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Randomized Controlled Trial Comparing Cerebral Perfusion Pressure–Targeted Therapy Versus Intracranial Pressure–Targeted Therapy for Raised Intracranial Pressure due to Acute CNS Infections in Children*

Kumar, Ramesh MD, DM; Singhi, Sunit MD; Singhi, Pratibha MD; Jayashree, Muralidharan MD; Bansal, Arun MD; Bhatti, Anuj MD, DM

doi: 10.1097/CCM.0000000000000298
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Objective: In children with acute CNS infection, management of raised intracranial pressure improves mortality and neuromorbidity. We compared cerebral perfusion pressure–targeted approach with the conventional intracranial pressure–targeted approach to treat raised intracranial pressure in these children.

Design: Prospective open-label randomized controlled trial.

Setting: PICU in a tertiary care academic institute.

Patients: Hundred ten children (1–12 yr) with acute CNS infections having raised intracranial pressure and a modified Glasgow Coma Scale score less than or equal to 8 were enrolled.

Interventions: Patients were randomized to receive either cerebral perfusion pressure–targeted therapy (n = 55) (maintaining cerebral perfusion pressure ≥ 60 mm Hg, using normal saline bolus and vasoactive therapy—dopamine, and if needed noradrenaline) or intracranial pressure–targeted therapy (n = 55) (maintaining intracranial pressure < 20 mm Hg using osmotherapy while ensuring normal blood pressure). The primary outcome was mortality up to 90 days after discharge from PICU. Secondary outcome was modified Glasgow Coma Scale score at 72 hours after enrollment, length of PICU stay, duration of mechanical ventilation, and hearing deficit and functional neurodisability at discharge and 90-day follow-up.

Measurements and Main Results: A 90-day mortality in intracranial pressure group (38.2%) was significantly higher than cerebral perfusion pressure group (18.2%; relative risk = 2.1; 95% CI, 1.09–4.04; p = 0.020). The cerebral perfusion pressure group in comparison with intracranial pressure group had significantly higher median (interquartile range) modified Glasgow Coma Scale score at 72 hours (10 [8–11] vs 7 [4–9], p < 0.001), shorter length of PICU stay (13 d [10.8–15.2 d] vs 18 d [14.5–21.5 d], p = 0.002) and mechanical ventilation (7.5 d [5.4–9.6 d] vs 11.5 d [9.5–13.5 d], p = 0.003), lower prevalence of hearing deficit (8.9% vs 37.1%; relative risk = 0.69; 95% CI, 0.53–0.90; p = 0.005), and neurodisability at discharge from PICU (53.3% vs 82.9%; relative risk = 0.37; 95% CI, 0.17–0.81; p = 0.005) and 90 days after discharge (37.8% vs 70.6%; relative risk = 0.47; 95% CI, 0.27–0.83; p = 0.004).

Conclusion: Cerebral perfusion pressure–targeted therapy, which relied on more frequent use of vasopressors and lesser use of hyperventilation and osmotherapy, was superior to intracranial pressure–targeted therapy for management of raised intracranial pressure in children with acute CNS infection in reducing mortality and morbidity.

Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

* See also p. 1936.

This study was performed at Postgraduate Institute of Medical Education and Research, Chandigarh, India.

CTRI/2012/05/002650: Trial registered as “A pilot study to compare the outcome of CPP-targeted therapy versus ICP-targeted therapy in children with acute meningitis.”

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Supported, in part, by institutional and departmental funds.

The authors have disclosed that they do not have any potential conflicts of interest.

Address requests for reprints to: Sunit Singhi, MD, Department of Pediatrics, Pediatric Emergency and Intensive Care, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. E-mail:

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins