Noninvasive Methods for Measurement of Intracranial Pressure in Patients with Acute Neurotrauma: A Systematic Review and Meta-Analysis

Abstract

Invasive intracranial pressure (ICP) monitoring provides essential guidance for the treatment of patients with suspected head injuries; however, it remains incompatible with prehospital use. While several noninvasive ICP-measuring methods exist, previous studies have not adequately addressed their potential in a prehospital setting. In this systematic review and meta-analysis of diagnostic test accuracy, we explore the accuracy of existing noninvasive methods for ICP monitoring and assess their potential usefulness in prehospital screening for elevated ICP. This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Embase, Scopus, PubMed, CENTRAL, and Cochrane databases were sought for relevant articles on June 23, 2025. All studies evaluating minimally invasive and transportable methods for ICP assessment were included. Animal studies, in vitro studies, reviews, and meta-analyses were excluded. Study selection was performed by two independent reviewers, and conflicts were resolved by a third reviewer. Potential for prehospital use of each method was evaluated using four predetermined criteria. Summary receiver operator characteristic curves and summarized sensitivity and specificity were reported if multiple studies investigating the same method were eligible for meta-analysis. The applicability and risk of bias of the included studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool for diagnostic test accuracy studies. Fifty-five articles were included. Ultrasound of optic nerve sheath diameter (ONSD) was the method with the highest potential for prehospital use. We found a summarized sensitivity of 92.6% (95% confidence interval [CI]: 87.0; 95.9%) and a summarized specificity of 85.1% (95% CI: 74.1; 92.0%) for detecting increased ICP through ONSD measurement. Other methods for diagnosing elevated ICP diagnosis showed poor diagnostic accuracy or low potential for prehospital use. We found ultrasound estimation of the ONSD to show the highest potential for prehospital use. Prospective studies are needed to verify their diagnostic capability in the prehospital setting.

Keywords

acute neurotrauma intracranial pressure prehospital

Introduction

Intracranial pressure (ICP) monitoring is an established component in monitoring patients with severe hemorrhagic stroke and severe traumatic brain injury (TBI). It serves as a guide for therapeutic interventions and the detection of intracranial mass lesions.¹ Elevated ICP can lead to cerebral ischemia, brain herniation, and death when left untreated and is associated with considerable morbidity and mortality.² The insidious onset and nonspecific symptoms complicate early detection.³ Early diagnosis of elevated ICP in a prehospital setting, which could enable direct transportation of patients to a neurosurgical center and earlier intervention, may decrease the risk of secondary injury.^1,4 Accurately measuring ICP requires the placement of invasive pressure monitors by experienced neurosurgeons in a highly specialized setting. Previous research has shown that in-field detection of elevated ICP relies on clinical tools that tend to have low accuracy.⁵ However, ultrasound-based methods have shown potential for noninvasive detection of intracranial pathology.⁶ While several techniques for noninvasive ICP estimation have been proposed, an in-depth analysis of the available options and their compatibility with prehospital ICP screening is essential to strengthen the development of these noninvasive technologies. In this review and meta-analysis, we aim to find the most reliable noninvasive modalities for exploring the feasibility and accuracy of ICP monitoring modalities with potential for prehospital use.

Methods

Search strategy

The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria.⁷ Embase, Scopus, PubMed, CENTRAL, and Cochrane databases were sought for relevant articles on June 23, 2025, using a search strategy containing keywords identifying the cohort, keywords identifying emergency or prehospital settings, and terms defining the intervention of measuring intracranial pressure, without filters or limits. The full search strategy can be found in Supplementary Data. Original articles cited in systematic reviews and meta-analyses that were identified through the initial literature search were included in the abstract screening process equally to other search results. Articles found this way were categorized as citation-searched results, and the systematic reviews and meta-analyses from which they were found were later excluded during the abstract screening process.

Eligibility criteria and study selection

We included all studies evaluating methods of ICP assessment with potential use in a prehospital setting, defined as noninvasive or minimally invasive methods performed with transportable devices. Studies were excluded if the full text in English language was not available. We also excluded in vitro studies, animal studies, reviews, and meta-analyses. Articles were managed using the web-based software Covidence.⁸ All articles were initially assessed for eligibility by two investigators (A.N.R.L., M.H.K.) based on abstract and title. The selected articles were then full-text screened for eligibility by the same investigators (A.N.R.L., M.H.K.). Disagreements were resolved by a third investigator (M.F.G.). Data were extracted by one investigator (A.N.R.L.) and validated by a second investigator (V.H.).

Data extraction and outcomes

Data describing each method for ICP estimation were collected, including the reference standard test used, standard cutoff values for a positive index test, and technical details on the devices used.

Data describing the population in each study were extracted, including patient characteristics, number of participants, study design, and clinical setting of the study.

Data on index test accuracy were collected, including the number of true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) test results, reported sensitivity, specificity, positive predictive values, negative predictive values, and area under the curve (AUC) for receiver operating characteristic (ROC) curves.

Data were extracted as available from articles and supplementary material. Studies were not excluded based on the availability of data. All studies meeting the inclusion criteria were included in the systematic review. Meta-analysis was performed for methods where diagnostic test accuracy was tested in multiple studies with invasive ICP monitoring as a reference test. Only studies reporting TP, FP, TN, and FN, or reporting sufficient data to calculate these, were included in the meta-analysis.

Invasive ICP measurement was considered the gold standard test, and measurements of >20 mmHg were considered elevated.²

Quality assessment

The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.⁹ Quality assessment was performed by two independent investigators (A.N.R.L., V.H.), and conflicts were solved through consensus.

Statistical analysis and evaluation

Analyses were performed using RevMan 5.4 software¹⁰ and MetaDTA software,^11,12 designed for meta-analysis of diagnostic test accuracy studies. For studies included in the meta-analysis, we report forest plots of sensitivity and specificity of each study with 95% confidence intervals (CIs) and summary ROC curves using a bivariate model with a 95% confidence area.

Suitability for prehospital use of each method was assessed by evaluation of the following four properties: (1) The device is sufficiently mobile, that is, small in size or based on equipment already widely used in ambulances or helicopters. (2) The method can provide a valid assessment of ICP in <5 min. (3) The device has minimal or no sterilization requirements. (4) ICP assessment can be performed by one person with minimal training requirements (<7 h, equivalent to 1 day). Studies were deemed of high potential for prehospital use, if they fulfilled ≥3/4 evaluation criteria.

Results

Study selection and quality assessment

We identified 2603 studies, and 1713 duplicates were removed. The remaining 965 studies were screened by title and abstract, and 124 studies were selected for full-text review. Twenty-two articles were excluded due to the unavailability of the full-text study in English. In total, 55 studies were included in the review and meta-analysis (Fig. 1). An overview of study characteristics and quality assessment for each study is found in Table 1 and Supplementary Table S1.

FIG. 1.

PRISMA flow diagram. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Table 1.

Characteristics of Included Studies

Study ID	Participant characteristics	Clinical setting	Study design	Target condition definition	Index test	Reference standard	Sample size
Abramo 2022¹³	Children with suspected cerebral edema in diabetic ketoacidosis	Emergency department	Case-control study	Need of hypertonic saline infusion	Cerebral oximetry	Clinical evaluation	61 cases 43 controls
Bellner 2004¹⁴	Neurosurgical patients	n/a	Prospective observational study	ICP > 20 mmHg	TCD—PI	Invasive ICP	81 patients
Blaivas 2003¹⁵	Stable patients with head trauma or signs of intracranial hemorrhage	Emergency department	Prospective observational study	Elevated ICP^a	ONSD	CT scan	35 patients
Brandi 2010¹⁶	Sedated patients with severe TBI	Neuro-ICU	Prospective observational study	ICP ≥ 20 mmHg	TCD—Bellner equation	Invasive ICP	45 patients
					TCD—Schmidt equation
					TCD—Edouard equation
Canakci 2018¹⁷	Patients admitted with headache without trauma	Emergency room	Prospective observational study	Abnormal CT	ONSD	CT	100 patients
Cardim 2016¹⁸	Sedated TBI patients	Neuro-ICU	Prospective observational study	ICP ≥ 20 mmHg	TCD—black-box conversion	Invasive ICP	40 patients
					TCD—diastolic flow velocity
					TCD—critical closing pressure
					TCD—PI
Dutton 2005¹⁹	Blunt trauma patients	Trauma center	Prospective observational study	Abnormal CT scan	Brain acoustics monitor	CT scan	206 patients
El Ahmadieh 2021²⁰	Blunt TBI patients with abnormal CT scans	Emergency department	Prospective observational study	Need for surgical intervention	Automated pupillometry	Clinical assessment	36 patients
Figaji 2009²¹	Children with severe TBI	Children’s hospital	Prospective study	ICP ≥ 20 mmHg	TCD—PI	Invasive ICP	34 patients and 275 recordings
Frumin 2014²²	Patients requiring invasive ICP monitor	Neurocritical care unit	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	27 patients
Geeraerts 2007²³	Patients with severe TBI	Surgical critical care unit	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	31 patients
Geeraerts 2007²³	Patients with severe TBI	Surgical critical care unit	Prospective observational study	ICP ≥ 20 mmHg	TCD—PI	Invasive ICP	31 patients
Geeraerts 2008²⁴	Patients with severe TBI	Surgical critical care unit	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	37 patients and 78 recordings
Girisgin 2007²⁵	Patients with elevated ICP vs. healthy volunteers	Emergency department	Case-control study	Elevated ICP^a	ONSD	CT	28 patients and 26 controls
Hakeem 2025²⁶	Patients with isolated TBI	Trauma center	Prospective Observational Study	Elevated ICP	ONSD	CT and clinical evaluation	180 patients
Hall 2013²⁷	Children with suspected ventriculoperitoneal shunt failure	Neuropediatric department	Prospective observational study	VP-shunt failure	ONSD	Intervention for shunt failure	35 patients and 39 encounters
Hansen 1997²⁸	Patients with suspected cerebrospinal fluid absorption disorder undergoing intrathecal infusion test	Neurological department	Intervention study	ICP ≥ 20 mmHg	ONSD	Cerebrospinal fluid pressure	12 patients and 36 recordings
Homburg 1993²⁹	Patients with head injury	Neurosurgical ICU	Prospective observational study	ICP ≥ 20 mmHg	TCD—PI	Epidural pressure	10 patients
Houzé-Cerfon 2019³⁰	Patients with moderate or severe TBI	Prehospital	Feasibility study	—	ONSD	—	23 patients
Huo 2021³¹	Patients with idiopathic intracranial hypertension	Emergency department	Case report	Idiopathic intracranial hypertension	ONSD	—	5 patients
Jenjitranant 2020³²	Patients with TBI	Emergency department	Retrospective observational study	Elevated ICP^a	ONSD	CT	63 patients
Jeon 2017³³	Patients with abnormal CT/MRI, who required external ventricular drain for ICP control	Emergency department and ICU	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	62 patients
Jiang 2024³⁴	Patients with severe TBI	Surgical ICU	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	57 patients
					Pcv-aCO₂/Ca-cvO₂
					Combined ONSD and Pcv-aCO₂/Ca-cvO₂
Kahraman 2009³⁵	Patients with severe TBI requiring ICP monitoring	Trauma center	Retrospective observational study	ICP ≥ 20 mmHg	Heart rate variability	Invasive ICP	25 patients
Kimberly 2008³⁶	Patients with TBI or spontaneous intracerebral hemorrhage	Emergency department and ICU	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	15 patients and 38 scans
Komut 2016³⁷	Patients with suspected intracranial event	Emergency department	Prospective observational study	CT abnormality	ONSD	CT	100 patients
Le 2009³⁸	Children with suspected or confirmed elevated ICP	Pediatric ICU and emergency department	Prospective observational study	Elevated ICP^a	ONSD	CT	64 patients
Maissan 2015³⁹	ICP-monitored TBI patients	ICU	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	18 patients
Major 2011⁴⁰	Patients requiring head CT	Emergency department	Prospective observational study	Elevated ICP^a	ONSD	CT	26 patients
Malayeri 2005⁴¹	Children with elevated ICP vs. controls	Neurological and neurosurgical departments, and ICU	Case-control study	Elevated ICP^a	ONSD	CT and/or Ophthalmoscopy	78 cases and 78 controls
Martin 2019⁴²	Patients with severe TBI	Trauma center	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	54 patients
Martin 2019⁴²	Patients with severe TBI	Trauma center	Prospective observational study	ICP ≥ 20 mmHg	TCD—PI	Invasive ICP	54 patients
McQuire 1998⁴³	Patients with serious head injury	Emergency room	Observational study	Space-occupying lesion or swelling	TCD—PI	CT	22 patients and 39 recordings
Melo 2011⁴⁴	Children <15 years old with severe TBI	Pediatric trauma center	Retrospective cross-sectional study	ICP ≥ 20 mmHg	TCD	Invasive ICP	117 patients
Momtaz 2022⁴⁵	Adults with intracranial pathology or injury	ICU	Case-control study	Elevated ICP^a	ONSD	CT	76 cases and 65 controls
Moretti 2009⁴⁶	Patients with intracranial hemorrhage vs. with no intracranial pathology	ICU	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	53 patients
Muchnok 2012⁴⁷	Patients undergoing lumbar puncture	Emergency department	Prospective observational study	ICP ≥ 20 mmHg	Intraocular pressure measurement	Lumbar puncture opening pressure	32 patients
Netteland 2023⁴⁸	TBI patients	Neuro-ICU	Observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	25 patients and 43 recordings
Netteland 2024⁴⁹	TBI patients	Neuro-ICU	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	26 patients and 44 examinations
Netteland 2025⁵⁰	aSAH patients where basal cisterns had not been entered	Neurosurgical department	Prospective observational study	ICP ≥ 15 mmHg (≥20 mmHg for meta-analysis)	ONSD	Invasive ICP	18 examinations
O’Brien 2015⁵¹	Children with severe TBI and ICP monitor	Pediatric ICU	Prospective observational study	ICP ≥ 20 mmHg	TCD—PI	Invasive ICP	36 patients and 148 recordings
Qayyum 2013⁵²	Patients with suspected elevated ICP	Emergency department	Prospective observational study	Elevated ICP^a	ONSD	CT	24 patients
Raffiz 2017⁵³	Patients requiring EVD or invasive ICP monitoring	Neurosurgical ICU	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	41 patients and 75 recordings
Rajajee 2011⁵⁴	Patients at risk for developing elevated ICP	ICU	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	65 patients and 536 recordings
Rasulo 2017⁵⁵	Patients with acute brain injury and invasive ICP monitoring	Neurocritical care unit	Prospective observational study	ICP ≥ 20 mmHg	TCD	Invasive ICP	38 patients and 114 recordings
Robba 2017⁵⁶	Patients with severe TBI	Neurocritical care unit	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	64 patients and 445 recordings
					TCD—diastolic flow velocity
					TCD—systolic venous flow velocity
					TCD—PI
Robba 2018⁵⁷	Patients with invasive ICP monitor	Neuro-ICU	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	22 patients and 110 recordings
					TCD—diastolic flow velocity
					TCD—PI
Singer 2021⁵⁸	Patients with TBI and/or invasive ICP monitor	Trauma center	Prospective observational study	ICP ≥ 20 mmHg	ONSD	invasive ICP	66 patients
					Pupillometry
					TCD—PI
Strumwasser 2011⁵⁹	Patients with severe TBI	Trauma center	Prospective observational study	ICP ≥ 20 mmHg	ONSD	Invasive ICP	10 patients
Tayal 2007⁶⁰	Patients with suspected head injury	Emergency department	Prospective observational study	Elevated ICP^a	ONSD	CT	59 patients
Tsung 2005⁶¹	Children with head trauma	Pediatric emergency department	Case report	Elevated ICP^a	ONSD	—	3 patients
Voulgaris 2005⁶²	Patients with severe head injury and invasive ICP monitoring	ICU	Prospective observational study	ICP ≥ 20 mmHg	TCD—PI	Invasive ICP	37 patients and 165 recordings
Wakerley 2014⁶³	Patient with acute headache	n/a	Case report	n/a	TCD—PI	—	1 patient
Wakerley 2015⁶⁴	Patients undergoing lumbar puncture	n/a	Prospective observational study	ICP ≥ 20 mmHg	TCD—PI	Lumbar puncture manometry	78 patients and 91 readings
Weatherall 2012⁶⁵	Healthy volunteers	Prehospital setting	Feasibility study	—	Cerebral oximetry	—	65 transfers
Zeiler 2018⁶⁶	TBI patients	Neurocritical care unit	Feasibility study	—	TCD	—	10 patients
Zweifel 2012⁶⁷	Patients with closed head injury	Neuro-ICU	Prospective observational study	ICP ≥ 20 mmHg	TCD—PI	Invasive ICP	290 patients and 762 recordings

Elevated ICP as diagnosed by CT without invasive ICP measurement to confirm. Diagnostic sign on CT included midline shift, space-occupying lesions, effacement of sulci or basal cisterns, brain herniation, etc.

ICP, intracranial pressure; ICU, intensive care unit; ONSD, optic nerve sheath diameter; PI, pulsatility index; TBI, traumatic brain injury; TCD, transcranial Doppler; CT, computed tomography; MRI, magnetic resonance imaging; aSAH, aneurysmal subarachnoid hemorrhage.

Prehospital suitability

Optic nerve sheath diameter for diagnosing elevated ICP

A total of 31 studies investigated the use of optic nerve sheath diameter (ONSD) for predicting elevated ICP^{15,17,22–26,28,30–34,36,37,39,40,42,45,46,48–50,52–54,56–60} in adult patients. ONSD was measured by ocular ultrasound through a closed eyelid using a linear probe. The diameter was measured 3 mm proximally to the optic disc perpendicular to the optic nerve. As a standard, ONSD was considered normal if <5 mm and increased if ≥5 mm.

Ultrasound of ONSD was performed using standard ultrasound equipment, taking a median of 4 min to obtain a valid measurement,³⁰ in a noninvasive manner, and after 4 h of training.³⁰ Thus, the method fulfilled 4/4 of the evaluation criteria for prehospital suitability (Table 2).

Table 2.

Prehospital Suitability of the Included Methods

	Mobility	Time consumption	Sterilization requirements	Personnel requirements
US of ONSD	✓	✓	✓	✓
US of ONSD	US equipment	Median 4 min³⁰	Noninvasive	4 h training for experienced sonographers
Automated pupillometry	✓	✓	✓	(✓)
Automated pupillometry	Handheld pupillometer	Measured over 3.2 sec⁵⁸	Noninvasive	Training requirements not reported Device is automated
Cerebral oximetry	✓	✓	✓	—
Cerebral oximetry	Tested in prehospital vehicles⁵⁰	Average < 2 min⁵⁰	Noninvasive	Training requirements not reported
Heart rate and pulse pressure	✓	(✓)	✓	—
Heart rate and pulse pressure	Heart rate monitor	5 min intervals used	Noninvasive	Training requirements not reported
Transcranial Doppler	✓	✗	✓	(✗)
Transcranial Doppler	US equipment	5–10 min per side⁵⁸	Noninvasive	Extensive training is required.⁶² Further details not reported
Intraocular pressure	✓	(✗)	✓	✗
Intraocular pressure	Handheld tonometer	Time not reported. Requires calibration	Noninvasive	Training requirements not reported
Brain acoustics monitor	(✗)	—	✓	—
Brain acoustics monitor	Size not reported Sensitive to movement⁶⁴	Time to assessment not reported	Noninvasive	Training requirements not reported
Pcv-aCO₂/Ca-cvO₂	—	—	✓	—
Pcv-aCO₂/Ca-cvO₂	Size or availability of equipment not reported	Time to assessment not reported	Minimally invasive	Training requirements not reported

Overview of the prehospital suitability of each included method in four predefined areas. (1) The device is sufficiently mobile, i.e., small in size or based on equipment already installed in ambulances or helicopters. (2) The method can provide a valid assessment of ICP in <5 min. (3) The device has minimal or no sterilization requirements. (4) ICP assessment can be performed by one person with minimal training requirements (<7 h, equivalent to 1 day).

Methods were deemed suitable for prehospital use, if they fulfilled ≥3 out of 4 criteria.

US, ultrasound.

Pupillometry

Two studies investigated the use of neuropupillary index (NPI) score and the correlation to elevated ICP.^20,58 Both studies used an infrared pupillometer, which automatically measured pupil size, response latency, and constriction and relaxation velocity, and computed these measures into the NPI score between 0 and 5 for each eye.

Pupillometry-based estimation of ICP was performed using a handheld automated pupillometer, evaluating the NPI over 3.2 sec,⁵⁸ in a noninvasive manner with unknown training requirements. Thus, the method fulfilled 3/4 of the evaluation criteria for prehospital suitability (Table 2).

Cerebral tissue oximetry

Noninvasive cerebral tissue oximetry was investigated in two of the included studies.^13,65 Two cerebral oximetry probes were placed on the forehead of the patients, and regional cerebral oxygen saturation (r_cSO₂) was recorded at short time intervals by near-infrared spectroscopy. Cerebral oximetry was performed using portable cerebral oximetry probes, tested during transport in a prehospital setting, taking on average <2 min to obtain a valid measurement,⁶⁵ in a noninvasive manner, with unknown training requirements. Thus, the method fulfilled 3/4 of the evaluation criteria for prehospital suitability (Table 2).

Heart rate and pulse pressure

One study investigated the correlation between heart rate and pulse pressure and ICP³⁵ in 25 patients with severe TBI. Heart rate and pulse-pressure-based estimation of ICP was performed using a standard heart monitor, for 5-min intervals, in a noninvasive manner with unknown training requirements. Thus, the method fulfilled 3/4 of the evaluation criteria for prehospital suitability (Table 2).

Transcranial Doppler

A total of 19 studies investigated the use of transcranial Doppler (TCD) for estimating elevated ICP^{14,16,18,21,24,29,42–44,51,55–58,62–64,66,67} patients with confirmed or suspected head injury or other intracranial pathology; of these, 13 studies investigated the use of pulsatility index (PI) to predict elevated ICP in adult patients.^{14,18,23,29,42,43,56–58,62–64,67}

PI was found through TCD examination of the middle cerebral artery and calculated as the ratio between the difference in systolic flow velocity (FVs) and diastolic flow velocity (FVd), and the mean flow velocity (FVm); $PI = \frac{FVs - FVd}{FVm}$ . TCD-based estimation of ICP was performed using standard ultrasound equipment, needing 5–10 min per side to obtain a valid measurement,⁵⁸ in a noninvasive manner and with extensive training.⁴⁴ Thus, the method fulfilled 2/4 of the evaluation criteria for prehospital suitability (Table 2).

Intraocular pressure

One study investigated the use of intraocular pressure (IOP) measurement for diagnosing elevated ICP.⁴⁷ IOP measurement was performed using a handheld tonometer in a noninvasive manner, with unknown requirements for time and personnel training. Thus, the method fulfilled 2/4 of the evaluation criteria for prehospital suitability (Table 2).

Brain acoustics monitoring

One study investigated the use of the brain acoustics monitor (BAM) for diagnosing elevated ICP.¹⁹ The BAM records sound waves from the skull through a sensor placed on the patient’s forehead.

The BAM was used to estimate ICP noninvasively, with unknown requirements for space, time, and training. However, the BAM was reported sensitive to patient movement. Thus, the method fulfilled 1/4 of the evaluation criteria for prehospital suitability (Table 2).

Pcv-aCO₂/Ca-cvO₂

One study investigated the use of the ratio between central venous (cv) minus arterial (a) CO₂ pressure and arterial minus central venous O₂ ( $\frac{Pcv - aC O_{2}}{Ca - cv O_{2}}$ ) calculated blood samples from venous and arterial catheters³⁴. Calculating Pcv − aCO₂/Ca − cvO₂ required minimally invasive procedures. The requirements for space, time, and training were not reported. Thus, the method fulfilled 1/4 of the evaluation criteria for prehospital suitability (Table 2).

Diagnostic accuracy

In the following, we present a review and meta-analysis of the diagnostic accuracy of the methods with high potential for prehospital use, that is, fulfilling ≥3/4 evaluation criteria for prehospital suitability. A review of the remaining methods can be found in Supplementary Data.

ONSD for diagnosing elevated ICP

In 24 studies, the optimal cutoff value in adult patients was found to be 4.7–6.3 mm.^{15,17,22–24,26,28,31,33,34,36,37,39,40,42,45,46,50,52,54,56,57,59,60} One study found an optimal cutoff value of 3.15 mm.³²

Twenty studies reported ROC curves of ONSD for diagnosing elevated ICP (>20 mmHg). Nineteen studies^{26,33,34,36,37,39,42,45,48–50,52–54,56,57} found a good diagnostic accuracy, with an AUC of 0.72–1.00, while one study⁵⁹ found the test to be insufficient with an AUC of 0.36.

Two studies evaluated mean ONSD in patients with elevated ICP compared with patients without. One study found no correlation between ONSD and elevated ICP,⁵⁸ while the other found a significantly higher mean ONSD in patients with elevated ICP compared with patients with normal ICP.²⁵

One study tested the quality of ONSD measurements performed in a prehospital setting by physicians experienced in sonography, who received 4 h of training in ocular ultrasound prior to the study.³⁰ ONSD measurements were obtainable and validated by experts in 80% of cases during ambulance transportation, 71% in the field, and 43% during helicopter transportation.

The sensitivity and specificity of ultrasound of ONSD for detecting elevated ICP in adults found in each study included in the meta-analysis are summarized in Figure 2. We found a summarized sensitivity of 92.6% (95% CI: 87.0; 95.9%) and a summarized specificity of 85.1% (95% CI: 74.1; 92.0%) across 15 studies evaluating the diagnostic accuracy of ultrasound of ONSD for detecting elevated ICP on invasive monitoring^{22–24,28,33,34,36,42,46,50,53,54,56,57,60} (Fig. 3A). Risk of bias and applicability concerns in the included studies are illustrated in Figure 4. Furthermore, summary ROC curves for different cutoff values are shown in Figure 3B. Studies using 5.2 mm as a cutoff value showed the highest summarized diagnostic odds ratio of 92.2 (95% CI: 20.8; 407.9) across three studies.

FIG. 2.

Forest plot for studies evaluating optic nerve sheath diameter. Forest plot of sensitivity and specificity of optic nerve sheath diameter for diagnosing elevated ICP for studies included in the meta-analysis.

FIG. 3.

Summary receiver operator curve of ONSD for detecting elevated ICP. (A) Summary ROC curve for optic nerve sheath diameter compared with invasive ICP measurement with 95% confidence area marked by the dotted line. Circles indicate sensitivity and specificity reported in each of the included studies. (B) Summary ROC curves for different cutoff values reported in the studies included in the meta-analysis. ICP, intracranial pressure; ROC, receiver operator characteristic.

FIG. 4.

Summary of quality assessment of studies included in the meta-analysis. Summary of risk of bias and applicability concerns in each domain for studies included in the meta-analysis, assessed using the QUADAS-2 tool for diagnostic test accuracy studies. (A) Distribution of risk of bias in studies evaluating US of ONSD. (B) Distribution of applicability concern in studies evaluating US of ONSD. QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies 2.

Four studies evaluated the use of ONSD for diagnosing elevated ICP in pediatric patients, using the same measuring technique as for adults.^27,38,41,61 All studies used cutoff values of ≥4.0 mm for children <1 year and ≥4.5 mm for children >1 year. One study found a significant difference in mean ONSD between cases with elevated ICP and a control group with normal ICP.⁴¹ Two studies reporting sensitivity and specificity of ONSD for detecting elevated ICP³⁸ or neurosurgical intervention for shunt failure²⁷ found a sensitivity of 61.1–83% and a specificity of 22.2–38%.

Cerebral tissue oximetry

One study¹³ investigated the use of cerebral tissue oximetry in pediatric patients with suspected cerebral edema diabetic ketoacidosis (SCEDKA), comparing readings before and after hypertonic saline solution (HTS) infusion as a proxy for elevated ICP. They found that r_cSO₂ was significantly lower after infusion of HTS. They also found a significant difference in r_cSO₂ between SCEDKA patients and controls, both before and after HTS infusion.

Another study⁶⁵ investigated the feasibility of cerebral tissue oximetry in a prehospital setting and during transportation in 33 healthy volunteers and found that the probes provided successful bilateral monitoring for over 70% of the monitoring period in 100% of volunteers during road transport and 85.7% of volunteers during helicopter transport. However, they also found that in 50% of cases, the probes could not provide monitoring when used in ambient light due to light contamination.

Pupillometry

One study²⁰ found a significantly lower NPI score in 9 TBI patients who later underwent neurosurgical intervention than in 27 TBI patients who did not. Three patients with bilaterally normal NPI (≥3) underwent invasive ICP monitoring and did not show elevated ICP. Two patients had a low NPI score (<3) in one or both pupils and were monitored with invasive ICP monitoring. Both patients had consistently increased ICP.

Another study⁵⁸ found no correlation between pupillometry-derived measures and ICP measurements in 36 severe TBI and 39 nontrauma patients with invasive ICP monitors.

Heart rate and pulse pressure

One study³⁵ found that pulse pressure, heart rate variability (HRV), and pulse pressure variability (PPV) increased with increasing ICP when cerebral perfusion pressure (CPP) remained stable and that HRV and PPV decreased significantly when CPP decreased to ≤60 mmHg.

Discussion

In this systematic review and meta-analysis, we have explored ICP measuring devices with potential for use in the prehospital environment. We found a range of different methods for noninvasive ICP estimation performed with transportable equipment, potentially suitable for prehospital use.

After evaluating each of the methods on four predefined criteria for prehospital suitability, we found that four of the seven identified methods fulfilled at least 3/4 criteria and thus showed high potential for prehospital use.

Of these, the most extensively researched method was the measurement of ONSD. One of the advantages of this method is that ultrasound equipment is inexpensive and readily available in most parts of the world. While the need for an experienced sonographic operator is a limitation, studies indicate a rapid learning curve for ONSD ultrasound for both experienced sonographers and novices.⁶⁰ Furthermore, automated modalities for monitoring ONSD are available, reducing the need for operator experience and limiting interoperator variability,⁴⁸ though these options have not yet been thoroughly tested.

As one of the main limitations of sonographic ICP estimation in a prehospital setting seems to be time consumption,³⁰ this is a crucial factor to consider. However, one of the included studies indicated that valid ultrasonic ONSD measurements were obtainable in 80% of cases during ambulance transportation, when performed by experienced sonographers,³⁰ limiting the time needed to perform this assessment on scene.

Our meta-analysis showed a summarized sensitivity of 92.6% (95% CI: 87.0; 95.9%) and a summarized specificity of 85.1% (95% CI: 74.1; 92.0%), indicating a high diagnostic accuracy of ONSD. While the overall accuracy of the test is important when used for prehospital screening for elevated ICP, a test with high sensitivity should be prioritized to ensure the identification of most cases with elevated ICP. It is likely that higher diagnostic accuracy and predictive value may be obtained by combining two or more ICP estimation methods; however, using multiple measures may also increase the time needed to assess ICP, thus limiting the use in acute situations.

Methods like heart rate variability and pupillometry showed poor correlation with ICP and limited potential for diagnosing elevated ICP, and the research on these methods was likewise limited. Thus, the value of these methods as a prehospital tool for diagnosing elevated ICP remains undetermined.

Finding and implementing an affordable and accessible noninvasive method for prehospital evaluation of increased intracranial pressure could be of great value, especially in low income or rural areas, where computed tomography scan or neurosurgical expertise may not be readily available. In these situations, a way of diagnosing early stages of increased ICP could mean both early prehospital intervention and a timelier decision to transport patients to a facility with neurosurgical capabilities.

Limitations

There was substantial heterogeneity in the specifics of the tested methods, the reference standard, the defined thresholds for a positive test, and the patient populations investigated in the included studies, reducing the generalizability. In a prehospital setting, the aim of measuring ICP would be to determine the need for neurosurgical intervention in patients without clear signs of intracranial pathology, while most of the included study populations consisted of patients with severe injuries, where clinical signs are typically more distinct.

In the absence of a validated method for assessing prehospital suitability, the potential for prehospital use was assessed through four major criteria formulated by investigators with extensive prehospital qualifications and experience. However, other factors, such as power requirements and durability when exposed to adverse conditions, including humidity, temperature changes, and dirt or dust, that could potentially influence the suitability of a device for prehospital use should be carefully considered and assessed before implementation.

The meta-analysis in this study was conducted based on a dichotomous evaluation of whether ICP was elevated. In a clinical setting, a more graded evaluation of the relation between ONSD and ICP across studies could be valuable; however, the reported data in the included studies were insufficient to perform a meta-analysis of this aspect.

In several studies, the index test was performed by one or a few trained physicians, limiting the ability to examine inter-rater variability. Most included studies were conducted in hospitals in emergency departments or intensive care units, further reducing the transferability to a prehospital setting. Quality assessment showed a high risk of bias in 50% of studies included in the meta-analysis in relation to the index test, primarily due to the lack of blinding during test result interpretation, and in 33% of studies in relation to the patient population, primarily due to a nonrandom inclusion process. The proportion of high risk of bias was low in the remaining domains. Between 14% and 33% of studies included in the meta-analysis were assessed to have high or unclear applicability concerns regarding patient population, index test, and reference standard.

Conclusion

Several portable, noninvasive methods for detecting elevated ICP are available; however, no single method has been sufficiently investigated. In this review, we found ultrasonic measurement of the ONSD to have the highest potential for prehospital use; however, most of the studies found through this systematic review and meta-analysis were performed in emergency departments and ICU settings with a very limited number of investigators performing the test. Further prospective studies evaluating the use of this method in a prehospital setting are needed to verify the value and diagnostic capability.

Transparency, Rigor, and Reproducibility Summary

This study was not formally registered. The analysis plan was not formally preregistered, but the team member with primary responsibility for the analysis certifies that the analysis plan was prespecified. Data were acquired between April 2023 and June 2025. Data were collected using Covidence.⁸ Data were analyzed using RevMan.¹⁰ All datasets were analyzed at the same time. All equipment and software used to perform acquisition and analysis are widely available from Covidence.org and Cochrane.org. The primary prehospital eligibility criteria have not been established as a standard in the field. The criteria were formulated by investigators with extensive prehospital qualifications and experience. The statistical tests used were based on the assumptions of independent measurements. The authors agree or have agreed to publish the article using the Mary Ann Liebert, Inc. “Open Access” option under appropriate license.

Authors’ Contributions

A.N.R.L.: Conceptualization, formal analysis, investigation, methodology, writing—original draft, writing—review and editing, and visualization; M.H.K.: Investigation and writing—review and editing; V.H.: Conceptualization, investigation, validation, and writing—review and editing; M.R.: Methodology and writing—review and editing; K.U.K.: Writing—review and editing; A.G.: Writing—review and editing; R.M.: Writing—review and editing; L.K.R.: Writing—review and editing; C.Z.S.: Writing—review and editing; M.F.G.: Investigation and writing—review and editing; A.R.K.: Conceptualization, validation, resources, writing—original draft, writing—review and editing, visualization, supervision, project administration, and funding acquisition.

Footnotes

Author Disclosure Statement

A.R.K. reports grants from IRRAS AB to Aarhus University Hospital to support the ACTIVE study and personal fees from IRRAS AB for a presentation at a scientific symposium describing his experiences with the IRRAflow technology during the conduct of the study; grants from IRRAS AB to Aarhus University Hospital to support the development of a neuromonitoring technology related to IRRAflow outside the submitted work. In addition, A.R.K. has a patent for a neuromonitoring technology pending with relation to the IRRAflow technology. The remaining authors have no conflicts of interest to declare.

Funding Information

A.R.K. is supported by grants from the Danish Cancer Society (R304-A17698-B5570 and R295-A16770), the Lundbeck Foundation (R325-2019-1490), and the Independent Research Fund Denmark (903900307B) unrelated to this study. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; and decision to submit the article for publication.

Supplemental Material

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Supplementary Material

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Noninvasive Methods for Measurement of Intracranial Pressure in Patients with Acute Neurotrauma: A Systematic Review and Meta-Analysis

Abstract

Keywords

Introduction

Methods

Search strategy

Eligibility criteria and study selection

Data extraction and outcomes

Quality assessment

Statistical analysis and evaluation

Results

Study selection and quality assessment

Prehospital suitability

Optic nerve sheath diameter for diagnosing elevated ICP

Pupillometry

Cerebral tissue oximetry

Heart rate and pulse pressure

Transcranial Doppler

Intraocular pressure

Brain acoustics monitoring

Pcv-aCO2/Ca-cvO2

Diagnostic accuracy

ONSD for diagnosing elevated ICP

Cerebral tissue oximetry

Pupillometry

Heart rate and pulse pressure

Discussion

Limitations

Conclusion

Transparency, Rigor, and Reproducibility Summary

Authors’ Contributions

Footnotes

Author Disclosure Statement

Funding Information

Supplemental Material

References

Supplementary Material

Pcv-aCO₂/Ca-cvO₂