Clinical short communication
Prognostic significance of early pyrexia in acute intracerebral haemorrhage: The INTERACT2 study

https://doi.org/10.1016/j.jns.2021.117364Get rights and content

Highlights

  • Elevated body temperature predicts worse outcomes after stroke.

  • Early pyrexia is associated with greater mortality and larger perihaematomal oedema in intracerebral haemorrhage.

  • Early pyrexia is associated with larger volume of perihaematomal oedema.

Abstract

Introduction

Uncertainty exists over the prognostic significance of pyrexia in acute intracerebral haemorrhage (ICH). We aimed to determine the association of elevated body temperature with clinical and imaging outcomes among participants of the main Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2).

Methods

Post-hoc analyses of INTERACT2, an international open, blinded outcome assessed, randomised trial of 2839 patients with spontaneous ICH (<6 h of onset) and elevated systolic blood pressure (SBP, 150–220 mmHg) randomly assigned to intensive (SBP target <140 mmHg) or guideline-recommended (SBP target < 180 mmHg) BP management. Multivariable logistic regression was used to determine associations of elevated baseline body temperature (<37.5 vs. ≥37.5 °C) and 90-day clinical outcome defined on the modified Rankin scale (mRS). Analysis of covariance determined relations of body temperature and haematoma and perihaematomal oedema (PHE) volumes, at baseline and 24 h post-randomisation.

Results

Of 2792 participants with data available at admission, 39 (1.4%) patients had elevated body temperature ≥ 37.5 °C. Elevated body temperature was significantly associated with 90-day mortality (adjusted odds ratio 2.44; 95% confidence interval 1.02–5.82; P = .044) but not with major disability alone (mRS scores 3–5) and combination death or major disability (mRS scores 3–6). Elevated body temperature was also associated with larger PHE volume at baseline (10.89 vs. 3.14 cm3, P < .001;) and 24 h (12.43 vs 5.76 cm3, P = .018) but not with haematoma volumes at these time points.

Conclusion

Early pyrexia in mild to moderate ICH is associated with greater mortality and larger PHE volume, suggesting an early inflammatory-mediated reaction.

Clinical trial registration

www.clinicaltrials.gov (NCT00716079).

Introduction

Acute spontaneous intracerebral haemorrhage (ICH) is the most serious type of stroke, with high mortality and disability [1]. Pyrexia occurs in 30–40% of ICH patients, in relation to infection and central mechanisms [2]. Preclinical studies in acute ischaemic stroke have shown that high body temperature is associated with large infarcts and higher mortality [[3], [4], [5]], while in ICH it predicts high mortality, greater haematoma growth and residual disability [[6], [7], [8], [9]]. A retrospective study of 251 patients with spontaneous ICH admitted within 24 h of onset and body temperature measured on admission and during the first 72 h found that elevated body temperature independently predicted poor functional outcome [6], which lends support for an immune-inflammatory reaction to perihaematomal oedema [10]. We aimed to determine associations of early elevation in body temperature on key clinical and imaging outcomes in ICH patients who participated in the main phase of the international Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) [11].

Section snippets

Study design and participants

The INTERACT2 study was a multicentre, prospective, open, blinded outcome assessed, randomised controlled trial in which the efficacy of intensive (target systolic blood pressure (SBP) <140 mmHg within 1 h and maintained for 7 days) was compared with contemporaneous guideline-recommended (<180 mmHg) BP management in patients with spontaneous ICH (<6 h) with elevated SBP (150–220 mmHg) [11]. Written informed consent was obtained from each participant or their legal surrogate. The study protocol

Results

In 2829 INTERACT2 participants, there were 2792 (98.7%) with admission body temperature and 90-day clinical outcomes data, including 966 (34.1%) with baseline and 24-h CT scans, available for analyses (Supplemental fig. A.1, online only). Overall, there were 39 (1.4%) patients with baseline elevated body temperature within 6 h of ICH onset. Table 1 shows that patients with baseline elevated body temperature had higher heart rate, leucocyte count, NIHSS scores, lower GCS scores, and more IVH and

Discussion

In these post-hoc analyses of the INTERACT2 dataset, we have shown that an early elevation in body temperature after the onset of spontaneous ICH was associated with higher mortality, and larger PHE volume at baseline and 24 h.

Our results are consistent with other studies showing associations between pyrexia and poor outcomes in ischaemic and mixed stroke patients [7, 13], and with exacerbated neuronal damage and cerebral oedema in all forms of brain injury induced by temperature elevation [6,15

Funding

INTERACT2 was supported by program (571281) and project grant (512402 and 1004170) from the National Health and Medical Research Council (NHMRC) of Australia.

Declarations of interest

Dr. Anderson reports receiving grants, speaker fees and travel reimbursement from Takeda China. AM, SJ, CD, and DZ report no conflict of interest.

Acknowledgements

None.

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  • 1

    For a full list of INTERACT2 Investigators, see reference [11].

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