Doctor of Department of Emergency and Critical Care Medicine, Zhoupu Hospital Affiliated With Shanghai University of Medicine and Health Sciences, Shanghai 201318, PR China
Phase: NA
Conditions: Traumatic Brain Injury, Mechanical Ventilation Complication
Sponsor: Hongpeng Li

 
 
Effects of positive end-expiratory pressure on intracranial 
pressure in patients with severe traumatic brain injury  
Hongpeng Li a, Dongsheng Chen b, Zhihui Cheng a, Wei Qua 
 
aDepartment of Emergency and Critical Care Medicine, Zhoupu Hospital affiliated with 
Shanghai University of Medicine and Health Sciences, Shanghai 201318, PR China  
bDepartment of Critical Care Medicine, Yuncheng Central Hospital, Shanxi 044000, PR 
China 
Corresponding author:  
Dr. Hongpeng Li, No. 1500 Zhouyuan Road, Pudong District, Shanghai 201318, PR China. 
E-mail: liroc119@163.com (H. Li) 
Tel: +86-68135590-3352 
 
 
D ocum ent  D ata: 2016-12-1

 
 
Background: Mechanical ventilation (MV) with positive end-expiratory 
pressure (PEEP) is commonly applied in patients with severe traumatic brain 
injury (sTBI). However, the relationship between PEEP and intracranial 
pressure (ICP) remains unclear. 
Objective：To clarify the exact relationship between levels of PEEP and ICP. 
Design and Methods： 
Patient Selection Criteria 
This clinical study was conducted between August 2016 and August 2017 in the 
intensive care unit (ICU) of Zhoupu Hospital, affiliated with Shanghai University of 
Medicine and Health Sciences. Approval for study conduct was granted by the 
clinical research ethics committee (no.ZPYYLL-2016-12). Written informed consent 
was obtained from all participating patients or their legal guardians prior to study 
enrolment.  
All patients diagnosed with sTBI (Glasgow Coma Scale [GCS] ≤8) and started on 
MV (Drager Infinity C500, Drager, Germany) were initially included. Exclusion 
criteria were: brain death; age below 18 or over 80 years; pregnancy; hemodynamic 
instability (eg, heart rate >120 bpm or CPP <60 mmHg); bulbous lung or 
pneumothorax; myocardial infarction; and refusal/inability to provide informed 
consent. 
Design and measurement  
The ICP was continuously monitored (Codman ICP ExpressTM, Johnson, 

 
 
USA) through a ventricular catheter (Codman ICP Transducer, Johnson, USA) 
that was associated with a closed external ventricular drain during each 
measurement. Both central venous and arterial catheters were inserted to 
measure intra-arterial MAP, CVP, and jugular bulb pressure (Pj). All patients 
were deeply sedated (continuous intravenous infusion of midazolam 
0.05–0.20 mg/kg/h and sufentanil 0.2 μg/kg/h) to maintain the Richmond 
Agitation-Sedation Scale (RASS) score −5 and, thus, to remove the 
interference of cough and other neuronal and confounding factors on ICP. 
Ventilator settings remained consistent for each enrolled patient. The tidal 
volume was adjusted and maintained at 8 to 10 mL/kg of predicted body 
weight. Support pressure was maintained at 12 to 14 cmH2O, and fraction of 
inspired oxygen (FiO2) was set at 45% to 100%. An end-tidal carbon dioxide 
pressure (PetCO2) device (Drager Mainstream CO2, SN:ASHM-0552, Drager, 
German) was applied for each patient to avoid any effect of carbon dioxide 
pressure on ICP, and PetCO2 was maintained at 30 to 35 mmHg during the 
study. 
In this study, all patients were exposed to incremental PEEP levels of 0, 5, 
10, and 15 cmH2O with 100% FiO2.  Measurements were undertaken every 8 
hours at the bedside on stabilized hemodynamics and ICP untill MV or ICP 
monitoring was discontiued, and discontinued and remedied accordingly in 
case of: (1) CPP < 60 mmHg (norepinephrine 0.3–1.0 μg/kg/min was used); (2) 
ICP > 25 mmHg (PEEP was restored to 0); (3) increase in pressure 
plateau >35 cmH2O (tidal volume was decreased and PetCO2 was maintained 

 
 
at 30–35 mmHg); (4) pulse oxygen saturation (SpO2) <90% (PEEP was 
restored to 0); and (5) suspicion of pneumothorax (PEEP was restored to 0, 
and chest radiography was undertaken). An equilibration period (≥90 s) was 
entailed to ensure a normalized baseline PetCO2 through modulation of tidal 
volume and respiratory rate. 
The ICP, CVP, Pj, and MAP were measured three times at each level of 
PEEP for consecutive days after admission until MV or ICP monitoring was 
withdrawn. The CPP was calculated according to the following equation: 
CPP = MAP − ICP. Based on the difference between baseline ICP and CVP 
(intracranial central venous pressure difference, IVPD), subjects were 
categorized into the following three groups based on our research hypothesis 
and specific relationship between CVP and PEEP 
13-15: Group I, 
IVPD≤3 mmHg; Group II, 3 < IVPD ≤ 6 mmHg; and Group III, 
IVPD >6 mmHg. Relationships between PEEP and ICP, CVP and MAP, as 
well as CVP and Pj were analyzed in each group, respectively.  
Statistical analysis 
Continuous covariates, including hemodynamic variables ICP, MAP, CVP, Pj, 
and CPP, were expressed as means ± standard errors. Data were analyzed by 
one-way analysis of variance (ANOVA) followed by the Bonferroni post hoc 
test for multiple comparisons. Analysis of covariance was used to detect 
possible changes in continuous variables at different levels of PEEP in every 
group.  A p-value less than 0.05 was considered as being statistically 

 
 
significant. 
Flow chart of study patient disposition as follow: 
 
 
 
 
 
 
Initially enrolled (n=43)
Enrolled in the final analysis (n=38)
Measurement of ICP, CVP, and CPP, paired with PEEP adjustment (n=301) 
Divided into 3 groups based on IVPD
Group III
IVPD >6 mmHg
Analysis of the 
correlation between 
PEEP, ICP, CVP,MAP 
and  Pj (n=129)
Group II
3 <IVPD<or=6 mmHg
Analysis of the 
correlation between 
PEEP, ICP, CVP,MAP 
and  Pj (n=82)
Group I
IVPD<or=3mmHg
Analysis of the 
correlation between 
PEEP, ICP, CVP,MAP and  
Pj(n=90)
Analysis of the correlation between 
PEEP, ICP, CVP,MAP and  Pj (n=301)
Excluded:
1) < 18 years (n=1),
2) fluid resuscitation and norepinephrine applied     
to maintain the CPP>60mmHg (n=2)
3) pneumothorax (n=2)