Fever in the ICU: More Questions Than Answers
By Karen L. Johnson, RN, PhD, CCRN
Have you noticed that there are some critically ill patients who seem to get "better" once we stop treating them? Sometimes in spite of all our technology, formulas, and invasive monitoring . . . less is better? It’s a phenomenon I have called "therapeutic neglect." And it may be that therapeutic neglect is the most effective treatment for fever in the non-brain injured critically ill adult patient. This article reviews what we know about fever, how to evaluate it, and how to manage it. Unfortunately, at the conclusion of this review, you will have more questions than answers.
What is Fever?
Fever has been defined as a "state of elevated core temperature, which is often, but not necessarily, part of the defensive response of multi-cellular organisms (host) to the invasion of live (microorganisms) or inanimate matter recognized as pathogenic or alien by the host."1 Fever is a component of the febrile response. Clinically, fever has been defined as a temperature greater than 38.3°C (101°F).2 The febrile response is a complex physiologic response that involves activation of the immune and neuroendocrine systems. The increase in body temperature that occurs during fever (hyperpyrexia) must be distinguished from hyperthermia.
Hyperthermia and hyperpyrexia are different conditions. Hyperthermia is the result of hypothalamic injury or excessive environmental heat and a loss of compensatory cooling responses. Hyperthermia involves dysfunction of thermoregulatory ability. In hyperpyrexia, thermoregulatory responses remain intact, although body temperature is maintained at a higher level.
Humans maintain a fairly constant internal temperature (36.2-37.8°C). Any deviation from this range prompts physiologic warming or cooling mechanisms. Thermal balance is accomplished by a thermoregulatory control loop. Receptors, distributed throughout the body, receive and integrate thermal inputs from internal and external stressors. These inputs are sent via ascending pathways to the hypothalamus. In the hypothalamus is a "thermostatic comparer" region that detects deviations from the set point range. Any deviation triggers cooling/warming responses to correct the deviation.
Fever appears to run a dynamic course of 3 distinct phases beginning with the rapid production of heat.3 The initial phase is the "chill phase." The sensed discrepancy between existing temperature and the new set point makes the febrile patient complain that he or she "feels cold." Chills may be present. The second phase is the "plateau phase." Here, warming responses have driven central temperatures to a new set point range. Now normal thermoregulation is maintained at a higher temperature. The third phase, "defervescence," occurs as diaphoresis and flushing promote heat loss through evaporation and radiation. The hypothalamus then resets to euthermic levels.
What is the Pathogenesis of Fever?
Cytokines play a key role in the pathogenesis of fever. The primary cytokines involved include tumor necrosis factor (TNF-alpha), and interleukins one and six (IL-1, IL-6). These cytokines bind to specific receptor and results in the liberation of arachidonic acid as substrate for the cyclo-oxygenase pathway. Prostaglandin E-2 diffuses across the blood brain barrier and decreases the firing rate of warm sensitive neurons, which leads to responses designed to decrease heat loss and increase heat production.4
Questions about the risks and benefits of fever have generated much controversy. There is the argument (based on what we know in the animal kingdom) that fever may be beneficial. Most reptiles, mammals, amphibians, and fish have been shown to manifest fever in response to a microorganism challenge. This has been viewed as evidence that fever is an adaptive response because the metabolic increase in body temperature, which accompanies the febrile response, would not have evolved and been preserved unless fever had some net benefit to the host.5 Increased body temperature has been shown to enhance the resistance of animals to infection.6 Elevated temperatures have also been shown to enhance immune function including antibody production, T-cell activation, production of cytokines, and enhanced neutrophil and macrophage function.4 The benefits of fever must be considered in conjunction with known adverse effects, particularly the effect of increased metabolic rate. This is especially important in critically ill patients who are already metabolically taxed. Oxygen consumption has been shown to increase by 10% per degree Celsius.7
How Should Fever be Evaluated in the ICU?
In many ICUs, a newly elevated temperature in a patient triggers an automatic order set, which includes multiple diagnostic tests that are time consuming and expensive (see Table 1). In an era when use of hospital resources is under intense scrutiny, it is appropriate to assess how such fevers should be evaluated in a prudent and cost-effective manner. Recognizing this need, a task force with members from the American College of Critical Care Medicine, Society of Critical Care Medicine, and the Infectious Disease Society of America developed the "Practice parameters for evaluating new fevers in the ICU," which have been published elsewhere.2 The parameters were developed with the goals of promoting rational consumption of resources and promoting an efficient evaluation of onset of new fever in critically ill patients.
Table 1
Typical Costs Associated with Fever Evaluation
Test Costs Blood cultures (× 2) $50 Urine culture & sensitivity $19 Sputum culture & sensitivity $28 Wound culture & sensitivity $19 Portable chest x-ray $75 Total $191When Should Fevers be Treated?
There is a strong tendency to treat fever as an abnormal pathologic condition that should be corrected as soon as possible.8 Choices to intervene aggressively should be made with the individual patient’s physiologic status in mind. In patients who have compromised cardiac, pulmonary, or neurologic systems, the metabolic costs of fevers may outweigh potential benefits.3,8,9 The following recommendations have been made for patients without brain injury: 1) Do not treat mild temperature elevations up to 39°C. There are few detrimental effects and the immune system may be enhanced with mild temperature elevations; 2) Do treat high fevers (> 39°C) or rigors and shivering.3,8,9 Most papers reviewed by Holtzclaw3 agreed that fevers ³ 40°C do not enhance the immune process and should be avoided.
How Should Fevers be Treated?
Almost all ICU patients who become febrile are treated with an antipyretic and an external cooling method to render the patient afebrile.4 Antipyretics affect the hypothalamic set point, although their precise mechanism of action is not fully understood. It is thought that antipyretic therapy with cyclooxygenase inhibitor drugs (ASA, acetaminophen, NSAIDs) prevents the conversion of arachidonic acid to Prostaglandin E-2 and Thromboxane A-2. If decisions are made to treat fever, based on physiologic knowledge, the treatment of choice should be prostaglandin inhibitors such as antipyretic drugs to alter brain regulation.10 But there are more questions than answers with regard to the use of these drugs in the treatment of fever. How well are antipyretics absorbed in the gut of critically ill febrile patients? Which type of antipyretic is most effective for treating fever? Which route of administration is most effective?
In an extensive review of the literature on fever related interventions, Henker11 found the following: 1) fever is known to alter gastrointestinal motility, and changes in motility have additional effects on the pharmacokinetics of antipyretics such as acetaminophen; 2) there are no published reports of studies that have compared the effects of various antipyretics on fever in the critically ill adult; and 3) no comparison of the route of administration of antipyretics in critically ill adults has been reported.
What is the Most Effective Method of External Cooling?
External cooling methods are interventions aimed at promoting heat loss through a variety of means (see Table 2). The application of exogenous cooling for treatment of fever is frequently at the discretion of nurses.12 O’Donnell et al13 found that 74% of all hypothermia units requested from central supply during a 1-year period were requested by critical care units. However, only 15% of the patients had a physician order for the cooling blanket. Communication between physicians making diagnostic decisions and the nurses administering cooling interventions is imperative.3
|
Table 2 |
|
|
External Cooling Interventions |
|
| Intervention | Method of Heat Loss |
| Sponge Bath | Evaporative |
| Ice packs, cooling blankets | Conductive |
| Fan | Convective |
| Skin exposure | Radiation |
Hypothermia blankets are frequently used in ICU patients with febrile episodes. Two studies have demonstrated that hypothermia blankets were no more effective in cooling patients than antipyretics alone.13,14 Rainer and colleagues15 found that oxygen consumption rose 35-40% during hypothermia blanket therapy for febrile subjects. Henker11 concluded that there continue to be more questions than answers with regard to the use of hypothermia units: 1) Where should the cooling blanket be placed (under the patient vs over the patient)?; and 2) At what temperature should one set the hypothermia unit? No reports of studies that compared the effectiveness of anterior vs. posterior placement were found. We have long believed that placing the blanket under the patient increases body surface area in contact with the cooling blanket. But we have also been concerned that the cold blanket and its vasoconstricting action on the peripheral skin of the sacral region predispose the patient to sacral decubitus formation. What is the incidence of sacral decubitus formation in patients on hypothermia units?
At what temperature should the hypothermia unit be set? Many nurses believe the hypothermia unit should be placed at the lowest temperature possible in an effort to bring down the patient’s temperature. The effects of 4 cooling blanket temperatures (7.2°C, 12.8°C, 18.3°C, 23.9°C) on the rate of temperature decrease was evaluated and found to have no difference in the amount of time required to decrease temperature.16
Sponge baths cause evaporation. Several early studies demonstrated that sponge baths were no more effective in lowering body temperature than antipyretics alone.14,17 However, a more recent study reported that the application of a sponging protocol (cloths plunged into ice water and placed on most of the body surface and changed every 15-30 min) resulted in decreased temperature (mean 39.1°C to 37.1°C; P < 0.0001), a decrease in energy expenditure (mean 2034 mL/min to 1791 mL/min; P < 0.004) and decreased oxygen consumption by 12%.9 Large prospective studies using randomization procedures are needed to more fully evaluate the effects of sponge baths on the febrile response.
Nurses often use ice packs, which are placed on the groin or axilla to promote the loss of heat by conduction. Despite the widespread use of ice packs, there have been no studies of their efficacy. Despite widespread use of fans, there are no studies that document their effectiveness in cooling febrile patients.
So to answer the question, of which if any of these external-cooling measures is most effective, one must ask, are any of these measures effective at all? In a recent study on the effect of external cooling, Gozzoli and colleagues9 found that fever resolved within 24 hours with or without external cooling. Physiologically, it is counter-productive to use external cooling measures because they go against the body’s compensatory mechanisms. Externally cooling the body without changing the regulatory set point in the hypothalamus will lead to the generation of heat through shivering. External cooling should not be considered for conventional treatment of fever in the critically ill adult patient, but it should be reserved for cases in which it is necessary to reduce fever and metabolic demand in patients who are resistant to antipyretic drugs.9,10
More Questions
Think about the treatment of fever in your own practice. How is fever defined? How are fevers evaluated? When are fevers treated? How are fevers treated? Do you use antipyretics? By what route are they given? Are they effective? Do you use external cooling measures? If so, which ones? Is there good communication between the physicians and nurses as to the selection of these interventions? Does your institution use hypothermia blankets? Are they placed over or under the patient? At what temperature is the blanket set? Do the nurses use ice packs, sponge baths, and/or fans? Do any of these measures really work to decrease fever and oxygen consumption? Like many clinical situations in the ICU, we have multiple fancy gadgets to get data, but we’re not sure how to act on the data. Once again, we’re left with more questions than answers.
References
1. IUPS Thermal Commission. Glossary of terms for thermal physiology (2nd ed). Pflugers Arch. 1987; 410:657-587.
2.. O’Grady NP, et al. Practice parameters for evaluating new fever in critically ill adult patients. Crit Care Med. 1998;26:392-408.
3. Holtzclaw BJ. The febrile response in critical care: State of the science. Heart Lung. 1992;21:482-501.
4. Marik PE. Fever in the ICU. Chest. 2000;117:855-869.
5. Mackowiak PA. Concepts of fever. Arch Intern Med. 1998;158:1870-1881.
6. Kluger MJ, et al. Fever and survival. Science. 1975; 188:166-168.
7. Manthous CA, et al. Effects of cooling on oxygen consumption in febrile critically ill patients. Am J Respir Crit Care Med. 1995;151:10-14.
8. Saper CB, Breder CD. The neurologic basis of fever. N Engl J Med. 1994;330:1880-1886.
9. Gozzoli V, et al. Is it worth treating fever in intensive care unit patients? Arch Intern Med. 2001;161:121-123.
10. Henker R, Shaver J. Understanding the febrile state according to an individual adaptation framework. AACN Clinical Issues in Critical Care. 1994;5:186-193.
11. Henker R. Evidence based practice: Fever related interventions. Am J Crit Care. 1999;8:481-487.
12. Isaacs SN, Axelrod PI, Lorber B. Antipyretic orders in a university hospital. Am J Med. 1990;88:31-35.
13. O’Donnell J, et al. Use and effectiveness of hypothermia blankets for febrile patients in the intensive care unit. Clin Infect Dis. 1997;24:1208-1213.
14. Morgan SP. A comparison of three methods of managing fever in the neurologic patient. J Neurosci Nurs. 1990;22:19-24.
15. Rainer L, et al. The effects of physical treatment on induced fever in humans. Am J Med. 1999;106: 550-555.
16. Caruso CC, et al. Cooling effects and comfort of four cooling blanket temperatures in humans with fever. Nurs Res. 1992;41:68-72.
17. Newman J. Evaluation of sponging to reduce body temperature in febrile children. Can Med Assoc J. 1985; 132:641-642.
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