Neurocrit Care (2015) 22:348–359 DOI 10.1007/s12028-015-0133-x
REVIEW ARTICLE
Regional Brain Monitoring in the Neurocritical Care Unit Jennifer Frontera1 • Wendy Ziai2 • Kristine O’Phelan3 • Peter D. Leroux4 • Peter J. Kirkpatrick5 • Michael N. Diringer6 • Jose I. Suarez7 • the Second Neurocritical Care Research Conference Investigators
Published online: 2 April 2015 Ó Springer Science+Business Media New York 2015
Abstract Regional multimodality monitoring has evolved over the last several years as a tool to understand the mechanisms of brain injury and brain function at the cellular level. Multimodality monitoring offers an important augmentation to the clinical exam and is especially useful in comatose neurocritical care patients. Cerebral microdialysis, brain tissue oxygen monitoring, and cerebral blood flow monitoring all offer insight into permutations in brain chemistry and function that occur in the context of brain injury. These tools may allow for development of individual therapeutic strategies that are mechanistically driven and
The Second Neurocritical Care Research Conference Investigators are listed in ‘‘Appendix’’ & Jennifer Frontera [email protected]; [email protected] 1
Cerebrovascular Center, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland Clinic Mail Code S80, Cleveland, OH 44195, USA
2
Department of Neurology, Neurological Surgery, Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA
3
Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA
4
Main Line Health Brain and Spine Center, Wynnewood, PA, USA
5
Division of Neurosurgery, University of Cambridge, Cambridge, UK
6
Section Neurological Critical Care, Department of Neurology, Neurosurgery, and Anesthesiology, Washington University, St Louis, MO, USA
7
Division of Vascular Neurology and Neurocritical Care, Department of Neurology, Baylor College of Medicine, Houston, TX, USA
123
goal-directed. We present a summary of the discussions that took place during the Second Neurocritical Care Research Conference regarding regional brain monitoring. Keywords Neuromonitoring Neurocritical care Microdialysis Brain tissue oxygenation Cerebral blood flow
Introduction One of the missions of the Neurocritical Care Research Network (NCRN) is to enhance the understanding of neurocritical care disorders and improve outcomes among neurocritically ill patients. The goal of the Second Neurocritical Care Research Conference held in May 2012 was to explore multimodality monitoring (MMM) in an interdisciplinary, international setting with the objective of outlining research priorities, tools, and trial designs utilizing MMM. This paper aims to summarize regional MMM techniques including microdialysis (presented by Kristine O’Phelan), brain tissue oxygenation (presented by Peter D LeRoux), regional cerebral blood flow (CBF) monitoring (presented by Peter Kirkpatrick), and global CBF monitoring (presented by Michael Diringer).
Presentations Cerebral Microdialysis Cerebral microdialysis is an accurate and continuous way of monitoring brain chemistry at a cellular level. It is an established technique that has been studied in experimental models for decades [1–3]. In humans, over 163 articles on
Neurocrit Care (2015) 22:348–359
microdialysis have been published over the last 20 years [4, 5]. Microdialysis probes are typically placed in the subcortical white matter either via a tunneling technique (often performed intraoperatively during a craniotomy) or a bolt. Tunneling offers the advantage of more accurate targeting of penumbral or peri-lesional tissue, while bolting can be performed easily at the bedside, and is often used in patients without a planned neurosurgical intervention. Bolts are typically placed at Kocher’s point, which may limit penumbral targeting. In general, probes should be positioned in the key area of interest. In cases of focal brain injury, contralateral probes may reflect normal brain biochemistry due to the small regional sampling area of the probe and are of limited utility in guiding management. Artificial CSF dialysate is perfused at a standard rate (typically 0.3 lL/min) through the microdialysis catheter (10 mm membrane). Molecules below the cutoff size of the semipermeable membrane (usually 10,000–20,000 daltons) diffuse from the extracellular space into the perfusion fluid. The perfusion fluid containing these molecules can then be collected and analyzed at the bedside to provide information about capillary micronutrient and drug delivery and neuronal and glial metabolites. The most commonly measured interstitial brain analytes are lactate, pyruvate (and lactate to pyruvate ratio), glucose, glutamate, and glycerol. Normative values have been established and are listed in Table 1 [6]. Low glucose values correlate with increased tissue injury and poor outcome. The lactate to pyruvate ratio (LPR) indicates energy failure and ischemia. The LPR threshold for ischemia is hotly debated in the literature, with some advocating LRP >25 and others >40 as indicative of ischemia [5, 7–9]. Glycerol is a marker of cellular stress, low oxygen, or low glucose levels. Glycerol levels increase with intracellular calcium entry, which activates phospholipases leading to phospholipid degradation and cellular membrane breakdown. Finally, glutamate is an excitatory amino acid neurotransmitter that is likely a marker of late injury. Currently, microdialysis is frequently used and has been well studied in patients with traumatic brain injury (TBI). Metabolic consequences of TBI include alterations in glucose metabolism [10, 11], and reductions in the cerebral metabolic rate for oxygen (CMRO2) [12, 13]. CMRO2 may be decreased by up to 50 % acutely after TBI due to calcium-mediated impairment of mitochondrial function. Ion fluxes across membranes that occur after TBI result in loss of membrane potential, neurotransmitter release, and reuptake. Activation of such high energy processes can lead to ischemia if oxygen and glucose supply is inadequate or if mitochondrial functions are impaired. Additionally, ischemia and shear injury can cause excitatory amino acid release, calcium influx, and potassium efflux from glial cells resulting in astrocyte swelling, direct compression of
349 Table 1 Normative values for brain and subcutaneous microdialysis Analyte
Brain
Subcutaneous
Glucose
1.5–2 mM
5 mM
Lactate
2 mM
Pyruvate
120 lM
Lactate/pyruvate
15–20
Glycerol
50 lM
Glutamate
10 lM
200 lM
microvessels by astrocyte foot processes, vessel spasm, and consequent decrease in CBF and ischemia. Systemic hypotension and hypoxia following trauma, globally elevated ICP, and locally reduced perfusion due to cerebral contusion or hematoma all conspire to produce tissue ischemia and necrosis. It is important to note, however, that ischemia and cellular stress may be different. In a microdialysis study of 19 patients, 25 % had elevated LPR, though only 2.4 % showed PET evidence of ischemia, suggesting that mitochondrial failure may be the culprit for metabolic distress, rather than inadequate substrate delivery [14]. Future uses of microdialysis might include probes to measure higher molecular weight molecules such as cytokines or inflammatory markers. Additionally, microdialysis might be used to provide local drug delivery or to monitor the effect of systemic medications on the biochemistry of the central nervous system. In a research context, microdialysis might offer a useful biomarker surrogate endpoint to study brain metabolism at the tissue level. Brain Oxygen Monitoring The aim of MMM is to integrate several different measures of brain activity along with the clinical exam. MMM is particularly helpful in patients with limited neurological exams, such as comatose patients with subarachnoid hemorrhage or TBI. Indeed, MMM has been most widely studied in TBI patients. TBI is the most common cause of death worldwide and causes more deaths in men aged 15 min). Of those with hypoxia 73 % had unfavorable outcome and 55 % died compared to 43 % with poor outcome and 22 % mortality rate among those without hypoxia (OR 4.0, 95 % CI 1.9–8.2 for worse outcome; OR 4.6, 95 % CI 2.2–9.6 for death) [16]. The rate of adverse events related to the PbtO2 probe was 0.7 %. The duration and burden of brain tissue hypoxia (duration of time < 15 mmHg) have also been associated with worse outcome at 30 days, even after adjusting for Marshall CT score, age, admission Glasgow Coma Scale (GCS), APACHE II score, and ICP (adjusted OR for favorable outcome 0.89, 95 % CI 0.79–0.99, p = 0.04) [17, 18]. These data demonstrate that PbtO2 is not merely a surrogate for ICP or CPP, but is independently associated with outcome. Since brain tissue hypoxia has been associated with worse outcomes, the next logical question is whether PbtO2-guided interventions to limit the incidence and duration of hypoxia will have an impact on outcome. Different therapeutic strategies exist to ameliorate brain tissue hypoxia. Figure 1 shows different interventions and their corresponding response rate in terms of improving PbtO2 values. In a systematic review of clinical studies in severe TBI, PbtO2-based therapy in combination with ICP/ Table 2 Local and systemic factors that influence brain oxygenation Local factors O2 consumption by neurons and glia O2 diffusion conditions/gradients in tissue Number of perfused capillaries per tissue volume Length and diameter of perfused capillaries Capillary perfusion rate and microflow pattern Hemoglobin oxygen release in microcirculation Systemic factors Arterial blood pressure ICP PaO2 PaCO2 pH Temperature Blood hemoglobin content Viscosity Hematocrit
Neurocrit Care (2015) 22:348–359
Fig. 1 Medical Interventions for Brain Hypoxia. Figure 2 of Bohman et al. [38]
CPP-guided therapy was compared to ICP/CPP-guided therapy alone. Among 491 patients analyzed, 61 % of those with PbtO2-guided therapy had a favorable outcome compared to 42 % in the ICP/CPP alone group (favorable outcome OR 2.1, 95 % CI 1.4–3.1) [19]. However, systematic reviews cannot control for institutional practice variations and differences in patient demographics at different sites. Nevertheless, such studies provide proof of concept evidence for larger prospective studies. The BOOST II trial is a NIH/NINDS sponsored multicenter, phase II, randomized, single blind, controlled study of the efficacy of combined PbtO2 and ICP monitor-guided care versus ICP monitor-guided care alone in severe TBI patients. The primary outcome is the reduction in the fraction of time that brain oxygen levels are below the critical threshold of 20 mmHg. Secondary outcomes include safety and feasibility. The BOOST II trial prescribes certain treatment suggestions based on ICP and PbtO2 values that may serve as treatment options in general practice (Table 3(A), (B)). The future of brain oxygen monitoring depends on determining if targeted management improves outcomes since it is not the monitor that makes the difference, rather the treatment that is given in response to monitoring. More monitoring and more treatment may not necessarily translate to better outcomes. The BOOST trial should provide vital data to answer this question. Further studies that track patient-identified meaningful outcomes are required. Regional CBF Monitoring It has now been established that Neurointensive care can improve outcomes and we can ask whether manipulation of
351
CBF plays a significant role. All secondary injuries resulting from acute brain injury (increased ICP, hypoxia, hypotension, hyperthermia, inflammation, seizures and excitotoxicity) can theoretically be linked to pathologies directly or indirectly related to vascular tone and CBF. However, raw CBF measurements may be of limited value due to extensive overlap between normal and abnormal ranges, where CBF thresholds are largely unknown, constantly changing with time, and are likely to be pathology and patient specific. At the extremes, CBF can be shown to correlate directly with cortical failure, for example in the presence of massive ICP elevation where CPP falls below 60 mmHg. As mentioned above, the goal of MMM at this time is to provide better direction and ultimately goal-directed therapy where utility has yet to be proven. This requires a research-oriented software such as ICM+ installed in a standard IBM PC equipped with a low-cost analog-todigital converter computer system that is able to integrate the results of analysis of ICP, CPP, transcranial Doppler (TCD) blood flow velocity, jugular bulb oxygen saturation, laser Doppler blood flow, and NIRS [20]. The ICM+ software gives real-time data on these parameters some of which have better prognostic value than ICP and CPP in isolation. Currently, ICP and CPP monitoring have thresholds defining survivors from fatalities, but it does not tell us how well patients will survive [21]. Using secondary ICP characteristics (i.e., Pressure Reactivity Index: PRx), over a relatively normal range of CPP, there is a dramatic statistical change in PRx which can be measured reliably and appears to have prognostic value [22]. As CPP falls below 60 mmHg, PRx rises with a linear inverse relationship between positive autoregulation, dysautoregulation, and poor outcome. PRx has been previously described in this review. The pressure–volume compensatory reserve (RAP) index is an ICP-derived index which evaluates dynamics of pressure–volume compensatory reserve [23]. The ICP waveform has three components each with different frequencies: pulse waveform, respiratory waveform, and ‘‘slow waves’’ (Lundberg B waves). The amplitude of the most prominent component of the pulse waveform (which has a frequency equal to the heart rate) is called AMP. The RAP is the correlation coefficient between the AMP and the mean ICP produced by a linear correlation between 40 consecutive, time-averaged (over 6–10 s) data points of AMP and ICP. It represents the ‘‘pressure–volume curve,’’ and is a measure of cerebral compliance. Values of RAP close to 0 represent good pressure–volume compensation (no synchronization between changes in AMP (intracranial volume) and ICP); RAP close to 1 indicates a high correlation between AMP and ICP and that the pressure–volume
123
123 Tier 2 1. Adjust ventilator parameters to increase PaO2 by increasing FiO2 to 100 % 2. Increase PaO2 by adjusting PEEP 3. Increase CPP up to a maximum >70 mmHg with vasopressors 4. Adjust ventilator rate to increase PaCO2 to 45–50 mmHg 5. Transfuse PRBCs to reach Hgb > 10 g/dL
2. High-dose mannitol >1 g/kg
3. Repeat CT to determine if increased size of intracranial mass lesions
4. Treat surgically remediable lesions with craniotomy according to guidelines
5. Adjust temperature to 35–37 °C using active cooling measures
8. Consider adding AEDs, either phenytoin or levetiracetam for 1 week only
1. Adjust ventilator rate to lower PaCO2 to 32–35 mmHg
7. Hypertonic saline 8. Adjust ventilator parameters to increase PaO2 by increasing FiO2 to 60 %
7. Add EEG monitoring
Tier 2
6. Standard dose of mannitol (0.25–1.0 g/kg) to be administered as bolus infusion
6. Increase PaO2 by adjusting PEEP
5. Transfuse to Hgb C 10 g/dL
4. Increase PaO2 by increasing PEEP
2. Increase CPP up to a maximum of 70 mmHg with vasopressors 3. Adjust ventilator parameters to increase PaO2 by increasing FiO2 to 100 %
1. High-dose mannitol 1 g/kg or frequent boluses standard dose mannitol
Tier 2
11. Consider AEDs, either phenytoin or levetiracetam for 1 week only
10. Consider EEG monitoring
9. Increase PaO2 by adjusting PEEP
5. Increase CPP up to a maximum > 70 mmHg with fluid bolus
4. CSF drainage (if EVD available)
3. Pharmacologic analgesia and sedation
2. Ensure temperature < 38 °C
6. Hypertonic saline: titrate to ICP control and maintain serum Na+ 155–160
3. Increase CPP to 70 mmHg with fluid bolus
3. Adjust pharmacologic analgesia and sedation: titrate to effect 4. Optimize hemodynamics
2. Ensure temperature
REVIEW ARTICLE
Regional Brain Monitoring in the Neurocritical Care Unit Jennifer Frontera1 • Wendy Ziai2 • Kristine O’Phelan3 • Peter D. Leroux4 • Peter J. Kirkpatrick5 • Michael N. Diringer6 • Jose I. Suarez7 • the Second Neurocritical Care Research Conference Investigators
Published online: 2 April 2015 Ó Springer Science+Business Media New York 2015
Abstract Regional multimodality monitoring has evolved over the last several years as a tool to understand the mechanisms of brain injury and brain function at the cellular level. Multimodality monitoring offers an important augmentation to the clinical exam and is especially useful in comatose neurocritical care patients. Cerebral microdialysis, brain tissue oxygen monitoring, and cerebral blood flow monitoring all offer insight into permutations in brain chemistry and function that occur in the context of brain injury. These tools may allow for development of individual therapeutic strategies that are mechanistically driven and
The Second Neurocritical Care Research Conference Investigators are listed in ‘‘Appendix’’ & Jennifer Frontera [email protected]; [email protected] 1
Cerebrovascular Center, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland Clinic Mail Code S80, Cleveland, OH 44195, USA
2
Department of Neurology, Neurological Surgery, Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA
3
Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA
4
Main Line Health Brain and Spine Center, Wynnewood, PA, USA
5
Division of Neurosurgery, University of Cambridge, Cambridge, UK
6
Section Neurological Critical Care, Department of Neurology, Neurosurgery, and Anesthesiology, Washington University, St Louis, MO, USA
7
Division of Vascular Neurology and Neurocritical Care, Department of Neurology, Baylor College of Medicine, Houston, TX, USA
123
goal-directed. We present a summary of the discussions that took place during the Second Neurocritical Care Research Conference regarding regional brain monitoring. Keywords Neuromonitoring Neurocritical care Microdialysis Brain tissue oxygenation Cerebral blood flow
Introduction One of the missions of the Neurocritical Care Research Network (NCRN) is to enhance the understanding of neurocritical care disorders and improve outcomes among neurocritically ill patients. The goal of the Second Neurocritical Care Research Conference held in May 2012 was to explore multimodality monitoring (MMM) in an interdisciplinary, international setting with the objective of outlining research priorities, tools, and trial designs utilizing MMM. This paper aims to summarize regional MMM techniques including microdialysis (presented by Kristine O’Phelan), brain tissue oxygenation (presented by Peter D LeRoux), regional cerebral blood flow (CBF) monitoring (presented by Peter Kirkpatrick), and global CBF monitoring (presented by Michael Diringer).
Presentations Cerebral Microdialysis Cerebral microdialysis is an accurate and continuous way of monitoring brain chemistry at a cellular level. It is an established technique that has been studied in experimental models for decades [1–3]. In humans, over 163 articles on
Neurocrit Care (2015) 22:348–359
microdialysis have been published over the last 20 years [4, 5]. Microdialysis probes are typically placed in the subcortical white matter either via a tunneling technique (often performed intraoperatively during a craniotomy) or a bolt. Tunneling offers the advantage of more accurate targeting of penumbral or peri-lesional tissue, while bolting can be performed easily at the bedside, and is often used in patients without a planned neurosurgical intervention. Bolts are typically placed at Kocher’s point, which may limit penumbral targeting. In general, probes should be positioned in the key area of interest. In cases of focal brain injury, contralateral probes may reflect normal brain biochemistry due to the small regional sampling area of the probe and are of limited utility in guiding management. Artificial CSF dialysate is perfused at a standard rate (typically 0.3 lL/min) through the microdialysis catheter (10 mm membrane). Molecules below the cutoff size of the semipermeable membrane (usually 10,000–20,000 daltons) diffuse from the extracellular space into the perfusion fluid. The perfusion fluid containing these molecules can then be collected and analyzed at the bedside to provide information about capillary micronutrient and drug delivery and neuronal and glial metabolites. The most commonly measured interstitial brain analytes are lactate, pyruvate (and lactate to pyruvate ratio), glucose, glutamate, and glycerol. Normative values have been established and are listed in Table 1 [6]. Low glucose values correlate with increased tissue injury and poor outcome. The lactate to pyruvate ratio (LPR) indicates energy failure and ischemia. The LPR threshold for ischemia is hotly debated in the literature, with some advocating LRP >25 and others >40 as indicative of ischemia [5, 7–9]. Glycerol is a marker of cellular stress, low oxygen, or low glucose levels. Glycerol levels increase with intracellular calcium entry, which activates phospholipases leading to phospholipid degradation and cellular membrane breakdown. Finally, glutamate is an excitatory amino acid neurotransmitter that is likely a marker of late injury. Currently, microdialysis is frequently used and has been well studied in patients with traumatic brain injury (TBI). Metabolic consequences of TBI include alterations in glucose metabolism [10, 11], and reductions in the cerebral metabolic rate for oxygen (CMRO2) [12, 13]. CMRO2 may be decreased by up to 50 % acutely after TBI due to calcium-mediated impairment of mitochondrial function. Ion fluxes across membranes that occur after TBI result in loss of membrane potential, neurotransmitter release, and reuptake. Activation of such high energy processes can lead to ischemia if oxygen and glucose supply is inadequate or if mitochondrial functions are impaired. Additionally, ischemia and shear injury can cause excitatory amino acid release, calcium influx, and potassium efflux from glial cells resulting in astrocyte swelling, direct compression of
349 Table 1 Normative values for brain and subcutaneous microdialysis Analyte
Brain
Subcutaneous
Glucose
1.5–2 mM
5 mM
Lactate
2 mM
Pyruvate
120 lM
Lactate/pyruvate
15–20
Glycerol
50 lM
Glutamate
10 lM
200 lM
microvessels by astrocyte foot processes, vessel spasm, and consequent decrease in CBF and ischemia. Systemic hypotension and hypoxia following trauma, globally elevated ICP, and locally reduced perfusion due to cerebral contusion or hematoma all conspire to produce tissue ischemia and necrosis. It is important to note, however, that ischemia and cellular stress may be different. In a microdialysis study of 19 patients, 25 % had elevated LPR, though only 2.4 % showed PET evidence of ischemia, suggesting that mitochondrial failure may be the culprit for metabolic distress, rather than inadequate substrate delivery [14]. Future uses of microdialysis might include probes to measure higher molecular weight molecules such as cytokines or inflammatory markers. Additionally, microdialysis might be used to provide local drug delivery or to monitor the effect of systemic medications on the biochemistry of the central nervous system. In a research context, microdialysis might offer a useful biomarker surrogate endpoint to study brain metabolism at the tissue level. Brain Oxygen Monitoring The aim of MMM is to integrate several different measures of brain activity along with the clinical exam. MMM is particularly helpful in patients with limited neurological exams, such as comatose patients with subarachnoid hemorrhage or TBI. Indeed, MMM has been most widely studied in TBI patients. TBI is the most common cause of death worldwide and causes more deaths in men aged 15 min). Of those with hypoxia 73 % had unfavorable outcome and 55 % died compared to 43 % with poor outcome and 22 % mortality rate among those without hypoxia (OR 4.0, 95 % CI 1.9–8.2 for worse outcome; OR 4.6, 95 % CI 2.2–9.6 for death) [16]. The rate of adverse events related to the PbtO2 probe was 0.7 %. The duration and burden of brain tissue hypoxia (duration of time < 15 mmHg) have also been associated with worse outcome at 30 days, even after adjusting for Marshall CT score, age, admission Glasgow Coma Scale (GCS), APACHE II score, and ICP (adjusted OR for favorable outcome 0.89, 95 % CI 0.79–0.99, p = 0.04) [17, 18]. These data demonstrate that PbtO2 is not merely a surrogate for ICP or CPP, but is independently associated with outcome. Since brain tissue hypoxia has been associated with worse outcomes, the next logical question is whether PbtO2-guided interventions to limit the incidence and duration of hypoxia will have an impact on outcome. Different therapeutic strategies exist to ameliorate brain tissue hypoxia. Figure 1 shows different interventions and their corresponding response rate in terms of improving PbtO2 values. In a systematic review of clinical studies in severe TBI, PbtO2-based therapy in combination with ICP/ Table 2 Local and systemic factors that influence brain oxygenation Local factors O2 consumption by neurons and glia O2 diffusion conditions/gradients in tissue Number of perfused capillaries per tissue volume Length and diameter of perfused capillaries Capillary perfusion rate and microflow pattern Hemoglobin oxygen release in microcirculation Systemic factors Arterial blood pressure ICP PaO2 PaCO2 pH Temperature Blood hemoglobin content Viscosity Hematocrit
Neurocrit Care (2015) 22:348–359
Fig. 1 Medical Interventions for Brain Hypoxia. Figure 2 of Bohman et al. [38]
CPP-guided therapy was compared to ICP/CPP-guided therapy alone. Among 491 patients analyzed, 61 % of those with PbtO2-guided therapy had a favorable outcome compared to 42 % in the ICP/CPP alone group (favorable outcome OR 2.1, 95 % CI 1.4–3.1) [19]. However, systematic reviews cannot control for institutional practice variations and differences in patient demographics at different sites. Nevertheless, such studies provide proof of concept evidence for larger prospective studies. The BOOST II trial is a NIH/NINDS sponsored multicenter, phase II, randomized, single blind, controlled study of the efficacy of combined PbtO2 and ICP monitor-guided care versus ICP monitor-guided care alone in severe TBI patients. The primary outcome is the reduction in the fraction of time that brain oxygen levels are below the critical threshold of 20 mmHg. Secondary outcomes include safety and feasibility. The BOOST II trial prescribes certain treatment suggestions based on ICP and PbtO2 values that may serve as treatment options in general practice (Table 3(A), (B)). The future of brain oxygen monitoring depends on determining if targeted management improves outcomes since it is not the monitor that makes the difference, rather the treatment that is given in response to monitoring. More monitoring and more treatment may not necessarily translate to better outcomes. The BOOST trial should provide vital data to answer this question. Further studies that track patient-identified meaningful outcomes are required. Regional CBF Monitoring It has now been established that Neurointensive care can improve outcomes and we can ask whether manipulation of
351
CBF plays a significant role. All secondary injuries resulting from acute brain injury (increased ICP, hypoxia, hypotension, hyperthermia, inflammation, seizures and excitotoxicity) can theoretically be linked to pathologies directly or indirectly related to vascular tone and CBF. However, raw CBF measurements may be of limited value due to extensive overlap between normal and abnormal ranges, where CBF thresholds are largely unknown, constantly changing with time, and are likely to be pathology and patient specific. At the extremes, CBF can be shown to correlate directly with cortical failure, for example in the presence of massive ICP elevation where CPP falls below 60 mmHg. As mentioned above, the goal of MMM at this time is to provide better direction and ultimately goal-directed therapy where utility has yet to be proven. This requires a research-oriented software such as ICM+ installed in a standard IBM PC equipped with a low-cost analog-todigital converter computer system that is able to integrate the results of analysis of ICP, CPP, transcranial Doppler (TCD) blood flow velocity, jugular bulb oxygen saturation, laser Doppler blood flow, and NIRS [20]. The ICM+ software gives real-time data on these parameters some of which have better prognostic value than ICP and CPP in isolation. Currently, ICP and CPP monitoring have thresholds defining survivors from fatalities, but it does not tell us how well patients will survive [21]. Using secondary ICP characteristics (i.e., Pressure Reactivity Index: PRx), over a relatively normal range of CPP, there is a dramatic statistical change in PRx which can be measured reliably and appears to have prognostic value [22]. As CPP falls below 60 mmHg, PRx rises with a linear inverse relationship between positive autoregulation, dysautoregulation, and poor outcome. PRx has been previously described in this review. The pressure–volume compensatory reserve (RAP) index is an ICP-derived index which evaluates dynamics of pressure–volume compensatory reserve [23]. The ICP waveform has three components each with different frequencies: pulse waveform, respiratory waveform, and ‘‘slow waves’’ (Lundberg B waves). The amplitude of the most prominent component of the pulse waveform (which has a frequency equal to the heart rate) is called AMP. The RAP is the correlation coefficient between the AMP and the mean ICP produced by a linear correlation between 40 consecutive, time-averaged (over 6–10 s) data points of AMP and ICP. It represents the ‘‘pressure–volume curve,’’ and is a measure of cerebral compliance. Values of RAP close to 0 represent good pressure–volume compensation (no synchronization between changes in AMP (intracranial volume) and ICP); RAP close to 1 indicates a high correlation between AMP and ICP and that the pressure–volume
123
123 Tier 2 1. Adjust ventilator parameters to increase PaO2 by increasing FiO2 to 100 % 2. Increase PaO2 by adjusting PEEP 3. Increase CPP up to a maximum >70 mmHg with vasopressors 4. Adjust ventilator rate to increase PaCO2 to 45–50 mmHg 5. Transfuse PRBCs to reach Hgb > 10 g/dL
2. High-dose mannitol >1 g/kg
3. Repeat CT to determine if increased size of intracranial mass lesions
4. Treat surgically remediable lesions with craniotomy according to guidelines
5. Adjust temperature to 35–37 °C using active cooling measures
8. Consider adding AEDs, either phenytoin or levetiracetam for 1 week only
1. Adjust ventilator rate to lower PaCO2 to 32–35 mmHg
7. Hypertonic saline 8. Adjust ventilator parameters to increase PaO2 by increasing FiO2 to 60 %
7. Add EEG monitoring
Tier 2
6. Standard dose of mannitol (0.25–1.0 g/kg) to be administered as bolus infusion
6. Increase PaO2 by adjusting PEEP
5. Transfuse to Hgb C 10 g/dL
4. Increase PaO2 by increasing PEEP
2. Increase CPP up to a maximum of 70 mmHg with vasopressors 3. Adjust ventilator parameters to increase PaO2 by increasing FiO2 to 100 %
1. High-dose mannitol 1 g/kg or frequent boluses standard dose mannitol
Tier 2
11. Consider AEDs, either phenytoin or levetiracetam for 1 week only
10. Consider EEG monitoring
9. Increase PaO2 by adjusting PEEP
5. Increase CPP up to a maximum > 70 mmHg with fluid bolus
4. CSF drainage (if EVD available)
3. Pharmacologic analgesia and sedation
2. Ensure temperature < 38 °C
6. Hypertonic saline: titrate to ICP control and maintain serum Na+ 155–160
3. Increase CPP to 70 mmHg with fluid bolus
3. Adjust pharmacologic analgesia and sedation: titrate to effect 4. Optimize hemodynamics
2. Ensure temperature
