Received: 15 March 2002Accepted: 4 September 2002Published online: 4 October 2002© Springer-Verlag 2002

Abstract Objectives: (a) To quanti-fy the occurrence of pyrexia duringthe first week after head injury; (b)to elucidate the relationships be-tween pyrexia and neurological se-verity, length of stay in the ICU, in-tracranial hypertension, and cerebralperfusion pressure (CPP); and (c) todescribe the effects of antipyretictherapy on temperature, intracranialpressure (ICP) and CPP. Design andsetting: Multicenter retrospective ob-servational study in three ICUs inthe Milan area. Patients: 110 pa-tients with traumatic brain injury.Measurements and results: Eightypatients suffered pyrexia, defined asan external temperature higher than38°C or internal temperature higherthan 38.4°C. Occurrence and dura-tion of pyrexia were associated withthe degree of neurological impair-ment and with prolonged ICU stay.In patients with normal perimesence-phalic cisterns the episodes of in-

creased ICP were more frequent infebrile cases. Various antipyretictherapies were used in 66 patients.Pharmacological treatment wasslightly effective (mean temperaturereduction 0.58±0.7°C) but caused asignificant drop in CPP(6.5±12.5 mmHg). Conclusions: Py-rexia is extremely frequent in theacute phase after head injury. Its in-cidence is higher in more severecases and is correlated with a longerICU stay. It may affect ICP, but itscontribution is difficult to assesswhen other major causes of in-creased intracranial volume are present. Antipyretic therapy is poor-ly effective for controlling body tem-perature and may be deleterious forCPP.

Keywords Antipyretic therapy ·Brain injury · Cerebral perfusionpressure · Pyrexia · Intracranial pressure

Intensive Care Med (2002) 28:1555–1562DOI 10.1007/s00134-002-1513-1 O R I G I N A L

Nino StocchettiSandra RossiElisa Roncati ZanierAngelo ColomboLuigi BerettaGiuseppe Citerio

Pyrexia in head-injured patients admittedto intensive care

Introduction

Pyrexia exacerbates ischemic neuronal damage andphysiological dysfunction after acute brain injury [1].Various experimental models have demonstrated thatpostischemic injury is related to the degree of pyrexia [2,3, 4]. In a model of focal cerebral ischemia pyrexia sig-nificantly accelerated the transformation of partiallydamaged tissue to cerebral infarction [5]. The deleteriouseffect of pyrexia was confirmed in models of traumaticand cryogenic brain injury [6, 7]. In the clinical settingan association has been found between pyrexia and ini-

tial stroke severity, infarct size, mortality, and outcomein 390 patients admitted with acute stroke [8]. In patientswith intracerebral hemorrhage the duration of pyrexiawas associated with poor outcome [9]. Furthermore, in aseries of head injury patients admitted to intensive carethe duration of pyrexia was a significant predictor ofmortality [10].

Pyrexia affects the acutely injured brain in manyways: it increases glutamate release [11], arises oxygenradical production [12], markedly augments the perme-ability of the blood/brain barrier worsening edema [7],and increases cytoskeletal protein degradation [13]. In

N. Stocchetti (✉) · S. Rossi · E.R. ZanierA. ColomboTerapia Intensiva Neuroscienze, Ospedale Maggiore, Policlinico IRCCS,Via S. Sforza, 3520 122 Milan, ItalyTel.: +39-02-55035517Fax: +0039-02-55035560

L. BerettaNeurorianimazione Ospedale S. Raffaele,Milan, Italy

G. CiterioTerapia Intensiva Ospedale S. Gerardo,Monza, Italy

the experimental setting hypothermia seems to blunt thiscascade of events [14]. Mild or moderate hypothermiahas therefore been tested in patients with a view of re-ducing secondary brain damage [15, 16], controlling in-tracranial pressure [15, 17], and improving outcome[18]. However, a large series has not confirmed thatmoderate hypothermia is safe and effective in traumaticbrain damage [19].

Several clinical studies have shown that followinghead injury brain temperature exceeds core temperature.The mean difference between brain and core temperatureranges from 0.3 to 1.6°C, depending on the patient’s se-lection, on the thermocouples position, and on changesin clinical variables such as cerebral perfusion pressure(CPP) and the temperature itself [20, 21, 22, 23]. Thegap between brain and core temperature significantly in-creases as core temperature increases. This highlightsthat core temperature may markedly underestimate braintemperature while pyrexia is rising and emphasizes evenmore the importance of temperature control in the acutebrain-injured patient. Avoidance of pyrexia remains amajor aim in the management of severe head injury [24,25, 26]. However, this apparently simple goal is notcommonly achieved and pyrexia, and its treatment, isstill a clinical problem.

The goals of this study were: (a) to quantify the oc-currence of pyrexia during the first week after head inju-ry, (b) to elucidate the relationships between pyrexia andneurological severity, length of stay in the ICU, intracra-nial hypertension, and CPP, and (c) to describe the ef-fects of antipyretic therapy on temperature intracranialpressure (ICP) and CPP.

Materials and methods

We retrospectively studied 110 head-injured patients older than13 years admitted during 2 years (1996–1997) to three intensivecare units (ICUs). There were 93 men and 17 women (median age34 years, range 14–83). Median Glasgow Coma Scale (GCS) onadmission was 7 (range 3–14). Seven patients admitted with aGCS higher than 8 deteriorated during the first few hours. The ad-mission computed tomography revealed 23 epidural hematomas,38 subdural hematomas, 32 contusions, and 17 cases of diffusedamage. Forty-four patients had compressed or absent basal cis-terns. All epidural and subdural hematomas were surgically re-moved on admission.

All patients were treated according to the protocol describedelsewhere [27], based on combined surgical and medical treatmentof intracranial hypertension. ICP and CPP were recorded as theend-hour single value. Temperature was measured externallyand/or internally. External temperature was measured by axillarythermometers, internal temperature by rectal or bladder probes orby the thermistor part of Swan-Ganz catheters. The gold standardfor measuring core temperature is considered to be pulmonary ar-tery (PA) temperature. Rectal temperature has been shown to over-estimate PA temperature by 0.5°C in the perioperative period [28].This difference is probably due to the rectum’s insulation proper-ties when the core is rapidly cooled. However, a study by Ful-brook [29] found rectal temperature closely to reflect PA tempera-

ture, with a mean difference of 0.1±0.09°C when measured in ICUpatients over a 7-day period. In the absence of hemodynamic indi-cations, due to the highly invasive nature of the monitoring proce-dures it is not recommended to measure PA blood temperature. Inthis case either the bladder or the rectum is an accurate site formeasurement of core body temperature since both closely approxi-mate to PA blood temperature [29, 30, 31]. For the purpose of ourstudy temperatures measured by rectal or bladder probes or by thethermistor part of Swan-Ganz catheters were pooled under the cat-egory of internal temperatures.

The frequency of temperature measurement varied from hourlyto at least four times a day. Temperature was measured a total of7147 times, with 2846 external temperature readings in 88 patients(mean 26±30.4 measurements per patient) and 4301 internal mea-surements in 87 patients (average 39.1±44.7 measurements pa-tient). Both external and internal temperatures were measured in65 patients. Internal temperature was measured 3321 times by rec-tal probes, 768 by bladder probes, and 212 by Swan-Ganz thermis-tors. When internal and external temperatures were simultaneouslyrecorded, the mean difference was 0.4°C. We therefore definedpyrexia as an external temperature higher than 38°C or internaltemperature higher than 38.4°C [32]. Only temperature data col-lected during the first week after trauma were analyzed. Pyrexiawas classified based on the number of days in which at least oneepisode of pyrexia was detected. Quartiles were used to describethe duration. Pyrexia was treated in most cases with nonsteroidalanti-inflammatory drugs.

In some cases physical perfrigeration was induced by icepacks, alcohol rubs, or gastric lavage with saline at 4°C. The ef-fects of these interventions on systemic and intracranial parame-ters in the 4 h after antipyretic therapy were recorded. Outcomewas evaluated after 6 months according the Glasgow OutcomeScale using a structured interview [33]. The local ethics boardwaived the requirement for formal approval.

Data are presented as mean ±standard deviation in the case ofnormal distribution; medians were reported in the other cases. Theχ2 test or Fisher’s exact test when required was used to analyzedifferences in frequency among groups. Differences betweenlengths of stay (LOS) were assessed by the Kruskal-Wallis test be-cause this distribution is clearly non-normal. Logistic regressionwas used to identify independent predictors. For the analysis ofchanges in variables with two time points (before and after antipy-retic treatment) the paired t test was used, considering differenceswith a p value less than 5% as statistically significant.

Results

Frequency of pyrexia

Figure 1 shows the distribution of internal and externaltemperatures: 726 external temperature (26%), and 1395internal temperature recordings (32%) were above thethreshold of pyrexia. Eighty patients (73%) suffered pyrex-ia. Twenty-eight patients had one or 2 days when pyrexiawas detected (lower quartile); in 13 cases pyrexia occurredon 3 days, in 20 cases it persisted for 4–5 days and 19 pa-tients suffered pyrexia during 6 or 7 days (upper quartile).There was a strict relationship in each quartile between thedays of pyrexia and the time above the threshold of pyrex-ia, calculated as a percentage of the total temperature mea-surements. These percentages were 6% for patients in thelower quartile, 21% in the second quartile, 38% in the thirdquartile, and 54% in the upper quartile.

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Pyrexia and neurological severity

Occurrence and duration of pyrexia were associated withseverity of head injury (Table 1). Among the 23 patientswith GCS higher than 8, 11 did not suffer pyrexia; noneof the other 12 had suffered pyrexia for more than5 days. In contrast, 68 patients (78%) with severe neuro-logical presentation (GCS <9) suffered pyrexia, and only19 (22%) did not. This different distribution of pyrexia isstatistically significant (p=0.0092).

Pyrexia and length of stay in the ICU

Average LOS in the ICU was 12.5±8.3 days (range1–34 days, median 12 days). The occurrence of pyrexiawas associated with a longer stay (Table 2). Patientswithout pyrexia had a mean LOS of 8±6.8 days (median6 days) compared with 14.2±8.2 days (median 13 days)for patients with pyrexia (p=0.0001). The LOS of pa-tients who suffered pyrexia for more than 5 days (upperquartile) was more than double that of cases without py-rexia (p=0.0006). Since LOS was longer for the most se-

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Fig. 1 Distribution of tempera-ture during the first week. Alltemperature measurements(7,146 determinations) areshown. Above External temper-ature (2,845 determinations).Below Internal temperature(4,301 determinations)

Table 1 Occurrence, durationof pyrexia, and severity of headinjury. Distribution of quartileof pyrexia in all patients, in pa-tients with GCS after stabiliza-tion lower than 9 vs. higherthan 8 (p=0.0092)

Days of pyrexia Quartile All patients (n=110) GCS<9 (n=87) GCS>8 (n=23)

n % n % n %

0 Overall 30 27.3 19 21.8 11 47.81–2 Lowest 28 25.4 20 23 8 34.83 2nd 13 11.8 11 12.6 2 8.74–5 3rd 20 18.2 18 20.7 2 8.76–7 Highest 19 17.3 19 21.8 0 –

vere cases, we analyzed the relationships between thelength of stay, occurrence of pyrexia, and neurologicalseverity assessed by the GCS. Logistic regression analy-sis identified the presence of pyrexia (odds ratio 4.686,95% confidence interval 1.754–12.521) and a GCS lessthan 9 (odds ratio 3.126, 95% confidence interval1.063–9.193) as independent predictors of a LOS of12 days or longer (which was chosen as a threshold be-cause it represents the median LOS of the entire sample).

Pyrexia and infection

Infections were diagnosed in 96 patients. The majoritywere in the respiratory tract (pneumonia in 64 cases).Pyrexia was more frequent in infected than noninfectedpatients. Among the 14 patients without infections 7(50%) did not suffer pyrexia, 6 (43%) suffered pyrexiafor 1–2 days, and only one (7%) suffered pyrexia for6 days. In contrast, 73 patients with infections (76%) hadpyrexia; 38 (40%) for more than 4 days. This differencein distribution of pyrexia between infected and nonin-fected patients is statistically significant (p=0.03).

Intracranial pressure, cerebral perfusion pressure and pyrexia

The mean duration of ICP recording was 5.4±3.1 days(range 2–13). Sixty-one patients suffered episodes ofICP higher than 25 mmHg. Mean arterial pressure(MAP) was 90.7±11 in patients who did not have pyrex-ia and 95.3±8.2 mmHg in patients with pyrexia(p=0.0193). Mean CPP was 77.3±13.5 mmHg; 70 pa-tients had episodes of CPP below 60 mmHg. There wasno relationship between ICP and the occurrence and du-ration of pyrexia when all patients were analyzed togeth-er. Accordingly, CPP was not significantly different incases with or without pyrexia.

Intracranial pressure, basal cisterns and pyrexia

Basal perimesencephalic cisterns were normal in 66 pa-tients and were absent or compressed in 44 cases. ICP

was analyzed in two subgroups: normal or abnormal cis-terns. Mean ICP was higher in patients with compressedor absent cisterns (38.2±21.5 mmHg) than in those withnormal cisterns (26.8±15.3 mmHg; p=0.0015). In thesubgroup with normal cisterns there was a tendency to-ward intracranial hypertension in cases with pyrexia: pa-tients without pyrexia had a mean ICP of24±13.9 mmHg, while those with pyrexia for more than5 days had a mean of 34±12 mmHg; (NS). Episodes ofICP above 25 mmHg were more frequent in cases withpyrexia than in those without (Table 3). Only 5 of 17 pa-tients (29%) without pyrexia in fact had ICP rises, com-pared with 11 of 13 (85%) with prolonged pyrexia(p<0.02). No relationship was found between the occur-rence or duration of pyrexia, the severity of intracranialhypertension, and the number of episodes of raised ICPin patients with compressed cisterns.

Cerebral perfusion pressure, basal cisterns, and pyrexia

CPP was lower in patients with compressed or absentbasal cisterns (44.2±19.8 mmHg) than in those with nor-mal cisterns (57.1±12.8 mmHg) (p<0.0001). Cases withnormal basal cisterns and no pyrexia had a CPP of57.2±16.7 mmHg; in cases with pyrexia CPP rangedfrom 61.1±7 to 51.6±9 mmHg (NS). When cisterns werecompressed or absent, patients without pyrexia had sig-nificantly lower CPP than cases with various duration ofpyrexia (p<0.01), reflecting the higher MAP in febrilepatients. No relationship was found between pyrexia andthe occurrence of episodes of low CPP in these sub-groups (Table 4).

Antipyretic therapy

Pyrexia was treated in 66 patients. Nonsteroidal anti-in-flammatory drugs were used in 63, for a total of 252 dos-es. For the purpose of analysis all the recorded episodesof active treatment against pyrexia were divided into

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Table 2 Intensive care length of stay and pyrexia [p=0.0006 pa-tients with pyrexia longer 5 days (highest quartile) vs. patientswithout pyrexia]

Quartile Mean ±SD Median Range

Overall 8±6.8 6 1–26Lowest 13.7±9.1 14 1–292nd 13.5±8.2 11 4–333rd 11.9±5.6 12 5–22Highest 17.8±8.5 17 7–34

Table 3 Intracranial pressure and pyrexia in patients with normalor pathological cisterns. Patients showing at least one episode ofintracranial hypertension are subdivided according to two criteria:duration of pyrexia (rows) and status of perimesencephalic cis-terns on admission computed tomography (columns). The resultsof χ2 analysis for each column across all quartiles are reported

Normal cisterns Compressed or absent cisterns

Quartile n % n %Overall 5 29 11 85Lowest 5 28 6 602nd 4 50 3 603rd 5 50 5 50Highest 11 85 6 100p 0.02 0.16

three groups: physical perfrigeration alone (n=3), drugsplus perfrigeration (n=23), and pharmacological treat-ment alone (n=40; details reported in Table 5). Whenphysical perfrigeration was used alone, temperature fellonly slightly (mean reduction was 0.32±0.8°C), with noeffects on ICP or CPP. The combination of the two treat-ments caused a greater temperature reduction(0.54±0.7°C) but still not statistically significant. Thegreatest effect on temperature was with drugs, whichgave a mean reduction of 0.58±0.7°C. This reduction, al-though significant (p=0.005), was on average still clini-cally negligible. No significant changes in ICP were ob-served with pharmacological therapy; however, this ther-apy alone or with physical perfrigeration caused a signif-

icant reduction in MAP. This was reflected in a corre-sponding reduction in CPP, which fell on average by6.5 mmHg in response to the drugs, and 5 mmHg whenperfrigeration was combined with pharmacological treat-ment. In both cases the CPP reduction was slight but sig-nificant. When drugs were administered alone, CPP fellbelow 70 mmHg in 63% of patients (40/63) and below60 mmHg in 25.4% (16/63).

Outcome

At 6 months 57 patients (54.8%) had a favorable outcome,including cases with good recovery and moderate disabili-ty, 21 patients (20.2%) did not recover, remaining with se-vere disability, and 26 (25%) had died. Six patients werelost to follow-up. Neurological presentation after stabili-zation and age were analyzed in relation to outcome in alogistic regression model, using their median values ascutoff. The odds ratio for an unfavorable outcome was5.414 (95% confidence interval 1.934–15.155) when post-stabilization GCS was 7 or less and 5.752 (95% confi-dence interval 2.298–14.397) when age was higher than34 years. We did not find any relationship between out-come at 6 months and presence or duration of pyrexia.

Discussion

Pyrexia is part of the inflammatory response and is com-mon after trauma [10]. It has protective effects againstthe development of infection [34, 35] and in many criti-cally ill patients it is generally felt to be more protectivethan dangerous. Brain-injured patients are an exception,since in them the deleterious effects of pyrexia may ex-ceed the benefits [35]. The first goal of this study was todefine the pattern of pyrexia in a multicenter collectionof head injured patients admitted to intensive care.

Definition of the pyrexia threshold is still debated. Insome reports pyrexia is diagnosed when temperature ex-ceeds 37.5°C [8, 36, 37]. We defined pyrexia as an inter-nal temperature greater than 38.4°C; using this threshold,we found pyrexia to be frequent, since 80 patients (73%of the study population) suffered pyrexia. This is close tothe frequencies reported in the literature, obtained usingvarious definitions in comparable series: Albrecht et al.[38] reported pyrexia in 68%, and Jones et al. [10] pub-lished a series with 85% of pyrexia. To grade the severi-ty of pyrexia we chose a system based on the durationrather than the peak [39]. Since multiple episodes of py-rexia during any specific day were much more commonthan a single isolated episode, the percentage of mea-surements above the threshold closely reflected the quar-tile distribution. Therefore the number of days with atleast one episode of pyrexia properly reflected the per-sistence of pyrexia during the week considered.

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Table 4 Cerebral perfusion pressure and pyrexia in patients withnormal or pathological cisterns. Patients showing at least one epi-sode of low cerebral perfusion pressure subdivided according totwo criteria: duration of pyrexia (rows) and status of perimesence-phalic cisterns on admission computed tomography (columns).The results of χ2 analysis for each column across all quartiles arereported

Normal cisterns Compressed or absent cisterns

Quartile n % n %Overall 7 41 13 100Lowest 8 44 6 602nd 3 38 3 603rd 6 60 8 80Highest 11 85 5 83p 0.10 0.14

Table 5 Effects of antipyretic therapy (before vs. after) on tem-perature, intracranial pressure (ICP), mean arterial pressure(MAP), and cerebral perfusion pressure (CPP) (NSAIDs nonstero-idal anti-inflammatory drugs, physical physical perfrigerationalone, NSAIDs and physical combination of nonsteroidal anti-in-flammatory drugs and perfrigeration used simultaneously, n num-ber of episodes collected for each treatment)

Physical NSAIDs and NSAIDs (n=40) physical (n=20) (n=232)

Temp (°C)Before 38.8±0.6 38.9±0.7 38.7±0.7After 38.4±0.9* 38.3±0.5* 38.1±0.7**

ICP (mmHg)Before 17.8±12 16±7.1 15.7±7.5After 19±11.2 18±7 16±8.1

MAP (mmHg)Before 93.6±15.3 89.8±10 96.2±12.4After 93.1±14.1 85.8±9.3 89±12.1**

CPP (mmHg)Before 76.1±13.6 73.9±12.3 80.4±13.2After 75.6±13.7 69.1±10.4* 73.9±13.4**

Having established this grading, we found a signifi-cant relationship between the severity of pyrexia and thedegree of neurological impairment, as indicated by theGCS. Pyrexia was uncommon in patients with preservedneurological function after head injury, but much morefrequent in comatose patients. The deeper the coma, thelonger the pyrexia lasted. Since we analyzed the poststa-bilization GCS, there is a clear association between theseverity of initial injury and the subsequent developmentof pyrexia, but it is impossible to clarify how much py-rexia contributed to further neurological worsening.

Pyrexia was correlated with a longer stay in the ICU;since the LOS was longer also for cases with worse neu-rological presentation, we investigated whether pyrexiaitself is an independent predictor of LOS. There was thepossibility in fact that pyrexia seemed related to the LOSsimply because a longer LOS and a longer duration ofpyrexia were both features of patients with low GCS.Logistic regression identified both GCS and pyrexia asindependent predictors of LOS, suggesting that pyrexiaplays a role per se.

Providing a detailed report of infection in ICU head-in-jured patients was not the aim of this investigation, and thedata collected allow no definitive conclusions. The majori-ty of patients with pyrexia were diagnosed as infected,pneumonia being the most frequent infection. However,there were cases with pyrexia in which no specific diagno-sis was made. This means that we cannot clarify whetherpyrexia has a causative role since when a relationship wasdetected between pyrexia and a clinical variable, such asthe LOS, we could not establish whether it was due to thepyrexia itself or to the infection of which the pyrexia was asign. Since infection was often diagnosed as the cause ofpyrexia, the association between neurological severity andpyrexia very likely indicates a relationship between severi-ty and infection as well. Head-injured patients suffer intra-cranial hypertension for many reasons, including brainedema, vascular engorgement, and intracranial masses.With these major intracranial problems, it is unlikely that amarginal contribution to the total intracranial volume, ascaused by pyrexia, would be detected.

When perimesencephalic cisterns are compressed orabsent, the total intracranial volume is increased, and thissign is a good predictor of intracranial hypertension [40].When cisterns are normal, the intracranial content is notlikely to be significantly increased. We assumed that inthis situation the potential deleterious effect of pyrexiawould not be overshadowed by other, more obvious caus-es of raised ICP, and therefore it could be assessed. Pa-tients with compressed cisterns suffered the worst intra-cranial hypertension, but pyrexia in these cases did notappear to cause any further rise. Patients with preservedcisterns, on the other hand, had a lower mean ICP butwith distinctive features: pyrexia was associated withmore episodes of intracranial hypertension, and mean ICPwas higher in case of pyrexia, although this difference

was not statistically significant. We recently reported alack of correlation between absolute values of brain tem-perature and ICP. However, we found a significant rela-tionship between changes in brain temperature (≥0.7°C)and corresponding rises or decreases in ICP [23]. A re-cent study [41] supports the idea that effective treatmentof pyrexia can help in controlling ICP. This study testedthe effectiveness and the short-term safety of continuousintravenous infusion of diclofenac sodium (0.02–0.08 mg/kg per hour) in attaining normothermia in asmall group of acute cerebral damaged patients (sevenwith severe traumatic brain injury, five with subarachnoidhemorrhage). Diclofenac sodium lowered the temperatureto normal levels in all patients, and this effect was associ-ated with a significant reduction in ICP. However, beforethis approach can be considered for conventional therapy,further study is needed to clarify the impact of diclofenacsodium on infection, long-term side effects, and outcome.

All the treatments used for controlling pyrexia in ourseries gave scant effects. Drugs had the most effect ontemperature, but only of the order of 0.5°C; they did notdecrease ICP while MAP and CPP underwent a moder-ate but statistically significant decrease. The outcomewas acceptable in this series, with 25% mortality and55% favorable outcome at 6 months. The severity ofneurological impairment (GCS score) and age werestrongly related to outcome, whereas pyrexia and its du-ration during the first week after trauma did not affectthe final results. This apparently contradicts experimen-tal evidence of the deleterious role of pyrexia in the in-jured brain. Pyrexia, however, has been studied mainlyin models of ischemic damage. Some clinical studies ofhead injury have identified pyrexia as an important pre-dictor of outcome in one series [10] but not others [16,32]. A stronger relationship between pyrexia and out-come was found in stroke [8] and intracerebral hemor-rhage [9]. Pyrexia may have greater impact on the brainand consequently on outcome when ischemia rather thantrauma is the main mechanism involved.

Conclusions

Pyrexia is extremely frequent in head-injured patientsadmitted to intensive care. It is more frequent in moresevere cases and is correlated with a longer stay in theICU. It probably affects ICP, but its contribution can on-ly be suspected when other, more relevant causes of in-creased intracranial volume are not present. Pharmaco-logical antipyretic therapy is only poorly effective, forcontrolling body temperature does not decrease ICP, andit may slightly reduce CPP. Pyrexia still affects the clini-cal course of traumatic brain injury patients, and currenttherapies give only modest results. Further studies areneeded to find more effective strategies to achieve andmaintain normothermia.

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