Timing of Invasive Intracranial Pressure Monitoring Between Neurosurgeons and Intensive Care Physicians
Conditions: Intracranial Hypertension, Timing of Invasive Intracranial Pressure Monitoring
Sponsor: Università degli Studi di Brescia

                                               
  
                 
 
              
 
 
Timing of Invasive intracranial pressure MonitorIng between NeurosurGeons 
and Intensive Care Physicians 
(TIMING-ICP) 
versione 2.0 
 
 
                              
 
              
 
_____________________________________ 
 
                                
 
 
  
 
Principal Investigator: 
 
- Frank A. Rasulo 
 
Scientific Steering committee 
 
- Anselmo Caricato 
- Carlo Alberto Castioni 
- Corrado Iaccarino 
- Marina Munari 
- Roberto Stefini 
- Simone M. Zerbi 
- Antonio Biroli 
 
 
 
Date – 30/03/2021 

 
 
      
 
 
      
  
                 
 
              
 
Timing of Invasive intracranial pressure MonitorIng between NeurosurGeons 
and Intensive Care Physicians 
(TIMING-ICP) 
versione 2.0 
2
Table of contents  
 
Introduction…………………………………………………………………………………….……..3 
 
Aim of the study………………………………………………………………. …………………….5 
 
Materials and methods…………………………………………………………………………… ….6 
 
Statistical analysis plan and sample size assessment…...…………………………………………… 8 
 
Bibliography…………………………………………………………………………………….…….9 
 
Time-line……………………………………………………………………………………………..10 
 
 
 
 
 
 
 
 
 
 
 
            

 
 
      
 
 
      
  
                 
 
              
 
Timing of Invasive intracranial pressure MonitorIng between NeurosurGeons 
and Intensive Care Physicians 
(TIMING-ICP) 
versione 2.0 
3
 Introduction 
 
Invasive intracranial pressure monitoring takes on essential importance in patients with 
traumatic brain injury and in all cerebral pathologies in which intracranial hypertension is the 
main cause of death1.  
The dose of intracranial pressure (ICP), meant as the time for which intracranial pressure 
exceed the reference values, has been related to poor outcome2,3. “Time is brain” is a concept 
which highlights the importance of preempt and perform the proper therapeutic strategies, in 
order to reduce complications in the context of a rapidly and irreversibly compromised cerebral 
tissue as a result of a brain injury.  
On these bases, it is essential to perform an accurate intracranial pressure monitoring as soon as 
possible, to detect and possibly treat intracranial hypertension, which would definitively 
compromise brain parenchyma.  
Invasive intracranial pressure monitoring performed by placing an intracerebral catheter 
(intraventricular or intraparenchymal) is currently the gold standard technique for continuous 
ICP invasive monitoring.  
This maneuver has usually been performed by neurosurgeons, but in an effort to optimize as 
much as possible the timing of ICP monitoring, reducing time between urgent request for 
invasive ICP monitoring placement and the placement itself, this procedure (specifically 
intraparenchymal catheter placement) has more often been carried out by intensive care 
physicians at the bedside, in the last few years4-7.   
In the setting of clinical practice, multidisciplinary management of intracranial pressure 
handling and treatment is therefore achieved by joint decisions between neurosurgeons and 
intensive care physicians, but differences in logistic matters and in the executive availability 
could impact on the dose of intracranial pressure to which patient is exposed.  
 

 
 
      
 
 
      
  
                 
 
              
 
Timing of Invasive intracranial pressure MonitorIng between NeurosurGeons 
and Intensive Care Physicians 
(TIMING-ICP) 
versione 2.0 
4
The aim of this study is to compare timing of invasive intracranial pressure monitoring 
placement performed by intensive care physicians and neurosurgeons and to detect possible 
differences in the incidence of complications between the two groups.  
 

 
 
      
 
 
      
  
                 
 
              
 
Timing of Invasive intracranial pressure MonitorIng between NeurosurGeons 
and Intensive Care Physicians 
(TIMING-ICP) 
versione 2.0 
5
Aim of the study 
 
Primary outcome: 
- 
To compare timing of invasive intracranial pressure monitoring performed by intensive care 
physicians and neurosurgeons, from time T1 (defined as the moment in which invasive 
intracranial pressure monitoring indication is stated) to time T2 (skin incision).  
 
Secondary outcome: 
- 
Comparative evaluation of post-procedural complications (meningitis, catheter-placement related 
bleedings, wrong placement) between intensivists and neurosurgeons 
- 
Length of ICU stay, length of hospital stay, duration of mechanical ventilation, Glasgow 
Outcome Score at 3 months. 
- 
To compare timing and complications of invasive intracranial pressure monitoring between 
placement of intraparenchymal catheters and extraventricular drains 
 
 
           

 
 
      
 
 
      
  
                 
 
              
 
Timing of Invasive intracranial pressure MonitorIng between NeurosurGeons 
and Intensive Care Physicians 
(TIMING-ICP) 
versione 2.0 
6
Materials and methods 
 
Inclusion criteria:  
- 
All patients with acute cerebral pathology with urgent indication to invasive intracranial pressure 
monitoring (intraparenchymal and intraventricular) 
- 
Age greater than or equal to 18 years 
 
Exclusion criteria: 
- 
Patients in whom indication to intraventricular catheter placement is stated for reasons other than 
the need of ICP monitoring (e.g. CSF drainage)  
- 
Patients in whom indication to invasive intracranial pressure monitoring is not an urgent request  
- 
Patients in whom a significative coagulation disorder is a contraindication for procedure  
 
Timings are defined as: 
- 
T0: suspect of pathology at risk for developing intracranial hypertension  
- 
T1: neurointensive and neurosurgical indication to invasive ICP monitoring (it could be the time 
when brain CT is performed or, in the absence of a brain CT, the time at which indication to 
invasive ICP monitoring is stated)  
- 
T2: skin incision at skull for BOLT/EVD placement 
 
Place of positioning: 
The place (intensive care unit or operating room, specifying if it’s a dedicated OR or a surgical 
unit) where the procedure is carried out must be declared.  
 
 

 
 
      
 
 
      
  
                 
 
              
 
Timing of Invasive intracranial pressure MonitorIng between NeurosurGeons 
and Intensive Care Physicians 
(TIMING-ICP) 
versione 2.0 
7
Complications which will be analyzed:  
- 
Catheter-related intracranial bleedings, with or without the need of neurosurgical operation (all 
the patients enrolled in the study must have been screened for coagulation disorders)  
- 
Meningitis (actually related to procedure), with microorganism causing meningitis demonstrated 
by culture (not a contaminant microorganism) 
- 
Wrong positioning of catheter and/or its malfunction (e.g., a correct placed catheter penetrates 
the parenchyma for few millimeters/absence of ICP wave). Malfunction is considered as such if 
it occurs up to 12 hours after placement.  
 
 
 
 
             

 
 
      
 
 
      
  
                 
 
              
 
Timing of Invasive intracranial pressure MonitorIng between NeurosurGeons 
and Intensive Care Physicians 
(TIMING-ICP) 
versione 2.0 
8
Statistical analysis plan 
 
Delta time in the placement of invasive ICP monitoring is assumed as T2-T1, declared in 
minutes.  
Typology operator (neurosurgeon vs intensivist) impact on delta time will be evaluated through 
a multilevel model elaborated with a linear mixed model. The model will assume the center in 
which the maneuver is carried out as clustering factor. The place where the maneuver is carried 
out (intensive care unit vs operating room) and the confidence in performing the procedure 
(routine vs sporadic, defined as less than 5 times a year) will be assumed as covariates.  
The incidence of complications, valued as a binary variable, will be evaluated through logistic 
model GLMM (generalized linear mixed model) with the organization exposed in the dedicated 
data element.  
Sample size assessment 
Sample size assessment has been performed by Monte Carlo simulation (B=500). Assuming a 
timing decrease (T2-T1) of 20 minutes in the procedure carried out by an intensivist compared 
to a neurosurgeon, with a mean time of 100 minutes, a standard deviation between center and 
intra-center of 10 minutes, 16 centers, each one with the same number of patients and a balance 
1:1 between the two groups (intensivist:neurosurgeon), a total number of 64 patients  (32 
treated by intensivists and 32 by neurosurgeons), it allows to evaluate the interest effect with a 
power of at least 95%, and a significance level of 5%.  
This elevated power has been decided according to the simplicity of the assumed design (same 
number of entities and conditions for center) and not evaluable in his real configuration. 
 
 
 

 
 
      
 
 
      
  
                 
 
              
 
Timing of Invasive intracranial pressure MonitorIng between NeurosurGeons 
and Intensive Care Physicians 
(TIMING-ICP) 
versione 2.0 
9
Bibliography 
 
1) Balestreri, M., Czosnyka, M., Hutchinson, P. et al. Impact of intracranial pressure and cerebral perfusion pressure 
on severe disability and mortality after head injury. Neurocrit Care 4, 8–13 (2006). 
 
2)Vik A, Nag T, Fredriksli OA, Skandsen T, Moen KG, Schirmer-Mikalsen K, Manley GT. Relationship of "dose" 
of intracranial hypertension to outcome in severe traumatic brain injury. J Neurosurg. 2008 Oct;109(4):678-84. 
 
3) Sheth KN, Stein DM, Aarabi B, Hu P, Kufera JA, Scalea TM, Hanley DF. Intracranial pressure dose and outcome 
in traumatic brain injury. Neurocrit Care. 2013 Feb;18(1):26-32. 
 
4) Ko K, Conforti A. Training Protocol for Intracranial Pressure Monitor Placement by Non-neurosurgeons:  
5-Year Experience. J Trauma 2003; 55:480-483. 
 
5) Ehtisham A, Taylor S, Bayless L, Klein MW, Janzen JM. Placement of external ventricular drains and intracranial 
pressure monitors by neurointensivists. Neurocrit Care. 2009;10(2):241-7. 
 
6) Barber MA, Helmer SD, Morgan JT, Haan JM. Placement of intracranial pressure monitors by non-
neurosurgeons: excellent outcomes can be achieved. J Trauma Acute Care Surg. 2012 Sep;73(3):558-63. 
 
7) Sadaka F, Kasal J, Lakshmanan R, Palagiri A. Placement of intracranial pressure monitors by neurointensivists: 
case series and a systematic review. Brain Inj. 2013;27(5):600-4. 
 
 
 
 
 

 
 
      
 
 
      
  
                 
 
              
 
Timing of Invasive intracranial pressure MonitorIng between NeurosurGeons 
and Intensive Care Physicians 
(TIMING-ICP) 
versione 2.0 
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Time-line