*7.5.1 Liver cirrhosis with encephalopathy and liver failure*

Several studies show that CBF is compromised in patients with acute or chronic severe liver disease, especially in the presence of hepatic encephalopathy (HE). In this condition, there is impairment of brain autoregulation and, consequently, the variation of MAP may be associated with changes in CBF. Although hyperammonemia is the main cause of HE, recent evidence suggests that abnormalities in CBF may also have some relationship in its pathophysiology. There is a hypothesis that cirrhotic patients with encephalopathy present cerebral vasoconstriction more pronounced and, consequently, progressive PI elevation and BHI reduction as the disease progresses (score CTP ≥ 7 or MELD ≥14). The more severe encephalopathy, the more changes are observed in cerebral hemodynamics [69].

In mild HE, there is also an increase in brain microcirculatory resistance and, consequently, an increase in PI and RI, with a significant correlation with the increase in Child-Pugh score. Therefore, TCD may be an aid in the diagnosis of HE in cirrhotic patients. An important complication of severe HE is intracranial hypertension. This is due to three main mechanisms: 1) brain swelling secondary to the cytotoxic effect of hyperammonemia; 2) breakage of the blood brain barrier and 3) hyperemia secondary to CAR impairment. TCD can provide information regarding the dynamics of brain blood flow in patients with ICH and assess CAR [70].

### *7.5.2 Sepsis and sepsis-associated encephalopathy*

Hemodynamic impairment is a fundamental feature of sepsis. Brain microcirculation can be gradually compromised and, consequently, cause significant changes in CBF. These factors play an important role in the etiology of sepsis-associated encephalopathy (SAE) [71]. SAE is a frequent brain dysfunction that occurs in 50% of patients admitted to intensive care units, being one of the most common causes of delirium in this population. In addition, SAE is associated with an increase in mortality.

In the early phase of sepsis, there are progressive increases in Mv and PI over time, which are evident 24 hours after onset; at this stage, CAR may remain unchanged. In contrast, in the posterior stage of sepsis (patients with severe sepsis or septic shock), there are progressive reductions in Mv and PI, as well as impairment of CAR. The increase in PI associated with increased cerebrovascular resistance has been correlated with a higher prevalence of delirium and coma. Many of the factors that lead to changes in CBF (such as changes in CVR and CAR) are often the result of a dysfunction of brain tissue microcirculation due to the release of inflammatory mediators.

The use of TCD to assess brain hemodynamic patterns has some clinical advantages: 1) TCD can be used to identify cerebral hemodynamic patterns in sepsis that may precede systemic hemodynamic signs; 2) increased PI in confused patients may be an early sign of sepsis and help decrease time to diagnosis [71]; and 3) the identification of real-time CBF changes with TCD, correlating with systemic hemodynamic changes, may improve the management of blood pressure and blood volume in septic patients.

#### **7.6 Brain death**

Brain death is defined as total and definitive cessation of all brain functions. TCD is valued in the medical literature as an examination of choice for this purpose due to the advantages of being noninvasive, of being performed at the bedside and of allowing repetition, if necessary38. TCD sensitivity for brain death diagnosis reaches values greater than 95% and specificity of 100% [50].

TCD should show no bilateral blood flow in the arteries of the intracranial carotid system and the vertebro-basilar system under normal body temperature conditions for at least 30 minutes. The criteria are: 1) presence of oscillatory flow (systolic velocity equal to reverse diastolic velocity – final flow zero) or 2) systolic spikes or 3) disappearance of intracranial flow with typical signs observed in the extracranial circulation [72].
