Data from a retrospective study of 636,051 patients showed that although the presence of fever in the first 24 h after ICU admission was associated with an increased risk of mortality in patients without infection, it was associated with a decreased risk of mortality in those with an infection [11]. In this study the adjusted in-hospital mortality risk progressively decreased with increasing peak temperature in patients with infection. Similarly, Weinstein and colleagues reported that patients with spontaneous bacterial peritonitis had improved survival if they had a temperature greater than 38 °C [12]. While fever is generally regarded as a beneficial response to infection, up to 70 % of ICU patients with a fever are treated with antipyretic agents [13]. Yet, the preponderance of data suggest that treating a fever in this setting is harmful. Schulman et al., investigated the benefit of fever control in patients admitted to a trauma ICU [14]. Patients were randomized to an active treatment group in which acetaminophen and cooling blankets were used to aggressively cool patients as compared to a permissive group in which fever was only treated once it reached 40 °C. In this study there was a strong trend towards increased mortality in the active treatment group; all the patients who died in the aggressive treatment group had an infectious etiology as the cause of the fever. Lee et al. performed a prospective observational study to determine the association between antipyretic treatment of fever and mortality in 1,425 critically ill patients with and without sepsis [15]. These authors demonstrated that that treatment with non-steroidal anti-inflammatory drugs or acetaminophen independently increased 28-day mortality for septic patients (OR: NSAIDs: 2.61, p = 0.028, acetaminophen: 2.05, p = 0.01), but not for non-septic patients. Doran et al. demonstrated that children with varicella who were treated with acetaminophen had a more prolonged illness [16]. Bernard and colleagues conducted a randomized, double-blind, placebo-controlled trial of intravenous ibuprofen given every 6 h for 8 doses in 455 patients who had severe sepsis [17]. In this study treatment with ibuprofen decreased fever, tachycardia, oxygen consumption, and lactic acidosis, but it did not prevent the development of shock or ARDS and did not improve survival Against this background of convincing evidence demonstrating the harm of antipyresis in patients with sepsis, Schortgen and colleagues performed a multicenter, RCT in which vasopressor dependent febrile patients with septic shock were randomized to external cooling to achieve normothermia for 48 h or no external cooling [18]. In this study, there was a greater reduction of pressor use, more rapid shock reversal and a lower mortality at 14 days (19 vs. 34 %; p = 0.013) in the cooling group. However, the difference in mortality was no longer significant at ICU or hospital discharge. Based on the results of this single study and the fact that fever is widely believed to be beneficial in the setting of infection external cooling cannot be recommend at this time. This study however does raise the possibility that external cooling may be beneficial in vasodilatory shock while anti-pyretic agents may be harmful. The HEAT trial is an ongoing prospective, multicentre, concealed, RCT comparing the administration of acetaminophen for antipyresis with a permissive temperature strategy in critically ill patients with known or suspected infection [19]. The results of this study should hopefully help resolve this controversial issue.

In contrast to patients with infectious disorders, patients with acute cerebral insults (ischemic stroke, hemorrhagic stroke, SAH, head injury, post cardiac arrest) have worse outcomes with increased temperature. For these patients the current recommendation is to maintain the patient’s temperature in the normothermic range. Antipyresis must always include an anti-pyretic agent, as external cooling alone increases heat generations and catecholamine production [20]. Furthermore, acute hepatitis may occur in ICU patients with reduced glutathione reserves (alcoholics, malnourished etc.) who have received regular therapeutic doses of acetaminophen.

Fever from an infectious cause should not be treated unless the patient has limited cardio-respiratory reserve or the temperature exceeds 40 °C (104 °F).

The prevalence of nosocomial infection in ICUs has been reported to vary from 3 to 31 %. The most common nosocomial infectious disorders are listed below [22, 23]:

Note: Catheter Associated Urinary Tract Infection (CAUTI) is an exceedingly uncommon cause for a patient developing a fever in the ICU (see Chap. 16—Hospital Acquired Infections)

A large number of non-infectious conditions result in tissue injury with inflammation and a febrile reaction. Those non-infectious disorders which should be considered in ICU patients are listed below. For reasons that are not entirely clear most non-infectious disorders usually do not lead to a fever in excess of 38.9 °C (102 °F); therefore, if the temperature increases above this threshold the patient should be considered to have an infectious etiology as the cause of the fever [24]. However, patients with drug fever may have a temperature >102 °F. Similarly, fever secondary to blood transfusion may exceed 102 °F. In patients with a temperature above 40 °C (104 °F) neuroleptic malignant syndrome, malignant hyperthermia, the serotonin syndrome and subarachnoid hemorrhage must always be considered. Most of the clinical conditions listed below are clinically obvious and do not require additional diagnostic tests to confirm their presence. However, a few of these disorders require special consideration.

The most common non-infectious causes of a fever in ICU patients include drug fever, transfusion of blood and blood products, alcohol withdrawal, postoperative fever and thromboembolic disease. Acalculous cholecystitis is a relatively uncommon cause of fever in ICU patients; however, as it may be associated with severe morbidity and mortality it should always be considered in the differential diagnosis.