• Users Online: 505
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2017  |  Volume : 4  |  Issue : 4  |  Page : 209-212

Role of transcranial Doppler and FOUR score in assessment of sepsis-associated encephalopathy

Critical Care Medicine Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Date of Submission25-Nov-2016
Date of Acceptance26-Feb-2017
Date of Web Publication11-Oct-2017

Correspondence Address:
Dina H Zidan
Critical Care Medicine Department, Faculty of Medicine, Alexandria University, Alexandria, 21521
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/roaic.roaic_109_16

Rights and Permissions

Monitoring of the septic complications on the brain is useful in management and in attenuating the effect of sepsis-related cerebral complications on outcome.
Patients and methods
A transcranial Doppler probe was applied through the temporal bone window at both sides of the skull within the first day of diagnosing sepsis for 10 s. The values of the brain side with the highest peak systolic velocity (PSV) and end diastolic velocity (EDV) were registered. We calculated the pulsatility index (PI) as follows: PI=(PSV−EDV)/mean velocity; the neurological status was evaluated 6 h after sedation cessation, using Glasgow Coma Scale and Full Outline of UnResponsiveness score.
There was a significant difference in the PI between conscious patients and patients suffering from sepsis-associated encephalopathy.
PI is a predictor of sepsis-associated encephalopathy in septic patients.

Keywords: Full Outline of UnResponsiveness score, Glasgow Coma Scale, pulsatility index, sepsis-associated encephalopathy, transcranial Doppler

How to cite this article:
Zidan DH, Helmy TA, Taha A. Role of transcranial Doppler and FOUR score in assessment of sepsis-associated encephalopathy. Res Opin Anesth Intensive Care 2017;4:209-12

How to cite this URL:
Zidan DH, Helmy TA, Taha A. Role of transcranial Doppler and FOUR score in assessment of sepsis-associated encephalopathy. Res Opin Anesth Intensive Care [serial online] 2017 [cited 2020 Jun 4];4:209-12. Available from: http://www.roaic.eg.net/text.asp?2017/4/4/209/216445

  Introduction Top

Sepsis-associated encephalopathy (SAE) is a known complication in systemically ill patients. The syndrome is defined by diffuse brain dysfunction associated with sepsis in the absence of central nervous system infection, structural abnormality, or other types of metabolic encephalopathy (e.g. hepatic or uremic encephalopathy and electrolyte imbalance), as detected using clinical or standard laboratory tests. This cerebral dysfunction is caused by mediators released during sepsis, as it can occur in patients with no identified cause.

Patients suffering from SAE show features of sepsis or systemic SAE that manifests as a spectrum of disturbed cerebral function ranging from mild delirium to coma. As mortality is increased with severity of SAE, early identification and management of patients with SAE are useful to reduce associated morbidity and mortality [1].

Although its pathophysiology is still complicated, two mechanisms are involved: a neuroinflammatory-mediating process and an ischemic process. The former is due to a physiological brain signaling on one hand and a pathophysiological response that includes endothelial activation and blood–brain barrier alteration on the other. The ischemic mechanism is due to cerebral perfusion impairment. These two processes are integrated and synergistic [2].

Faced with such complex scenario, adequate observation of the septic brain would potentially be of great help for prevention, management, and prognostication and, ideally, to attenuate the effect of sepsis-related cerebral complications on outcome. Transcranial Doppler (TCD), although it does not directly measure the cerebral blood flow, is an available noninvasive tool to assess cerebral autoregulation [3].

  Patients and methods Top

Informed consent was obtained from the patient or, if not possible, from the next of kin. We have received the approval of ethical committee in faculty of medicine, Alexandria University. This study was designed as a case–control study and was performed in Critical Care Medicine Department. We had two groups of patients. The first group included 58 adult patients with sepsis for fewer than 24 h, suffering from acute onset of disturbed conscious level (SAE) with normal computed tomography of the brain and with no acute metabolic derangement. The second group included 58 fully conscious patients suffering from sepsis for fewer than 24 h. Sepsis was defined according to standard international criteria. Septic shock was defined as the need for vasopressors or vasoactive medication to maintain a mean arterial blood pressure of 65 mmHg or higher after adequate fluid resuscitation, with the presence of a high lactate (>2 mmol/l) [4]. Exclusion criteria were as follows: (a) age less than 18 years, (b) known cerebral lesions (ischemic or hemorrhagic cerebrovascular insult and neoplasm), (c) cerebral infection, (d) patient support with intra-aortic balloon pump, (e) intoxication due to drugs, (f) known severe carotid stenosis (>70%), (g) pregnancy, (h) hepatic, uremic, or metabolic encephalopathy, and (i) hypoglycemic brain insult.

Both groups were eligible for demographic information collection, such as length of stay in the ICU and source of sepsis. Routine monitoring included electrocardiography and mean arterial pressure measured directly by means of invasive monitoring in the radial or the femoral artery. Clinical and laboratory data concerning organ failure were also obtained. The severity of illness was assessed with the sequential organ failure assessment score Sequential Organ Failure Assessment (SOFA) score.

Blood velocity in the middle cerebral artery was measured in both groups with a 3-MHz TCD probe using Philips equipment (Netherlands), applied through the temporal bone window at both sides of the skull within the first day of sepsis for 10 s. The values of the brain side with the highest peak systolic velocity (PSV) and end diastolic velocity (EDV) were registered. During the examination, patients were placed in the supine position with a head elevation of no more than 30°.

At the time of examination, the patients were deemed to have a stable hemodynamic status.

We calculated PI [(PSV−EDV)/mean velocity] and resistivity index [(PSV−EDV)/PSV].

The neurology status was evaluated at the end of the routinely performed daily sedation pause (if patient is sedated) in the first 24 h of sepsis diagnosis, using Glasgow Coma Scale (GCS) and Full Outline of UnResponsiveness (FOUR) score by the attending intensivists; both scores were determined within the same hour [5].

  Results Top

This study included 116 patients with sepsis and septic shock. The first group included 58 patients suffering from SAE, whereas the second group included 58 conscious patients. Patients’ characteristics are expressed in [Table 1].
Table 1 Patient characteristics

Click here to view

Receiver operating characteristic curve analysis in predicting SAE in the first patient group is presented in [Table 2] and [Figure 1]. The GCS score area under the curve (AUC) was significantly higher compared with SOFA score (P<0.0001), FOUR score (P=0.02), pulsatility index (PI) (P<0.0001), and resistive index (P<0.0001).
Table 2 Areas under the receiver operating characteristic curves in predicting sepsis-associated encephalopathy

Click here to view
Figure 1 Receiver operating characteristic in predicting sepsis-associated encephalopathy. FOUR, Full Outline of UnResponsiveness; GCS, Glasgow Coma Scale; SOFA, SOFA, Sequential Organ Failure Assessment.

Click here to view

The FOUR score AUC was significantly higher compared with SOFA score (P<0.0001), PI (P=0.0001), and resistive index (P<0.0001).

The differences in AUC between SOFA score, PI, and resistive index were not statistically significant.

There was a statistically significant difference between the two groups of patients as regards PI and resistivity index ([Table 3]) (P<0.0001).
Table 3 Comparison between the two groups of patients as regards the pulsatility index and resistivity index

Click here to view

  Discussion Top

TCD is a noninvasive ultrasound tool used to measure cerebral blood flow velocity in the major intracranial vessels.

It involves the use of low-frequency (≤2 MHz) ultrasound waves to insonate the basal cerebral arteries through relatively thin bone windows. It is relatively inexpensive and reproducible, and its portability offers increased convenience over other diagnostic imaging methods, allowing continuous bedside monitoring of cerebral blood flow velocity, which is particularly useful in the intensive care setting [6].

Neurological disturbances are considered a greater challenge in the critically ill patients. The GCS has been the gold standard for assessing the level of consciousness in patients with significant brain injury since it was developed in 1974. The GCS is widely used and accepted but has many limitations in the assessment of brainstem function, eye opening and tracking, and respiratory patterns.

Since its introduction in 2005, FOUR score has been used clinically, and its usefulness has been confirmed by hundreds of neurosurgical patients and doctors. FOUR score is simple and provides far better information, particularly for intubated patients. The FOUR score is a good predictor of the prognosis of critically ill patients and has important advantages over the GCS in the ICU setting [7].

We found that the PI was a fair predictor in predicting SAE in septic patient. This is in accordance with the findings of Pierrakos et al. [8], who found that PI measured within the first 24 h after sepsis initiation is related to clinical signs of SAE. The value of 1.3 represents a cutoff point that can be used in clinical practice, whereas our cutoff value in delirium prediction was 1.02. The PI is a parameter that is commonly used to describe the Doppler wave. In-vitro and in-vivo studies show that the PI is related to changes in peripheral vascular resistances. Increased PI is associated with angiographically demonstrated diffuse intracranial vessel pathology, and the PI has been found to be increased in diabetic patients with microangiopathy or in patients suffering from advanced cirrhosis with encephalopathy. The increased values of the PI should be interpreted as a manifestation of enhanced vascular resistance in the cerebral circulation during sepsis [8].

Moreover, Pierrakos et al. [8] found increased values of PI and reported that the increased values observed in septic patients (compared with control critically ill patients) should be interpreted as a manifestation of increased vascular resistance in the cerebral circulation during early sepsis. Our results are contradictory to the findings of Pfister et al. [9], who found that cerebral perfusion assessed with TCD and near-infrared spectroscopy did not differ between patients with and those without sepsis-associated delirium. Recently, Pierrakos et al. [10] studied the association between cerebral perfusion perturbations in sepsis with possible cognitive decline after patients’ discharge from the ICU; they found that only on the first day patients with cognitive decline had higher PI, thus concluding that delirium, but not cerebral perfusion alterations, is an independent risk factor for cognitive impairment in septic patients who were discharged from the ICU.

Moreover, Wijdicks et al. [5] concluded that FOUR score has greater neurological refinement and is valid when confronted with a patient who has an impaired consciousness. This disagreement with our results could be attributed to our homogenous group of medical ICU patients, and Iyver et al. [11] investigated the validity of FOUR score in medical ICU. These results reported that the AUC for the FOUR score was 0.86 and that for the GCS was 0.82. Similarly, calculations of the predictive power for poor neurologic outcome (Rankin score, 3–6) showed that the AUC was 0.75 for the FOUR score and 0.76 for the GCS score. Again we can explain that these higher AUC values could be related to the larger number of patients included and to different patient population types.

  Conclusion Top

We can conclude from the previous work that the PI is a good predictor of SAE in patients with sepsis and septic shock.


This study is limited by the use of a small patient population. Further studies are warranted to confirm the results of our work and evaluate the utility of TCD to guide therapies applied in septic patients.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Gofton T, Young G. Sepsis-associated encephalopathy. Net Rev Neurol 2012; 8:557–566.  Back to cited text no. 1
Adam N, Kandelman S, Mantz J, Chrétien F, Sharshar T. Sepsis-induced brain dysfunction. Expert Rev Anti Infect Ther 2013; 11:211–221.  Back to cited text no. 2
Oddo M, Taccone F. How to monitor the brain in septic patients? Minerva Anestesiol 2015; 81:776–788.  Back to cited text no. 3
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315:801–810.  Back to cited text no. 4
Wijdicks E, Bamlet W, Maramattom B, Manno E, McClelland R. Validation of a New Coma Scale: the FOUR Score. Ann Neurol 2005; 58:585–593.  Back to cited text no. 5
Naqvi J, Yap K, Ahmad G, Ghosh J. Transcranial Doppler ultrasound: a review of the physical principles and major applications in critical care. Int J Vasc Med 2013; 2013:629378.  Back to cited text no. 6
Pierrakos C, Attou R, Decorte L, Kolyviras A, Malinverni S, Gottignies P et al. Transcranial Doppler to assess sepsis-associated encephalopathy in critically ill patients. BMC Anesthesiol 2014; 14:45.  Back to cited text no. 7
Pierrakos C, Antoine A, Velissaris D, Michaux I, Bulpa P, Evrard P et al. Transcranial Doppler assessment of cerebral perfusion in critically ill septic patients: a pilot study. Ann Intensive Care 2013; 3:28.  Back to cited text no. 8
Pfister D, Siegemund M, Dell-Kuster S, Smielewski P, Rüegg S, Strebel SP et al. Cerebral perfusion in sepsis associated delirium. Crit Care 2008; 12:R63.  Back to cited text no. 9
Pierrakos C, Attou R, Decorte L, Velissaris D, Cudia A, Gottignies P et al. Cerebral perfusion alterations and cognitive decline in critically ill sepsis survivors. Acta Clin Belg 2017; 72:39–44.  Back to cited text no. 10
Iyer V, Mandrekar J, Danielson R, Zubkov A, Elmer J, Wijdicks E. Validity of the FOUR score coma scale in the medical intensive care unit. Mayo Clin Proc 2009; 84:694–701.  Back to cited text no. 11


  [Figure 1]

  [Table 1], [Table 2], [Table 3]

This article has been cited by
1 The current significance of the FOUR score: A systematic review and critical analysis of the literature
Dimitrios M. Anestis,Parmenion P. Tsitsopoulos,Christos A. Tsonidis,Nikolaos Foroglou
Journal of the Neurological Sciences. 2019; : 116600
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Patients and methods
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded118    
    Comments [Add]    
    Cited by others 1    

Recommend this journal