American Journal of Emergency Medicine (2012) 30, 1357-1363

Original Contribution

Optic nerve ultrasound for the detection of Elevated intracranial pressure in the hypertensive patient

Pedro J. Roque MD^a,?, Teresa S. Wu MD^b, Laura Barth MD^a, Dave Drachman PhD^c, Kai-Ning Khor BA, MPH^a, Frank LoVecchio DO, MPH^a, Stephan Stapczynski MD^a

^aDepartment of Emergency Medicine, Maricopa Medical Center, Phoenix, AZ 85008, USA

^bDepartment of Emergency Medicine, EM Ultrasound Program & Fellowship, Maricopa Medical Center,

Phoenix, AZ 85008, USA

^cDepartment of Research, Maricopa Medical Center, Phoenix, AZ 85008, USA

Received 25 August 2011; revised 21 September 2011; accepted 23 September 2011

Abstract

Purpose: We sought to determine whether dilation of the optic nerve sheath diameter (ONSD), as detected at the bedside by emergency ultrasound (US), could reliably correlate with patient blood pressure and whether there was a blood pressure cutoff point where you would start to see abnormal dilation in the ONSD.

Methods: This was a single-blinded, prospective, observational trial from September 2010 to April 2011. One hundred fifty patients presenting to the emergency department were enrolled. There were 3 arms to the study with 50 patients in each arm: (1) ONSD in normotensive/asymptomatic patients; (2) ONSD in hypertensive/asymptomatic patients; and (3) ONSD in hypertensive/symptomatic patients. Ocular US was conducted on all subjects.

Results: Neither the number of symptoms nor the type of symptom present in the hypertensive/symptomatic group was able to significantly predict the average ONSD before treatment (P = .818 and .288, respectively). There was a significant correlation between both systolic blood pressure (SBP) and diastolic blood pressure with the ONSD in all Hypertensive patients. The best SBP and DBP cutoff point for abnormal ONSD was 166/82 mm Hg. Decrease in ONSD observed after blood pressure treatment was not statistically significant (P = .073).

Conclusions: In conclusion, our study shows that practitioners can use bedside ocular US and a blood pressure cutoff point to help predict whether patients require more aggressive management of their symptomatic hypertension. Knowing the SBP and DBP readings that lead to increased ONSD and increased intracranial pressure can help guide management and Treatment decisions at the bedside.

(C) 2012

* Corresponding author. Department of Emergency Medicine Research, Maricopa Medical Center, Phoenix, AZ 85008, USA.

E-mail address: [email protected] (P.J. Roque).

0735-6757/$ - see front matter (C) 2012 doi:10.1016/j.ajem.2011.09.025

Introduction

The diagnosis of elevated intracranial pressure is both challenging and critical. Prompt recognition and treatment are essential to prevent possible brain damage or even death. Elevated ICP may be present in emergency department (ED) patients with malignant hypertension [1,2]. These patients present to the ED with hypertension generally greater than 180/120 mm Hg and signs of end-organ dysfunction [3]. Early diagnosis of acute Intracranial hypertension in the hypertensive population would be extremely useful to the treating physicians because it would lead to earlier blood pressure treatment and improved outcomes.

In recent years, bedside ultrasound (US) in the ED has been shown to be a safe, effective, and noninvasive technique that can be used to measure ICP. Up until this point, measuring ICP was not possible without using invasive measures [4]. Using US to evaluate ICP hinges on the close embryological relationship between the optic nerve sheath diameter and the central nervous system. Because the optic nerve is surrounded by the same CSF that surrounds the brain, any pressure variations within the skull are directly transmitted to the optic nerve. The optic nerve sheath increases in diameter in response to increased ICPs. The upper limit of ONSD for adult patients has been shown to be 5 mm. An ONSD

greater than 5 mm has been shown to correlate with increased ICP with a sensitivity of 88% and specificity 93% [5-7].

In evaluating patients with profound hypertension, it would be useful to know if their Elevated blood pressure is causing an increase in their ICP. To our knowledge, the relationship between blood pressure and ONSD using emergency bedside US has not been investigated. We sought to determine whether dilation of the ONSD, as detected at the bedside by emergency US, could reliably correlate with patient blood pressure and whether there was a blood pressure cutoff point where you would start to see abnormal dilation in the ONSD.

Methods

Study design

This was a prospective, observational study of the ONSD in patients with varying degrees of blood pressures and presenting symptoms in an urban ED. The study used a convenience sample of patients. This study was approved by the hospital’s institutional review board before commence- ment of data collection. All patients provided informed consent before enrollment.

ED Convenience Patient Sample

Yes No

Hypertensive? (SBP>=140 or DBP>=90)

Control Group: 50 Patients

Excluded

Hypertensive, Asymptomatic Group: 50Patients

Hypertensive, Symptomatic Group:

50 Patients

Symptomatic?

Symptomatic?

Yes

No

Yes

No

Fig. 1 Study protocol. Symptomatic refers to the presence of headache, diplopia, blurry vision, chest pain, shortness of breath, dizziness, vertigo, nausea/vomiting, abdominal pain, and extremity pain/weakness.

1. Age < 18
2. Incarceration
3. Medically unstable patients requiring immediate medical management
4. Normotensive, symptomatic patients
5. Patients unable to consent

Exclusion Criteria:

Study setting and population

This study was conducted at Maricopa Medical Center in Phoenix, AZ. The Maricopa Medical Center is an urban level 1 academic 449-bed teaching hospital with an ED census of 60 000 patients per year. The ED is staffed by board-certified emergency medicine attending physicians and emergency medicine residents. An intradepartmental credentialing system is in place to allow emergency physicians to make Clinical decisions based on the results of their emergency US scans. Residents and attending physicians perform all bedside US examinations in the ED. All emergency residents and attending physicians attended a 2-hour lecture and hands-on training session for optic nerve USs directed by our US director before initiation of the study. All US images were reviewed by the US director periodically throughout the study.

Study protocol

We used the 2 variables, blood pressure and presence of “symptoms,” to stratify our subject population into 3 separate study arms. The 3 study arms were normotensi- ve/asymptomatic, hypertensive/asymptomatic, and hyper- tensive/symptomatic (Fig. 1). We defined hypertension as either a systolic blood pressure (SBP) 140 mm Hg or more or a diastolic blood pressure (DBP) 90 mm Hg or more. An average of the left and right blood Pressure measurements were used as the final blood pressure measurement. A patient was deemed to be symptomatic if they complained of headache, diplopia, blurry vision, chest pain, shortness of breath, dizziness, vertigo, nausea/vomiting, abdominal pain or extremity pain, or weakness. All of these symptoms could represent a sign of end-organ dysfunction, thereby shifting the diagnosis from hypertensive urgency to Hypertensive emergency.

Exclusion criteria included age younger than 18 years, incarceration, inability to provide consent, medically unsta- ble patients who required immediate medical intervention, and normotensive/symptomatic patients. Previous ocular pathology did not exclude patients from our study. Data collection was suspended if participation in the research study interfered with patient care at any point.

All patients were screened upon entering the ED and placed into 1 of 3 study groups once all inclusion/ exclusion criteria were satisfied. Patients in the hyper- tensive/symptomatic group underwent blood pressure treatment emergently in the ED. For these patients, the ONSD was measured before treatment and then 20 minutes after blood pressure treatment. Practitioners were asked to record the specific antihypertensive agent used and the change in blood pressure readings achieved in this study group.

Ocular USs were performed using a 10 to 13 MHz linear probe on a SonoSite M-Turbo US machine

(SonoSite, Inc, Bothell, WA), following the standard techniques described in the literature [3]. All patients were placed in a supine position for their ocular scans (Fig. 2). Conductive, water-based US gel was placed over each closed eyelid. A Linear probe was then be used to obtain axial Cross-sectional imaging of the optic nerve. Once the ONSD was visualized, the measurement was taken exactly

0.3 cm posterior to the orbit. Each study physician recorded 2 measurements on each eye (Fig. 3). The final ONSD measurement was derived from the average of all 4 measurements to minimize variability. An ONSD of 0.50 cm or greater was considered abnormal. All US images were saved into a password-protected file for review by the US fellowship director.

Data analysis

Demographic data were collected from the study participants including medical record number, age, sex, height, weight, blood pressure in left arm, blood pressure in right arm, symptoms, treatment rendered, and any previous ocular or intracranial pathology, surgery, or trauma. All data were entered into a Microsoft Excel spreadsheet. All statistical analyses were performed using the statistical program SPSS version 15 (SPSS, Chicago, IL). Independent associations were assessed via ?2 and Fischer exact tests for categorical variables. Pearson Correlation coefficients were calculated to determine the overall effect that systolic and DBP had on the ONSD variation within each group. The square of this value gave us the percentage of variation in ONSD that can be attributed to the SBP in the symptomatic group. Sensitivity, specificity, and positive and negative predic-

Fig. 2 Evaluation of the ONSD using a high-frequency linear array transducer. Patients are instructed to keep his/her eyes closed throughout the entire procedure.

Fig. 3 Optic nerve overview. Optic nerve sheath diameter is measured 3 mm posterior to the globe. Two measurements are made: 1 in the sagittal plane and 1 in the transverse plane. The gray strip between the 2 crosses represents the ONSD.

Table 1 Optic nerve size and presenting symptom in the hypertensive/symptomatic group

ONSD vs blood pressure

Symptom

Average ONS before treatment

?

Mean Count Lower confidence limit

Point estimate

Upper confidence limit

tive values with 95% confidence intervals (CIs) were also calculated.

Results

A total of 150 patients were enrolled in this study, with 50 patients in each arm of the study (normotensive/asymp- tomatic, hypertensive/asymptomatic, and hypertensive/- symptomatic). In our study, only the symptom of blurry vision was significantly associated with ONSD (? = .057; 95% CI, 0.013-0.012) (Table 1). Neither the number of symptoms nor the type of symptom present in the hypertensive/symptomatic group was able to significantly predict the average ONSD before treatment (correlation, 0.087; 95% CI, -0.074 to 0.243; and R² = 0.244; 95% CI,

0.082-0.406; respectively). There was a significant corre- lation between both SBP and DBP with the ONSD in all hypertensive patients (correlation, 0.396; 95% CI, 0.216-

0.550; and correlation, 0.228; 95% CI, 0.033-0.406; respectively). The best SBP and DBP cutoff point for abnormal ONSD was 166/82 mm Hg. The decrease in ONSD observed after blood pressure treatment was not statistically significant (difference, 0.067; 95% CI, -0.007

to 0.141).

There was a significant correlation between both SBP and DBP with the ONSD in all hypertensive patients (Table 2). The overall Pearson correlation coefficient for the SBP in all groups (0.454 or 20.6% variation) was higher than that of the DBP in all groups (0.331 or 11.0% variation). The Pearson correlation coefficients for the normotensive/asymptomatic patients were 0.059 for the SBP and -0.16 for the DBP, suggesting that 0.35% and 0.02% of the ONSD size are influenced by the SBP and DBP in the normotensive/a- symptomatic group, respectively.

Blurry vision	0.50	13	.013	.057	.102
Shortness of breath	0.48	11	-.037	.015	.067
Chest pain	0.47	15	-.028	.021	.070
Extremity pain/weakness	0.47	10	-.047	.008	.062
Headache	0.46	27	-.041	.005	.052
Abdominal pain	0.45	6	-.050	.021	.092
Nausea/vomiting	0.44	13	-.070	-.026	.017
Dizziness	0.44	6	-.073	-.010	.053
Diplopia	0.44	4	-.077	-.004	.070
Vertigo	0.43	3	-.164	-.071	.021
Optic nerve size was calculated using the average of the 2 left ONSD and the 2 right ONSD measurements. Symptom type did not significantly predict average optic nerve size before treatment (F10,39 = 1.256, P = .288). ONS indicates optic nerve size.

size		Lower confidence limit	Point estimate	Upper confidence limit		Lower confidence limit	Point estimate	Upper confidence limit
HTN, symptomatic	50	0.227	0.475	0.665	-0.027		0.253	0.496
HTN, asymptomatic	50	0.130	0.394	0.606	-0.016		0.263	0.504
Non-HTN, asymptomatic	50	-0.223	0.059	0.332	-0.293		-0.016	0.264
Overall	100	0.317	0.454	0.573	0.131		0.331	0.505

In our study, patients with abnormal ONSD had significantly higher blood pressures than those with normal ONSD: 170/95.4 mm Hg (P = .001) vs 142.3/82.9 mm Hg

Table 2 Optic nerve sheath diameter compared with both systolic and DBPs in all 3 groups ONSD vs blood pressure

Group Sample Correlation with SBP Correlation with DBP

Optic nerve sheath diameter was calculated using the average of the 2 left ONSD and the 2 right ONSD measurements. Hypertension was defined as SBP 140 mm Hg or more or DBP 90 mm Hg or more. If treatment was rendered, an average of the left and right blood pressure measurements were taken before treatment. Pearson correlation coefficient: the square of this value gives us the percentage of variation in ONSD that can be explained by the SBP or DBP within each group. HTN indicates hypertension.

(P = .0005), respectively (Table 3). For average SBP, the area under the receiver operating characteristic curve was 0.732 (95% CI, 0.626-0.838), which is significantly greater than the null hypothesis of 0.500. Youden’s index (sensitivity + specificity - 1) was at a maximum at SBP, 166 mm Hg, suggesting that this is the best SBP cutoff for abnormal ONSD. For average DBP, the area under the receiver operating characteristic curve was 0.698 (95% CI, 0.594-0.801), which is significantly greater than the null hypothesis of 0.500. Youden’s index (sensitivity + specific- ity - 1) was at a maximum at DBP, 82 mm Hg, suggesting that this is the best DBP cutoff for abnormal ONSD.

There were a total of 11 patients who were treated for their blood pressure within the hypertensive/symptomatic group. The ONSD decreased after the blood pressure was lowered with medical management. The average ONSD before and after blood pressure treatments were 0.517 and 0.450 cm, respectively, with a mean difference of 0.067 cm (P = .073, t₁₀ = 2.006).

Discussion

Of the various Traditional methods for the detection of elevated ICP in acutely ill patients, none except physical

examination can be performed rapidly and noninvasively at the bedside. Traditional physical examination tech- niques, such as fundoscopic examination of the optic discs looking for papilledema, only yield a sensitivity of 20% to 30% and can vary greatly based on the physician’s ability to perform the examination [7,8]. In addition, papilledema from elevated ICP tends to be delayed in its appearance by up to several hours [7]. Although many physicians practice in an environment where computed tomography is readily available, there are several circumstances where a faster noninvasive bedside test for elevated ICP could be useful. Bedside US provides critical data in a quick and noninvasive manner without exposing the patient to radiation or the risks of transport out of the ED. To our knowledge, the relationship between blood pressure and ONSD measure- ments via bedside US has yet to be investigated.

Our study found a significant a correlation between ONSD and both SBP and DBP in all hypertensive patients. As expected, only hypertensive patients had significantly abnormal ONSDs on US. Before data collection, we hypothesized that the DBP would carry a higher association with abnormal ONSD in hypertensive patients as compared with the SBP. In our study, we found the opposite to be true (Table 2). Based on the square of the Pearson correlation coefficients, the SBP was found to be more closely associated with ONSD than the DBP (0.454²/20.6% and 0.331²/11.0%, respectively) (Table 2). Our data showed that 20.6% of the abnormal ONSDs was associated

Table 3 Average blood and its relationship to normal or abnormal ONSD Blood pressure cutoff point for abnormal ONSD

Group Count Average SBP Average DBP T value P SBP cutoff (mm Hg) DBP cutoff (mm Hg)

Normal ONSD (b0.50 cm) 118 142.3 82.9 4.18 b.0005 N/A N/A

Abnormal ONSD (>=0.50 cm) 32 170.0 95.4 3.46 .001 166 82

The SBP cutoff for an abnormal ONSD (>=0.50 cm) is 166, and the DBP cutoff for an abnormal ONSD (>=0.50 cm) is 82. The difference in SBP between the normal and abnormal ONSDs was 17.7 mm Hg (95% CI, 17.3-38.2). The difference in diastolic blood pressure between the normal and abnormal ONSDs was 12.5 mm Hg (95% CI, 6.8-18.2).

Fig. 4 These are optic nerve US images from a 70-year-old male patient with a history of diabetes, cardiac disease, and hypertension presenting to the ED with chest pain, blurry vision, and a blood pressure of 251/117 mm Hg. Initial fundoscopic examination was negative. The patient was treated with a nitroglycerin drip. The left image represents a pretreatment optic nerve US at a blood pressure of 251/117 mm Hg, and the right image represents a posttreatment optic nerve US at a blood pressure of 170/90 mm Hg.

with SBP and that 11.0% of the abnormal ONSDs was associated with DBP. At this time, it is unclear as to why DBP is not more closely associated with changes in the ONSD. Further studies will need to be performed to delineate the exact pathophysiologic relationship and associated US findings.

Based on the results of our study, blood pressure readings greater than 166/82 mm Hg were associated with signifi- cantly increased ONSD on bedside US (Table 3). This suggests that symptomatic patients who present with a SBP greater than 166 mm Hg or a DBP greater than 82 mm Hg should be managed more aggressively given their risk for increased ICPs. In our study, we also found that the ONSD in the symptomatic, hypertensive patient decreases in size once the hypertension was treated (P = .073). Fig. 4 illustrates the significant decrease in ONSD once the patient was treated for her hypertension. Future studies should be designed to include a larger sample size to determine if ONSD reliably decreases as blood pressures are lowered in the short-term phase.

There were a few limitations to our study that will need to be evaluated further in future studies concerning this topic. Interrater reliability was not an issue with our study because 97% of the ocular USs were performed or supervised by a single user (145/150 studies). Future studies should evaluate whether these results can be reproduced using multiple sonologists and practitioners with varying levels of US experience. Another potential limitation of this study includes the lack of comparison with a criterion standard imaging modality such as computed tomography or magnetic resonance imaging. The study was designed under the premise that an ONSD greater than 0.5 cm is a reliable indicator of increased ICP as demonstrated in multiple other trials.

A potential source of bias would be the lack of blinding to the stratification of the study subjects into the 3 study arms. We found this to be difficult because subjects necessitating blood pressure treatment (hypertensive/symp- tomatic study arm) require both pre- and posttreatment ultrasonographic ONSD measurements. One other limitation to this study is the relatively small sample size. This is the first study of its kind to evaluate the direct relationship between blood pressure, Patient symptoms, and ONSDs on ocular US. Subsequent research should be designed to evaluate these variables with a larger sample size from various institutions nationwide.

In conclusion, emergency US continues to improve the quality of care provided to patients in the ED. Recent studies have demonstrated that increased ONSD correlates with increased ICPs. Our study shows that practitioners can use bedside ocular US and a blood pressure cutoff point to help predict whether patients require more aggressive management of their symptomatic hypertension. Although elevated blood pressure with symptoms is not necessarily synonymous with malignant hypertension, knowing the SBP/DBP readings that lead to increased ONSD and increased ICP could help guide management and treatment decisions at the bedside.

References

1. Munch EC, Bauhuf C, Horn P, Roth HR, Schmiedek P, Vajkoczy P. Therapy of malignant intracranial hypertension by controlled lumbar cerebrospinal fluid drainage. Crit Care Med 2001;29:976-81.
2. Eisenberg HM, Gary Jr HE, Aldrich EF, et al. initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. J Neurosurg 1990;73:688-98.
3. Tintinalli JE, Stapczynski JS, Ma OJ, Cline DM, Cydulka RK, Meckler GD, editors. Tintinalli’s Emergency Medicine Seventh Edition: A

Comprehensive Study Guide. New York: McGraw Medical; 2011.

p. 442.

1. Moretti R, Pizzi B. Optic nerve ultrasound for detection of intracranial hypertension in intracranial hemmorrhage patients. J Neurosurg Anesthesiol 2009;21(1):16-20.
2. Harbison Kimberly H, Shah S, Marill K, et al. Correlation of optic nerve sheath with direct measurement of intracranial pressure. Acad Emerg Med 2008;15:201-4.
3. Hansen HC, Helmke K. Validation of the optic nerve sheath response to changing cerebrospinal fluid pressure: ultrasound findings during intrathecal infusion tests. J Neurosurg 1997;87:34-40.
4. Geeraerts T, Launey Y, Martin L, et al. Ultrasonography of the optic nerve sheath may be useful for detecting raised intracranial pressure after severe brain injury. Intensive Care Med 2007;33:1704-11.
5. Trobe JD. Papilledema: the vexing issues. J Neuroophthalmol 2011;31(2):175-86.