**4. Intracranial compliance in real world**

The next paragraphs will provide information on how to incorporate waveform information of ICP into clinical daily life, adding this information to the clinical set and adjunct with other diagnostic methods in different pathologies. It is worth mentioning that this information has been shown to be useful in situations where subjects present suspicion, risk or diagnosis of changes in ICC.

#### **4.1 Aneurysm**

Non-traumatic subarachnoid hemorrhage (SAH) is a situation that often results from the rupture of an intracerebral aneurysm [25]. SAH is associated with high morbidity and mortality and requires a multidisciplinary treatment, because of its high risk of complications [26].

Upon recognition, improved outcomes are dependent upon treatment by qualified high-volume centers with adequate neurovascular teams. Expeditiously determining the precipitating factor and subsequent mitigation of the cause(s) are the initial primary focus. Treatment involves early securing of a ruptured aneurysm, whether a surgical procedure or endovascular. Prior to securing the aneurysm, securing the airway, maintaining proper circulation, treating hydrocephalus, and managing blood pressure remain top priorities. After intervention, ICU observation and routine exams are compulsory.

Once patients presenting with aneurysmal SAH are acutely stabilized, they are evaluated for pathology-specific complications such as development of hydrocephalus and re-hemorrhage. Various grading scales are employed early in management to communicate the severity and prognosis of the pathology. Following stabilization and initial evaluation, patients should be transferred and admitted to intensive care units with a multidisciplinary team. Interim/short-term acute care strategies are employed to prevent rebleeding, assess hydrocephalus, maintain normotension, and reverse anticoagulant/antiplatelet agents. The risk of acute rebleed and long-term prevention of rebleed is not completely attenuated until aneurysm exclusion is performed.

Concurrent to the those risks above mentioned, in the extreme acute phase (first 48 hours) of SAH, the encephalic microvascular constriction promoted by hemoglobin degradation in the subarachnoid space may lead to a low cerebral blood flow (CBF) phenomena, with potential for brain swelling and ICC impairment. Techniques for monitoring ICC and CBF (such as transcranial Doppler) may play a crucial role in this phase.

Later, in the subsequent SAH phase, an inverse behavior is commonly seen in accordance with bleed severity, the so-called hyperemic phase. In this situation subjects present microvascular dilation, this time leading to ICC impairment for excess of CBF. An optimal therapy here is adapting CBF for satisfactory neuronal supply, under ICC adequate limits.

An additional threat for patients in this phase is the development of vasospasm, a complication which elevates risk of delayed cerebral ischemia, in opportunities needing endovascular management. The latter, associated with medical complications including fever, hyperglycemia, hyponatremia, cardiac and pulmonary complications, deep venous thrombosis and anemia may raise risk of ICC impairment. While scores classifications exist to determine an admission grade in order to provide prognostic information, outcomes are influenced by many additional

**7**

*Intracranial Pressure Waveform: History, Fundamentals and Applications in Brain Injuries*

items, including a patient's values and preferences, comorbidities, social support,

The incidence and survival of patients with neuro-oncologic conditions have been increasing. Both primary central nervous and other types of cancer patients live longer due to early diagnosis and better treatment options. Global Burden Disease Study in 2016, there were 330,000 incident cases of CNS cancer and 227,000 deaths worldwide that year. It reflects the 17.3% increase in incidence

Extension of life expectancy and on the incidence of cancer itself predisposes to an increment in the occurrence of a variety of neurologic complications that can

These conditions often result in hospital admissions, generally in an ICU bed, creating a heavy burden to the health care system since primary cancer patients' treatment costs 20-times more than age-matched controls without cancer [33].

The complications could occur due to a direct result of the tumor itself, to an indirect effect of cancer, or as a result of chemotherapy, radiotherapy, and other medical interventions. Recognizing the mechanism might help one early diagnosis and initiate treatment. As a mass effect directly, or even a compromise of CSF transit because of ventricle compression, intracranial neoplasm may lead to ICC impairment.

The World Health Organization considers traumatic brain injury (TBI) an important global health priority as it is a critical public health problem involving young adults worldwide. The leading causes of TBI are road traffic collisions, falls and interpersonal violence. This injury not only causes a large number of deaths, impairments and disabilities for individuals and their families, but also incurs great economic cost to healthcare systems due to required long-term care, rehabilitation,

TBI can be classified by clinical severity (mild, moderate, or severe) according to the Glasgow Coma Scale (GCS); pathoanatomic type (focal or diffuse) according to the extent of damaged area; and mechanism of injury (penetrating or blunt)

The TBI-related cellular injury involves two different processes. The primary damage occurs on the moment of trauma, immediately by the direct impact and/or structural lesion. It includes vascular and tissue tearing that causes various types of hemorrhage and nerve fibers disruption (axotomy). The secondary damage involves cellular reactive processes such as inflammation and biochemical cascades that gradually develop over the course of hours, days, even weeks after the trauma. It causes metabolic changes potentially leading to brain swelling or hydrocephalus but can also be caused by low blood pressure, hypoxia, seizures, or central nervous system infection [37, 38].

Both processes are intertwined and can contribute to complications, for instance, hemorrhagic progression of a contusion, a breakdown in the blood–brain barrier (BBB), and increased intracranial pressure (ICP). The expansion of an intracranial bleeding not only alters the dynamic shared space of encephalic parenchyma, vascular structures, and cerebral spinal fluid (CSF) inside cranial cavity – inferred intracranial compliance – but also triggers cytotoxic responses of brain cells. In addition, if there is a dysfunction of BBB its permeability changes letting plasma, proteins and proinflammatory mediators influx into the interstitial compartment causing edema, neurotransmitters imbalance, compressing all structures [38, 39].

*DOI: http://dx.doi.org/10.5772/intechopen.94077*

resilience, and time for recovery [27–31].

result in high morbidity and mortality [32, 33].

**4.2 Tumor**

between 1990 and 2016.

**4.3 Traumatic brain injury**

and loss of productivity [34].

according to the kinematics (**Table 1**) [35–38].

*Intracranial Pressure Waveform: History, Fundamentals and Applications in Brain Injuries DOI: http://dx.doi.org/10.5772/intechopen.94077*

items, including a patient's values and preferences, comorbidities, social support, resilience, and time for recovery [27–31].

### **4.2 Tumor**

*Advancement and New Understanding in Brain Injury*

**4. Intracranial compliance in real world**

**4.1 Aneurysm**

high risk of complications [26].

crucial role in this phase.

supply, under ICC adequate limits.

subjects present suspicion, risk or diagnosis of changes in ICC.

ICU observation and routine exams are compulsory.

indicators of diminished compliance and can also be present in patients with normal ICP [24]. Finally, C waves are products of cardiac and respiratory cycles interactions.

The next paragraphs will provide information on how to incorporate waveform information of ICP into clinical daily life, adding this information to the clinical set and adjunct with other diagnostic methods in different pathologies. It is worth mentioning that this information has been shown to be useful in situations where

Non-traumatic subarachnoid hemorrhage (SAH) is a situation that often results from the rupture of an intracerebral aneurysm [25]. SAH is associated with high morbidity and mortality and requires a multidisciplinary treatment, because of its

Upon recognition, improved outcomes are dependent upon treatment by qualified high-volume centers with adequate neurovascular teams. Expeditiously determining the precipitating factor and subsequent mitigation of the cause(s) are the initial primary focus. Treatment involves early securing of a ruptured aneurysm, whether a surgical procedure or endovascular. Prior to securing the aneurysm, securing the airway, maintaining proper circulation, treating hydrocephalus, and managing blood pressure remain top priorities. After intervention,

Once patients presenting with aneurysmal SAH are acutely stabilized, they are evaluated for pathology-specific complications such as development of hydrocephalus and re-hemorrhage. Various grading scales are employed early in management to communicate the severity and prognosis of the pathology. Following stabilization and initial evaluation, patients should be transferred and admitted to intensive care units with a multidisciplinary team. Interim/short-term acute care strategies are employed to prevent rebleeding, assess hydrocephalus, maintain normotension, and reverse anticoagulant/antiplatelet agents. The risk of acute rebleed and long-term prevention of rebleed is not completely attenuated until aneurysm exclusion is performed. Concurrent to the those risks above mentioned, in the extreme acute phase (first 48 hours) of SAH, the encephalic microvascular constriction promoted by hemoglobin degradation in the subarachnoid space may lead to a low cerebral blood flow (CBF) phenomena, with potential for brain swelling and ICC impairment. Techniques for monitoring ICC and CBF (such as transcranial Doppler) may play a

Later, in the subsequent SAH phase, an inverse behavior is commonly seen in accordance with bleed severity, the so-called hyperemic phase. In this situation subjects present microvascular dilation, this time leading to ICC impairment for excess of CBF. An optimal therapy here is adapting CBF for satisfactory neuronal

An additional threat for patients in this phase is the development of vasospasm, a complication which elevates risk of delayed cerebral ischemia, in opportunities needing endovascular management. The latter, associated with medical complications including fever, hyperglycemia, hyponatremia, cardiac and pulmonary complications, deep venous thrombosis and anemia may raise risk of ICC impairment. While scores classifications exist to determine an admission grade in order to provide prognostic information, outcomes are influenced by many additional

**6**

The incidence and survival of patients with neuro-oncologic conditions have been increasing. Both primary central nervous and other types of cancer patients live longer due to early diagnosis and better treatment options. Global Burden Disease Study in 2016, there were 330,000 incident cases of CNS cancer and 227,000 deaths worldwide that year. It reflects the 17.3% increase in incidence between 1990 and 2016.

Extension of life expectancy and on the incidence of cancer itself predisposes to an increment in the occurrence of a variety of neurologic complications that can result in high morbidity and mortality [32, 33].

These conditions often result in hospital admissions, generally in an ICU bed, creating a heavy burden to the health care system since primary cancer patients' treatment costs 20-times more than age-matched controls without cancer [33].

The complications could occur due to a direct result of the tumor itself, to an indirect effect of cancer, or as a result of chemotherapy, radiotherapy, and other medical interventions. Recognizing the mechanism might help one early diagnosis and initiate treatment. As a mass effect directly, or even a compromise of CSF transit because of ventricle compression, intracranial neoplasm may lead to ICC impairment.

#### **4.3 Traumatic brain injury**

The World Health Organization considers traumatic brain injury (TBI) an important global health priority as it is a critical public health problem involving young adults worldwide. The leading causes of TBI are road traffic collisions, falls and interpersonal violence. This injury not only causes a large number of deaths, impairments and disabilities for individuals and their families, but also incurs great economic cost to healthcare systems due to required long-term care, rehabilitation, and loss of productivity [34].

TBI can be classified by clinical severity (mild, moderate, or severe) according to the Glasgow Coma Scale (GCS); pathoanatomic type (focal or diffuse) according to the extent of damaged area; and mechanism of injury (penetrating or blunt) according to the kinematics (**Table 1**) [35–38].

The TBI-related cellular injury involves two different processes. The primary damage occurs on the moment of trauma, immediately by the direct impact and/or structural lesion. It includes vascular and tissue tearing that causes various types of hemorrhage and nerve fibers disruption (axotomy). The secondary damage involves cellular reactive processes such as inflammation and biochemical cascades that gradually develop over the course of hours, days, even weeks after the trauma. It causes metabolic changes potentially leading to brain swelling or hydrocephalus but can also be caused by low blood pressure, hypoxia, seizures, or central nervous system infection [37, 38].

Both processes are intertwined and can contribute to complications, for instance, hemorrhagic progression of a contusion, a breakdown in the blood–brain barrier (BBB), and increased intracranial pressure (ICP). The expansion of an intracranial bleeding not only alters the dynamic shared space of encephalic parenchyma, vascular structures, and cerebral spinal fluid (CSF) inside cranial cavity – inferred intracranial compliance – but also triggers cytotoxic responses of brain cells. In addition, if there is a dysfunction of BBB its permeability changes letting plasma, proteins and proinflammatory mediators influx into the interstitial compartment causing edema, neurotransmitters imbalance, compressing all structures [38, 39].


#### **Table 1.**

*Different classifications of TBI.*

As a result of this intricate association the ICP may rise if intrinsic compensatory mechanisms are not preserved and the sustained hypertension can prevent adequate perfusion depriving the brain of oxygen and nutrition. The combination of all situations related to TBI mentioned above need specific and adequate management through the whole trauma assistance from the pre-hospital setting to the critical care unit (CCU) and subsequent rehabilitation [36, 40].

The main method of assessment and management of severe TBI is monitoring and treatment of ICP. It is a level II-B of evidence recommended to reduce inhospital and 2-week post-injury mortality [23, 41].

Neurocritical care specialists routinely base their clinical reasoning looking at the absolute value of ICP – measured in mmHg or cmH2O – combined with imaging exams – CT-scan or MRI. However, the numbers may not translate the entire complexity of intracranial dynamic. It is suggested that the ICP waves and the study of its morphology could bring differential evidence of altered intracranial compliance and changes of pressure regimen [14, 23, 42, 43].

A qualitative analysis of the ICP waveform [44] described the relationship between amplitude of ICP pulse wave, values of ICP, values of cerebral perfusion pressure (CPP), and the outcome of severe head-injured patients. Intracranial hypertension was evidenced by absolute values of ICP and CT-scan parameters. In those with fatal outcomes there was an increase in the ICP waveform amplitude along with an increase of ICP value up to 25 mmHg, however, above this value the amplitude began to decrease. This breakpoint trend in the amplitude-value relationship was not present in patients with good/moderate outcome. Thus, it is suggested that the physics involving ICP, CPP and parenchyma dynamics inside intracranial cavities was somehow translated into the waveforms, and its analysis and correlations could be a useful additional tool for outcome prediction.

Another study [45] involving TBI patients described the ICP plateau waves characteristics using multimodal brain monitoring as well as calculated indices of brain compensatory reserve and cerebrovascular reactivity. Plateau waves are associated with working cerebrovascular reactivity and occur in situations of

**9**

**Figure 5.**

**Figure 6.**

*Intracranial Pressure Waveform: History, Fundamentals and Applications in Brain Injuries*

decreased volume-pressure compensatory reserve such as TBI and many other brain pathologies. It consists of sudden increases in ICP to peaks of 40-100 mmHg that persists for 5–20 minutes [14, 45, 46]. The study observed plateau waves in 44% of the patients and that abrupt increase of ICP above 40 mmHg was associated with an increase in amplitude of ICP pulse waveform and also with important decrease in CPP, cerebral blood flow and oxygenation, despite stable cardiovascular variables

When analyzing ICP pulse waveform during plateau waves, a statistically significant increase in amplitude and a change in its shape were noted. The ICP pulse

Although slight increases in ICP that last for short period are not usually associated with poor outcome, if plateau waves are sustained over 30 minutes it could have a negative impact on patient's recovery as intracranial hypertension compromises cerebral perfusion and implicates neuronal deterioration [14, 23, 42, 43, 46]. The analysis of ICP absolute values and waveform patterns over time could provide important information for early detection of ICH in TBI patients of

The debate about how ICP waveform analysis could provide improved clinical benefit and a more actionable evidence to bedside addresses integrated metrics on brain's intrinsic compensatory capacity (autoregulation) and oxygenation, besides computational analysis of multiple continuous streams of neuro-monitoring data and equipment development to easily display this information [14, 23, 42–46]. In this way, non-invasive techniques are coming forward to give quick ICP information to neurocritical care team, including transcranial Doppler, optic nerve sheath diameter, near-infrared spectroscopy, tympanic membrane displacement, visual-evoked potentials, some other measurements of the optic nerve,

*Example of multimodal brain monitoring recording during plateau wave, extracted from Dias et al. [45].*

*Altered ICP pulse waveform indicating compromised intracranial compliance, extracted from Dias et al. [45].*

*DOI: http://dx.doi.org/10.5772/intechopen.94077*

the mentioned study [45].

of arterial blood pressure and heart rate (**Figure 5**) [45].

components (P1 < P2 > P3) showed altered ICC [45] (**Figure 6**).

#### *Intracranial Pressure Waveform: History, Fundamentals and Applications in Brain Injuries DOI: http://dx.doi.org/10.5772/intechopen.94077*

decreased volume-pressure compensatory reserve such as TBI and many other brain pathologies. It consists of sudden increases in ICP to peaks of 40-100 mmHg that persists for 5–20 minutes [14, 45, 46]. The study observed plateau waves in 44% of the patients and that abrupt increase of ICP above 40 mmHg was associated with an increase in amplitude of ICP pulse waveform and also with important decrease in CPP, cerebral blood flow and oxygenation, despite stable cardiovascular variables of arterial blood pressure and heart rate (**Figure 5**) [45].

When analyzing ICP pulse waveform during plateau waves, a statistically significant increase in amplitude and a change in its shape were noted. The ICP pulse components (P1 < P2 > P3) showed altered ICC [45] (**Figure 6**).

Although slight increases in ICP that last for short period are not usually associated with poor outcome, if plateau waves are sustained over 30 minutes it could have a negative impact on patient's recovery as intracranial hypertension compromises cerebral perfusion and implicates neuronal deterioration [14, 23, 42, 43, 46]. The analysis of ICP absolute values and waveform patterns over time could provide important information for early detection of ICH in TBI patients of the mentioned study [45].

The debate about how ICP waveform analysis could provide improved clinical benefit and a more actionable evidence to bedside addresses integrated metrics on brain's intrinsic compensatory capacity (autoregulation) and oxygenation, besides computational analysis of multiple continuous streams of neuro-monitoring data and equipment development to easily display this information [14, 23, 42–46].

In this way, non-invasive techniques are coming forward to give quick ICP information to neurocritical care team, including transcranial Doppler, optic nerve sheath diameter, near-infrared spectroscopy, tympanic membrane displacement, visual-evoked potentials, some other measurements of the optic nerve,

**Figure 5.** *Example of multimodal brain monitoring recording during plateau wave, extracted from Dias et al. [45].*

**Figure 6.**

*Altered ICP pulse waveform indicating compromised intracranial compliance, extracted from Dias et al. [45].*

*Advancement and New Understanding in Brain Injury*

**Classification Categories Examples** Clinical severity Mild GCS: 13–15

Pathoanatomic type Focal (one concise area) Skull fracture

Mechanism of injury Penetrating Gunshot wound/projectile

As a result of this intricate association the ICP may rise if intrinsic compensatory mechanisms are not preserved and the sustained hypertension can prevent adequate perfusion depriving the brain of oxygen and nutrition. The combination of all situations related to TBI mentioned above need specific and adequate management through the whole trauma assistance from the pre-hospital setting to the critical

Blunt Head rotation

Moderate GCS: 9–12 Severe GCS ≤ 8

Diffuse (widespread area) Diffuse axonal injury

Contusion Epidural hematomas Subdural hematomas Subarachnoid hemorrhage Intraparenchymal hemorrhage

Concussion

Jolt/blast

Chronic traumatic encephalopathy

Pierced object/weapons (knife, etc.)

Acceleration-deceleration

The main method of assessment and management of severe TBI is monitoring

Neurocritical care specialists routinely base their clinical reasoning looking at the absolute value of ICP – measured in mmHg or cmH2O – combined with imaging exams – CT-scan or MRI. However, the numbers may not translate the entire complexity of intracranial dynamic. It is suggested that the ICP waves and the study of its morphology could bring differential evidence of altered intracranial compliance and

A qualitative analysis of the ICP waveform [44] described the relationship between amplitude of ICP pulse wave, values of ICP, values of cerebral perfusion pressure (CPP), and the outcome of severe head-injured patients. Intracranial hypertension was evidenced by absolute values of ICP and CT-scan parameters. In those with fatal outcomes there was an increase in the ICP waveform amplitude along with an increase of ICP value up to 25 mmHg, however, above this value the amplitude began to decrease. This breakpoint trend in the amplitude-value relationship was not present in patients with good/moderate outcome. Thus, it is suggested that the physics involving ICP, CPP and parenchyma dynamics inside intracranial cavities was somehow translated into the waveforms, and its analysis and correla-

Another study [45] involving TBI patients described the ICP plateau waves characteristics using multimodal brain monitoring as well as calculated indices of brain compensatory reserve and cerebrovascular reactivity. Plateau waves are associated with working cerebrovascular reactivity and occur in situations of

and treatment of ICP. It is a level II-B of evidence recommended to reduce in-

care unit (CCU) and subsequent rehabilitation [36, 40].

tions could be a useful additional tool for outcome prediction.

hospital and 2-week post-injury mortality [23, 41].

changes of pressure regimen [14, 23, 42, 43].

**8**

**Table 1.**

*Different classifications of TBI.*

retina, and pupil, besides the routinely used imaging exams of CT-scan and MRI [23, 42, 43, 45]. There is also a new non-invasive method of ICP monitoring that provides morphological data of ICP waves and intracranial compliance, adding celerity to this multimodal scenario [47, 48].

It is well established that ICH is an important issue after TBI because of its relationship to overall outcomes and all guidelines recommend a comprehensive ICP assessment – either invasively or non-invasively. Information about absolute values and waveform characteristics of ICP may together contribute to direct optimal management of TBI and good patient care [23, 42, 43, 45, 47, 48].

### **4.4 Increased ICP outside ICU environment**

The brain constitutes approximately 80% of intracranial volume, and blood and CSF each account for 10% [49–51]. The first compensatory mechanism for maintenance of normal ICP involves displacement and reduction of the CSF compartment, reduction of CBF, and lastly, displacement of cerebral parenchyma causing herniation. The slower the increment in ICP, the more useful this regulatory system. Therefore, rapidly growing masses like malignant gliomas have a higher risk of causing brain herniation than slow-growing tumors like meningiomas or nerve sheath tumors [52].

Transient elevation in ICP, generally from 50 to 100 mmHg and 5 to 20 minutes, leads to plateau wave phenomena. It can occur spontaneously or start after coughing, sneezing, or changes in position. This transient intracranial hypertension period may be accompanied also by transient headache, transient alteration of the level of consciousness and focal deficits [49, 50].

Obesity and its relation with sleep apnea obstructive syndrome may show ICC impairment due to overnight hypercarbia leading to cerebral vasodilation. Also, this population is likely to develop chronic idiopathic intracranial hypertension. Moreover, hydrocephalus patients of any etiology, migraineurs, progressive neurological focal and/or gait disorders, all these situations mentioned here for outpatients practice raise the yellow sign on the need for ICC evaluation.
