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Introduction Endotracheal suctioning (ETS) is essential for patient care in an ICU but may represent a cause of cerebral secondary injury. Ketamine has been historically contraindicated for its use in head injury patients, since an increase of intracranial pressure (ICP) was reported; nevertheless its use was recently suggested in neurosurgical patients. In this prospective observational study we investigated the effect of ETS on ICP, cerebral perfusion pressure (CPP), jugular oxygen saturation(SjO2) and cerebral blood flow velocity(mVMCA) before and after the administration of ketamine. Methods In the control phase, ETS was performed on patients sedated with propofol and remifentanil in continuous infusion. If a cough was present, patients were assigned to the intervention phase, and 100 γ/kg/min of racemic ketamine for 10 minutes was added before ETS. Results In the control group ETS stimulated the cough reflex, with a median cough score of 2 (interquartile range (IQR) 1 to 2). Furthermore, it caused an increase in mean arterial pressure (MAP) (from 89.0 ± 11.6 to 96.4 ± 13.1 mmHg; P<0.001), ICP (from 11.0 ± 6.7 to 18.5 ± 8.9 mmHg; P<0.001), SjO2 (from 82.3 ± 7.5 to 89.1+5.4; P = 0.01) and mVMCA (from 76.8 ± 20.4 to 90.2 ± 30.2 cm/sec; P = 0.04). CPP did not vary with ETS. In the intervention group, no significant variation of MAP, CPP, mVMCA, and SjO2 were observed in any step; after ETS, ICP increased if compared with baseline (15.1 ± 9.4 vs 11.0 ± 6.4 mmHg; P<0.05). Cough score was significantly reduced in comparison with controls (P<0.0001). Conclusions Ketamine did not induce any significant variation in cerebral and systemic parameters. After ETS, it maintained cerebral hemodynamics without changes in CPP, mVMCA and SjO2, and prevented cough reflex. Nevertheless ketamine was not completely effective when used to control ICP increase after administration of 100γ/kg/min for 10 minutes. [ABSTRACT FROM AUTHOR]