Table 2.

Summary of studies employing antipyretic agents in post-ICH fever analyses (✓ = yes, ✕ = no)

Reference	Antipyretic strategy	Dose (mg)	Rate (hours)	Administration route	ICH patients (N)	ICH subgroup analysis	Temperature measured	Temperature measurement site	Patient population	Primary finding(s) (compared to control groups)
Diringer 2014	Acetaminophen, surface cooling vs. catheter-based normothermia	650	4–6	Oral, rectal	60	✕	✓	N/A	ICH, IS, SAH, TBI	Acetaminophen & surface cooling were ineffective at reducing fever burden compared to catheter-based normothermia
Den Hertog et al. 2009	Acetaminophen vs. placebo control	1000	6	Oral, rectal	173	✓	✓	Tympanic, rectal	ICH, IS	Acetaminophen reduced body temperature by 0.26 °C, with no significant impact on mRS vs. placebo controls
Broessner et al. 2009	Acetaminophen, ibuprofen, surface cooling vs. catheter-based normothermia	500	4	Oral	41	✓	✓	Bladder	SAH, ICH, IS	Acetaminophen group had greater fever burden vs. catheter-based normothermia
Kallmunzer et al. 2011	Acetaminophen, Metamizole, surface cooling vs. historical control group	1000	6	IV	25	✕	✓	Tympanic	ICH, IS	Combined acetaminophen, metamizole, calf packing & saline was more effective than fanning & acetaminophen at reducing fever vs. historical controls
Middleton et al. 2011	Acetaminophen (+ multidisciplinary care) vs. conventional care	N/A	N/A	IV, oral, rectal	51	✕	✓	N/A	ICH, IS	Combined acetaminophen, metamizole, calf packing & saline was more effective than fanning & acetaminophen at reducing fever
Picetti et al. 2014	Acetaminophen & surface cooling	1000	Single dose	IV	2	✕	✓	Bladder, endovascular	ICH, IS, SAH, TBI	Acetaminophen reduced cerebral perfusion pressure and mean arterial pressure
Lord et al. 2014	Acetaminophen, surface cooling vs. historical controls	650	4–6	Oral	80	✓	✓	Bladder	ICH	Acetaminophen reduced temperature (~ 0.5 °C-1°C), increased length of stay, and incidence of hyperglycemia vs. historical controls
De Ridder et al. 2017	Acetaminophen vs. placebo controls	1000	4	Oral, rectal	20	✓	✓	Tympanic, rectal	ICH, IS	Acetaminophen had no effect on temperature, mRS, or adverse events compared to placebo controls
Hervella et al. 2020	Acetaminophen,Metamizole, (retrospectively dichotomized into response categories)	1000	8	Oral	795	✓	✓	Axillary	ICH	Acetaminophen increased mRS scores and decreased perihematomal hypodensity in responders vs. non-responders
Lee et al. 2021	Acetaminophen, Metamizole, surface cooling vs. conventional care	1000	6	IV	16	✕	✓	Tympanic	ICH, IS, SAH	Combined acetaminophen, metamizole, calf packing reduced fever duration vs. historical conventional care group

IV intravenous, SAH subarachnoid hemorrhage, TBI traumatic brain injury, IS ischemic stroke, ICH intracerebral hemorrhage, mRS Modified Rankin Scale