pimpec-Barthes, M. Riquet, and E. Fabre. Obesity and Lung Cancer: Incidence and Repercussions on Epidemiology, Pathology and Treatments. Revue De Pneumologie Clinique 2015; 71: 37-43. 5. Carron, M., and S. Veronese. Atropine Sulfate for Treatment of Bradycardia in a Patient with Morbid Obesity: What May Happen When You Least Expect It. BMJ Case Reports 20156. Ronenson, AM, SI Sitkin, and LuV Savel'eva. Effect of Intra-abdominal Pressure in Pregnant Women on Level of Spina Block and Frequency of Hypotension during Cesarean Section. Anesteziologiia I Reanimatologiia 2014; 59: 26-29.7. Morris, S.D., A.J. Morris, and M.A. Rockoff. Freeman Allen: Boston's Pioneering Physician Anesthetist. Anesthesia and Analgesia 2014; 119: 1186-193.8. Robinson, Daniel H., and Alexander H. Toledo. Historical Development of Modern Anesthesia. Journal of Investigative Surgery 2012; 25: 141-49.9. LeVasseur, R., and S.P. Desai. Ebenezer Hopkins Frost (1824-1866): William T.G. Morton's First Identified Patient and Why He Was Invited to the Ether Demonstration of October 16, 1846. Anesthesiology 2012; 117: 238-42.10. You Won't Feel A Thing: Your Brain On Anesthesia. NPR 2011