In this weeks class, we introduced the idea of normal in medicine. What is normal? Can the concept of adaptation help guide what to do with an “abnormal finding”? We confront these questions all the time in the hospital. Now it is your turn to weigh in.
Lets start with a patient case: He is 48 years old, with a history of alcohol abuse, and a fever for 2 days. He has been coughing with grey sputum and bloody streaks for the last 24 hours. Increasingly short of breath, he calls 911 and is brought to the emergency department.
His chest x-ray looks like this:
His temperature is 40°C. Anything above 38°C (100.4 °F) is considered a fever.
Blood cultures are drawn and antibiotics given. He is transferred to the ICU because his oxygen levels and blood pressure continue to drop. In the ICU, his doctor diagnoses him with septic shock. She also orders a dose of acetaminophen (also known as tylenol or paracetamol) to reduce the fever. Medications like tylenol that reduce fever are known as antipyretics, and are commonly prescribed for febrile patients in and out of the hospital.
Was the tylenol a good move or a bad one?
Evidence from animal studies support the view that fever is beneficial (read the abstracts in the links in this section). Matthew Kluger back in the early 1970s showed that a behavioral fever was critical in keeping lizards alive after experimental infection with gram-negative bacteria. Kluger subsequently showed that fever improves bacterial killing by immune cells.
One relevant fact, arguing for the evolution of fever, is the fact that it exists in a wide variety of organisms, as reviewed here. Even some invertebrate organisms exhibit a behavioral fever, including grasshoppers, honeybees and snails. Animal studies suggest that antipyretic use (aspirin) increases mortality from Streptococcus pneumoniae infection With these lines of evidence, you would think that we should certainly not treat fever with tylenol. But we still do, all the time. The human data is not as clear as the animal studies. Some evidence suggests that treating fever is not harmful for our patients.
Carefully read all the links in this section:
1) Young and Saxena’s review in the journal Critical Care on fever and its treatment.
“Remarkably, at present we do not know what effect treating fever in critically ill patients with infections has on patient-centered outcomes.” In other words, legitimate controversy exists about whether to give a patient tylenol or not.
2) Drewry and Hotchkiss argue for giving antipyretic treatment for patients with sepsis (blood infection).Point- Should Antipyretic Therapy Be Given Routinely to Febrile Patients in Septic Shock? Yes
3) Moer and Doerschug argue against using antipyretics in sepsis.Counterpoint- Should Antipyretic Therapy Be Given Routinely to Febrile Patients in Septic Shock? No
Optional: Schortgen et al, about using external cooling blankets for critically ill patients. I recommend reading this if you think we should be treating fever.
Writing assignment – consider the following statement (Young and Saxena 2014):
“arguments based on the evolutionary importance of the febrile response do not necessarily apply to critically ill patients who are, by definition, supported beyond the limits of normal physiological homeostasis. Humans are not adapted to critical illness.”
This logic was expressed by Foddy (2012) who wrote: “The argument from evolution assumes some degree of continuity in environmental circumstances, but at present there are strong discontinuities in the structure of our world. Given these changes, it would be foolish to place too much trust in the adaptive quality of traits that evolved across aeons of nomadic hunting and gathering.” One such discontinuity is the availability of ICU care, right?
On the other hand, consider the argument from Fukuyama (2002) who wrote:
“There are good prudential reasons to defer to the natural order of things and not to think that human beings can easily improve on it through causal intervention. This has proven true with regard to the environment: ecosystems are interconnected wholes whose complexity we frequently don’t understand, building a dam or introducing a plant monoculture into an area disrupts unseen relationships and destroys the system’s balance in totally unanticipated ways. So too with human nature … doing nature one better isn’t always that easy, evolution may be a blind process, but it follows a ruthless adaptive logic that makes organisms fit for their environments.”
Depending on your point of view, fever, even if evolved, might or might not be helpful or adaptive for our sickest patients. The ICU is a novel environment that keeps (some) patients alive who would otherwise die. It is not the environment that humans evolved in (think gene-environment mismatch). With this in mind, do you think that evolution and adaptation is irrelevant for hospital patients who are closest to death? Defend your answer with your own logic, and with examples from the readings and quotations above. Should we treat patients with fever in the ICU with tylenol (yes or no)?
Strongly recommended – listed to this excellent talk by an expert on fever:
Skip the intro by going to minute 3:48.
Additional optional references:
Best and Schwartz. Fever Evolution Medicine and Public Health (2014) 2014 (1): 92. doi: 10.1093/emph/eou014
Fukuyama, F. (2002). Our posthuman future: consequences of the biotechnology revolution. New York: Farrar, Straus and Giroux.
Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine